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2,329,000 | Minimal exposure maximal precision ventriculoperitoneal shunt: how I do it. | Ventriculoperitoneal shunt is among the most frequent neurosurgical procedures, complicated by infection and obstruction. The first is influenced by number of skin incisions, catheter exposure and manipulation, and the latter by catheter position.</AbstractText>Presenting our neuronavigated laparoscopic-assisted minimal exposure shunt technique performed on 40 consecutive adults. No patient presented infection or distal catheter migration (mean follow-up 12 months). Ventricular catheter malpositioning associated with electromagnetic neuronavigation inaccuracy occurred in two patients with slit ventricles.</AbstractText>This technique demonstrates low infection/malfunction rate, postoperative pain, and cosmetic advantages. Limiting factors are availability of laparoscopic surgeons and neuronavigation if not familiar with the approach.</AbstractText> |
2,329,001 | Tertiary lymphoid structures in the choroid plexus in neuropsychiatric lupus. | The central nervous system manifestations of systemic lupus erythematosus (SLE) remain poorly understood. Given the well-defined role of autoantibodies in other lupus manifestations, extensive work has gone into the identification of neuropathic autoantibodies. However, attempts to translate these findings to patients with SLE have yielded mixed results. We used the MRL/MpJ-Faslpr/lpr mouse, a well-established, spontaneous model of SLE, to establish the immune effectors responsible for brain disease. Transcriptomic analysis of the MRL/MpJ-Faslpr/lpr choroid plexus revealed an expression signature driving tertiary lymphoid structure formation, including chemokines related to stromal reorganization and lymphocyte compartmentalization. Additionally, transcriptional profiles indicated various stages of lymphocyte activation and germinal center formation. The extensive choroid plexus infiltrate present in MRL/MpJ-Faslpr/lpr mice with overt neurobehavioral deficits included locally proliferating B and T cells, intercellular interactions between lymphocytes and antigen-presenting cells, as well as evidence for in situ somatic hypermutation and class switch recombination. Furthermore, the choroid plexus was a site for trafficking lymphocytes into the brain. Finally, histological evaluation in human lupus patients with neuropsychiatric manifestations revealed increased leukocyte migration through the choroid plexus. These studies identify a potential new pathway underlying neuropsychiatric lupus and support tertiary lymphoid structure formation in the choroid plexus as a novel mechanism of brain-immune interfacing. |
2,329,002 | Effect of Ambrisentan Therapy on the Expression of Endothelin Receptor, Endothelial Nitric Oxide Synthase and NADPH Oxidase 4 in Monocrotaline-induced Pulmonary Arterial Hypertension Rat Model. | Elevated endothelin (ET)-1 level is strongly correlated with the pathogenesis of pulmonary arterial hypertension (PAH). Expression level of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 is increased in the PAH patients. Ambrisentan, a selective endothelin receptor A (ERA) antagonist, is widely used in PAH therapy. The current study was undertaken to evaluate the effects of ambrisentan treatment in the monocrotaline (MCT)-induced PAH rat model.</AbstractText>Rats were categorized into control group (C), monocrotaline group (M) and ambrisentan group (Am). The M and Am were subcutaneously injected 60 mg/kg MCT at day 0, and in Am, ambrisentan was orally administered the day after MCT injection for 4 weeks. The right ventricle (RV) pressure was measured and pathological changes of the lung tissues were observed by Victoria blue staining. Protein expressions of ET-1, ERA, endothelial nitric oxide synthase (eNOS) and NOX4 were confirmed by western blot analysis.</AbstractText>Ambrisentan treatment resulted in a recovery of the body weight and RV/left ventricle+septum at week 4. The RV pressure was lowered at weeks 2 and 4 after ambrisentan administration. Medial wall thickening of pulmonary arterioles and the number of intra-acinar arteries were also attenuated by ambrisentan at week 4. Protein expression levels of ET-1 and eNOS were recovered at weeks 2 and 4, and ERA levels recovered at week 4.</AbstractText>Ambrisentan administration resulted in the recovery of ET-1, ERA and eNOS protein expression levels in the PAH model. However, the expression level of NOX4 remained unaffected after ambrisentan treatment.</AbstractText>Copyright © 2019. The Korean Society of Cardiology.</CopyrightInformation> |
2,329,003 | Androgen-deprivation therapy impairs left ventricle functions in prostate cancer patients. | Androgen-deprivation therapy (ADT) is a treatment option for locally advanced and metastatic prostate cancer (PCA). The aim of the study was to evaluate the effect of ADT on left ventricular (LV) functions assessed by speckle-tracking echocardiography (STE) in prostate cancer (PCA) patients.</AbstractText>Forty-nine consecutive PCA patients (mean age 71.5 ± 6.7 years) who would be treated with radiotherapy and ADT and 32 consecutive PCA patients (mean age 71.9 ± 7.0 years) who would be treated with radical or partial prostatectomy and 42 age-matched healthy men (mean age 70.5 ± 9.1 years) were included in our study. The left ventricular functions were assessed by both conventional echocardiography and STE at baseline and 6 months later.</AbstractText>There were not any significant difference in characteristics of the patients and controls. There were not any significant differences in conventional echocardiographic measures at baseline and at 6th month among the PCA patients and controls. Although there were not any significant differences in STE measures at baseline among the PCA patients and controls, the strain measures of the PCA patients receiving ADT decreased significantly at the 6th month and were significantly lower compared to strain measures of PCA patients undergoing prostatectomy and controls. There was not any statistically significant difference in baseline and 6th-month strain measures of the PCA patients undergoing prostatectomy.</AbstractText>ADT might be associated with decrease in LV longitudinal, circumferential, and radial strain measures in patients with PCA. STE might be useful for early identification of LV subclinical impairment in PCA patients treated with ADT.</AbstractText> |
2,329,004 | Association of Choroid Plexus Enlargement With Cognitive, Inflammatory, and Structural Phenotypes Across the Psychosis Spectrum. | The choroid plexus is an important physiological barrier and produces CSF and neurotrophic, angiogenic, and inflammatory factors involved in brain development. Choroid plexus abnormalities have been implicated in both schizophrenia and bipolar disorder. A previous choroid plexus transcriptomic analysis of schizophrenia identified an upregulation of immune and inflammatory genes that correlated with peripheral inflammatory markers. The purpose of this study was to examine choroid plexus volume in probands across the psychosis spectrum and in their first-degree and axis II cluster A relatives, as well as choroid plexus familiality and choroid plexus covariance with clinical, cognitive, brain, and peripheral marker measures.</AbstractText>Choroid plexus volume was quantified (using FreeSurfer) in psychosis probands, their first-degree and axis II cluster A relatives, and healthy control subjects, organized by DSM-IV-TR diagnosis. Analyte, structural connectivity, and genotype data were collected from a subset of study subjects.</AbstractText>Choroid plexus volume was significantly larger in probands compared with first-degree relatives or healthy control subjects; first-degree relatives had intermediate enlargement compared with healthy control subjects; and total choroid plexus volume was significantly heritable. Larger volume was associated with worse cognition, smaller total gray matter and amygdala volume, larger lateral ventricle volume, and lower structural connectivity in probands. Associations between larger volume and higher levels of interleukin 6 in probands was also observed.</AbstractText>These findings suggest the involvement of the choroid plexus across the psychosis spectrum with a potential pathophysiological mechanism involving the neuroimmune axis, which functions in maintaining brain homeostasis and interacting with the peripheral immune and inflammatory system. The choroid plexus may be an important target in future research.</AbstractText> |
2,329,005 | Effects of autophagy on synaptic-plasticity-related protein expression in the hippocampus CA1 of a rat model of vascular dementia. | This study aimed to explore the relationship between autophagy and synaptic plasticity in the pathogenesis of vascular dementia (VD). The autophagy inhibitor 3-methyladenine (3-MA) and the autophagy agonist rapamycin (Rap) were injected into the lateral ventricles of rats, and a rat VD model was established using a modified four-vessel occlusion method. The expression of LC3-II, synaptophysin (Syn), and postsynaptic density protein 95 (PSD-95) in the CA1 area of the rat hippocampus were detected using western blotting. Decreased Syn and PSD-95 expression in the VD group was accompanied by an increased LC3-II/LC3-I ratio. The expression of Syn and PSD-95 increased after 3-MA application, but decreased following Rap application. The LC3-II/LC3-I ratio was negatively correlated with Syn and PSD-95 expression. These findings suggest that autophagy may regulate synaptic plasticity in the hippocampus in a VD model of rats. Inhibition of autophagy is beneficial to the remodeling of synapses in the hippocampal CA1 area of the VD rat model, and this may provide a theoretical basis for the treatment and prevention of VD. |
2,329,006 | The "Twitching Technique": A New Space-Irrespective Laparoscopic Ligation Technique Using a JAiMY Needle Holder. | <b><i>Background:</i></b> Laparoscopic intracorporeal sutures and knots require advanced techniques in children. The JAiMY<sup>®</sup> needle holder (Endocontrol Company, Grenoble, France), a flexible jaw with both clockwise and anticlockwise revolving functions, enables the placement of sutures in very small working spaces. Using this tool, a novel new ligation method, which we named "twitching technique," can be performed. <b><i>Methods:</i></b> To perform the "twitching technique," first grasp the long tail of the thread with the JAiMY and the forceps on the needle side. Then, rotate the tip of the needle holder halfway in either direction and bring the forceps closer to the needle holder to make a ring using the thread. Grasp the thread at the crossing point with the forceps, and then catch the short tail through the ring with the needle holder. <b><i>Results (Case Presentation):</i></b> A 1-year-old boy presented with vomiting because of esophageal hiatal hernia. He was being treated for single ventricle and asplenia at our hospital. Laparoscopic esophageal hiatus plication was performed. Although the working space was extremely limited, the JAiMY and the "twitching technique" enabled steady suture placement and ligation. <b><i>Conclusions:</i></b> The "twitching technique" is an easy, steady, and safe method for performing ligation in difficult situations and may facilitate the performance of many laparoscopic surgeries in pediatric fields. |
2,329,007 | p38α MAPK inhibition translates to cell cycle re-entry of neonatal rat ventricular cardiomyocytes and de novo nestin expression in response to thrombin and after apex resection. | The present study tested the hypothesis that p38α MAPK inhibition leads to cell cycle re-entry of neonatal ventricular cardiomyocytes (NNVMs) and de novo nestin expression in response to thrombin and after apex resection of the neonatal rat heart. Thrombin (1 U/ml) treatment of 1-day old NNVMs did not induce cell cycle re-entry or nestin expression. Acute exposure of NNVMs to thrombin increased p38α MAPK and HSP27 phosphorylation and p38α/β MAPK inhibitor SB203580 abrogated HSP27 phosphorylation. Thrombin and SB203580 co-treatment of NNVMs led to bromodeoxyuridine incorporation and nestin expression. SB203580 (5 mg/kg) administration immediately after apex resection of 1-day old neonatal rat hearts and continued for two additional days shortened the fibrin clot length sealing the exposed left ventricular chamber. SB203580-treatment increased the density of troponin-T<sup>(+)</sup>-NNVMs that incorporated bromodeoxyuridine and expressed nuclear phosphohistone-3. Nestin<sup>(+)</sup>-NNVMs were selectively detected at the border of the fibrin clot and SB203580 potentiated the density that re-entered the cell cycle. These data suggest that the greater density of ventricular cardiomyocytes and nestin<sup>(+)</sup>-ventricular cardiomyocytes that re-entered the cell cycle after SB203580 treatment of the apex-resected neonatal rat heart during the acute phase of fibrin clot formation may be attributed in part to inhibition of thrombin-mediated p38α MAPK signalling. |
2,329,008 | Transcriptome and proteome profiling of neural stem cells from the human subventricular zone in Parkinson's disease. | It is currently accepted that the human brain has a limited neurogenic capacity and an impaired regenerative potential. We have previously shown the existence of CD271-expressing neural stem cells (NSCs) in the subventricular zone (SVZ) of Parkinson's disease (PD) patients, which proliferate and differentiate towards neurons and glial cells in vitro. To study the molecular profile of these NSCs in detail, we performed RNA sequencing and mass spectrometry on CD271<sup>+</sup> NSCs isolated from human post-mortem SVZ and on homogenates of the SVZ. CD271<sup>+</sup> cells were isolated through magnetic cell separation (MACS). We first compared the molecular profile of CD271<sup>+</sup> NSCs to the SVZ homogenate from control donors and then compared CD271<sup>+</sup> cells to CD11b<sup>+</sup> microglia. These results confirmed their neural stem cell identity. Finally we compared controls and PD patients to establish a specific molecular profile of NSCs and the SVZ in PD. While our transcriptome analysis did not identify any differentially expressed genes in the SVZ between control and PD patients, our proteome analysis revealed several proteins that were differentially expressed in PD. Some of these proteins are involved in cytoskeletal organization and mitochondrial function. Transcriptome and proteome analyses of NSCs from PD revealed changes in the expression of genes and proteins involved in metabolism, transcriptional activity and cytoskeletal organization. Our data suggest that NSCs may transit into a primed-quiescent state, that is in an "alert" non-proliferative phase in PD. Our results not only confirm pathological hallmarks of PD (e.g. impaired mitochondrial function), but also show that the NSCs from SVZ undergo significant changes at both transcriptome and proteome level following PD. |
2,329,009 | Calcimimetic R568 improved cardiac remodeling by classic and novel renin-angiotensin system in spontaneously hypertensive rats. | One major cause of cardiac mortality is heart disease caused by hypertension. The formation of cyclic adenosine monophosphate (cAMP) is inhibited by calcium-sensitive receptor (CaSR) activation which increases intracellular Ca2+</sup> concentrations and suppresses renin release. As we know, renin-angiotensin system (RAS) is closely related to development of essential hypertension (EH). Therefore, we focused on exploring the roles of NPSR568 (R568)-activated CaSR in cardiac remodeling of spontaneously hypertensive rats (SHRs), as well as the activity of classic and novel RAS. Wistar-Kyoto rats (WKYs) and SHRs were treated by R568 for four and eight weeks, respectively, and their blood pressure (BP), echocardiographic values, heart-to-body weight ratio (HW/BW%), and left ventricle-to-body weight ratio (LVW/BW%) were evaluated. Then Masson’s trichrome staining and hematoxylin and eosin staining as well as RT-qPCR analysis of β-isoform of myosin heavy chain and brain natriuretic peptide mRNA expression were performed. A Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and analysis of apoptosis marker proteins were used to assess the extent of myocardial apoptosis. The CaSR expression and the activity of classic and novel RAS were examined by immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay. The present study revealed that the development of hypertension was accompanied by increased BP, apoptosis, hypertrophy, and fibrosis, along with decreased expression of CaSR, decreased novel RAS, and increased classic RAS in myocardial tissues. R568 administration for four and eight weeks reduced BP and myocardial remodeling and reversed the low expression of CaSR; moreover, classic RAS was suppressed and novel RAS was activated in the myocardium. Taken together, these data indicate that R568 may effectively inhibit EH myocardial remodeling by inhibiting classic RAS and activating novel RAS in SHRs.</AbstractText>Our study reveals that low calcium-sensitive receptor (CaSR) expression is associated with the occurrence and development of essential hypertension-mediated myocardial remodeling. The activation of CaSR can reverse adverse myocardia remodeling by inhibiting local classical renin-angiotensin system (RAS) and activating novel RAS in cardiac tissues. CaSR is closely related to many cardiovascular diseases, but its specific mechanism remains not to be elucidated. To date, CaSR has not been investigated with regard to cardiovascular treatment; however, given the important relationship between CaSR and cardiovascular disease, CaSR regulators can be potential drugs for the treatment of cardiovascular disease.</AbstractText> |
2,329,010 | Role of Secondary Endoscopic Third Ventriculostomy in Children: Review of an Institutional Experience. | Endoscopic third ventriculostomy (ETV) has become a standard and safe procedure for obstructive hydrocephalus. ETV can also play an important role in children presenting with shunt malfunction with an added advantage of shunt independence. Secondary ETV can be defined as either a redo endoscopic ventriculostomy done after primary ETV stoma closure or that done in cases presenting with shunt malfunction.</AbstractText>The aim of our study was to evaluate the role of secondary ETV in the pediatric age group patients.</AbstractText>This is a retrospective analysis of 36 children (<18 years) who underwent ETV after shunt malfunction and 4 children with ETV done after previous ETV stoma closure from 2004 until 2018. In all patients, the obstructive pattern suggesting aqueduct outflow obstruction was observed on MRI. Patients were followed up for a mean period of 4.25 years.</AbstractText>ETV was considered successful if the patient avoided a shunt insertion later on in their life. Considering this definition, a success rate of 72% was observed with secondary ETV for shunt malfunction whereas a success rate of 75% was observed after primary ETV failure without any major side effects in any of the patients.</AbstractText>ETV can be considered a primary treatment modality in children with shunt malfunction and has a good success rate in cases presenting with closure of previously performed ETV stoma.</AbstractText>© 2019 S. Karger AG, Basel.</CopyrightInformation> |
2,329,011 | Cellular inflammation in pulmonary hypertension: Detailed analysis of lung and right ventricular tissue, circulating immune cells and effects of a dual endothelin receptor antagonist. | Growing evidence suggests that inflammation is crucially involved in the pathogenesis of pulmonary hypertension (PH) and consecutive right heart failure. The present study analyzed the inflammatory response in lung and right ventricle in a rat model of PH and evaluated the effects of the dual endothelin receptor antagonist (ERA) Macitentan. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in Sprague-Dawley rats (PH, n = 10) and compared to healthy controls (CON, n = 10) as well as monocrotalin-induced, macitentan-treated rats (THER, n = 10). Detection of Dendritic cells (DCs), regulatory T cells (Tregs) and others as well as RT-PCR based inflammatory gene expression analysis were performed. Circulating DCs and Tregs were quantified by flow cytometry in the rat model and in PH patients (n = 70) compared to controls (n = 52). Inflammatory cells were increased in lung and right ventricular tissue, whereas DCs and Tregs were decreased in blood. Expression of 17 genes in the lung and 20 genes in the right ventricle were relevantly (>2.0 fold) regulated in the PH group. These effects were, at least in part, attenuated in response to Macitentan treatment. In humans as well as rats, immune cells showed significant correlations to clinical, echocardiographic, and haemodynamic parameters. PH is accompanied by a distinct inflammatory response in lung and right but not left ventricular tissue attenuated by Macitentan. Correlations of circulating DCs as well as tissue resident immune cells with parameters reflecting right ventricular function raise the idea of both, promising biomarkers and novel treatment strategies. |
2,329,012 | [Effect of electroacupuncture on myocardial infarct size and expression of inflammatory cytokines and sympathetic-active substances in the myocardial ischemic tissue of rats]. | To investigate the effect of electroacupuncture (EA) on the expression of interleukin-8 (IL-8), interleukin-10 (IL-10), tyrosine hydroxylase (TH), β3-adrenergic receptor (β3AR), and endothelial nitric oxide synthase (eNOS) in myocardial tissue in ischemic myocardial injury rats, so as to reveal its underlying mechanisms in myocardial protection via anti-inflammation and sympathetic nerve remodeling.</AbstractText>A total of 48 male Sprague-Dawley rats were randomly divided into sham-operation (sham, n</i>＝9), sham ＋EA (n</i>＝9), model (n</i>＝15) and EA (n</i>＝15) groups. The myocardial ischemia (MI) model was established by ligation of the left anterior descending branch of the left coronary artery. EA (2 Hz/15 Hz，1.5－2 mA) was applied to bilateral "Neiguan" (PC6) for 30 min, once daily for 4 days. The myocardial infarct size was detected by 2, 3, 5 triphenyltetrazolium chloride (TTC) staining, myocardial histopathological changes and inflammatory infiltration were assessed by H．E. staining, and the expression of IL-8, IL-10, TH, β3AR, and eNOS in the myocardium was determined by using Western blot.</AbstractText>Compared with the sham group, a marked myocardial infarction was found in the left ventricle tissue, accompanied with disordered arrangement of myocardial fibers and higher degree of inflammatory cell infiltration, and increased expression of IL-8, TH, β3AR and eNOS in the myocardium in the model group (P</i><0.01), but without significant change in the expression of IL-10 (P</i>>0.05). After EA intervention and in comparison with the model group, the myocardial infarct size was significantly reduced (P</i><0.01), the severity of inflammatory cell infiltration and disordered arrangement of myocardial fibers were relieved, and the expression of IL-10 and eNOS proteins were significantly up-regulated (P</i><0.05), and the markedly up-regulated expression of IL-8, TH, and β3AR were significantly suppressed in the EA group (P</i><0.01)．.</AbstractText>EA intervention can reduce the myocardial infarct size (protective effect) in MI rats possibly by reducing inflammatory reaction and sympathetic nerve remodeling.</AbstractText> |
2,329,013 | Novel 3D heart left ventricle muscle segmentation method for PET-gated protocol and its verification. | The aim of this study was to propose and verify a universal method of left ventricular myocardium segmentation, able to operate on heart gated PET data with different sizes, shapes and uptake distributions. The proposed method can be classified as active model method and is based on the BEAS (B-spline Explicit Active Surface) algorithm published by Barbosa et al. The method was implemented within the Pmod PCARD software package. Method verification by comparison with reference software and phantom data is also presented in the paper.</AbstractText>The proposed method extends the BEAS model by defining mechanical features of the model: tensile strength and bending resistance. Formulas describing model internal energy increase during its stretching and bending are proposed. The segmentation model was applied to the data of 60 patients, who had undergone cardiac gated PET scanning. QGS by Cedars-Sinai and ECTb by Emory University Medical Centre served as reference software for comparing ventricular volumes. The method was also verified using data of left ventricular phantoms of known volume.</AbstractText>The results of the proposed method are well correlated with the results of QGS (slope: 0.841, intercept: 0.944 ml, R2</sup>: 0.867) and ECTb (slope: 0.830, intercept: 2.109 ml, R2</sup>: 0.845). The volumes calculated by the proposed method were very close to the true cavity volumes of two different phantoms.</AbstractText>The analysis of gated PET data by the proposed method results in volume measurements comparable to established methods. Phantom experiments demonstrate that the volume values correspond to the physical ones.</AbstractText> |
