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2,328,700 | Sleep or deplete: how the choroid plexus helps to keep neural stem cells in balance. | The activity of stem cells in the adult brain is controlled by various niche-dependent mechanisms. A new article by Lepko et al (2019) shows that proliferation of neural stem cells in the ventricular-subventricular zone is regulated by choroid plexus-derived miR-204, identifying a novel mechanism of how the delicate balance between stem cell quiescence and activation is controlled. |
2,328,701 | Overexpression of the medium‑conductance calcium‑activated potassium channel (SK4) and the HCN2 channel to generate a biological pacemaker. | Ion channels serve important roles in the excitation‑contraction coupling of cardiac myocytes. Previous studies have shown that the overexpression or activation of intermediate‑conductance calcium‑activated potassium channel (SK4, encoded by KCNN4) in embryonic stem cell‑derived cardiomyocytes can significantly increase their automaticity. The mechanism underlying this effect is hypothesized to be associated with the activation of hyperpolarization‑activated cyclic nucleotide‑gated channel 2 (HCN2). The aim of the present study was to explore whether a biological pacemaker could be constructed by overexpressing SK4 alone or in combination with HCN2 in a rat model. Ad‑green fluorescent protein (GFP), Ad‑KCNN4 and Ad‑HCN2 recombinant adenoviruses were injected into the left ventricle of Sprague‑Dawley rat hearts. The rats were divided into a GFP group (n=10), an SK4 group (n=10), a HCN2 group (n=10) and an SK4 + HCN2 (SK4/HCN2) group (n=10). The isolated hearts were perfused at 5‑7 days following injection, and a complete heart block model was established. Compared with the GFP group, overexpressing SK4 alone did not significantly increase the heart rate after establishment of a complete heart block model [98.1±8.9 vs. 96.7±7.6 beats per min (BPM)], The heart rates in the SK4/HCN2 (139.9±21.9 BPM) and HCN2 groups (111.7±5.5 BPM) were significantly increased compared with the GFP and SK4 groups, and the heart rates in the SK4/HCN2 group were significantly increased compared with the SK4 or HCN2 groups. In the HCN2 (n=8) and the SK4/HCN2 (n=7) groups, the shape of the spontaneous ventricular rhythm was the same as the pacing‑induced ectopic rhythm in the transgenically altered site. By contrast, these rhythms were different in the SK4 (n=10) and GFP (n=10) groups. There were no significant differences in action potential duration alternans or ventricular arrhythmia inducibility between the four groups (all P>0.05). Western blotting, reverse transcription‑quantitative PCR and immunohistochemistry analyses showed that the expression levels of SK4 and HCN2 were significantly increased at the transgene site. Biological pacemaker activity could be successfully generated by co‑overexpression of SK4 and HCN2 without increasing the risk of ventricular arrhythmias. The overexpression of SK4 alone is insufficient to generate biological pacemaker activity. The present study provided evidence that SK4 and HCN2 combined could construct an ectopic pacemaker, laying the groundwork for the development of improved biological pacing mechanisms in the future. |
2,328,702 | High-Resolution <i>Ex Vivo</i> Microstructural MRI After Restoring Ventricular Geometry via 3D Printing. | Computational modeling of the heart requires accurately incorporating both gross anatomical detail and local microstructural information. Together, these provide the necessary data to build 3D meshes for simulation of cardiac mechanics and electrophysiology. Recent MRI advances make it possible to measure detailed heart motion <i>in vivo</i>, but <i>in vivo</i> microstructural imaging of the heart remains challenging. Consequently, the most detailed measurements of microstructural organization and microanatomical infarct details are obtained <i>ex vivo</i>. The objective of this work was to develop and evaluate a new method for restoring <i>ex vivo</i> ventricular geometry to match the <i>in vivo</i> configuration. This approach aids the integration of high-resolution <i>ex vivo</i> microstructural information with <i>in vivo</i> motion measurements. The method uses <i>in vivo</i> cine imaging to generate surface meshes, then creates a 3D printed left ventricular (LV) blood pool cast and a pericardial mold to restore the <i>ex vivo</i> cardiac geometry to a mid-diastasis reference configuration. The method was evaluated in healthy (N = 7) and infarcted (N = 3) swine. Dice similarity coefficients were