2,329,014 | Quantitative brain morphological analysis in CHARGE syndrome. | CHARGE syndrome (CS) is a rare congenital syndrome characterized by coloboma, heart anomaly, choanal atresia, retardation of growth and development, and genital and ear anomalies. While several neuroimaging studies have revealed abnormalities such as hypoplasia of the semicircular canal, olfactory nerve, cerebellum, and brainstem, no quantitative analysis of brain morphology in CS has been reported. We quantitatively investigated brain morphology in CS participants using structural magnetic resonance imaging (MRI) (N = 10, mean age 14.7 years old) and high-angular resolution diffusion MRI (HARDI) tractography (N = 8, mean age 19.4 years old) comparing with gender- and age-matched controls. Voxel-based analyses revealed decreased volume of the bilateral globus pallidus (left and right; p = 0.021 and 0.029), bilateral putamen (p = 0.016 and 0.011), left subthalamic nucleus (p = 0.012), bilateral cerebellum (p = 1.5 × 10<sup>-6</sup> and 1.2 × 10<sup>-6</sup>), and brainstem (p = 0.031), and the enlargement of the lateral ventricles (p = 0.011 and 0.0031) bilaterally in CS. Surface-based analysis revealed asymmetrically increased cortical thickness in the right hemisphere (p = 0.013). The group-wise differences observed in global cortical volume, gyrification index, and left cortical thickness were not statistically significant. HARDI tractography revealed reduced volume, elongation, and higher ADC values in multiple fiber tracts in patients in CS compared to the controls, but FA values were not statistically significantly different between the two groups. Facial features are known to be asymmetric in CS, which has been recognized as an important symptom in CS. Our results revealed that the cortex in CS has an asymmetric appearance similar to the facial features. In addition, the signal pattern of high ADC with statistically unchanged FA values of tractography pathways indicated the presence of other pathogenesis than vasogenic edema or myelination dysfunction in developmental delay in CS. |
2,329,015 | Systematic review and meta-analysis of MRI signs for diagnosis of idiopathic intracranial hypertension. | To systematically review the potential value of MRI signs in the assessment of intracranial hypertension (IIH).</AbstractText>MEDLINE and Embase were systematically searched for original studies investigating the accuracy of MRI signs in diagnosing IIH. Methodologic quality of included studies was assessed. Sensitivity and specificity were pooled with a bivariate random-effects model.</AbstractText>Twenty-one studies, comprising a total of 724 patients with IIH, were included. All studies had a case-control design. "Empty" sella (11 studies), posterior displacement of pituitary stalk (2 studies), meningoceles (2 studies), posterior globe flattening (8 studies), optic nerve head protrusion (6 studies), optic nerve enhancement (3 studies), optic nerve sheath distension (12 studies), optic nerve tortuosity (7 studies), slit-like ventricles (4 studies), tight subarachnoid spaces (3 studies), and inferior position of cerebellar tonsils (4 studies) had pooled sensitivity ranging between 6.1% and 68.6%, and pooled specificity ranging between 84.0% and 99.2%. Transverse sinus stenosis (8 studies) had pooled sensitivity of 84.4%; (95% CI: 65.9-93.9%) and pooled specificity of 94.9% (95% CI: 91.7-96.9%).</AbstractText>"Empty" sella, posterior pituitary stalk displacement, meningoceles, posterior globe flattening, optic nerve head protrusion, optic nerve enhancement, optic nerve sheath distension, optic nerve tortuosity, slit-like ventricles, tight subarachnoid spaces, and inferior position of cerebellar tonsils have overall high specificity but low sensitivity. Transverse sinus stenosis appears to be the most useful sign, because it has high specificity and fairly high sensitivity.</AbstractText>Copyright © 2019 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,329,016 | In vivo serial MRI of age-dependent neural progenitor cell migration in the rat brain. | The subventricular zone (SVZ) is a neurogenic niche in the mammalian brain, giving rise to migratory neural progenitor cells (NPC). In rodents, it is well-established that neurogenesis decreases with aging. MRI-based cell tracking has been used to measure various aspects of neurogenesis and NPC migration in rodents, yet it has not yet been validated in the context of age-related decrease in neurogenesis. This validation is critical to using these MRI techniques to study changes in neurogenesis that arise in diseases prevalent in aging populations and their combination with advanced cellular therapeutic approaches aiming to combat neurodegeneration. As such, in this work we used MRI-based cell tracking to measure endogenous neurogenesis and cell migration from the SVZ along the rostral migratory stream to the olfactory bulb, for 12 days duration, in rats aged 9 weeks to 2 years old. To enable the specific detection of NPCs by MRI, we injected micron sized particles of iron oxide (MPIOs) into the lateral ventricle to endogenously label cells within the SVZ, which then appeared as hypo-intensive spots within MR images. In vivo MRI data showed that the rate of NPC migration was significantly different between all ages examined, with decreases in the distance traveled and migration rate as age progressed. The total number of MPIO-labeled cells within the olfactory bulb on day 12, was significantly decreased when compared across ages in ex vivo high-resolution scans. We also demonstrate for the first-time, provocative preliminary data suggesting age-dependent MPIO uptake within the dentate gyrus (DG) as well. Histology to identify doublecortin-positive NPCs, verified the decrease in cell labeling as a function of aging, for both regions. The dramatic reduction of NPC labeling within the SVZ observed with MRI, validates the sensitivity of MRI-based cell tracking to neurogenic potential and demonstrates the importance of understanding the impact of age on the relationship of NPC and disease. |
2,329,017 | Increased oxytocinergic system activity in the cardiac muscle in spontaneously hypertensive SHR rats. | The present study aimed to determine whether the presence of cardiac hypertrophy due to arterial hypertension is associated with a change in the activity of the oxytocinergic system in cardiomyocytes.</AbstractText>The experiments were performed on male, spontaneously hypertensive rats (SHR, n</i> = 10) and normotensive Wistar-Kyoto rats (WKY, n</i> = 12). Blood samples were collected from both SHR and WKY animals to asses plasma oxytocin (OT) concentration; the rats were sacrificed by decapitation. Samples of the left and right ventricles were harvested for the analysis of the OT and oxytocin receptor (OTR) protein by ELISA, and OT and OTR mRNA expression by RT-PCR. Immunohistopathological studies were performed to confirm the presence of OTR receptors in the cardiac muscle of the ventricles.</AbstractText>Plasma OT concentration did not differ between SHR and WKY rats. In the SHR rats, the expression of OT mRNA and the OT protein level was higher in the left and the right ventricle, while OTR mRNA expression was significantly lower in both the left and the right ventricle. However, the level of OTR protein was higher only in the left ventricle of the SHR rats. The presence of OTR receptors was confirmed by immunohistochemical analysis in the muscle of the right and left ventricle.</AbstractText>The presence of arterial hypertension is associated with increased activity of the oxytocinergic system in the heart, especially in the area of the left ventricle. These findings support the important role of this system in the maintenance of cardiovascular homeostasis.</AbstractText>Copyright: © 2019 Termedia & Banach.</CopyrightInformation> |
2,329,018 | 14-3-3ζ protein protects against brain ischemia/reperfusion injury and induces BDNF transcription after MCAO in rat. | Brain ischemia is a leading cause of death and disability worldwide that occurs when blood supply of the brain is disrupted. Brain-derived neurotrophic factor (BDNF) is a protective factor in neurodegenerative conditions. Nevertheless, there are some problems when exogenous BDNF is to be used in the clinic. 14-3-3ζ is a pro-survival highly-expressed protein in the brain that protects neurons against death. This study evaluates 14-3-3ζ effects on BDNF transcription at early time point after ischemia and its possible protective effects against ischemia damage. Human 14-3-3ζ protein was purified after expression. Rats were assigned into four groups, including sham, ischemia, and two treatment groups. Stereotaxic cannula implantation was carried out in the right cerebral ventricle. After one week, rats underwent middle cerebral artery occlusion (MCAO) surgery and received 14-3-3ζ (produced in our laboratory or standard form as control) in the middle of ischemia time. At 6 h of reperfusion after ischemia, brain parts containing the hippocampus, the cortex, the piriform cortex-amygdala and the striatum were collected for real time PCR analysis. At 24 h of reperfusion after ischemia, neurological function evaluation and infarction volume measurement were performed. The present study showed that 14-3-3ζ could up-regulate BDNF mRNA at early time point after ischemia in the hippocampus, in the cortex and in the piriform cortex-amygdala and could also improve neurological outcome and reduce infarct volume. It seems that 14-3-3ζ could be a candidate factor for increasing endogenous BDNF in the brain and a potential therapeutic factor against brain ischemia. |
2,329,019 | Corticosteroid signaling at the brain-immune interface impedes coping with severe psychological stress. | The immune system supports brain plasticity and homeostasis, yet it is prone to changes following psychological stress. Thus, it remains unclear whether and how stress-induced immune alterations contribute to the development of mental pathologies. Here, we show that following severe stress in mice, leukocyte trafficking through the choroid plexus (CP), a compartment that mediates physiological immune-brain communication, is impaired. Blocking glucocorticoid receptor signaling, either systemically or locally through its genetic knockdown at the CP, facilitated the recruitment of <i>Gata3-</i> and <i>Foxp3</i>-expressing T cells to the brain and attenuated post-traumatic behavioral deficits. These findings functionally link post-traumatic stress behavior with elevated stress-related corticosteroid signaling at the brain-immune interface and suggest a novel therapeutic target to attenuate the consequences of severe psychological stress. |
2,329,020 | The rise of circulatory endothelin (ET)-1 and endothelin receptors (ET<sub>A</sub>, ET<sub>B</sub>) expression in kidney of obese wistar rat. | Endothelin (ET)-1, a circulatory protein, and its receptors (ETA</sub> and ETB</sub>) in various organs were reported to play a pivotal role in many diseases, including obesity. However, the changes of ETA</sub> and ETB</sub> expression in ventricle and kidney in obesity was less reported. The study is designed to observe the level of circulatory ET-1 and expression of ETA</sub>/ETB</sub> in ventricle and kidney of obese, as compared to non-obese, Wistar</i> rats.</AbstractText>Groups of obese 14 and 34 weeks Wistar</i> rats were compared to non-obese controls at similar ages. The obesity status was achieved by feeding the with high calories protein diet CP 551 + milk powder, while the control group was fed with a standard calorie protein AD II diet. The concentration of circulatory ET-1, ETA</sub> and ETB</sub> of ventricle and kidney were measured by Enzyme Linked Immunosorbent Assay (ELISA) technique after the termination of both groups at 14th</sup> and 24th</sup> weeks.</AbstractText>The level of circulatory ET-1, expression of ETA</sub> and ETB</sub> in kidney, and LDL of obese rats were significantly higher than control rats (T-Test, P<0.05) in the elder groups, while no differences of the ETA</sub> and ETB</sub> were found in the ventricle. No differences of the levels of circulatory ET-1, ETA</sub> and ETB</sub> expression were found between obese and control groups of younger rats (P>0.05). HDL levels were under normal value for both groups.</AbstractText>Obesity in elder obese rats leads to dysregulation of kidney vessels through activity of ET-1 and ETA</sub>/ETB</sub>.</AbstractText> |
2,329,021 | CRANIOPHARYNGIOMA - CLINICAL AND THERAPEUTIC OUTCOME DATA IN A MIXED COHORT OF ADULT AND PAEDIATRIC CASES. | Craniopharyngiomas are benign but locally invasive tumours of the sellar region that arise from ectopic embryonic remnants of Rathke's pouch, affecting both children (adamantinomatous type -aCP) and adults (papillary type -pCP) and associated with significant morbidity.</AbstractText>To study the clinical presentation of CRF as well as the posttreatment evolution of craniopharyngioma in children versus</i> adults in a large mixed cohort.</AbstractText>We performed a retrospective review of CRF patients evaluated in the National Institute of Endocrinology in Bucharest between 1990 and 2016.</AbstractText>A total of 107 patients (72 adults, 35 children) with a mean follow-up of 6.2 years were included. The presenting symptoms were mostly headache, visual impairment, symptoms of hypopituitarism, diabetes insipidus. Some symptoms or hormonal abnormalities were significantly more prevalent in the children group (p<0.05): nausea/ vomiting (47.8% vs 16.7%), photophobia (21.7% vs 5.6%), diabetes insipidus(28.5% vs 8.3%), GH deficiency (68.8% vs 17.1%). Impaired visual acuity (67.6%of cases) or visual fields (71.4%) were more frequent in adults compared to children (44.1%; 51.6%). The tumor dimensions were similar in both groups (3.05± 1.05 cm in children; 2.7± 1.07 cm in adults). Massive suprasellar extension reaching the third ventricle was frequently present in all cases. All cases underwent surgery but only a minority of those not cured received postoperative adjuvant radiotherapy. Frequent postoperative complications were: aggravation of the endocrine deficit (>80% of cases in both groups needed chronic replacement therapy), central diabetes insipidus (68.2% children, 34.3% of adults).</AbstractText>Despite similar tumor dimensions and extension compared to adults, craniopharyngioma in children is more frequently associated with signs of intracranial pressure. The results and complications of treatment are similar in adults and children.</AbstractText> |
2,329,022 | Changes of third ventricle diameter (TVD) mirror changes of the entire ventricular system after initial therapy and during follow-up in pediatric hydrocephalus. | Regular measurement of ventricular size is important in children with hydrocephalus. After closure of the fontanelle this is currently addressed by repetitive cranial MRI or CT imaging, coming along with risks of anaesthesia or radiation. As the third ventricle is accessible via the temporal bone window using ultrasound, determination of its diameter might be an easy and radiation-free alternative to assess the ventricular system. An essential precondition is that changes of the third ventricle diameter (TVD) mirror changes of the whole ventricular system. This study compares changes of TVD with changes of ventricular indices before and after initial treatment of hydrocephalus and during the following evolution.</AbstractText>MRT/CT images from 117 children with hydrocephalus were evaluated at time of diagnosis, after initial therapy and during follow-up with functional shunts. Measurements included axial TVD and three standard linear measures of the lateral ventricles (Evans Index - EI, fronto-occipital horn ratio - FOHR Index, and Cella Media Index - CMI). Furthermore, a correlation within subjects was calculated in 8 patients over the entire available follow-up.</AbstractText>Relative changes of TVD were significantly correlated to relative changes of all ventricular indices (r = 0.48, r = 0.68 and r = 0.701 for EI, FOHR and CMI, respectively, p < 0.01). The correlation within subjects was outstanding for EI (r = 0.988), FOHR (r = 0.99) and CMI (r = 0.99).</AbstractText>TVD showed a significant correlation with all three linear indices at the time of diagnosis and during follow-up changes independently of age, aetiology and ventricular width. TVD and its changes are therefore a reliable surrogate of changes in ventricular size in pediatric hydrocephalus undergoing treatment.</AbstractText>Copyright © 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation> |
2,329,023 | The Atrioventricular Junction: A Potential Niche Region for Progenitor Cells in the Adult Human Heart. | A stem cell niche is a microenvironment where stem cells reside in a quiescent state, until activated. In a previous rat model, we combined 5-bromo-2-deoxy-uridine labeling with activation of endogenous stem cells by physical exercise and revealed a distinct region, in the atrioventricular junction (AVj), with features of a stem cell niche. In this study, we aim to investigate whether a similar niche exists in the human heart. Paired biopsies from AVj and left ventricle (LV) were collected both from explanted hearts of organ donors, not used for transplantation (<i>N</i> = 7) and from severely failing hearts from patients undergoing heart transplantation (<i>N</i> = 7). Using antibodies, we investigated the expression of stem cell, hypoxia, proliferation and migration biomarkers. In the collagen-dense region of the AVj in donor hearts, progenitor markers, MDR1, SSEA4, ISL1, WT1, and hypoxia marker, HIF1-α, were clearly detected. The expression gradually decreased with distance from the valve. At the myocardium border in the AVj costaining of the proliferation marker Ki67 with cardiomyocyte nuclei marker PCM1 and cardiac Troponin-T (cTnT) indicated proliferation of small cardiomyocytes. In the same site we also detected ISL1<sup>+</sup>/WT1<sup>+</sup>/cTnT cells. In addition, heterogeneity in cardiomyocyte sizes was noted. Altogether, these findings indicate different developmental stages of cardiomyocytes below the region dense in stem cell marker expression. In patients suffering from heart failure the AVj region showed signs of impairment generally displaying much weaker or no expression of progenitor markers. We describe an anatomic structure in the human hearts, with features of a progenitor niche that coincided with the same region previously identified in rats with densely packed cells expressing progenitor and hypoxia markers. The data provided in this study indicate that the adult heart contains progenitor cells and that AVj might be a specific niche region from which the progenitors migrate at the time of regeneration. |
2,329,024 | Morphological and histopathological evaluation of autopsied patients with hypertensive cardiopathy. | Physiopathological processes in hypertensive heart disease are controlled by complex interactions between cardiomyocytes, extracellular matrix, microvasculature and other cells present in the myocardium.</AbstractText>To analyze morphological changes in hypertensive cardiopathy and to describe and compare findings in order to help clarify determinant factors.</AbstractText>42 fragments of the left ventricular myocardium and circumflex branch of the left coronary artery were obtained from individuals autopsied at the Clinical Hospital of the Federal University of Triângulo Mineiro (UFTM) in the period ranging from 1984 to 2018. Groups were split into individuals with hypertensive heart disease (HD) and individuals without heart disease (ND). Wall thickness was measured with a digital caliper and Computed Tomography. Quantification of collagen fibers was conducted by computerized morphometry and mast cell density was assessed by immunohistochemical methods.</AbstractText>There was a significant increase of heart weight in the HD group compared to the ND group, (p = 0.0002). There was a significant increase of thickness of the middle third of the free wall in the HD group compared to the ND group, (p = 0.04). There was a significant increase of collagen fibers in the left ventricle in the HD group compared to the ND group, (p < 0.0001). Concerning mast cell density, there was a significant increase in the left ventricle of individuals with HD immuno-labeled by the set anti-chymase/anti-tryptase (p < 0.0001). There was a significant increase of mast cell density in the circumflex branch of the left coronary artery of individuals with HD immuno-labeled by the set anti-chymase/anti-tryptase (p = 0.01).</AbstractText>Mast cells are involved in the development of hypertensive heart disease, contributing to the remodeling of collagen fibers in this disease.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,025 | Genetic Deletion of Esr1 in the Mouse Preoptic Area Disrupts the LH Surge and Estrous Cyclicity. | Estrogen receptor α (ESR1) is critical for the generation of the preovulatory LH surge. Experiments in rodents have indicated a role for neurons located in the anteroventral periventricular area and preoptic periventricular nucleus [termed the rostral periventricular area of the third ventricle (RP3V)] in surge generation. In the current study, we aimed to examine whether ESR1 expressed by RP3V neurons was necessary for the LH surge. The estrous cycles of mice with estrogen receptor α (Esr1) exon 3 flanked by LoxP sites (Esr1 flox) and controls were monitored before and after bilateral stereotactic injection of adeno-associated virus encoding Cre recombinase into the RP3V. This resulted in 84% and 72% decreases in ESR1-immunoreactive cell numbers in the anteroventral periventricular area and preoptic periventricular nucleus, respectively, with no changes in the arcuate nucleus. Beginning three weeks after the adeno-associated virus injection, Esr1 flox mice began to show a loss of estrous cyclicity going, primarily, into constant estrus. Wild-type mice and Esr1 flox mice with injections outside the RP3V or unilateral ablations of ESR1 continued to exhibit normal estrous cycles. Mice were then gonadectomized and given an estradiol replacement regimen to generate the LH surge. This resulted in an absence of cFOS expression in GnRH neurons (1 ± 1% vs 28 ± 4% of GnRH neurons; P < 0.01) and markedly reduced LH surge levels (2.5 ± 0.6 vs 9.1 ± 1.0 ng/mL; P < 0.01) in Esr1 flox mice compared with controls. These results demonstrate that neurons expressing ESR1 within the RP3V are critical for the generation of the LH surge and estrous cyclicity in the mouse. |
2,329,026 | A case of mediastinitis with an exposed artificial blood vessel that was associated with right ventricular wall damage during treatment. | We report a serious case of right ventricular wall damage during mediastinitis treatment, which was successfully treated with negative-pressure wound therapy with continuous instillation (NPWT-CI). |
2,329,027 | Microsurgical Resection of the Epidermoid Tumor in the Cerebellopontine Angle. | In this video, we demonstrate epidermoid tumor microsurgical resection of the cerebellopontine angle (CPA) performed by the senior author (K.I.A.). Epidermoid tumors arise from ectoderm trapped within/displaced into the central nervous system. They show predilection for CPA Angle (up to 40%), 4th ventricle, suprasellar region, and spinal cord. 1 They are the 3rd most common CPA tumor, comprising approximately 7% of CPA pathology. CPA lesions can produce 5th and 7-12th cranial nerve neuropathies. 2 3 4 Recurrent episodes of aseptic meningitis caused by cyst content rupture may occur. Symptoms include fever, meningeal irritation, and hydrocephalus. A 26-year-old female presented with headaches. Head magnetic resonance imaging (MRI) revealed right CPA tumor with brain stem compression ( Fig. 1 , A - C ). There was evidence of restricted diffusion in diffusion-weighted imaging, typical of epidermoid tumor. Surgery was performed in prone position with head turned 25 degrees to the ipsilateral side using retrosigmoid craniotomy. 5 Tumor was ventral to the 7th and 8th cranial nerve complexes, between the 5th nerve as well as toward the brainstem. The surgical plan was gross total resection with tumor capsule resection to prevent recurrence. 6 (Small residuals can be left behind when capsule is adherent to critical structures.) Tumor was adherent to brain stem perforators which were preserved using meticulous dissection. Cranial nerves and vascular structures were also left intact. We irrigated with antibiotic saline and used perioperative treatment to prevent aseptic meningitis. The pathohistological diagnosis revealed epidermoid tumor cyst. Postoperative MRI revealed complete resection ( Fig. 1 , D - F ). The patient recovered fully and was neurologically intact. The link to the video can be found at: https://youtu.be/LyWl-KZUSGY . |
2,329,028 | Choroid Plexus Papilloma of the Fourth Ventricle: A Pediatric Patient. | Choroid plexus papilloma is a low-frequency entity in both the adult and pediatric populations. Its clinical presentation is very variable as it depends on its location and length. We must always do the differential diagnosis between papilloma and other intraventricular pathologies. This article is about a case report of a pediatric patient with a Choroid plexus papilloma located in the fourth ventricle, a location that is atypical for the pediatric population. |
2,329,029 | Comparative Study of Single Burr-Hole Craniostomy versus Twist-Drill Craniostomy in Patients with Chronic Subdural Hematoma. | Chronic subdural hematoma (CSDH) is predominantly a disease of the elderly. On accounting its risk-to-benefit ratio, there was always controversy regarding the management of the CSDH as to which procedure is superior.</AbstractText>The aim is to compare the clinical and radiological outcomes in patients of CSDH who have undergone single burr-hole craniostomy (BHC) versus twist-drill craniostomy (TDC).</AbstractText>A retrospective study was conducted in patients admitted with CSDH who had undergone single BHC or TDC between January 2014 and December 2016. Patients between 18 and 90 years of age were selected. Patients with CSDH showing computed tomography (CT) scan findings of homogeneous hypodensity, homogeneous isodensity, and mixed density were selected. CT scan findings of CSDH with hyperdense gravity-dependent fluid level were also selected. Patients with CT evidence of multiple septations were excluded from the study. Recurrent CSDH, bilateral CSDH, and CSDH with secondary acute bleed were also excluded. Diagnosis was done using noncontrast CT scan. The maximum thickness of the CSDH was measured in the axial film of CT scan. The presence of midline shift (MLS) was measured as any deviation of the septum pellucidum from the midline in axial CT film. The mass effect was determined by the effacement of the sulci, sylvian fissure obscuration, or compression of lateral ventricles. The decrease in the signs and symptoms in postoperative period was considered as the postoperative clinical improvement. Improvement in the postoperative CT scan was determined by the decrease in the thickness of CSDH and absence of the MLS with decrease in the mass effect. The presence of the CSDH with mass effect and MLS was considered as the significant residue in the postoperative CT scan. Patients with significant residue underwent reoperation.</AbstractText>There were 63 patients in BHC group and 46 patients in TDC group. The mean age in BHC and TDC groups was 61.39 ± 13.21 standard deviation (SD) and 73.36 ± 10.82 SD, respectively. There were 48 (76.19%) male and 15 (23.81%) female in BHC group. There were 32 (69.57%) male and 14 (30.43%) female in TDC group. In BHC group, 41.27% were on the right side and 58.73% on the left side. In TDC group, 50% were on the right side and 50% on the left side. In BHC group, 82.54% were in the frontotemporoparietal region, 9.52% in the frontoparietal region, 6.35% in the temporoparietal region and 1.58% in the parietooccipital region. In TDC group, 86.95% were in the frontotemporoparietal region, 8.69% in the frontoparietal region, 2.17% in the temporoparietal region, and 2.17% in the parietooccipital region. There was no significant difference in duration of symptoms and history of trauma in both the groups. The symptoms of the patients in BHC versus TDC include weakness of the limbs (44.44% vs. 73.91%), headache (50.79% vs. 32.60%), altered sensorium or decreased memory (44.44% vs. 54.4%), vomiting (19.04% vs. 6.52%), speech abnormalities (15.87% vs. 19.56%), urinary incontinence (25.39% vs. 15.21%), seizure (1.58% vs. 4.34%), and diplopia (4.76% vs. 0%). The mean preoperative Glasgow Coma Scale (GCS) score in BHC versus TDC was 13.44 ± 2.23 SD versus 12.47 ± 2.95 SD limb weakness was noted in 52.38% BHC group and 82.60% TDC group. There was significantly decreased GCS score in TDC group. The number of the patients with limb weakness on affected side was significantly more in TDC group. The mean maximum thickness of the CSDH (in millimeter) in axial CT scan was 17.22 ± 4.29 SD in BHC group and 22.21 ± 4.52 SD in TDC group. The number of patients with MLS was 59 (93.65%) in BHC group and 45 (97.82%) in TDC group. There was significant difference in thickness of CSDH in both the groups. However, there was no significant difference in MLS in both the groups. There was no significant difference in prothrombin time, International Normalized Ratio, and activated partial thromboplastin time values of both the groups. There was significant difference in platelet counts of both the groups. The mean duration of procedure (in minutes) in BHC versus TDC was 79.20 ± 26.76 SD versus 27.47 ± 4.80 SD. The duration of procedure was significantly more in BHC compared to TDC. In postoperative assessment, there was no significant difference in the GCS score, power improvement, power deterioration, clinical improvement, and improvement in CT scans of both the groups. Postoperative CSDH residue requiring reoperation was significantly more in TDC group against the BHC group (13.04% vs. 1.58%). There was no significant difference in the development of acute subdural hematoma (SDH) (4.76% vs. 8.6%), reoperation rate (6.35% vs. 17.39%), complications (9.52% vs. 15.21%), and death (4.76% vs. 10.87%) in BHC group vs. TDC group. There was no significant difference in the period of hospital stay (days) in BHC (8.90 ± 5.89 SD) and TDC groups (7 ± 4.24 SD).</AbstractText>The duration of procedure was significantly more in BHC than in TDC. In postoperative outcome, there was no significant difference in the GCS score, motor power improvement, motor power deterioration, overall clinical improvement, and improvement in CT scans of both the groups. Postoperative residue requiring reoperation was significantly more in TDC group. There was no significant difference in the development acute SDH, reoperation rate, complications, death, and hospital stay in both the groups. Avoiding the complications of general anesthesia and giving the equal postoperative improvement and complications of BHC, the TDC is considered as an effective alternative to the BHC in the surgical management of CSDH.</AbstractText> |
2,329,030 | Alzheimer's disease neuropathological change and loss of matrix/neuropil in patients with idiopathic Normal Pressure Hydrocephalus, a model of Alzheimer's disease. | Here, we assessed unique brain tissue samples, obtained from living subjects with idiopathic Normal Pressure Hydrocephalus (iNPH). Our cohort of 95 subjects with age ranging from 75 to 79 years, displayed a high prevalence of β-amyloid (Aβ) and hyperphosphorylated τ (HPτ) pathology (63 and 61%, respectively) in a frontal cortex biopsy obtained during shunt operation. These lesions, i.e., Alzheimer's Disease Neuropathologic Change (ADNC), increased within 5 years and were more frequent in females. The extent of HPτ pathology was sparse, primarily seen as neurites and stained dots. Noteworthy, concomitant pathology was seen in 49% of the whole cohort, indicating a severity of ADNC corresponding to a low/intermediate level following the current recommendations. This observation is predictable as based on previous publications a substantial number of subjects with iNPH over time develop AD. Thus, iNPH can be considered as a model of AD. We noted a surprisingly remarkable neuronal preservation assessing Neuronal Nuclei (NeuN) in parallel with a substantial depletion of matrix/neuropil. This finding is intriguing as it suggests that loss of matrix/neuropil might be one of the first lesion of ADNC but also a hallmark lesion of iNPH. The latter observation is in line with the enlarged ventricles, a cardinal feature of iNPH. Furthermore, a positive correlation was observed between the extent of Aβ and NeuN but only in females indicating a neuronal preservation even when Aβ pathology is present. The assessment of a surgical biopsy as described here is certainly informative and thus it is surprising that a neuropathologic assessment in the setting of iNPH, while inserting a shunt, is seldom performed. Here, we observed ADNC and surprisingly remarkable neuronal preservation in a substantial number of iNPH subjects. Thus, these subjects allow us to observe the natural course of the disease and give us an opportunity for intervention at the earliest stages of AD, prior to severe neuronal damage. |
2,329,031 | Enhanced Homing of Mesenchymal Stem Cells Overexpressing Fibroblast Growth Factor 21 to Injury Site in a Mouse Model of Traumatic Brain Injury. | Mesenchymal stem cells (MSCs) are emerging as a potential therapeutic intervention for brain injury due to their neuroprotective effects and safe profile. However, the homing ability of MSCs to injury sites still needs to be improved. Fibroblast Growth Factor 21 (FGF21) was recently reported to enhance cells migration in different cells type. In this study, we investigated whether MSCs that overexpressing FGF21 (MSC-FGF21) could exhibit enhanced homing efficacy in brain injury. We used novel Molday IONEverGreen™ (MIEG) as cell labeling probe that enables a non-invasive, high-sensitive and real-time MRI tracking. Using a mouse model of traumatic brain injury (TBI), MIEG labeled MSCs were transplanted into the contralateral lateral ventricle followed by real-time MRI tracking. FGF21 retained MSC abilities of proliferation and morphology. MSC-FGF21 showed significantly greater migration in transwell assay compared to control MSC. MIEG labeling showed no effects on MSCs' viability, proliferation and differentiation. Magnetic resonance imaging (MRI) revealed that FGF21 significantly enhances the homing of MSC toward injury site. Histological analysis further confirmed the MRI findings. Taken together, these results show that FGF21 overexpression and MIEG labeling of MSC enhances their homing abilities and enables non-invasive real time tracking of the transplanted cells, provides a promising approach for MSC based therapy and tracking in TBI. |
2,329,032 | Open-Source Routines for Building Personalized Left Ventricular Models From Cardiac Magnetic Resonance Imaging Data. | Creating patient-specific models of the heart is a promising approach for predicting outcomes in response to congenital malformations, injury, or disease, as well as an important tool for developing and customizing therapies. However, integrating multimodal imaging data to construct patient-specific models is a nontrivial task. Here, we propose an approach that employs a prolate spheroidal coordinate system to interpolate information from multiple imaging datasets and map those data onto a single geometric model of the left ventricle (LV). We demonstrate the mapping of the location and transmural extent of postinfarction scar segmented from late gadolinium enhancement (LGE) magnetic resonance imaging (MRI), as well as mechanical activation calculated from displacement encoding with stimulated echoes (DENSE) MRI. As a supplement to this paper, we provide MATLAB and Python versions of the routines employed here for download from SimTK. |
2,329,033 | Neural Stem Cells of the Subventricular Zone Contribute to Neuroprotection of the Corpus Callosum after Cuprizone-Induced Demyelination. | Myelin loss occurring in demyelinating diseases, including multiple sclerosis, is the leading cause of long-lasting neurological disability in adults. While endogenous remyelination, driven by resident oligodendrocyte precursor cells (OPCs), might partially compensate myelin loss in the early phases of demyelinating disorders, this spontaneous reparative potential fails at later stages. To investigate the cellular mechanisms sustaining endogenous remyelination in demyelinating disorders, we focused our attention on endogenous neural precursor cells (eNPCs) located within the subventricular zone (SVZ) since this latter area is considered one of the primary sources of new OPCs in the adult forebrain. First, we fate mapped SVZ-eNPCs in cuprizone-induced demyelination and found that SVZ endogenous neural stem/precursor cells are recruited during the remyelination phase to the corpus callosum (CC) and are capable of forming new oligodendrocytes. When we ablated SVZ-derived eNPCs during cuprizone-induced demyelination in female mice, the animals displayed reduced numbers of oligodendrocytes within the lesioned CC. Although this reduction in oligodendrocytes did not impact the ensuing remyelination, eNPC-ablated mice experienced increased axonal loss. Our results indicate that, in toxic models of demyelination, SVZ-derived eNPCs contribute to support axonal survival.<b>SIGNIFICANCE STATEMENT</b> One of the significant challenges in MS research is to understand the detrimental mechanisms leading to the failure of CNS tissue regeneration during disease progression. One possible explanation is the inability of recruited oligodendrocyte precursor cells (OPCs) to complete remyelination and to sustain axonal survival. The contribution of endogenous neural precursor cells (eNPCs) located in the subventricular zone (SVZ) to generate new OPCs in the lesion site has been debated. Using transgenic mice to fate map and to selectively kill SVZ-derived eNPCs in the cuprizone demyelination model, we observed migration of SVZ-eNPCs after injury and their contribution to oligodendrogenesis and axonal survival. We found that eNPCs are dispensable for remyelination but protect partially from increased axonal loss. |
2,329,034 | Characterization of the Subventricular-Thalamo-Cortical Circuit in the NP-C Mouse Brain, and New Insights Regarding Treatment. | Gliosis in Niemann-Pick type C (NP-C) disease is characterized by marked changes in microglia and astrocytes. However, the gliosis onset and progression in NP-C has not been systematically studied, nor has the mechanism underlying this finding. Here, we found early gliosis in the subventricular zone (SVZ) of NP-C mice. Neural progenitor damage by Npc1 mutation suppressed vascular endothelial growth factor (VEGF) expression and further induced microglia activation followed by astrogliosis. Interestingly, excessive astrogliosis in the SVZ induced neural progenitor retention and/or migration into thalamus via astrocyte-derived VEGF, resulting in acceleration of thalamic and cortical gliosis through thalamo-cortical pathways. Transplantation of VEGF-overexpressing neural stem cells into the SVZ improved whole-brain pathology of NP-C mice. Overall, our data provide a new pathological perspective on NP-C neural pathology, revealing abnormalities in the subventricular-thalamo-cortical circuit of NP-C mouse brain and highlighting the importance of the SVZ microenvironment as a therapeutic target for NP-C disease. |
2,329,035 | The prenatal causes of slight lateral ventricular enlargement in healthy infants. | The aim of this study was to determine the prenatal causes of slight lateral ventricular enlargement in healthy infants.</AbstractText>We examined 1089 healthy infants who weighed at least 2000 g and were born at a gestational age of at least 36 weeks. We assessed the presence of ventricular enlargement when an apparent space was observed in the frontal horn or body of the lateral ventricle of the brain by a transfontanel ultrasound scan. We investigated the relationships between slight lateral ventricular enlargement and various prenatal factors.</AbstractText>Slight lateral ventricular enlargement was observed in 497 (45.6%) infants. Slight lateral ventricular enlargement was related to maternal anemia (p</i> = .004; odds ratio = 1.630; 95% CI: 1.168-2.276), threatened premature labor (p</i> = .010; odds ratio = 1.441; 95% CI: 1.093-1.900), and diabetes mellitus (p</i> = .022; odds ratio = 2.020; 95% CI: 1.109-3.682) using multiple logistic regression analysis. The birth weight of the infants with slight lateral ventricular enlargement was heavier than that of those without ventricular enlargement at 36-40 weeks of gestation. Forty infants with ventricular enlargement had head circumferences greater than the 90th percentile, while only one infant without ventricular enlargement did (p</i> < .001). In addition, 22 infants with ventricular enlargement had head circumferences less than the 10th percentile, while only 4 infants without ventricular enlargement did (p</i> < .001). In 497 infants with ventricular enlargement, the numbers of infants with left side dominant, equivalent, and right side dominant ventricular enlargement were 289 (58.1%), 110 (22.1), and 98 (19.7%), respectively.</AbstractText>Slight lateral ventricular enlargement could be caused by several pathological conditions in utero</i>, including brain atrophy, ventricular enlargement, the influence of blood flow in the brain, and various pathological changes in different brain regions.</AbstractText> |
2,329,036 | Assessment of the Main Compounds of the Lipolytic System in Treadmill Running Rats: Different Response Patterns between the Right and Left Ventricle. | The aim of the present study was to investigate the time and intensity dependent effects of exercise on the heart components of the lipolytic complex. Wistar rats ran on a treadmill with the speed of 18 m/min for 30 min (M30) or 120 min (M120) or with the speed of 28 m/min for 30 min (F30). The mRNA and protein expressions of the compounds adipose triglyceride lipase (ATGL), comparative gene identification-58 (CGI-58), G0/G1 switch gene 2 (G0S2), hormone sensitive lipase (HSL) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were examined by real-time PCR and Western blot, respectively. Lipid content of free fatty acids (FFA), diacylglycerols (DG) and triacylglycerols (TG) were estimated by gas liquid chromatography. We observed virtually no changes in the left ventricle lipid contents and only minor fluctuations in its ATGL mRNA levels. This was in contrast with its right counterpart i.e., the content of TG and DG decreased in response to both increased duration and intensity of a run. This occurred in tandem with increased mRNA expression for ATGL, CGI-58 and decreased expression of G0S2. It is concluded that exercise affects behavior of the components of the lipolytic system and the lipid content in the heart ventricles. However, changes observed in the left ventricle did not mirror those in the right one. |
2,329,037 | A comparison of two mathematical models of the cerebrospinal fluid dynamics. | In this paper we provide the numerical simulations of two cerebrospinal fluid dynamics models by comparing our results with the real data available in literature (see Section 4). The models describe different processes in the cerebrospinal fluid dynamics: the cerebrospinal flow in the ventricles of the brain and the reabsorption of the fluid. In the appendix we show in detail the mathematical analysis of both models and we identify the set of initial conditions for which the solutions of the systems of equations do not exhibit blow up. We investigate step by step the accuracy of these theoretical outcomes with respect to the real cerebrospinal physiology and dynamics. The plan of the paper is provided in Section 1.5. |
2,329,038 | The leadless pacemaker: An innovative design to enhance pacemaking capabilities. | Smaller leadless pacemakers placed in the right ventricle can reduce the risk of lead fracture or dislodgement and subcutaneous pocket complications, which can occur with traditional transvenous cardiac pacemakers. This article describes new leadless pacemakers and their indications. |
2,329,039 | Tanycyte Gene Expression Dynamics in the Regulation of Energy Homeostasis. | Animal survival relies on a constant balance between energy supply and energy expenditure, which is controlled by several neuroendocrine functions that integrate metabolic information and adapt the response of the organism to physiological demands. Polarized ependymoglial cells lining the floor of the third ventricle and sending a single process within metabolic hypothalamic parenchyma, tanycytes are henceforth described as key components of the hypothalamic neural network controlling energy balance. Their strategic position and peculiar properties convey them diverse physiological functions ranging from blood/brain traffic controllers, metabolic modulators, and neural stem/progenitor cells. At the molecular level, these functions rely on an accurate regulation of gene expression. Indeed, tanycytes are characterized by their own molecular signature which is mostly associated to their diverse physiological functions, and the detection of variations in nutrient/hormone levels leads to an adequate modulation of genetic profile in order to ensure energy homeostasis. The aim of this review is to summarize recent knowledge on the nutritional control of tanycyte gene expression. |
2,329,040 | Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes? | Ever since Claude Bernards discovery in the mid 19th-century that a lesion in the floor of the third ventricle in dogs led to altered systemic glucose levels, a role of the CNS in whole-body glucose regulation has been acknowledged. However, this finding was later overshadowed by the isolation of pancreatic hormones in the 20th century. Since then, the understanding of glucose homeostasis and pathology has primarily evolved around peripheral mechanism. Due to scientific advances over these last few decades, however, increasing attention has been given to the possibility of the brain as a key player in glucose regulation and the pathogenesis of metabolic disorders such as type 2 diabetes. Studies of animals have enabled detailed neuroanatomical mapping of CNS structures involved in glucose regulation and key neuronal circuits and intracellular pathways have been identified. Furthermore, the development of neuroimaging techniques has provided methods to measure changes of activity in specific CNS regions upon diverse metabolic challenges in humans. In this narrative review, we discuss the available evidence on the topic. We conclude that there is much evidence in favor of active CNS involvement in glucose homeostasis but the relative importance of central vs. peripheral mechanisms remains to be elucidated. An increased understanding of this field may lead to new CNS-focusing pharmacologic strategies in the treatment of type 2 diabetes. |
2,329,041 | Long-Term Grey Matter Changes in First Episode Psychosis: A Systematic Review. | To determine possible progressive changes of the grey matter at the first stages of the schizophrenia spectrum disorders, and to determine what regions are involved in these changes.</AbstractText>We searched the literature concerning studies on longitudinal changes in grey matter in first-episode psychosis using magnetic resonance imaging, especially studies with an interval between scans of more than a year. Only articles published before 2018 were searched. We selected 19 magnetic resonance imaging longitudinal studies that used different neuroimaging analysis techniques to study changes in cerebral grey matter in a group of patients with a first episode of psychosis.</AbstractText>Patients with first episode of psychosis showed a decrease over time in cortical grey matter compared with a group of control subjects in frontal, temporal (specifically in superior regions), parietal, and subcortical regions. In addition to the above, studies indicate that patients showed a grey matter decrease in cerebellum and lateral ventricles volume.</AbstractText>The results suggest a decrease in grey matter in the years after the first episode of psychosis. Furthermore, the results of the studies showed consistency, regardless of the methods used in their analyses, as well as the time intervals between image collections.</AbstractText> |
2,329,042 | Neurogenic Bladder Dysfunction as Signal of Late Failure of Endoscopic Third Ventriculostomy in Child with Spina Bifida. | Endoscopic third ventriculostomy (ETV) is an option for hydrocephalus treatment in patients with myelomeningocele, mostly after a previous shunt dysfunction. Late failure of ETV is a rare event, traditionally associated with dramatic symptoms of intracranial hypertension. In patients with myelodysplasia and neurogenic bladder dysfunction, urodynamic deterioration can be a signal of neurologic worsening as a consequence of tethered cord or shunt problems.</AbstractText>We describe here a rare case of a 12-year-old female patient with myelomeningocele and evidence of a failure 10 years after a previously successful ETV whose initial symptoms were worsening of urinary complaints. After 2 months, she was admitted to the emergency department with seizures and acute hydrocephalus and was shunted.</AbstractText>Pediatric neurosurgeons must follow myelomeningocele patients with successful ETV for a long time and take care of subtle alterations of organic functions that have a close relationship with central nervous system integrity. A multidisciplinary approach can facilitate this strategy and avoid a tragic outcome.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,043 | The PROK2/PROKR2 signaling pathway is required for the migration of most olfactory bulb interneurons.<Pagination><StartPage>2931</StartPage><EndPage>2947</EndPage><MedlinePgn>2931-2947</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/cne.24719</ELocationID><Abstract><AbstractText>Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) to the olfactory bulb (OB). The PROK2 (prokineticin 2) and PROKR2 (prokineticin receptor 2) signaling pathway has been identified to cause human Kallmann syndrome, a developmental disease that associates hypogonadism with anosmia (OB developmental defects). However, the identities and properties of PROK2<sup>+</sup> and PROKR2<sup>+</sup> cells in the SVZ-RMS-OB remain largely unknown. Here we examine the expression patterns of Prok2 and Prokr2 in the SVZ-RMS-OB using Prok2<sup>EGFP</sup> transgenic and Prokr2<sup>LacZ/+</sup> knockin mice. Our results show that Prokr2 is expressed in postmitotic immature interneurons in the SVZ-RMS-OB. Prok2 is not expressed in the SVZ, but a few PROK2<sup>+</sup> cells are found in the medial part of the RMS; they are not neural progenitors or migrating neuroblasts. In the OB, Prok2 is expressed in a subset of granule cells and tufted cells, but no coexpression of Prok2 and Prokr2 in the OB cells is observed. In Prok2 and Prokr2 mutant mice, severe tangential and radial migration defects of neuroblasts in the SVZ-RMS-OB result in loss of ~75% of GABAergic interneurons in the OB. These analyses demonstrate that PROK2/PROKR2 signaling is crucial for the tangential and radial migration of OB interneurons.</AbstractText><CopyrightInformation>© 2019 Wiley Periodicals, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wen</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Zhuangzhi</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Zhenmeiyu</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Guoping</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tao</LastName><ForeName>Guangxu</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Xiaolei</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Zhejun</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shang</LastName><ForeName>Zicong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guo</LastName><ForeName>Teng</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Su</LastName><ForeName>Zihao</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Haotian</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>You</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jiada</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, Hunan, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Zhengang</ForeName><Initials>Z</Initials><Identifier Source="ORCID">0000-0003-2447-6540</Identifier><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>06</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Comp Neurol</MedlineTA><NlmUniqueID>0406041</NlmUniqueID><ISSNLinking>0021-9967</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005768">Gastrointestinal Hormones</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009479">Neuropeptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C486586">Prok2 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C526903">Prokr2 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D043562">Receptors, G-Protein-Coupled</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018000">Receptors, Peptide</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002465" MajorTopicYN="N">Cell Movement</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005768" MajorTopicYN="N">Gastrointestinal Hormones</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007395" MajorTopicYN="N">Interneurons</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058953" MajorTopicYN="N">Neural Stem Cells</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009479" MajorTopicYN="N">Neuropeptides</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009830" MajorTopicYN="N">Olfactory Bulb</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D043562" MajorTopicYN="N">Receptors, G-Protein-Coupled</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018000" MajorTopicYN="N">Receptors, Peptide</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Prok2</Keyword><Keyword MajorTopicYN="N">Prokr2</Keyword><Keyword MajorTopicYN="N">RMS</Keyword><Keyword MajorTopicYN="N">RRID: MMRRC_049216-UCD</Keyword><Keyword MajorTopicYN="N">SVZ</Keyword><Keyword MajorTopicYN="N">interneurons</Keyword><Keyword 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In addition, numerous aspects of the mitochondrial metabolic status such as membrane potential and substrate entry can also be estimated. To perform cardiac wall transmission optical spectroscopy, a commercially available side-firing optical fiber catheter is placed in the left ventricle of the isolated perfused heart as a light source. Light passing through the heart wall is collected with an external optical fiber to perform optical spectroscopy of the heart in near real- time. The transmission approach avoids numerous surface scattering interference occurring in widely used reflection approaches. Changes in transmural absorbance spectra were deconvolved using a library of chromophore reference spectra, providing quantitative measures of all the known cardiac chromophores simultaneously. This spectral deconvolution approach eliminated intrinsic errors that may result from using common dual wavelength methods applied to overlapping absorbance spectra, as well as provided a quantitative evaluation of the goodness of fit. A custom program was designed for data acquisition and analysis, which permitted the investigator to monitor the metabolic state of the preparation during the experiment. These relatively simple additions to the standard heart perfusion system provide a unique insight into the metabolic state of the heart wall in addition to conventional measures of contraction, perfusion, and substrate/oxygen extraction.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Femnou</LastName><ForeName>Armel N</ForeName><Initials>AN</Initials><AffiliationInfo><Affiliation>Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health; Department of Biomedical Engineering, The George Washington University.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giles</LastName><ForeName>Abigail</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Balaban</LastName><ForeName>Robert S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health; balabanr@nhlbi.nih.gov.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>Z01 HL004601</GrantID><Acronym>ImNIH</Acronym><Agency>Intramural NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType><PublicationType UI="D059040">Video-Audio Media</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>05</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Vis Exp</MedlineTA><NlmUniqueID>101313252</NlmUniqueID><ISSNLinking>1940-087X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009211">Myoglobin</NameOfSubstance></Chemical><Chemical><RegistryNumber>S88TT14065</RegistryNumber><NameOfSubstance UI="D010100">Oxygen</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057785" MajorTopicYN="Y">Catheters</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003326" MajorTopicYN="N">Coronary Circulation</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006321" MajorTopicYN="N">Heart</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008027" MajorTopicYN="N">Light</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008322" MajorTopicYN="N">Mammals</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009211" MajorTopicYN="N">Myoglobin</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055620" MajorTopicYN="N">Optical Phenomena</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010100" MajorTopicYN="N">Oxygen</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010477" MajorTopicYN="Y">Perfusion</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011817" MajorTopicYN="N">Rabbits</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013057" MajorTopicYN="Y">Spectrum Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList><CoiStatement>Disclosures. 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Physiological Reviews. 63 1–205 (1983).</Citation><ArticleIdList><ArticleId IdType="pubmed">6296890</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">31132045</PMID><DateCompleted><Year>2020</Year><Month>03</Month><Day>26</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>26</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>147</Issue><PubDate><Year>2019</Year><Month>May</Month><Day>11</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Intraventricular Transplantation of Engineered Neuronal Precursors for In Vivo Neuroarchitecture Studies. | Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) to the olfactory bulb (OB). The PROK2 (prokineticin 2) and PROKR2 (prokineticin receptor 2) signaling pathway has been identified to cause human Kallmann syndrome, a developmental disease that associates hypogonadism with anosmia (OB developmental defects). However, the identities and properties of PROK2<sup>+</sup> and PROKR2<sup>+</sup> cells in the SVZ-RMS-OB remain largely unknown. Here we examine the expression patterns of Prok2 and Prokr2 in the SVZ-RMS-OB using Prok2<sup>EGFP</sup> transgenic and Prokr2<sup>LacZ/+</sup> knockin mice. Our results show that Prokr2 is expressed in postmitotic immature interneurons in the SVZ-RMS-OB. Prok2 is not expressed in the SVZ, but a few PROK2<sup>+</sup> cells are found in the medial part of the RMS; they are not neural progenitors or migrating neuroblasts. In the OB, Prok2 is expressed in a subset of granule cells and tufted cells, but no coexpression of Prok2 and Prokr2 in the OB cells is observed. In Prok2 and Prokr2 mutant mice, severe tangential and radial migration defects of neuroblasts in the SVZ-RMS-OB result in loss of ~75% of GABAergic interneurons in the OB. These analyses demonstrate that PROK2/PROKR2 signaling is crucial for the tangential and radial migration of OB interneurons.<CopyrightInformation>© 2019 Wiley Periodicals, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wen</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Zhuangzhi</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Zhenmeiyu</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Guoping</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tao</LastName><ForeName>Guangxu</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Xiaolei</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Zhejun</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shang</LastName><ForeName>Zicong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guo</LastName><ForeName>Teng</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Su</LastName><ForeName>Zihao</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Haotian</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>You</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jiada</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, Hunan, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Zhengang</ForeName><Initials>Z</Initials><Identifier Source="ORCID">0000-0003-2447-6540</Identifier><AffiliationInfo><Affiliation>State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>06</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Comp Neurol</MedlineTA><NlmUniqueID>0406041</NlmUniqueID><ISSNLinking>0021-9967</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005768">Gastrointestinal Hormones</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009479">Neuropeptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C486586">Prok2 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C526903">Prokr2 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D043562">Receptors, G-Protein-Coupled</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018000">Receptors, Peptide</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002465" MajorTopicYN="N">Cell Movement</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005768" MajorTopicYN="N">Gastrointestinal Hormones</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007395" MajorTopicYN="N">Interneurons</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058953" MajorTopicYN="N">Neural Stem Cells</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009479" MajorTopicYN="N">Neuropeptides</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009830" MajorTopicYN="N">Olfactory Bulb</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D043562" MajorTopicYN="N">Receptors, G-Protein-Coupled</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018000" MajorTopicYN="N">Receptors, Peptide</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Prok2</Keyword><Keyword MajorTopicYN="N">Prokr2</Keyword><Keyword MajorTopicYN="N">RMS</Keyword><Keyword MajorTopicYN="N">RRID: MMRRC_049216-UCD</Keyword><Keyword MajorTopicYN="N">SVZ</Keyword><Keyword MajorTopicYN="N">interneurons</Keyword><Keyword MajorTopicYN="N">mouse</Keyword><Keyword MajorTopicYN="N">olfactory bulb</Keyword><Keyword MajorTopicYN="N">tufted cells</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>2</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>5</Month><Day>7</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>5</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>5</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>10</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>5</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31132148</ArticleId><ArticleId 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In addition, numerous aspects of the mitochondrial metabolic status such as membrane potential and substrate entry can also be estimated. To perform cardiac wall transmission optical spectroscopy, a commercially available side-firing optical fiber catheter is placed in the left ventricle of the isolated perfused heart as a light source. Light passing through the heart wall is collected with an external optical fiber to perform optical spectroscopy of the heart in near real- time. The transmission approach avoids numerous surface scattering interference occurring in widely used reflection approaches. Changes in transmural absorbance spectra were deconvolved using a library of chromophore reference spectra, providing quantitative measures of all the known cardiac chromophores simultaneously. This spectral deconvolution approach eliminated intrinsic errors that may result from using common dual wavelength methods applied to overlapping absorbance spectra, as well as provided a quantitative evaluation of the goodness of fit. A custom program was designed for data acquisition and analysis, which permitted the investigator to monitor the metabolic state of the preparation during the experiment. These relatively simple additions to the standard heart perfusion system provide a unique insight into the metabolic state of the heart wall in addition to conventional measures of contraction, perfusion, and substrate/oxygen extraction.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Femnou</LastName><ForeName>Armel N</ForeName><Initials>AN</Initials><AffiliationInfo><Affiliation>Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health; Department of Biomedical Engineering, The George Washington University.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giles</LastName><ForeName>Abigail</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Balaban</LastName><ForeName>Robert S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health; balabanr@nhlbi.nih.gov.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>Z01 HL004601</GrantID><Acronym>ImNIH</Acronym><Agency>Intramural NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType><PublicationType UI="D059040">Video-Audio Media</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>05</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Vis Exp</MedlineTA><NlmUniqueID>101313252</NlmUniqueID><ISSNLinking>1940-087X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009211">Myoglobin</NameOfSubstance></Chemical><Chemical><RegistryNumber>S88TT14065</RegistryNumber><NameOfSubstance UI="D010100">Oxygen</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057785" MajorTopicYN="Y">Catheters</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003326" MajorTopicYN="N">Coronary Circulation</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006321" MajorTopicYN="N">Heart</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008027" MajorTopicYN="N">Light</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008322" MajorTopicYN="N">Mammals</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009211" MajorTopicYN="N">Myoglobin</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055620" MajorTopicYN="N">Optical Phenomena</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010100" MajorTopicYN="N">Oxygen</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010477" MajorTopicYN="Y">Perfusion</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011817" MajorTopicYN="N">Rabbits</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013057" MajorTopicYN="Y">Spectrum Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList><CoiStatement>Disclosures. 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Physiological Reviews. 63 1–205 (1983).</Citation><ArticleIdList><ArticleId IdType="pubmed">6296890</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">31132045</PMID><DateCompleted><Year>2020</Year><Month>03</Month><Day>26</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>26</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>147</Issue><PubDate><Year>2019</Year><Month>May</Month><Day>11</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal><ArticleTitle>Intraventricular Transplantation of Engineered Neuronal Precursors for In Vivo Neuroarchitecture Studies.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.3791/59242</ELocationID><Abstract>Gene control of neuronal cytoarchitecture is currently the subject of intensive investigation. Described here is a simple method developed to study in vivo gene control of neocortical projection neuron morphology. This method is based on (1) in vitro lentiviral engineering of neuronal precursors as "test" and "control" cells, (2) their co-transplantation into wild-type brains, and (3) paired morphometric evaluation of their neuronal derivatives. Specifically, E12.5 pallial precursors from panneuronal, genetically labeled donors, are employed for this purpose. They are engineered to take advantage of selected promoters and tetON/OFF technology, and they are free-hand transplanted into neonatal lateral ventricles. Later, upon immunofluorescence profiling of recipient brains, silhouettes of transplanted neurons are fed into NeurphologyJ open source software, their morphometric parameters are extracted, and average length and branching index are calculated. Compared to other methods, this one offers three main advantages: it permits achieving of fine control of transgene expression at affordable costs, it only requires basic surgical skills, and it provides statistically reliable results upon analysis of a limited number of animals. Because of its design, however, it is not adequate to address non cell-autonomous control of neuroarchitecture. Moreover, it should be preferably used to investigate neurite morphology control after completion of neuronal migration. In its present formulation, this method is exquisitely tuned to investigate gene control of glutamatergic neocortical neuron architecture. Taking advantage of transgenic lines expressing EGFP in other specific neural cell types, it can be re-purposed to address gene control of their architecture. |
2,329,044 | [Epicardial Transplantation of Cardiac Progenitor Cells Based Cells Sheets is More Promising Method for Stimulation of Myocardial Regeneration, Than Conventional Cell Injections]. | Today, transplantation of stem / progenitor cells is a promising approach for the treatment of heart diseases. The therapeutic potential of transplanted cells directly depends on the method of delivery to the myocardium, which determines their regenerative properties. It is important for the development of effective methods of cell therapy. In this paper, we performed a comparative study of efficacy of cardiac progenitor cell (CPC) transplantation by intramyocardial needle injections and by tissue engineering constructs (TEC) - "cell sheets" consisting of cells and their extracellular matrix. It has been shown, that transplantation of TEC in comparison with the intramyocardial delivery provides more extensive distribution and retains more proliferating cellular elements in the damaged myocardium, attenuates the negative cardiac remodeling of the left ventricle and promotes its vascularization. |
2,329,045 | Assessment of neuropharmacological potential of low molecular weight components extracted from <i>Rhinella schneideri</i> toad poison. | Studies on toad poison are relevant since they are considered a good source of toxins that act on different biological systems. Among the molecules found in the toad poison, it can be highlighted the cardiotonic heterosides, which have a known mechanism that inhibit Na+</sup>/K+</sup>-ATPase enzyme. However, these poisons have many other molecules that may have important biological actions. Therefore, this work evaluated the action of the low molecular weight components from Rhinella schneideri</i> toad poison on Na+</sup>/K+</sup>-ATPase and their anticonvulsive and / or neurotoxic effects, in order to detect molecules with actions of biotechnological interest.</AbstractText>Rhinella schneideri</i> toad (male and female) poison was collected by pressuring their parotoid glands and immediately dried and stored at -20 °C. The poison was dialysed and the water containing the low molecular mass molecules (< 8 kDa) that permeate the dialysis membrane was collected, frozen and lyophilized, resulting in the sample used in the assays, named low molecular weight fraction (LMWF). Na+</sup>/K+</sup> ATPase was isolated from rabbit kidneys and enzyme activity assays performed by the quantification of phosphate released due to enzyme activity in the presence of LMWF (1.0; 10; 50 and 100 µg/mL) from Rhinella schneideri</i> poison. Evaluation of the L-Glutamate (L-Glu) excitatory amino acid uptake in brain-cortical synaptosomes of Wistar rats was performed using [3H]L-glutamate and different concentration of LMWF (10-5</sup> to 10 µg/µL). Anticonvulsant assays were performed using pentylenetetrazole (PTZ) and N-methyl-D-aspartate (NMDA) to induce seizures in Wistar rats (n= 6), which were cannulated in the lateral ventricle and treated with different concentration of LMWF (0.25; 0.5; 1.0; 2.0; 3.0 and 4.0 µg/µL) 15 min prior to the injection of the seizure agent.</AbstractText>LMWF induced a concentration-dependent inhibition of Na+</sup>/K+</sup>-ATPase (IC50%</sub> = 107.5 μg/mL). The poison induces an increased uptake of the amino acid L-glutamate in brain-cortical synaptosomes of Wistar rats. This increase in the L-glutamate uptake was observed mainly at the lowest concentrations tested (10-5</sup> to 10-2</sup> µg/µL). In addition, this fraction showed a very relevant central neuroprotection on seizures induced by PTZ and NMDA.</AbstractText>LMWF from Rhinella schneideri</i> poison has low molecular weight compounds, which were able to inhibit Na+</sup>/K+</sup>-ATPase activity, increase the L-glutamate uptake and reduced seizures induced by PTZ and NMDA.</b> These results showed that LMWF is a rich source of components with biological functions of high medical and scientific interest.</AbstractText> |
2,329,046 | MiR-135a-5p Is Critical for Exercise-Induced Adult Neurogenesis. | Physical exercise stimulates adult hippocampal neurogenesis and is considered a relevant strategy for preventing age-related cognitive decline in humans. The underlying mechanisms remains controversial. Here, we show that exercise increases proliferation of neural precursor cells (NPCs) of the mouse dentate gyrus (DG) via downregulation of microRNA 135a-5p (miR-135a). MiR-135a inhibition stimulates NPC proliferation leading to increased neurogenesis, but not astrogliogenesis, in DG of resting mice, and intriguingly it re-activates NPC proliferation in aged mice. We identify 17 proteins (11 putative targets) modulated by miR-135 in NPCs. Of note, inositol 1,4,5-trisphosphate (IP3) receptor 1 and inositol polyphosphate-4-phosphatase type I are among the modulated proteins, suggesting that IP3 signaling may act downstream miR-135. miR-135 is the first noncoding RNA essential modulator of the brain's response to physical exercise. Prospectively, the miR-135-IP3 axis might represent a novel target of therapeutic intervention to prevent pathological brain aging. |
2,329,047 | Modeling left ventricular dynamics with characteristic deformation modes. | A computationally efficient method is described for simulating the dynamics of the left ventricle (LV) in three dimensions. LV motion is represented as a combination of a limited number of deformation modes, chosen to represent observed cardiac motions while conserving volume in the LV wall. The contribution of each mode to wall motion is determined by a corresponding time-dependent deformation variable. The principle of virtual work is applied to these deformation variables, yielding a system of ordinary differential equations for LV dynamics, including effects of muscle fiber orientations, active and passive stresses, and surface tractions. Passive stress is governed by a transversely isotropic elastic model. Active stress acts in the fiber direction and incorporates length-tension and force-velocity properties of cardiac muscle. Preload and afterload are represented by lumped vascular models. The variational equations and their numerical solutions are verified by comparison to analytic solutions of the strong form equations. Deformation modes are constructed using Fourier series with an arbitrary number of terms. Greater numbers of deformation modes increase deformable model resolution but at increased computational cost. Simulations of normal LV motion throughout the cardiac cycle are presented using models with 8, 23, or 46 deformation modes. Aggregate quantities that describe LV function vary little as the number of deformation modes is increased. Spatial distributions of stress and strain change as more deformation modes are included, but overall patterns are conserved. This approach yields three-dimensional simulations of the cardiac cycle on a clinically relevant time-scale. |
2,329,048 | Endoscopic third ventriculostomy versus shunt for pediatric hydrocephalus: a systematic literature review and meta-analysis. | Optimized management of pediatric hydrocephalus remains the subject of debate. Ventriculoperitoneal shunt is largely considered the standard of care. However, the advancements and introduction of new cerebrospinal fluid (CSF) diversion approaches including the use of endoscopic third ventriculostomy (ETV) offer appealing alternatives that have been reported in numerous observational series.</AbstractText>To evaluate the comparative safety and efficacy of shunting and ETV in pediatric hydrocephalus cases.</AbstractText>This systematic literature review was performed according to the PRISMA guidelines. Eligible studies were identified through a search of PubMed (Medline) and Cochrane until October 2018. A random effects model meta-analysis was conducted and the I-square was used to assess heterogeneity. The ROBINS-1 tool and Cochrane tool were used to assess risk of bias in the observational and randomized studies, respectively.</AbstractText>Fourteen studies including 8419 patients were identified. Patients in the ETV group had a statistically significant lower risk of infection compared to shunt (OR: 0.19; 95% CI: 0.07-0.53; I2</sup>: 0%). All-cause mortality (OR: 0.77; 95% CI: 0.35-1.68; I2</sup>: 0%), post-operative CSF leak (OR: 1.53; 95% CI: 0.37-6.31; I2</sup>: 0%), and reoperation rates were similar between the two study groups (OR: 0.72; 95% CI: 0.39-1.32; I2</sup>: 93.5%). Subgroup analyses for re-operation demonstrated that ETV in Africa (OR: 0.13; 95% CI: 0.03-0.48; I2</sup>: 0%) and Europe (OR: 0.39; 95% CI: 0.30-0.52; I2</sup>:1.4%) was associated with significantly lower odds of re-operation compared to shunt, but not in USA/Canada (OR: 1.49; 95% CI: 0.85-2.63; I2</sup>:86.2%). Meta-regression analyses of age and duration of follow-up did not affect re-operation rates.</AbstractText>ETV was associated with a statistically significant lower risk of procedure-related infection compared to shunt. All-cause mortality, CSF leak, and re-operation rates were similar between the study groups. Subgroup analysis based on the geographic region showed that ETV is associated with statistically significant lower odds for re-operation in Europe and Africa, but not in USA/Canada. Future RCTs are needed to validate the results of this study and elucidate the cause of this heterogeneity.</AbstractText> |
2,329,049 | Comparison of Techniques for Involved-Site Radiation Therapy in Patients With Lower Mediastinal Lymphoma. | Patients with lower mediastinal lymphoma (LML) benefit dosimetrically from proton therapy (PT) compared with intensity modulated radiation therapy (IMRT). The added dosimetric benefit of deep-inspiration breath-hold (DIBH) is unknown; therefore, we evaluated IMRT versus PT and free-breathing (FB) versus DIBH among patients with LML.</AbstractText>Twenty-one patients with LML underwent 4-dimensional computed tomography and 3 sequential DIBH scans at simulation. Involved-site radiation therapy target volumes and organ-at-risk contours were developed for both DIBH and FB scans. FB-IMRT, DIBH-IMRT, FB-PT, and DIBH-PT plans were generated for each patient for comparison.</AbstractText>The median difference in lung volume between the DIBH and FB scans was 1275 mL; the average difference in clinical target volume was 5.7 mL. DIBH-IMRT produced a lower mean lung dose (10.8 vs 11.9 Gy; P < .001) than FB-IMRT, with no difference in mean heart dose (MHD; 16.1 vs 15.0 Gy; P = .992). Both PT plans produced a significantly lower mean dose to the lung, heart, left ventricle, esophagus, and nontarget body than DIBH-IMRT. DIBH-PT reduced the median MHD by 4.2 Gy (P < .0001); left ventricle dose by 5.1 Gy (P < .0001); and lung V5 by 26% (P < .0001) versus DIBH-IMRT. The 2 PT plans were comparable, with DIBH-PT reducing mean lung dose (7.0 vs 7.7 Gy; P = .063) and with no difference in MHD (10.3 vs 9.5 Gy; P = .992).</AbstractText>Among patients with LML, DIBH (IMRT or PT) improved lung dosimetry over FB but had little influence on MHD. PT (DIBH and FB) significantly reduced lung, heart, esophagus, and nontarget body dose compared with DIBH IMRT, potentially reducing the risk of late complications.</AbstractText>Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,050 | The rs-fMRI study of effects of fornix and hippocampus-related brain function after the transcallosal interforniceal approach. | The tumors in third ventricle are common intracranial tumors in children, characterized by various pathological types and difficult to be removed. The transcallosal interforniceal approach is often used for these tumors. The separation of bilateral fornix causes multiple surgical complications. In the past, complications could only be assessed by clinical feature and traditional imaging, lack of quantitative data to support. Resting-state functional magnetic resonance imaging (rs-fMRI) can assess brain functional connectivity between local regions and different regions in quiet state. The changes of ReHo, ALFF, fALFF and brain function connections (DMN and Hippocampus as ROI) can be used to evaluate the effects caused by operation.</AbstractText>To evaluate the effects of brain function caused by operation.</AbstractText>9 children patients with tumors in third ventricle were randomly selected in Yuquan hospital, and scanned by rs-fMRI before and after operation. ReHo, ALFF, fALFF and function connections (DMN and Hippocampus as ROI) were chosen to analyze rs-fMRI data.</AbstractText>The results of ReHo, ALFF, fALFF and brain function connections (DMN and Hippocampus as ROI) showed that: (1) Compared with preoperative state, ReHo decreased in left superior frontal gyrus in 1 month after operation, while increased in right middle occipital gyrus, right middle temporal gyrus, and left posterior central gyrus. In 2 months after operation, ReHo decreased in left superior temporal gyrus and right precentral gyrus compared with that in 1 month after operation. (2) Compared with preoperative state, ALFF decreased in left middle frontal gyrus and increased in left superior temporal gyrus in 1 month after operation; ALFF decreased in right fusiform gyrus and right supramarginal gyrus, while increased in left parahippocampal gyrus and left caudate nucleus in 2 months after operation. When compared with these in 1 month after operation, ALFF decreased in right fusiform gyrus and left precentral gyrus in 2 months after operation. (3) Compared with preoperative state, fALFF decreased in left superior frontal gyrus in 1 month after operation, and decreased in left middle frontal gyrus in 2 months after surgery. (4) The connections of DMN showed that enhanced connections of bilateral middle frontal gyrus and other regions in 1 month after operation, which restored to preoperative state in 3 months after operation. (5) There were changes of connections between bilateral hippocampus and related brain regions without any interruption occurred. The effects of approach can disappear in 3 months after operation.</AbstractText>The short-term effects of ReHo, ALFF and fALFF in brain regions of children patients can recover to preoperative state with time. The operation did not interrupt the connections between DMN and hippocampus related brain areas. The effects of surgery can restore to the preoperative state in 3 months after operation.</AbstractText>Copyright © 2019. Published by Elsevier Inc.</CopyrightInformation> |
2,329,051 | Evaluation of left and right ventricle by two-dimensional speckle tracking echocardiography in systemic sclerosis patients without overt cardiac disease. | <AbstractText Label="BACKGROUND/OBJECTIVE" NlmCategory="OBJECTIVE">The aim was to evaluate the left and right ventricular functions concurrently by two-dimensional speckle tracking echocardiography (STE) in systemic sclerosis (SSc) patients without overt cardiac disease.</AbstractText>A total of 47 patients with SSc and 36 age- and sex-matched controls were evaluated cross-sectionally. Two-dimensional STE was used to assess the longitudinal peak systolic strains (PSS) of both ventricles including apical long-axis (APLAX), apical four-chamber (4-CH), apical two-chamber (2-CH), and global longitudinal measurements. Any association of metabolic, cardiac, and inflammatory biomarkers with PSS was investigated.</AbstractText>The longitudinal PSS of the left ventricle [APLAX, 4-CH, 2-CH and global] were significantly lower in SSc patients than controls (- 18.2 ± 3.2 vs - 19.8 ± 2.7% p = 0.02; - 17.8 ± 3.5 vs. - 20.3 ± 3.3% p = 0.001; - 18.6 ± 3.1 vs. - 21.8 ± 3% p < 0.001; - 17.5 ± 5.7 vs. - 20.6 ± 2.7% p = 0.003, respectively). No difference was found between the groups for right ventricular strains. The longitudinal PSS-4CH correlated positively with CRP and ESR (r = 0.349, p = 0.016; r = 0.356, p = 0.014, respectively) and negatively with serum Galectin-3 (r = - 0.362, p = 0.012). Global longitudinal PSS-left ventricle (LV) correlated positively with CRP and homocysteine (r = 0.297, p = 0.043; r = 0.313, p = 0.041, respectively) and negatively with serum Galectin-3 (r = -0.314, p = 0.041). After multivariable adjustment, CRP remained the only predictor of longitudinal PSS-4CH (95% CI 0.35, 0.70, p = 0.028) and global longitudinal PSS of left ventricle (95% CI 0.004, 0.22, p = 0.043).</AbstractText>Biventricular evaluation of patients with SSc by two dimensional STE revealed reduced left ventricular longitudinal strains, despite preserved right ventricular strain, and no diastolic dysfunction. In SSc without overt cardiac disease, global cardiac assessment with 2DSTE is a promising method which seems to contribute to the detection of patients without clinical findings.</AbstractText>• Two dimensional STE revealed reduced left ventricular longitudinal strains, despite preserved right ventricular strain in SSc patients without overt cardiac disease. • CRP was the predictor of decreased longitudinal strains. • Cardiac assessment in SSc should be made globally.</AbstractText> |
2,329,052 | Matrix Metalloproteinases System and Types of Fibrosis in Rat Heart during Late Pregnancy and Postpartum. | <i>Background and objectives:</i> Cardiac remodeling in pregnancy and postpartum is poorly understood. The aim of this study was to evaluate changes in cardiac fibrosis (pericardial, perivascular, and interstitial), as well as the expression of matrix metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (Tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-4) during late pregnancy and postpartum in rat left ventricle. <i>Materials and Methods:</i> Female Sprague-Dawley rats were used for this study. Rats were divided three groups: non-pregnant, late pregnancy, and postpartum. The heart was weighed and cardiac fibrosis was studied by conventional histological procedures. The expression and transcript level of target proteins were evaluated using immunoblot techniques and quantitative PCR. <i>Results:</i> The experiments showed an increase of perivascular, pericardial, and interstitial fibrosis in heart during pregnancy and its reversion in postpartum. Moreover, in late pregnancy, MMP-1, MMP-2, and MMP-9 metalloproteinases were downregulated and TIMP-1 and TIMP-4 were upregulated in left ventricle. <i>Conclusions:</i> Our data suggest that the metalloproteinases system is involved in the cardiac extracellular matrix remodeling during pregnancy and its reversion in postpartum, this improves the knowledge of the adaptive cardiac remodeling in response to a blood volume overload present during pregnancy. |
2,329,053 | Level set distribution model of nested structures using logarithmic transformation. | In this study, we propose a method for constructing a multishape statistical shape model (SSM) for nested structures such that each is a subset or superset of another. The proposed method has potential application to any pair of shapes with an inclusive relationship. These types of shapes are often found in anatomy, such as the brain surface and ventricles. The main contribution of this paper is to introduce a new shape representation called log-transformed level set function (LT-LSF), which has a vector space structure that preserves the correct inclusive relationship of the nested shape. In addition, our method is applicable to an arbitrary number of nested shapes. We demonstrate the effectiveness of the proposed shape representation by modeling the anatomy of human embryos, including the brain, ventricles, and choroid plexus volumes. The performance of the SSM was evaluated in terms of generalization and specificity ability. Additionally, we measured leakage criteria to assess the ability to preserve inclusive relationships. A quantitative comparison of our SSM with conventional multishape SSMs demonstrates the superiority of the proposed method. |
2,329,054 | Platelet-derived growth factor receptor-α is essential for cardiac fibroblast survival. | Platelet-derived growth factor receptor α (PDGFRα), a receptor tyrosine kinase required for cardiac fibroblast development, is uniquely expressed by fibroblasts in the adult heart. Despite the consensus that PDGFRα is expressed in adult cardiac fibroblasts, we know little about its function when these cells are at rest. Here, we demonstrate that loss of PDGFRα in cardiac fibroblasts resulted in a rapid reduction of resident fibroblasts. Furthermore, we observe that phosphatidylinositol 3-kinase signaling was required for PDGFRα-dependent fibroblast maintenance. Interestingly, this reduced number of fibroblasts was maintained long-term, suggesting that there is no homeostatic mechanism to monitor fibroblast numbers and restore hearts to wild-type levels. Although we did not observe any systolic functional changes in hearts with depleted fibroblasts, the basement membrane and microvasculature of these hearts were perturbed. Through in vitro analyses, we showed that PDGFRα signaling inhibition resulted in an increase in fibroblast cell death, and PDGFRα stimulation led to increased levels of the cell survival factor activating transcription factor 3. Our data reveal a unique role for PDGFRα signaling in fibroblast maintenance and illustrate that a 50% loss in cardiac fibroblasts does not result in lethality.<b>NEW & NOTEWORTHY</b> Platelet-derived growth factor receptor α (PDGFRα) is required in developing cardiac fibroblasts, but a functional role in adult, quiescent fibroblasts has not been identified. Here, we demonstrate that PDGFRα signaling is essential for cardiac fibroblast maintenance and that there are no homeostatic mechanisms to regulate fibroblast numbers in the heart. PDGFR signaling is generally considered mitogenic in fibroblasts, but these data suggest that this receptor may direct different cellular processes depending on the cell's maturation and activation status. |
2,329,055 | Unedited microneurosurgery of a pineal region neuroepithelial cyst. | Neuroepithelial cysts are benign, well-circumscribed, nonenhancing CSF-like masses that might virtually present in any intracranial location. Common locations are the frontal lobe, thalamus, midbrain and pons, vermis, the lateral and fourth ventricles, and the choroid fissure (Choroid fissure cysts). Usually asymptomatic, cysts in the posterior fossa have been reported to cause cranial nerve palsies, focal brainstem dysfunction, and hydrocephalus. Supratentorial cysts might cause seizures or focal motor and/or sensory deficits. Histopathological examination reveals that neuroepithelial cysts are lined by ependymal (columnar epithelium) or choroid plexus cells (low cuboidal epithelium). The differential diagnosis includes enlarged perivascular spaces, infectious cyst-neurocysticercosis, porencephalic cyst, and arachnoid cyst.</AbstractText>A patient with a symptomatic histologically confirmed pineal region neuroepithelial cyst underwent park bench position and a right supracerebellar infratentorial approach. The pineal region was accessed over the right cerebellar hemisphere and the lesion was identified after a lateral opening of the quadrigeminal cistern. After a careful dissection of the lesion, the cyst was pulled out with long ring microforceps and long sharp bipolar forceps; both assisted by a thumb-regulated suction tube. A complete lesion was removed in a piece and meticulous attention was paid to any bleeding securing complete hemostasis of the surgical site. The postoperative course was uneventful. The patient underwent rehabilitation without recurrence of the lesion.</AbstractText>This unedited video offers all detailed aspects that a neurosurgeon as the senior author JH considers essential when performing an efficient and safe surgery into the pineal region for this very rarely documented pineal region neuroepithelial cyst.</AbstractText>http://surgicalneurologyint.com/videogallery/pineal-cyst-4.</AbstractText> |
2,329,056 | Right Ventricular Myocardial Stiffness and Relaxation Components by Kinematic Model-Based Transtricuspid Flow Analysis in Children and Adolescents with Pulmonary Arterial Hypertension. | We hypothesized that the kinematic model-based parameters obtained from the transtricuspid E-wave would be useful for evaluating the right ventricular diastolic property in pediatric pulmonary arterial hypertension (PAH) patients. The model was parametrized by stiffness/elastic recoil k, relaxation/damping c and load x. These parameters were determined as the solution of m⋅d<sup>2</sup>x/dt<sup>2</sup> + c⋅dx/dt + kx = 0, which is based on the theory that the E-wave contour is determined by the interplay of stiffness/restoring force, damping/relaxation force and load. The PAH group had a significantly higher k and c compared with the control group (182.5 ± 72.4 g/s vs. 135.7 ± 49.5 g/s<sup>2</sup>, p = 0.0232, and 21.9 ± 6.5 g/s vs. 10.6 ± 5.2 g/s, p <0.0001, respectively). These results indicate that in the PAH group, the right ventricle had higher stiffness/elastic recoil and inferior cross-bridge relaxation. The present findings indicate the feasibility and utility of using kinematic model parameters to assess right ventricular diastolic function. |
2,329,057 | The relationship between diurnal blood pressure abnormalities and target organ damage in normotensive subjects. Which is more important? Increased blood pressure levels or circadian blood pressure abnormalities. | <b>Objective</b>: Circadian blood pressure (CBP) abnormalities are well-known risk factors for many diseases such as cardiovascular, cerebrovascular, and chronic kidney disease. The object of this study was to evaluate the relationship between abnormalities in CBP rhythm and target organ damage (TOD) in normotensive non-dipper (non-DP) subjects.<b>Methods</b>: The 24-h ambulatory BP monitoring (ABPM) and echocardiography were performed and urinary albumin excretion (UAE) was measured in 127 normotensive dipper (DP) (42 males, 85 females) and 337 (89 males, 248 females) normotensive non-DP subjects.<b>Results</b>: When we compared DP and non-DP subjects; Pulse wave velocity (PWV) (7.12 ± 1.72 vs 7.57 ± 1.87 m/s, p = 0.02), the percentile of corrected PWV (cPWV) (7.1 vs. 20.2, p= 0.001) and the percentile of corrected augmentation index (cAIx) (23.5 vs. 33.9, p = 0.03), left ventricle mass index (LVMI) (78.00 ± 23.27 vs. 95.59 ± 18.29 g/m<sup>2</sup>, p = 0.01), relative wall thickness (RWT)(0.36 ± 0.13 vs 0.46 ± 0.09, p = 0.01), percentile of proteinuria (8.6 vs 29.2%, p = 0.00) were higher in non-DP group. In the correlation analyses, the PWV, LVMI, RWT were negatively correlated with the rate of systolic fall in nighttime (%)(-0.15, p = 0.01 vs. -0.23, p = 0.02 vs. -0.27, p = 0.00). It was observed that cPWV, cAIx, and UAE were independently associated with age and non-DP status (NDS), in logistic regression analysis.<b>Conclusions</b>: Our results suggested that normotensive persons with CBP abnormalities had TOD. In light of the data of this article, non-dipper status is detected in the early period and if the provision of diurnal blood pressure rhythm may reduce the incidence of future adverse events in nondipper normotensive subjects. |
2,329,058 | Ventricular Meningiomas: Surgical Strategies and a New Finding That Suggest an Origin From the Choroid Plexus Epithelium. | The aim of this study is to share our experiences on a series of 21 patients with intraventricular meningiomas (IVMs). Histopathologic examinations are reviewed in detail and the cell of origin of IVMs is discussed.</AbstractText>We retrospectively reviewed 1372 patients with intracranial meningioma who were surgically treated between September 1986 and July 2018. From this cohort, 21 patients with IVM were identified. The clinical, radiologic, surgical, and follow-up records were analyzed. The archival pathologic specimens were reviewed. Tissue microarray blocks were performed from the formalin-fixed, paraffin-embedded samples of all IVM cases, 2 choroid plexus tissue adjacent to the tumors, and 10 extraventricular fibrous meningioma cases selected as control randomly. Immunohistochemical staining with the antibodies S-100, SOX10, NGFR, and OTX2 was performed according to the protocols indicated by the manufacturers.</AbstractText>Surgical complications included hemiparesis in 1 patient (5%), postoperative seizure in 1 patient (5%), sensorial aphasia in 1 patient (5%), and preexisting headache in 1 patient (5%). Seventeen (81%) of the IVMs had grade I pathology and 4 (19%) had grade II pathology. The immunoprofile of IVMs is identical to the immunoprofile of normal choroid plexus epithelium.</AbstractText>Transcortical approaches using intraoperative ultrasonography and intraoperative monitoring with avoidance of eloquent cortical areas can achieve good outcomes. Resection of the choroidal attachments should be attempted. Our results indicate that IVMs do not show arachnoid cap cell phenotype and the findings support that IVMs originate from the choroid plexus epithelium or the progenitors of the choroid plexus epithelium.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,059 | A Single-Center Retrospective Descriptive Cohort Study of 211 Pediatric Patients: Cerebrospinal Fluid Leakage After Fourth Ventricle Tumor Resection. | Cerebrospinal fluid (CSF) leak remains a significant complication of posterior fossa tumor surgery. The goal of this study was to evaluate the wound CSF leakage rate in pediatric patients who underwent fourth ventricle tumor resection in a single-site setting and to explore the association of CSF leakage with the length of stay in the intensive care unit (ICU) and with dural sealant application.</AbstractText>Two hundred and eleven patients who underwent fourth ventricle tumor surgery between 2008 and 2016 were included in this study. Patient data were evaluated retrospectively.</AbstractText>Postoperative wound CSF leakage was observed in 6 patients (2.8%). One hundred and seventy-six patients (83.4%) stayed in the ICU for ≤1 day, and CSF leakage developed in 4 of these patients (2.3%). Thirty-five patients (16.6%) stayed in the ICU for >1 day, and CSF leakage was observed in 2 of these patients (5.7%). The observed difference was not statistically significant (P = 0.260). There were no statistically significant differences in the CSF leakage rates in groups with and without dural sealing before (n = 2 [3%] and n = 4 [2.8%], respectively; P = 0.99) and after (n = 2 [3.0%] and n = 4 [6.0%], respectively; P = 0.68) application of the propensity score matching algorithm.</AbstractText>The low CSF leakage rate (2.8%) identified in this study was associated with a certain algorithm of patient management. There was no strong evidence that the CSF leakage rate was associated with the length of stay in the ICU or with dural sealant application.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,060 | Aqueductal Cerebrospinal Fluid Stroke Volume Flow in a Rodent Model of Chronic Communicating Hydrocephalus: Establishing a Homogeneous Study Population for Cerebrospinal Fluid Dynamics Exploration. | Idiopathic normal pressure hydrocephalus (iNPH) is a cause of dementia that can be reversed when treated timely with cerebrospinal fluid (CSF) diversion. Understanding CSF dynamics throughout the development of hydrocephalus is crucial to identify prognostic markers to estimate benefit/risk to shunts.</AbstractText>To explore the cerebral aqueduct CSF flow dynamics with phase-contrast magnetic resonance imaging (MRI) in a novel rodent model of adult chronic communicating hydrocephalus.</AbstractText>Kaolin was injected into the subarachnoid space at the convexities in Sprague-Dawley adult rats. 11.7-T Bruker MRI was used to acquire T2-weighted images for anatomic identification and phase-contrast MRI at the cerebral aqueduct. Aqueductal stroke volume (ASV) results were compared with the ventricular volume (VV) at 15, 60, 90, and 120 days.</AbstractText>Significant ventricular enlargement was found in kaolin-injected animals at all times (P < 0.001). ASV differed between cases and controls/shams at every time point (P = 0.004, 0.001, 0.001, and <0.001 at 15, 60, 90, and 120 days, respectively). After correlation between the ASV and the VV, there was a significant correlation at 15 (P = 0.015), 60 (P = 0.001), 90 (P < 0.001), and 120 days. Moreover, there was a significant positive correlation between the VV expansion and the aqueductal CSF stroke between 15 and 60 days.</AbstractText>An initial active phase of rapid ventricular enlargement shows a strong correlation between the expansion of the VV and the increment in the ASV during the first 60 days, followed by a second phase with less ventricular enlargement and heterogeneous behavior in the ASV. Further correlation with complementary data from intracranial pressure and histologic/microstructural brain parenchyma assessments are needed to better understand the ASV variations after 60 days.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,061 | A model of brain morphological changes related to aging and Alzheimer's disease from cross-sectional assessments. | In this study we propose a deformation-based framework to jointly model the influence of aging and Alzheimer's disease (AD) on the brain morphological evolution. Our approach combines a spatio-temporal description of both processes into a generative model. A reference morphology is deformed along specific trajectories to match subject specific morphologies. It is used to define two imaging progression markers: 1) a morphological age and 2) a disease score. These markers can be computed regionally in any brain region. The approach is evaluated on brain structural magnetic resonance images (MRI) from the ADNI database. The model is first estimated on a control population using longitudinal data, then, for each testing subject, the markers are computed cross-sectionally for each acquisition. The longitudinal evolution of these markers is then studied in relation with the clinical diagnosis of the subjects and used to generate possible morphological evolutions. In the model, the morphological changes associated with normal aging are mainly found around the ventricles, while the Alzheimer's disease specific changes are located in the temporal lobe and the hippocampal area. The statistical analysis of these markers highlights differences between clinical conditions even though the inter-subject variability is quite high. The model is also generative since it can be used to simulate plausible morphological trajectories associated with the disease. Our method quantifies two interpretable scalar imaging biomarkers assessing respectively the effects of aging and disease on brain morphology, at the individual and population level. These markers confirm the presence of an accelerated apparent aging component in Alzheimer's patients but they also highlight specific morphological changes that can help discriminate clinical conditions even in prodromal stages. More generally, the joint modeling of normal and pathological evolutions shows promising results to describe age-related brain diseases over long time scales. |
2,329,062 | Gata4 regulates hedgehog signaling and Gata6 expression for outflow tract development. | Dominant mutations of Gata4, an essential cardiogenic transcription factor (TF), were known to cause outflow tract (OFT) defects in both human and mouse, but the underlying molecular mechanism was not clear. In this study, Gata4 haploinsufficiency in mice was found to result in OFT defects including double outlet right ventricle (DORV) and ventricular septum defects (VSDs). Gata4 was shown to be required for Hedgehog (Hh)-receiving progenitors within the second heart field (SHF) for normal OFT alignment. Restored cell proliferation in the SHF by knocking-down Pten failed to rescue OFT defects, suggesting that additional cell events under Gata4 regulation is important. SHF Hh-receiving cells failed to migrate properly into the proximal OFT cushion, which is associated with abnormal EMT and cell proliferation in Gata4 haploinsufficiency. The genetic interaction of Hh signaling and Gata4 is further demonstrated to be important for OFT development. Gata4 and Smo double heterozygotes displayed more severe OFT abnormalities including persistent truncus arteriosus (PTA). Restoration of Hedgehog signaling renormalized SHF cell proliferation and migration, and rescued OFT defects in Gata4 haploinsufficiency. In addition, there was enhanced Gata6 expression in the SHF of the Gata4 heterozygotes. The Gata4-responsive repressive sites were identified within 1kbp upstream of the transcription start site of Gata6 by both ChIP-qPCR and luciferase reporter assay. These results suggested a SHF regulatory network comprising of Gata4, Gata6 and Hh-signaling for OFT development. |
2,329,063 | Early fetal hydropic changes are associated with moderate dilatation of the brain ventricular system: A clue to a possible link between cervical lymphatic engorgement and ventricular dilatation? | The aim of this study is to assess whether early cervical lymphatic obstruction is associated with a sonographically detectable dilatation of the ventricular system in the 1st trimester of pregnancy. In particular, the objective is to assess whether fetuses with non-immune hydrops fetalis (NIHF), cystic hygroma, or enlarged nuchal translucency (NT) have a greater atrial width/biparietal diameter (AW/BPD) ratio than normal at time of the combined first trimester screening scan. This retrospective study included 96 first trimester fetuses (33 normal and 63 with various degree of cervical lymphatic engorgement). Inclusion criteria were CRL in the 45-84 mm range and availability of one or more three-dimensional volume datasets of the fetal head, acquired from the BPD plane. Each three-dimensional volume dataset was opened and multiplanar correlation employed to align the three orthogonal planes. The ratio between the atrial width and the BPD (AW/BPD ratio) was used to evaluate the possible presence of increased amount of cerebrospinal fluid. Abnormal cases were placed into 4 categories: 1) enlarged non-septated NT 2.5-3.9 mm, no hydrops; 2) grossly enlarged non-septated NT / edema >3.9 mm; 3) cystic hygroma and/ or NIHF; 4) major anomalies with NT <2.5 mm. Presence of dilatation of the laterocervical jugular lymphatic sacs, karyotype and presence of congenital anomalies were also recorded. The One-way ANOVA test was used to compare means. Intra- and inter-observer variability were also assessed. The AW/BPD ratio was found to be significantly higher in fetuses with grossly enlarged NT/nuchal edema and NIHF/septated cystic hygroma than in normal (p <0.05 and p <0.01, respectively). Also, the AW/BPD ratio was significantly higher in NIHF/septated cystic hygroma than in enlarged NT 2.5-3.9 mm (p <0.05). In case of enlarged NT (2.5-3.9 mm), the AW/BPD ratio is significantly higher in presence of JLS (p <0.01). At the end of the first trimester, presence of cervical lymphatic engorgement, in terms of grossly enlarged NT, nuchal edema, septated cystic hygroma, and NIHF, is statistically associated with a moderate dilatation of the ventricular system. Of note, among fetuses with moderately enlarged NT, those with evidence of dilatation of the JLS show a statistically significant increase in the AW/BPD ratio. |
2,329,064 | Umbilical Cord Cell Therapy Improves Spatial Memory in Aging Rats. | There is a growing interest in the potential of adult stem cells for implementing regenerative medicine in the brain. We assessed the effect of intracerebroventricular (icv) administration of human umbilical cord perivascular cells (HUCPVCs) on spatial memory of senile (27 mo) female rats, using intact senile counterparts as controls. Approximately one third of the animals were injected in the lateral ventricles with a suspension containing 4.8 X 10<sup>5</sup> HUCPVC in 8 μl per side. The other third received 4.8 X 10<sup>5</sup> transgenic HUCPVC overexpressing Insulin-like growth factor-1 (IGF-1) and the last third of the rats received no treatment. Spatial memory performance was evaluated using a modified version of the Barnes maze test. In order to evaluate learning ability as well as spatial memory retention, we assessed the time spent (permanence) by animals in goal sector 1 (GS<sub>1</sub>) and 3 (GS<sub>3</sub>) when the escape box was removed. Fluorescence microscopy revealed the prescence of Dil-labeled HUCPVC in coronal sections of treated brains. The HUCPVC were located in close contact with the ependymal cells with only a few labeled cells migrating into the brain parenchyma. After treatment with naïve or IGF-1 transgenic HUCPVC, permanence in GS<sub>1</sub> and GS<sub>3</sub> increased significantly whereas there were no changes in the intact animals. We conclude that HUCPVC injected icv are effective to improve some components of spatial memory in senile rats. The ready accessibility of HUCPVC constitutes a significant incentive to continue the exploration of their therapeutic potential on neurodegenerative diseases. |
2,329,065 | Nicotine Acts on Cholinergic Signaling Mechanisms to Directly Modulate Choroid Plexus Function. | Neuronal cholinergic circuits have been implicated in cognitive function and neurological disease, but the role of cholinergic signaling in other cellular populations within the brain has not been as fully defined. Here, we show that cholinergic signaling mechanisms are involved in mediating the function of the choroid plexus, the brain structure responsible for generating CSF and releasing various factors into the brain. The choroid plexus was found to express markers of endogenous cholinergic signaling, including multiple nicotinic acetylcholine receptor (nAChR) subtypes in a region-specific manner, and application of nicotine was found to induce cellular activation, as evidenced by calcium influx in primary tissue. During intravenous nicotine self-administration in male rats, nicotine increased expression of transthyretin, a protein selectively produced and released by the choroid plexus, and microRNA-204 (mir-204), a transcript found in high levels in the choroid plexus and CSF. Finally, human choroid plexus tissue from both sexes was found to exhibit similar nAChR, transthyretin and mir-204 expression profiles, supporting the translational relevance of the findings. Together, these studies demonstrate functionally active cholinergic signaling mechanisms in the choroid plexus, the resulting effects on transthyretin and mir-204 expression, and reveal the direct mechanism by which nicotine modulates function of this tissue. |
2,329,066 | Clinical diagnosis and mutation analysis of four Chinese families with succinic semialdehyde dehydrogenase deficiency. | Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessively-inherited defect of γ-aminobutyric acid (GABA) metabolism. The absence of SSADH, which is encoded by aldehyde dehydrogenase family 5 member A1 (ALDH5A1) gene, leads to the accumulation of GABA and γ-hydroxybutyric acid (GHB). Few cases with SSADH deficiency were reported in China.</AbstractText>In this study, four Chinese patients were diagnosed with SSADH deficiency in Tianjin Children's Hospital. We conducted a multidimensional analysis with magnetic resonance imaging (MRI) of the head, semi quantitative detection of urine organic acid using gas chromatography-mass spectrometry, and analysis of ALDH5A1 gene mutations. Two of the patients were admitted to the hospital due to convulsions, and all patients were associated with developmental delay. Cerebral MRI showed symmetrical hyperintense signal of bilateral globus pallidus and basal ganglia in patient 1; hyperintensity of bilateral frontal-parietal lobe, widened ventricle and sulci in patient 2; and widened ventricle and sulci in patient 4. Electroencephalogram (EEG) revealed the background activity of epilepsy in patient 1 and the disappearance of sleep spindle in patient 2. Urine organic acid analysis revealed elevated GHB in all the patients. Mutational analysis, which was performed by sequencing the 10 exons and flanking the intronic regions of ALDH5A1 gene for all the patients, revealed mutations at five sites. Two cases had homozygous mutations with c.1529C > T and c.800 T > G respectively, whereas the remaining two had different compound heterozygous mutations including c.527G > A/c.691G > A and c.1344-2delA/c.1529C > T. Although these four mutations have been described previously, the homozygous mutation of c.800 T > G in ALDH5A1 gene is a novel discovery.</AbstractText>SSADH deficiency is diagnosed based on the elevated GHB and 4, 5DHHA by urinary organic acid analysis. We describe a novel mutation p.V267G (c.800 T > G) located in the NAD binding domain, which is possibly crucial for this disease's severity. Our study expands the mutation spectrum of ALDH5A1 and highlights the importance of molecular genetic evaluation in patients with SSADH deficiency.</AbstractText> |
2,329,067 | Cortical Visual Impairment in Congenital Cytomegalovirus Infection. | To describe the presentation, evolution, and long-term outcome of cortical visual impairment (CVI) in patients with symptomatic congenital cytomegalovirus (CMV) infection, and to identify risk factors for the development of CVI in patients with symptomatic congenital CMV.</AbstractText>Retrospective subanalysis of a long-term prospective cohort study with data gathered from 1982 to 2013.</AbstractText>Eleven of 77 (14.3%) patients with symptomatic CMV, 0 of 109 with asymptomatic CMV, and 51 control patients had CVI. Overall, patients with symptomatic CMV had worse vision than patients with asymptomatic CMV, who in turn had worse vision than control patients. Microcephaly, intracranial calcification, dilatation of ventricles, encephalomalacia, seizure at birth, optic atrophy, chorioretinitis/retinal scars, strabismus, and neonatal onset of sensorineural hearing loss were risk factors associated with CVI.</AbstractText>CVI may result from symptomatic congenital CMV infection. The relationship of CVI and its risk factors in patients with CMV suggests the potential to predict the development of CVI through predictive modeling in future research. Early screening of CVI in children born with symptomatic congenital CMV can facilitate educational, social, and developmental interventions. [J Pediatr Ophthalmol Strabismus. 2019;56(3):194-202.].</AbstractText>Copyright 2019, SLACK Incorporated.</CopyrightInformation> |
2,329,068 | Role of left ventricle deformation analysis in stress echocardiography for significant coronary artery disease detection: A diagnostic study meta-analysis. | We compared the diagnostic accuracy of longitudinal strain (LS) imaging during stress echocardiography with visual assessment of wall motion (WM) for detecting significant coronary artery disease (CAD).</AbstractText>Our systematic search included studies reporting diagnostic measures for LS imaging and visual assessment of WM for detecting significant CAD during stress echocardiography. Summary diagnostic accuracy measures including area under the curve (AUC), sensitivity, specificity, diagnostic odds ratio (DOR), and likelihood ratios (LRs) were estimated.</AbstractText>In thirteen studies with 978 patients, ten studies used invasive coronary angiography as the reference standard. Pooled AUC for diagnosing significant CAD was 0.92 (95% confidence interval [CI] 0.89-0.94) for LS imaging as compared to 0.83 (95% CI 0.80-0.86), P < 0.001 for visual assessment of WM. LS imaging had higher sensitivity (88% [95% CI 84-92] vs 74% [95% CI 68-80], P < 0.001) and comparable specificity to visual assessment of WM (80% [95% CI 72-87] vs 83% [95% CI 74-90], P = 0.592). The DOR for LS imaging and visual assessment of WM was 31 and 15, P = 0.254, respectively. The positive LR was 4.5 for both; negative LR was 0.14 and 0.31, P = 0.002 for LS imaging and visual assessment of WM, respectively.</AbstractText>Longitudinal strain imaging during stress echocardiography has better diagnostic accuracy for detecting significant CAD as compared to visual assessment of WM. Studies using larger sample size and standardized techniques of strain measurement are required to further ascertain the added advantage of strain measurement over visual assessment alone.</AbstractText>© 2019 Wiley Periodicals, Inc.</CopyrightInformation> |
2,329,069 | Cardiac sympathetic innervation network shapes the myocardium by locally controlling cardiomyocyte size through the cellular proteolytic machinery. | The heart is innervated by a dense sympathetic neuron network which, in the short term, controls chronotropy and inotropy and, in the long term, regulates cardiomyocyte size. Acute neurogenic control of heart rate is achieved locally through direct neuro-cardiac coupling at specific junctional sites (neuro-cardiac junctions). The ventricular sympathetic network topology is well-defined and characteristic for each mammalian species. In the present study, we used cell size regulation to determine whether long-term modulation of cardiac structure is achieved via direct sympatho-cardiac coupling. Local density of cardiac innervation correlated with cell size throughout the myocardial walls in all mammalian species analysed, including humans. The data obtained suggest that constitutive neurogenic control of cardiomyocyte trophism occurs through direct intercellular signalling at neuro-cardiac junctions.</AbstractText>It is widely appreciated that sympathetic stimulation of the heart involves a sharp increase in beating rate and significant enhancement of contractility. We have previously shown that, in addition to these evident functions, sympathetic neurons (SNs) also provide trophic input to cardiomyocytes (CMs), regulating cell and organ size. More recently, we have demonstrated that cardiac neurons establish direct interactions with CMs, allowing neuro-cardiac communication to occur locally, with a 'quasi-synaptic' mechanism. Based on the evidence that cardiac SNs are unevenly distributed throughout the myocardial walls, we investigated the hypothesis that CM size distribution reflects the topology of neuronal density. In vitro analyses of SN/CM co-cultures, ex vivo confocal and multiphoton imaging in clarified hearts, and biochemical and molecular approaches were employed, in both rodent and human heart biopsies. In line with the trophic effect of SNs, and with local neuro-cardiac communication, CMs, directly contacted by SNs in co-cultures, were larger than the non-targeted ones. This property reflects the distribution of CM size throughout the ventricles of intact mouse heart, in which cells in the outer myocardial layers, which were contacted by more neuronal processes, were larger than those in the less innervated subendocardial region. Such differences disappeared upon genetic or pharmacological interference with the trophic SN/CM signalling axis. Remarkably, CM size followed the SN distribution pattern in other mammals, including humans. Our data suggest that both the acute and chronic influence of SNs on cardiac function and structure is enacted as a result of the establishment of specific intercellular neuro-cardiac junctions.</AbstractText>© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.</CopyrightInformation> |
2,329,070 | Feasibility study of highly accelerated phase-sensitive inversion recovery myocardial viability imaging using simultaneous multislice and parallel imaging techniques. | Phase-sensitive inversion recovery (PSIR) is a powerful cardiac MRI method to assess myocardial viability, which can eliminate the background phase and preserve the sign of the desired magnetization during inversion recovery.</AbstractText><AbstractText Label="PURPOSE/HYPOTHESIS">To shorten the acquisition time of myocardial viability imaging by introducing both simultaneous multislice (SMS) and parallel imaging (PI) into PSIR without additional acquisitions for calibration data.</AbstractText>Prospective study.</AbstractText>A high-resolution phantom and three vials with doped solutions matching typical postcontrast T1</sub> and T2</sub> values of scar, healthy myocardium, and blood; 18 patients (six with known myocardial infarction) were included in this study.</AbstractText><AbstractText Label="FIELD STRENGTH/SEQUENCE">3T/segmented fast spoiled gradient echo pulse sequence.</AbstractText>Phantom and in vivo experiments were performed to compare the performance of conventional PSIR, SMS accelerated PSIR (SMS-PSIR, 2× acceleration), and SMS as well as PI accelerated PSIR (SMS + PI-PSIR, 4× acceleration). In phantom experiments, the error maps, local signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated. In in vivo experiments, the image quality and artifact level of each study were qualitatively graded (by three radiologists). G-factor maps were calculated. The infarct size presented as a percentage of the left ventricle was measured (full-width half-maximum). Acquisition time of each study was recorded.</AbstractText>One-way analysis of variance, Kruskal-Wallis test.</AbstractText>In phantom experiments, SNR and CNR were well preserved for SMS-PSIR, while they dropped for SMS + PI-PSIR, as expected. In 15 subjects, the overall image quality scores were not significantly different among conventional PSIR (3.70 ± 1.06), SMS-PSIR (3.78 ± 0.99), and SMS + PI-PSIR (3.47 ± 0.94; P = 0.20). The artifact level scores were also comparable among conventional PSIR (3.67 ± 1.04), SMS-PSIR (3.77 ± 1.03), and SMS + PI-PSIR (3.45 ± 1.00; P = 0.22). SMS-PSIR achieved negligible g-factor noise amplification (1.04 ± 0.03) and SMS + PI-PSIR showed higher g-factors (2.83 ± 0.48). The infarct size was consistent among conventional PSIR (22.51 ± 25.05%) and SMS-PSIR (22.98 ± 26.19%), as well as SMS + PI-PSIR (22.93 ± 25.68%; P = 0.98). The acquisition time of two short-axis slices for SMS-PSIR (17.6 ± 1.7 sec, 16 heartbeats) and SMS + PI-PSIR (9.8 ± 1.9 sec, 8 heartbeats) was 30% and 17% of that for conventional PSIR (56.2 ± 8.5 sec, 32 heartbeats), respectively.</AbstractText>SMS can be implemented in PSIR without additional reference scan. The image quality is comparable with conventional PSIR, while the acquisition time is much shorter. The proposed method is also compatible with PI to further reduce the scan time.</AbstractText>2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1964-1972.</AbstractText>© 2019 International Society for Magnetic Resonance in Medicine.</CopyrightInformation> |
2,329,071 | RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome. | The Brugada syndrome (BrS) is an inherited cardiac disorder predisposing to ventricular arrhythmias. Despite considerable efforts, its genetic basis and cellular mechanisms remain largely unknown. The objective of this study was to identify a new susceptibility gene for BrS through familial investigation.</AbstractText>Whole-exome sequencing performed in a three-generation pedigree with five affected members allowed the identification of one rare non-synonymous substitution (p.R211H) in RRAD, the gene encoding the RAD GTPase, carried by all affected members of the family. Three additional rare missense variants were found in 3/186 unrelated index cases. We detected higher levels of RRAD transcripts in subepicardium than in subendocardium in human heart, and in the right ventricle outflow tract compared to the other cardiac compartments in mice. The p.R211H variant was then subjected to electrophysiological and structural investigations in human cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs). Cardiomyocytes derived from induced pluripotent stem cells from two affected family members exhibited reduced action potential upstroke velocity, prolonged action potentials and increased incidence of early afterdepolarizations, with decreased Na+ peak current amplitude and increased Na+ persistent current amplitude, as well as abnormal distribution of actin and less focal adhesions, compared with intra-familial control iPSC-CMs Insertion of p.R211H-RRAD variant in control iPSCs by genome editing confirmed these results. In addition, iPSC-CMs from affected patients exhibited a decreased L-type Ca2+ current amplitude.</AbstractText>This study identified a potential new BrS-susceptibility gene, RRAD. Cardiomyocytes derived from induced pluripotent stem cells expressing RRAD variant recapitulated single-cell electrophysiological features of BrS, including altered Na+ current, as well as cytoskeleton disturbances.</AbstractText>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.</CopyrightInformation> |
2,329,072 | Central Inhibition of Tumor Necrosis Factor Alpha Reduces Hypertension by Attenuating Oxidative Stress in the Rostral Ventrolateral Medulla in Renovascular Hypertensive Rats. | Inflammation in the central nervous system is being considered a key player linked to neurogenic hypertension. Using combined <i>in vivo</i> and <i>in vitro</i> approaches, we investigated the effects of central inhibition of TNF-α on blood pressure, sympathetic tone, baroreflex sensitivity, and oxidative stress in the rostral ventrolateral medulla (RVLM) of rats with 2-kidney-1-clip (2K1C) renovascular hypertension. Continuous infusion of pentoxifylline, a TNF-α inhibitor, into the lateral ventricle of the brain for 14 consecutive days reduced blood pressure and improved baroreflex sensitivity in renovascular hypertensive rats. Furthermore, central TNF-α inhibition reduced sympathetic modulation and blunted the increased superoxide accumulation in the RVLM of 2K1C rats. Our findings suggest that TNF-α play an important role in the maintenance of sympathetic vasomotor tone and increased oxidative stress in the RVLM during renovascular hypertension. |
2,329,073 | First-trimester cystic posterior fossa: reference ranges, associated findings, and pregnancy outcomes. | To report reference ranges for fetal cerebral posterior fossa measurements and to describe the sonographic findings, karyotype results, and pregnancy outcomes in fetuses presenting with cystic posterior fossa (CPF) in the first trimester of pregnancy.</AbstractText>Two groups of patients undergoing first-trimester sonographic screening at 11-13 weeks' gestation were studied. The first (control group) consisted of 253 consecutive fetuses with normal posterior fossa, in which the brainstem (BS), fourth ventricle, cisterna magna, and BS-occipital bone (BS-OB) diameter were prospectively measured and the BS/BS-OB diameter ratio was calculated. The second (study group) consisted of 14 fetuses in which a CPF was detected. Information on sonographic findings, prenatal karyotype results, and pregnancy outcomes was obtained by reviewing ultrasound reports and medical records. The results from the two groups were then compared.</AbstractText>In the control group, the size of all posterior fossa structures increased and the BS/BS-OB diameter ratio slightly decreased as the pregnancy progressed. In the study group, the BS diameter did not differ significantly from the measurements obtained in the control group. However, the BS-OB diameter and the fourth ventricle were significantly larger (p</i> < .05 and p</i> < .001, respectively) in the study group than in the control group. Additionally, the cisterna magna was not identified in 13 of the 14 fetuses (93%) in the study group, in comparison to zero out of the 253 fetuses in the control group (p</i> < .001). Finally, the BS/BS-OB diameter ratio was significantly smaller in the study group when compared with the control group (p</i> < .05). Regarding pregnancy outcomes, 12 of the 14 (86%) affected pregnancies underwent elective termination (n</i> = 11) or ended in an early intrauterine demise (n</i> = 1) due to the associated chromosomal abnormalities or structural defects. The two fetuses with isolated CPF had a normal second-trimester scan and resulted in the delivery of healthy newborn infants.</AbstractText>The detection of a CPF in the first trimester is associated with a high rate of chromosomal and structural defects. By using normative data, early sonographic screening and detection of mildly and moderately abnormal cases is possible. Fetuses with isolated CPF require further study with a detailed second-trimester scan. This is essential in order to differentiate cases with poor and good perinatal outcomes. Finally, our data also demonstrate that the main sonographic tool when screening for CPF in the first trimester is the assessment of the fourth ventricle, which is significantly larger in abnormal cases as the result of the wide communication between the fourth ventricle and the cisterna magna.</AbstractText> |
2,329,074 | A Bayesian risk analysis for Trisomy 21 in isolated choroid plexus cyst: combining a prenatal database with a meta-analysis. | The purpose of this study was to quantify the possible additional risk of a fetus with an isolated choroid plexus cyst (ICPC) for Trisomy 21 by combining a large controlled cohort study with data from existent studies.</AbstractText>We searched our prenatal database between 2000 and 2014 for all singleton pregnancies between 18 + 0 and 26 + 6 gestational weeks with either an isolated choroid plexus cyst (study group) or no abnormality found in the detailed ultrasound scan (control group). We assessed all prenatal karyotyping results if invasive testing was performed and attempted to collect the postnatal outcome reports of all patients. The prevalence of Down syndrome was calculated. By using previous studies that met our inclusion criteria, a meta-analysis following the Bayesian Independent Model was created. From this meta-analysis, we computed the posterior predictive distribution of the probability (Trisomy 21 | ICPC) = P1 including posterior means, standard deviations, quantiles (2.5, 50, and 97.5%). By calculating the posterior of the difference (Δ) between the probability (Trisomy 21 | ICPC) and the probability (Trisomy 21 | Normal Ultrasound) = P2, we investigated the additional risk of an ICPC (ΔB = P1-P2).</AbstractText>Overall, we detected 1220 fetuses with an isolated plexus cyst at 19-27 weeks of gestational age (GA). In our study group, the prevalence of Trisomy 21 was 2/1220 (0.16, 95% CI: 0.1-0.6%). The median of the pooled probability of Trisomy 21 given isolated PC across the studies included in the meta-analysis was 0.2% (CI: 0.1-0.4%). In the given periods (GA and time), 66,606 (74.8%) out of 89,056 investigated fetuses met the inclusion criteria and had a normal ultrasound result without any abnormality. The Δ between our study group and the control group was 0.08% (CIΔA: 0-0.5%). Including the meta-analysis, the median of the posterior distribution of Δ between P1 and P2 was 0.08% (CIΔB: 0-0.4%) (ΔB = P1-P2).</AbstractText>The posterior distribution of Δ between P1 and P2 including the meta-analysis corresponds to showing no difference between the cases and controls (95% CIΔB: 0-0.4%). The additional risk of a fetus with an ICPC for Trisomy 21 is 97.5% likely to be lower than 0.4% (about 1/250). However, in our collective, the positive predictive value of ICPC for Down syndrome was 0.16% (about 1/625). In prenatal counseling, the additional risk should be added to the individual risk (based on maternal age, earlier screening test results, and sonographic markers) and the diagnostic options including fetal DNA and diagnostic procedures should be discussed according to the posterior individual risk.</AbstractText> |
2,329,075 | Effect of Macro-Cyclic Bifunctional Chelators DOTA and NODAGA on Radiolabeling and <i>In Vivo</i> Biodistribution of Ga-68 Cyclic RGD Dimer. | <b><i>Introduction:</i></b> The advent of the Germanium-68 (Ge-68)/Gallium-68 (Ga-68) generator has contributed enormously to a plethora of molecular imaging approaches for <i>in vivo</i> identification of tumor characteristics. The present study compares the effect of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane,1-gluteric acid-4,7-acetic acid (NODAGA) bifunctional chelators on radiolabeling of arginine-glycine-aspartic acid (RGD) dimer, an antagonist of integrin α<sub>v</sub>β<sub>3</sub> with Ga-68 and their biodistribution in C57BL/6 mice bearing melanoma and in patients with breast carcinoma. <b><i>Methods:</i></b> Radiolabeling parameters for DOTA-(RGD)<sub>2</sub> and NODAGA-(RGD)<sub>2</sub> with Ga-68 were optimized in-house. After quality control procedures, preclinical studies were done in C57BL/6 mice bearing melanoma. The percent radioactivity associated with per gram of various organs and tumor (% ID/g) was analyzed. Positron emission tomography-computed tomography patient imaging was performed in clinically diagnosed locally advanced breast carcinoma patients (<i>n</i> = 30). The uptake of various organs and lesions for both radiotracers was compared. <b><i>Results:</i></b> Radiolabeling yield >95% was obtained by heating 15-20 μg of peptide at 95°C for 5-10 min and 3.5-4.0 reaction pH. NODAGA-(RGD)<sub>2</sub> could also be radiolabeled at room temperature, but 40-50 μg peptide was required. Animal biodistribution study revealed the kidney as the major excretory organ for both the radiotracers. Maximum counts were observed in tumor at 45 min. During the clinical study, liver, spleen, bilateral brain ventricles, salivary glands, and intestines were the organs with physiological uptake of both Ga-68-DOTA-(RGD)<sub>2</sub> and Ga-68 NODAGA-(RGD)<sub>2</sub>. The major excretory route was through kidneys. All primary lesions were picked by both the radiotracers. Additionally, in 5 patients, metastatic lesions were also picked up. <b><i>Conclusion:</i></b> DOTA- and NODAGA-chelated RGD<sub>2</sub> were successfully radiolabeled with Ga-68. Good tumor to background contrast exhibited by Ga-68-DOTA-(RGD)<sub>2</sub> and Ga-68 NODAGA-(RGD)<sub>2</sub> in both preclinical and clinical studies suggested that both radiotracers can be used as potential molecular tools for imaging angiogenesis. |
2,329,076 | A tale of two cousins: Ependymal cells, quiescent neural stem cells and potential mechanisms driving their functional divergence. | Recent work has suggested that stem cells exhibit far greater heterogeneity than initially thought. Indeed, their dynamic nature and shared traits with surrounding niche cells have made prospective identification of adult neural stem cells (NSCs) challenging. Refined fate mapping strategies and single-cell omics techniques have begun to clarify functionally distinct states within the adult NSC pool, the molecular signatures that govern these states, and the functional contributions/interactions with neighboring cells within the subventricular niche. Ependymal cells are the epithelial cells which line the ventricular system and reside in the same niche as NSCs. Our own work has revealed that, despite sharing similar embryonic origins with NSCs and close geographic proximity, ependymal cells are transcriptionally distinct and fail to exhibit stem cell function in vivo, even following injury. Intriguingly, comparison of ependymal cells with qNSCs revealed transcriptional signatures that are largely overlapping, suggesting that post-transcriptional regulation might underlie their divergent phenotypes. Additional analysis of ependymal versus qNSC gene regulatory network activation supports this notion. This Viewpoint summarizes the historical confusion regarding the identity of NSCs within the lateral ventricle niche and describes recent work that provides greater appreciation for the diverse functional states within the NSC niche. |
2,329,077 | The spiking and secretory activity of oxytocin neurones in response to osmotic stimulation: a computational model. | A quantitative model of oxytocin neurones that combines a spiking model, a model of stimulus-secretion coupling and a model of plasma clearance of oxytocin was tested. To test the model, a variety of sources of published data were used that relate either the electrical activity of oxytocin cells or the secretion of oxytocin to experimentally induced changes in plasma osmotic pressure. To use these data to test the model, the experimental challenges involved were computationally simulated. The model predictions closely matched the reported outcomes of the different experiments.</AbstractText>Magnocellular vasopressin and oxytocin neurones in the rat hypothalamus project to the posterior pituitary, where they secrete their products into the bloodstream. In rodents, both vasopressin and oxytocin magnocellular neurones are osmoresponsive, and their increased spiking activity is mainly a consequence of an increased synaptic input from osmoresponsive neurons in regions adjacent to the anterior wall of the third ventricle. Osmotically stimulated vasopressin secretion promotes antidiuresis while oxytocin secretion promotes natriuresis. In this work we tested a previously published computational model of the spiking and secretion activity of oxytocin cells against published evidence of changes in spiking activity and plasma oxytocin concentration in response to different osmotic challenges. We show that integrating this oxytocin model with a simple model of the osmoresponsive inputs to oxytocin cells achieves a strikingly close match to diverse sources of data. Comparing model predictions with published data using bicuculline to block inhibitory GABA inputs supports the conclusion that inhibitory inputs and excitatory inputs are co-activated by osmotic stimuli. Finally, we studied how the gain of osmotically stimulated oxytocin release changes in the presence of a hypovolaemic stimulus, showing that this is best explained by an inhibition of an osmotically regulated inhibitory drive to the magnocellular neurones.</AbstractText>© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.</CopyrightInformation> |
2,329,078 | Guizhi Decoction () Inhibits Cholinergic Transdifferentiation by Regulating Imbalance of NGF and LIF in Salt-Sensitive Hypertensive Heart Failure Rats. | To observe the imbalance of anatomical and functional innervation factors of sympathetic nerves, nerve growth factor (NGF) and leukemia inhibitory factor (LIF), in salt-sensitive hypertensive heart failure rats and to explore the effects of treatment with Guizhi Decoction () on sympathetic remodeling by inhibiting cholinergic transdifferentiation.</AbstractText>SS-13BN</sup> and Dahl salt-sensitive (DS) rats were divided into 3 groups: SS-13BN</sup> group (control group, n=9), DS group (model group, n=9) and GS group (Guizhi Decoction, n=9). After 10 weeks of a high-salt diet, the GS group rats were given Guizhi Decoction and other two groups were given saline at an equal volume as a vehicle. After 4 weeks' intragastric administration, rats were executed to detect the relevant indicators. Echocardiography and plasma n-terminal pro-B type natriuretic peptide (NT-proBNP) levels were used to assess cardiac function. Noradrenaline (NA) levels in the plasma and myocardium were detected to evaluate the sympathetic function. NGF and LIF expression were detected in the myocardium by Western blot or quantitative real-time PCR. Double immunofluorescence or Western blot was used to detect tyrosine hydroxylase (TH), choline acetyltransferase (CHAT) and growth associated protein 43 (GAP43) in order to reflect anatomical and functional changes of sympathetic nerves.</AbstractText>DS group had anatomical and functional deterioration of sympathetic nerves in the decompensation period of heart failure compared with SS-13BN</sup> group. Compared with the DS group, Guizhi Decoction significantly decreased the expression of LIF mRNA/protein (P<0.01), increased the expression of NGF (P<0.05 or P<0.01), enhanced the levels of TH+/GAP43+ and TH+/CHAT+ positive nerve fibers (P<0.01), and improved the protein expression of TH and GAP43 in left ventricle, but had no effect on CHAT (P>0.05). Guizhi Decoction inhibited inflammatory infiltration and collagen deposition of myocardial injury, increased the content of myocardial NA (P<0.05), reduced the plasma NA level (P<0.01), improved cardiac function (P<0.01), and improved weight and blood pressure to some extent (P<0.05), compared with DS group.</AbstractText>Guizhi Decoction could inhibit cholinergic transdifferentiation of sympathetic nerves, improve the anatomical and functional denervation of sympathetic nerves, and delay the progression of decompensated heart failure. The mechanism may be associated with the correction of the imbalance of NGF and LIF.</AbstractText> |
2,329,079 | COPD and heart failure: differential diagnosis and comorbidity. | Heart failure (HF) and chronic obstructive pulmonary disease (COPD) represent the most important differential diagnoses of dyspnea in elderly people. Heart failure is the inability of the heart to pump sufficient amounts of blood through the cardiovascular system. Pump failure is caused by compromised contractility and/or filling of the ventricles leading to forward and backward failure and subsequently to dyspnea. In COPD, the destruction and remodeling processes of the bronchiolar architecture inhibit proper exhalation of air, thereby leading to exhaustion of the thoracic muscles, insufficient oxygen diffusion, and dyspnea. Despite these fundamental differences in the pathophysiology of both disorders, their clinical presentation may be very similar. This renders accurate and timely diagnosis and therapy, especially in patients with coexisting disease, difficult. This clinical review summarizes typical problems in the diagnosis of COPD, HF, and coincident disease, and describes strategies that help avoid misdiagnosis and ineffective treatment. |
2,329,080 | Acute renal infarction, transient ischemic attack, and biventricular thrombi secondary to substance use disorder: A case report. | Cocaine is the second most used illicit drug; cocaine induces platelet activation and formation of thrombus. Thrombotic effects of cocaine can lead to vascular injuries, cerebrovascular accident and myocardial infarct. Less common, cocaine use disorder leads to thrombi formation in both ventricles and renal artery infarct as seen in our patient. |
2,329,081 | Dendritic and Synaptic Degeneration in Pyramidal Neurons of the Sensorimotor Cortex in Neonatal Mice With Kaolin-Induced Hydrocephalus. | Obstructive hydrocephalus is a brain disorder in which the circulation of cerebrospinal fluid (CSF) is altered in a manner that causes expansion of fluid-filled intracranial compartments particularly the ventricles. The pyramidal neurons of the sensorimotor cortex are excitatory in nature and their dendritic spines are targets of excitatory synapses. This study evaluated the effect of hydrocephalus on dendritic arborization and synaptic structure of the pyramidal neurons of the sensorimotor cortex of neonatal hydrocephalic mice. Sterile kaolin suspension (0.01 ml of 250 mg/mL) was injected intracisternally into day old mice. Control animals mice received sham injections. Pups were weighed and sacrificed on postnatal days (PND) 7, 14 and 21. Fixed brain tissue blocks were silver impregnated using a modified Golgi staining technique and immunolabeled with synaptophysin to determine dendritic morphology and synaptic integrity respectively. Data were analyzed using ANOVA at <i>α</i> <sub>0.05</sub>. Golgi staining revealed diminished arborization of the basal dendrites and loss of dendritic spines in the pyramidal neurons of hydrocephalic mice. Compared to age-matched controls, there was a significant reduction in the percentage immunoreactivity of anti-synaptophysin in hydrocephalic mice on PND 7 (14.26 ± 1.91% vs. 62.57 ± 9.40%), PND 14 (4.19 ± 1.57% vs. 93.01 ± 1.66%) and PND 21 (17.55 ± 2.76% vs. 99.11 ± 0.63%) respectively. These alterations suggest impaired neuronal connections that are essential for the development of cortical circuits and may be the structural basis of the neurobehavioral deficits observed in neonatal hydrocephalus. |
2,329,082 | Classification of Polar Maps from Cardiac Perfusion Imaging with Graph-Convolutional Neural Networks. | Myocardial perfusion imaging is a non-invasive imaging technique commonly used for the diagnosis of Coronary Artery Disease and is based on the injection of radiopharmaceutical tracers into the blood stream. The patient's heart is imaged while at rest and under stress in order to determine its capacity to react to the imposed challenge. Assessment of imaging data is commonly performed by visual inspection of polar maps showing the tracer uptake in a compact, two-dimensional representation of the left ventricle. This article presents a method for automatic classification of polar maps based on graph convolutional neural networks. Furthermore, it evaluates how well localization techniques developed for standard convolutional neural networks can be used for the localization of pathological segments with respect to clinically relevant areas. The method is evaluated using 946 labeled datasets and compared quantitatively to three other neural-network-based methods. The proposed model achieves an agreement with the human observer on 89.3% of rest test polar maps and on 91.1% of stress test polar maps. Localization performed on a fine 17-segment division of the polar maps achieves an agreement of 83.1% with the human observer, while localization on a coarse 3-segment division based on the vessel beds of the left ventricle has an agreement of 78.8% with the human observer. Our method could thus assist the decision-making process of physicians when analyzing polar map data obtained from myocardial perfusion images. |
2,329,083 | Effects of Intracerebroventricular and Intra-Arcuate Nucleus Injection of Ghrelin on Pain Behavioral Responses and Met-Enkephalin and β-Endorphin Concentrations in the Periaqueductal Gray Area in Rats. | Ghrelin is an endogenous ligand for orphan growth hormone secretagogue receptors. Ghrelin receptors have been found in central nervous system (CNS) areas responsible for pain modulation and transmission. This study investigated the effects of intracerebroventricular (ICV) and intra-arcuate nucleus (ARC) injection of ghrelin on pain behavioral responses and levels of β-endorphin (β-EP) and met-enkephalin (MENK) in the periaqueductal gray area (PAG) during the formalin test in rats. Thirty-five male rats were studied in five groups. Ghrelin was injected into the left lateral ventricle (ICV, 5 µL) or into the ARC (1 µL). After 15 min, formalin (2.5%) was subcutaneously injected into the left hind paw. Behavioral nociceptive scores were recorded for 60 min. MENK and β-EP were collected by microdialysis in the PAG and determined by high-performance liquid chromatography (HPLC). ICV and ARC injection of ghrelin significantly reduced pain in all phases of the formalin test (<i>p</i> < 0.001). Dialysate concentrations of MENK and β-EP in the PAG increased in all the phases (<i>p</i> < 0.01). In conclusion, the present study shows that the ARC nucleus and the endogenous opioid system are involved in ghrelin-induced pain modulation. |
2,329,084 | Distinct glycosylation in membrane proteins within neonatal versus adult myocardial tissue. | Mammalian hearts have regenerative potential restricted to early neonatal stage and lost within seven days after birth. Carbohydrates exclusive to cardiac neonatal tissue may be key regulators of regenerative potential. Although cell surface and extracellular matrix glycosylation are known modulators of tissue and cellular function and development, variation in cardiac glycosylation from neonatal tissue to maturation has not been fully examined. In this study, glycosylation of the adult rat cardiac ventricle showed no variability between the two strains analysed, nor were there any differences between the glycosylation of the right or left ventricle using lectin histochemistry and microarray profiling. However, in the Sprague-Dawley strain, neonatal cardiac glycosylation in the left ventricle differed from adult tissues using mass spectrometric analysis, showing a higher expression of high mannose structures and lower expression of complex N-linked glycans in the three-day-old neonatal tissue. Man<sub>6</sub>GlcNAc<sub>2</sub> was identified as the main high mannose N-linked structure that was decreased in adult while higher expression of sialylated N-linked glycans and lower core fucosylation for complex structures were associated with ageing. The occurrence of mucin core type 2 O-linked glycans was reduced in adult and one sulfated core type 2 O-linked structure was identified in neonatal tissue. Interestingly, O-linked glycans from mature tissue contained both N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), while all sialylated N-linked glycans detected contained only Neu5Ac. As glycans are associated with intracellular communication, the specific neonatal structures found may indicate a role for glycosylation in the neonatal associated regenerative capacity of the mammalian heart. New strategies targeting tissue glycosylation could be a key contributor to achieve an effective regeneration of the mammalian heart in pathological scenarios such as myocardial infarction. |
2,329,085 | MHC-mismatched Allotransplantation of Induced Pluripotent Stem Cell-derived Cardiomyocyte Sheets to Improve Cardiac Function in a Primate Ischemic Cardiomyopathy Model. | Although allogeneic-induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) exhibit potential in cardiomyogenesis for heart failure, whether major histocompatibility complex (MHC)-matched allogenic iPSC implantation (MMAI) minimizes immune rejection for cell survival or functional recovery remains unknown. We herein explored whether MMAI with an iPSC-CM sheet is stable for a longer period and therapeutically more effective than MHC-mismatched AI in a primate ischemic cardiomyopathy model.</AbstractText>Green fluorescent protein-transfected iPSC-CM sheets, derived from cynomolgus macaques with homozygous MHC haplotypes ''HT1,'' were transplanted on the left ventricle, generated by ligating the left anterior descending artery for 2 weeks in an ischemic model with or without heterozygous HT1 as MMAI and MHC-mismatched AI. Sham models were made by opening the chest at 14 days after left anterior descending ligation without any treatment.</AbstractText>Stereomicroscopy revealed that at 4 months after transplantation, green fluorescent protein intensity was higher in the MMAI group than in the MHC-mismatched AI group and the sham group. Immunohistochemistry staining revealed that host immune reaction with CD3-positive cells was stronger in MHC-mismatched AI than in MMAI at 3 months. Cardiac function improved both in MMAI and MHC-mismatched AI at 1 month after transplantation and was preserved until 6 months, whereas in the sham group, functional deterioration progressed over time.</AbstractText>Although MHC-homo-iPSCs are preferred to avoid immune rejection, MHC-mismatched iPSC-CMs can also induce comparable cardiac functional recovery at late follow-up, suggesting that MHC-mismatched iPSC-based cardiac regenerative therapy with immunosuppressants is a feasible option for treating heart failure in clinical settings.</AbstractText> |
2,329,086 | Age-Dependence of Flow Homeostasis in the Left Ventricle. | <b>Background:</b> Intracardiac flow homeostasis requires avoiding blood stasis and platelet activation during its transit through the cardiac chambers. However, the foundations of intraventricular blood washout and its exposure to shear stresses have been poorly addressed. We aimed to characterize and quantify these features in a wide population of healthy subjects and assess the relationships of these indices with age. <b>Methods:</b> We used color-Doppler echocardiography and custom post-processing methods to study 149 healthy volunteers from 26 days to 80 years old. From the intraventricular flow-velocity fields we obtained personalized maps of (1) the residence time of blood in the LV, and (2) the shear index, a metric accounting for the strongest occurrence of shear stresses inside the chamber. From these maps we derived quantitative indices of the overall intraventricular blood washout and shear exposure. We addressed the age-dependence of these indices and analyzed their relationship with age-related changes in filling-flow. <b>Results:</b> The entire intraventricular blood pool was replaced before 8 cycles. Average residence time of blood inside the LV was <3 cycles in all subjects and followed an inverse U-shape relationship with age, increasing from median (IQR) of 1.0 (0.7 to 1.2) cycles in the 1st year of life to 1.8 (1.4-2.2) cycles in young adults (17-30 years old), becoming shorter again thereafter. Shear index showed no relation with age and was bounded around 20 dyn·s/cm<sup>2</sup>. Regions with the longest residence time and highest shear index were identified near the apex. Differences in the degree of apical penetration of the filling waves and the duration of the late-filling phase explained the age-dependence of residence time ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msubsup><mml:mrow><mml:mtext>R</mml:mtext></mml:mrow> <mml:mrow><mml:mtext>adj</mml:mtext></mml:mrow> <mml:mrow><mml:mn>2</mml:mn></mml:mrow> </mml:msubsup> </mml:math> = 0.48, <i>p</i> < 0.001). <b>Conclusions:</b> In average, blood spends 1 to 3 beats inside the LV with very low shear stress rates. The apical region is the most prone to blood stasis, particularly in mid-aged adults. The washout of blood in the normal LV is age-dependent due to physiological changes in the degree of apical penetration of the filling waves. |
2,329,087 | Altered biogenesis of microRNA-1 is associated with cardiac dysfunction in aging of spontaneously hypertensive rats. | Currently we face the issues of aging-associated pathologies, particularly those leading to heart failure. With that in mind, in current research we focus on aging and hypertension combination as a widely spread threating problem. In a row with functional and morphological characterization of these aging- and hypertension-associated cardiac changes, we evaluate biogenesis of microRNA-1 being one of major microRNAs in the heart. The aim of this study was to check the hypothesis if dysregulation of microRNA-1 biogenesis is associated with heart failure in aged and especially aged hypertensive rats. The experiments were carried out on male SHR and Wistar rats of age 6 months (young) and 18 months (old). The evaluation of hemodynamic parameters was performed in heart left ventricles of narcotized rats using the ultra-small 2F catheter. The development of fibrosis was determined using light and electron microscopy. Levels of mature and immature forms of microRNA-1 and mRNA encoding the proteins involved in its biogenesis were determined using reverse transcription and quantitative PCR. Aging of both Wistar and SHRs is accompanied with altered hemodynamic parameters compared with correspondent younger mates. SHRs, especially old ones, demonstrated significant heart fibrosis. In aged animals, the level of primary microRNA-1 in Wistar rats were 7 times higher (p < 0.05) and in SHR 17 times higher (p < 0.05) in comparison with young rats of the same strain. We also observed 22 times higher level of immature microRNA-1 in the heart of Wistar and 5.9 times higher level for aged hypertensive rats (p < 0.05) compared to young rats. At the same time, the level of mature microRNA-1 occurred 2.5 and 3.2 times lower in respective groups (p < 0.05). In the current study, we observe the significant dysregulation of microRNA-1 processing in the heart associated with aging and arterial hypertension. |
2,329,088 | Motion-corrected free-breathing LGE delivers high quality imaging and reduces scan time by half: an independent validation study. | Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) sequences have evolved. Free-breathing motion-corrected (MOCO) LGE has potential advantages over breath-held (bh) LGE including minimal user input for the short axis (SAX) stack without breath-holds. It has previously been shown that MOCO-LGE delivers high image quality compared to bh-LGE. We sought to conduct an independent validation study to investigate real-world performance of bh-LGE versus MOCO-LGE in a high-throughput CMR center immediately after the introduction of the MOCO-LGE sequence and with elementary staff induction in its use. Four-hundred consecutive patients, referred for CMR and graded by clinical complexity, underwent CMR on either of two scanners (1.5 T, both Siemens) in a UK tertiary cardiac center. Scar imaging was by bh-LGE or MOCO-LGE (both with phase sensitive inversion recovery). Image quality, scan time, reader confidence and report reproducibility were compared between those scanned by bh-LGE versus MOCO-LGE. Readers had > 3 years CMR experience. Categorical variables were compared by χ<sup>2</sup> or Fisher's exact tests and continuous variables by unpaired Student's t-test. Inter-rater agreement of LGE reports was by Cohen's kappa. Image quality (low score = better) was better for MOCO-LGE (median, interquartile range [Q1-Q3]: 0 [0-0] vs. 2 [0-3], P < 0.0001). This persisted when just clinically complex patients were assessed (0 [0-1] vs. 2 [1-4] P < 0.0001). Readers were more confident in their MOCO-LGE rulings (P < 0.001) and reports more reproducible [bh-LGE vs. MOCO-LGE: kappa 0.76, confidence interval (CI) 0.7-0.9 vs. 0.82, CI 0.7-0.9]. MOCO-LGE significantly shortened LGE acquisition times compared to bh-LGE (for left ventricle SAX stack: 03:22 ± 01:14 vs 06:09 ± 01:47 min respectively, P < 0.0001). In a busy clinical service, immediately after its introduction and with elementary staff training, MOCO-LGE is demonstrably faster to bh-LGE, providing better images that are easier to interpret, even in the sickest of patients. |
2,329,089 | Transcript levels for extracellular matrix proteins are altered in MK5-deficient cardiac ventricular fibroblasts. | MK5 is a protein serine/threonine kinase activated by p38 MAPK and the atypical MAPKs ERK3 and ERK4. Although little is known of the physiological role of MK5 in the heart, both hypertrophic growth and the increase in collagen 1-α<sub>1</sub> mRNA induced by increased afterload are attenuated in hearts of MK5 haploinsufficient (MK5<sup>+/-</sup>) mice. MK5 transcripts are detected at high levels in the left ventricular myocardium; however, MK5 immunoreactivity is detected in adult cardiac fibroblasts, but not myocytes. The present study was to determine if MK5 has a potential role in remodeling of the extracellular matrix. Ventricular fibroblasts were isolated from MK5<sup>+/+</sup>, MK5<sup>+/-</sup>, or MK5<sup>-/-</sup> mice and maintained in culture on either compliant (8 kPa) or rigid substrates to obtain quiescent fibroblasts or activated myofibroblasts, respectively. In quiescent fibroblasts, reduced MK5 had little effect: BMP7 and TGF-β1 mRNA was increased in MK5<sup>+/-</sup> and MK5<sup>-/-</sup>.cells, respectively. Ang-II altered the abundance of numerous transcripts in an MK5-sensitive manner. Both collagen 1-α<sub>1</sub> mRNA and secreted type 1 collagen immunoreactivity were increased by Ang-II in wild type but not MK5-deficient fibroblasts. The effects of deleting MK5 were quite different in myofibroblasts: both the abundance of collagen 1-α<sub>1</sub> mRNA and secreted type 1 collagen immunoreactivity elevated in the absence of added Ang-II and addition of Ang-II failed to evoke a further increase in either. In addition, whereas type I collagen immunoreactivity was distributed throughout the cytosol of wild-type myofibroblasts, it was perinuclear in MK5<sup>-/-</sup> myofibroblasts. Furthermore, in MK5-deficient myofibroblasts the abundance of collagen 3-α<sub>2</sub>, Timp3, Smad 6, Smad 7, TGF-β3, and snail homolog 1 transcripts was increased whereas integrin β3, latent TGF-β binding protein 1, thrombospondin 1, hepatocyte growth factor, and interleukin 13 were decreased. Finally, fibroblast contraction was decreased upon knocking down MK5. These results indicate that MK5 may be involved in fibroblast-mediated regulation of extracellular matrix homeostasis. |
2,329,090 | Biology of multiciliated cells. | Multiciliated cells (MCCs) are specialized in fluid propulsion through directional beating of myriads of superficial motile cilia, which rest on modified centrioles named basal bodies. MCCs are found throughout metazoans, and serve functions as diverse as feeding and locomotion in marine organisms, as well as mucus clearance, cerebrospinal fluid circulation, and egg transportation in mammals. Impaired MCC differentiation or activity causes diseases characterized by severe chronic airway infections and reduced fertility. Through studies in Xenopus and mouse mainly, MCC biology has made significant progress on several fronts in recent years. The gene regulatory network that controls MCC specification and differentiation has been deciphered to a large extent. The enigmatic deuterosomes, which serve as centriole amplification platforms in vertebrate MCCs, have started to be studied at the molecular level. Principles of ciliary beating coordination within and between MCCs have been identified. |
2,329,091 | Overlapping migratory mechanisms between neural progenitor cells and brain tumor stem cells. | Neural stem cells present in the subventricular zone (SVZ), the largest neurogenic niche of the mammalian brain, are able to self-renew as well as generate neural progenitor cells (NPCs). NPCs are highly migratory and traverse the rostral migratory stream (RMS) to the olfactory bulb, where they terminally differentiate into mature interneurons. NPCs from the SVZ are some of the few cells in the CNS that migrate long distances during adulthood. The migratory process of NPCs is highly regulated by intracellular pathway activation and signaling from the surrounding microenvironment. It involves modulation of cell volume, cytoskeletal rearrangement, and isolation from compact extracellular matrix. In malignant brain tumors including high-grade gliomas, there are cells called brain tumor stem cells (BTSCs) with similar stem cell characteristics to NPCs but with uncontrolled cell proliferation and contribute to tumor initiation capacity, tumor progression, invasion, and tumor maintenance. These BTSCs are resistant to chemotherapy and radiotherapy, and their presence is believed to lead to tumor recurrence at distal sites from the original tumor location, principally due to their high migratory capacity. BTSCs are able to invade the brain parenchyma by utilizing many of the migratory mechanisms used by NPCs. However, they have an increased ability to infiltrate the tight brain parenchyma and utilize brain structures such as myelin tracts and blood vessels as migratory paths. In this article, we summarize recent findings on the mechanisms of cellular migration that overlap between NPCs and BTSCs. A better understanding of the intersection between NPCs and BTSCs will to provide a better comprehension of the BTSCs' invasive capacity and the molecular mechanisms that govern their migration and eventually lead to the development of new therapies to improve the prognosis of patients with malignant gliomas. |
2,329,092 | Unusual rupture of left ventricular pseudo-false aneurysm secondary to subacute anterolateral myocardial infarction: a case report.<Pagination><StartPage>93</StartPage><MedlinePgn>93</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">93</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1186/s13019-019-0915-x</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Left ventricular (LV) pseudo-false aneurysm is a rare complication secondary to myocardial infarction and is caused by intramyocardial dissecting hematoma due to fragile myocardium. Very occasionally, intramyocardial dissecting hematoma appears as a neocavitation entirely contained within the myocardial wall (so called "pseudo-false LV") and is an unusual form of subacute cardiac rupture.</AbstractText><AbstractText Label="CASE PRESENTATION" NlmCategory="METHODS">A 38-year-old male experienced chest discomfort 3 weeks ago, which improved within few days. However, after that episode, he presented at our hospital with rapidly deteriorating severe breathlessness in a preshock state with acute heart failure. Emergency coronary angiography revealed an occluded left anterior descending artery. An intra-aortic balloon catheter was inserted because of unstable hemodynamics. Enhanced computed tomography revealed extensive aneurysm formation in the LV anterior wall and contrast leakage from the inner cavity to the LV myocardium, with a moderately accumulated pericardial effusion. Emergency surgery revealed a large aneurysmal sac on the anterior wall, slightly attached to the pericardium. A 5-mm, slit-like, oozing-type, rupture site was detected in the LV after dissecting the pericardium.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">To our knowledge, this is the first report of a pseudo-false aneurysm on the LV anterior wall. Subacute rupture of pseudo-false LV aneurysm is rare.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Okada</LastName><ForeName>Masaho</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0003-4728-9385</Identifier><AffiliationInfo><Affiliation>Department of Cardiac Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, Japan. okmasaho123@gmail.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Watanuki</LastName><ForeName>Hirotaka</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Cardiac Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sugiyama</LastName><ForeName>Kayo</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Cardiac Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Futamura</LastName><ForeName>Yasuhiro</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Cardiac Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Matsuyama</LastName><ForeName>Katsuhiko</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Cardiac Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, Japan.</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>2019</Year><Month>05</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Cardiothorac Surg</MedlineTA><NlmUniqueID>101265113</NlmUniqueID><ISSNLinking>1749-8090</ISSNLinking></MedlineJournalInfo><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017541" MajorTopicYN="N">Aneurysm, False</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017542" MajorTopicYN="N">Aneurysm, Ruptured</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056988" MajorTopicYN="N">Anterior Wall Myocardial Infarction</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017023" MajorTopicYN="N">Coronary Angiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003937" MajorTopicYN="N">Diagnosis, Differential</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006322" MajorTopicYN="N">Heart Aneurysm</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="Y">Heart Ventricles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Intramyocardial dissecting hematoma</Keyword><Keyword MajorTopicYN="N">Left ventricular pseudo-false aneurysm</Keyword><Keyword MajorTopicYN="N">Subacute cardiac rupture</Keyword></KeywordList><CoiStatement>The authors declare that they have no competing interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>3</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>5</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>5</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>5</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>8</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31101055</ArticleId><ArticleId IdType="pmc">PMC6525427</ArticleId><ArticleId IdType="doi">10.1186/s13019-019-0915-x</ArticleId><ArticleId IdType="pii">10.1186/s13019-019-0915-x</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Lewis AJ, Burchell HB, Titus JL. 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Towards new understanding of the heart structure and function. Eur J Cardiothorac Surg. 2005;27(2):191–201. doi: 10.1016/j.ejcts.2004.11.026.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ejcts.2004.11.026</ArticleId><ArticleId IdType="pubmed">15691670</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">32091713</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK553840</ArticleId><ArticleId IdType="doi">10.1007/978-3-030-13864-6_11</ArticleId></ArticleIdList><Book><Publisher><PublisherName>Springer</PublisherName><PublisherLocation>Cham (CH)</PublisherLocation></Publisher><BookTitle book="spr9783030138646">Dilated Cardiomyopathy: From Genetics to Clinical Management</BookTitle><PubDate><Year>2019</Year></PubDate><AuthorList Type="editors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Sinagra</LastName><ForeName>Gianfranco</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Cardiovascular Department, Azienda Sanitaria Universitaria Integrata, Trieste, Italy</Affiliation><Identifier Source="GRID">grid.460062.6</Identifier><Identifier Source="ISNI">0000000459364044</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Merlo</LastName><ForeName>Marco</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Cardiovascular Department, Azienda Sanitaria Universitaria Integrata, Trieste, Italy</Affiliation><Identifier Source="GRID">grid.460062.6</Identifier><Identifier Source="ISNI">0000000459364044</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pinamonti</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Cardiovascular Department, Azienda Sanitaria Universitaria Integrata, Trieste, Italy</Affiliation><Identifier Source="GRID">grid.460062.6</Identifier><Identifier Source="ISNI">0000000459364044</Identifier></AffiliationInfo></Author></AuthorList><Isbn>9783030138639</Isbn><Isbn>9783030138646</Isbn><ELocationID EIdType="doi">10.1007/978-3-030-13864-6</ELocationID><Medium>Internet</Medium></Book><LocationLabel Type="chapter">Chapter 11</LocationLabel><ArticleTitle book="spr9783030138646" part="ch11">Regenerative Medicine and Biomarkers for Dilated Cardiomyopathy | Dilated cardiomyopathy is characterized by progressive cardiomyocyte loss leading to ventricle dilation and dysfunction. Over the last decade, multiple evidence has shown that treatment of this condition might be attempted through the administration of either cells of various derivations or nucleic acids. In the case of cell therapy, there is ample consensus that no stem cells can directly regenerate the myocardium; however some cell types could provide benefit through a paracrine function on resident cardiomyocytes. Various nucleic acids, including microRNAs and antisense locked nucleic acids targeting microRNAs and long non-coding RNAs, can stimulate regeneration by promoting the proliferation potential of endogenous cardiomyocytes. Albeit at the preclinical phase, these approaches hold a great promise for the development of innovative therapeutics. Patients with idiopathic dilated cardiomyopathy are generally young subjects. Therefore, the assessment of prognosis is essential. Biomarkers are nowadays widely available and are useful tools for risk stratification. Besides HF-dedicated biomarkers, such as natriuretic peptides, galectin-3, soluble ST2 and troponins, also the evaluation of inflammatory response (interleukins, growth factors), renal function (NGAL, KIM-1) and anaemia are particularly important for a correct prognostic stratification. Moreover, when all of these biomarkers are used and combined in a multimarker model, the prediction of prognosis becomes more accurate, reflecting the importance of a holistic evaluation of patients. |
2,329,093 | The Wishbone: A Cranial Midline Localizing Device. | The Wishbone device is designed to enable surgeons to quickly and accurately localize the cranial midline. It is intended to be of particular use when localizing the burr hole site during posterior ventriculoperitoneal shunt (VPS) surgery.</AbstractText>The Wishbone is a simple mechanical device with 2 adjustable caliper arms that reversibly attach to a patient's left and right external auditory canals. The Wishbone's laser localizer illuminates the midline scalp. The Wishbone was used to localize the posterior midline in a pilot series of patients undergoing VPS surgery. Midline localization and ventricular catheter placement accuracy were determined using findings from postoperative computed tomography scans.</AbstractText>The Wishbone is a mechanically robust device and proved easy for surgeons to use. Forty patients underwent VPS surgery using the Wishbone to localize the posterior midline. The localization procedure took less than 3 minutes. The average distance separating the Wishbone-localized midline scalp location and the computed tomography-defined anatomical midline was 2.9 mm (95% confidence interval 1.6-4.1 mm). In all cases, the ventricular catheter entered the ipsilateral lateral ventricle. The catheter tips were placed in the ipsilateral (n = 34) or contralateral (n = 5) frontal horn in all but 1 patient. In 1 patient, the catheter tip entered the parenchyma due to a burr hole localization error in the rostrocaudal dimension, unrelated to the Wishbone.</AbstractText>We describe a simple, efficient, and cost-effective system for accurately localizing the posterior cranial midline. A larger patient series is required to definitively compare its clinical utility relative to frameless stereotaxis-based midline localization methods.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,094 | PDE2 regulates membrane potential, respiration and permeability transition of rodent subsarcolemmal cardiac mitochondria. | Cyclic adenosine monophosphate (cAMP) production regulates certain aspects of mitochondria function in rodent cardiomyocytes, such as ATP production, oxygen consumption, calcium import and mitochondrial permeability transition (MPT), but how this cAMP pool is controlled is not well known. Here, expression, localization and activity of several cAMP-degrading enzymes, i.e. phosphodiesterases (PDEs), were investigated in isolated rodent cardiac mitochondria. In contrast to the heart ventricle where PDE4 is the major PDE, in cardiac mitochondria, cGMP-stimulated PDE2 activity was largest than PDE3 and PDE4 activities. PDE2 expression was mainly detected in subsarcolemmal mitochondria in association with the inner membrane rather than in interfibrillar mitochondria. PDE2, 3 and 4 activities were further confirmed in neonatal rat cardiomyocytes by real time FRET analysis. In addition, the pharmacological inhibition or the cardiac-specific overexpression of PDE2 modulated mitochondrial membrane potential loss, MPT and calcium import. In mitochondria isolated from PDE2 transgenic mice with a cardiac selective PDE2 overexpression, the oxidative phosphorylation (OXPHOS) was significantly lower than in wild-type mice, but stimulated by cGMP. Thus, cAMP degradation by PDEs represents a new regulatory mechanism of mitochondrial function. |
2,329,095 | Study on Umbilical Cord-Matrix Stem Cells Transplantation for Treatment of Acute Traumatic Brain Injury in Rats. | To evaluate the effect of umbilical cord derived mesenchymal stem cells (UC-MSCs) transplantation on traumatic brain injury (TBI).</AbstractText>UC-MSCs were isolated from human umbilical cord and TBI rat model was constructed. 30 male SD rats were randomly divided into 3 groups: control group, TBI group and MSCs transplantation group. Rats in MSCs group received the injection of a total of 1.5 Ć- 106 MSCs (25 Ī¼l) via ventricle at operated ventricular coordinates (0 at bregma, 1.5 mm at lateral, 1.1 mm at behind, 4.5 mm in depth).</AbstractText>80% confluence of cells was formed from tissue at day 10 and the amount of CD90, CD73, CD105 positive cells increased correspondingly. In TBI model, clear hyperemia, edema and obvious infiltration of inflammatory cells in brain tissue were found. However, the manifestations were alleviated after the treatment of MSCs. In MSCs group, GFP in the brain tissue and the area around the vessels were found after the injection, while the expression levels of micro-vessel density (MVD), brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) were elevated.</AbstractText>UC-MSCs transplantation for treatment of acute TBI could effectively reduce the injury and improve the vascular reconstruction.</AbstractText> |
2,329,096 | Effects of repeated daily acute heat challenge on the growth and metabolism of a cold water stenothermal fish. | Temperature is an important environmental factor influencing fish physiology that varies both spatially and temporally in ecosystems. In small north temperate zone lakes, cold water piscivores rely on nearshore prey; however, this region exceeds the optimal temperature of the foraging species during summer. To cope, piscivores make short excursions into the nearshore to feed and return to cold water to digest their meal, but the physiological impacts of these repeated acute exposures to warm water are not well understood. We exposed juvenile lake trout (<i>Salvelinus namaycush</i>) to treatments where they were held at ∼10°C and exposed to either 17 or 22°C for 5-10 min daily for 53 days mimicking warm-water forays. Control fish, held at an average temperature of ∼10°C but not exposed to thermal variation, consumed more food and grew slightly faster than heat challenged fish, with no clear differences in body condition, hepatosomatic index, ventricle mass, or muscle concentrations of lactate dehydrogenase and cytochrome c oxidase. Aerobic metabolic rates measured at 10°C indicated that standard metabolic rates (SMR) were similar among treatments; however, fish that were repeatedly exposed to 17°C had higher maximum metabolic rates (MMR) and aerobic scopes (AS) than control fish and those repeatedly exposed to 22°C. There were no differences in MMR or AS between fish exposed to 22°C and control fish. These results suggest that although SMR of fish are robust to repeated forays into warmer environments, MMR displays plasticity, allowing fish to be less constrained aerobically in cold water after briefly occupying warmer waters. |
2,329,097 | Turtles maintain mitochondrial integrity but reduce mitochondrial respiratory capacity in the heart after cold acclimation and anoxia. | Mitochondria are important to cellular homeostasis, but can become a dangerous liability when cells recover from hypoxia. Anoxia-tolerant freshwater turtles show reduced mitochondrial respiratory capacity and production of reactive oxygen species (ROS) after prolonged anoxia, but the mechanisms are unclear. Here, we investigated whether this mitochondrial suppression originates from downregulation of mitochondrial content or intrinsic activity by comparing heart mitochondria from (1) warm (25°C) normoxic, (2) cold-acclimated (4°C) normoxic and (3) cold-acclimated anoxic turtles. Transmission electron microscopy of heart ventricle revealed that these treatments did not affect mitochondrial volume density and morphology. Furthermore, neither enzyme activity, protein content nor supercomplex distribution of electron transport chain (ETC) enzymes changed significantly. Instead, our data imply that turtles inhibit mitochondrial respiration rate and ROS production by a cumulative effect of slight inhibition of ETC complexes. Together, these results show that maintaining mitochondrial integrity while inhibiting overall enzyme activities are important aspects of anoxia tolerance. |
2,329,098 | Choroid plexus volume after stroke. | Cerebrospinal fluid circulation is crucial for the functioning of the brain. Aging and brain pathologies such as Alzheimer's disease have been associated with a change in the morphology of the ventricles and the choroid plexus. Despite the evidence from animal models that the cerebrospinal fluid system plays an important role in neuroinflammation and the restoration of the brain after ischemic brain injury, little is known about changes to the choroid plexus after stroke in humans.</AbstractText>Our goal was to characterize structural choroid plexus changes poststroke.</AbstractText>We used an automatic segmentation tool to estimate the volumes of choroid plexus and lateral ventricles in stroke and control participants at three time points (at baseline, 3 and 12 months) over the first year after stroke. We assessed group differences cross-sectionally at each time point and longitudinally. For stroke participants, we specifically differentiated between ipsi- and contra-lesional volumes. Statistical analyses were conducted for each region separately and included covariates such as age, sex, total intracranial volume, and years of education.</AbstractText>We observed significantly larger choroid plexus volumes in stroke participants compared to controls in both cross-sectional and longitudinal analyses. Choroid plexus volumes did not exhibit any change over the first year after stroke, with no difference between ipsi- and contra-lesional volumes. This was in contrast to the volume of lateral ventricles that we found to enlarge over time in all participants, with more accelerated expansion in stroke survivors ipsi-lesionally.</AbstractText>Our results suggest that chronic stages of stroke are characterized by larger choroid plexus volumes, but the enlargement likely takes place prior to or very early after the stroke incident.</AbstractText> |
2,329,099 | Non-invasive myocardial performance mapping using 3D echocardiographic stress-strain loops. | Regional contribution to left ventricular (LV) ejection is of much clinical importance but its assessment is notably challenging. While deformation imaging is often used, this does not take into account loading conditions. Recently, a method for intraventricular pressure estimation was proposed, thus allowing for loading conditions to be taken into account in a non-invasive way. In this work, a method for 3D automatic myocardial performance mapping in echocardiography is proposed by performing 3D myocardial segmentation and tracking, thus giving access to local geometry and strain. This is then used to assess local LV stress-strain relationships which can be seen as a measure of local myocardial work. The proposed method was validated against <sup>18</sup>F-fluorodeoxyglucose positron emission tomography, the reference method to clinically assess local metabolism. Averaged over all patients, the mean correlation between FDG-PET and the proposed method was [Formula: see text]. In conclusion, stress-strain loops were, for the first time, estimated from 3D echocardiography and correlated to the clinical gold standard for local metabolism, showing the future potential of real-time 3D echocardiography (RT3DE) for the assessment of local metabolic activity of the heart. |
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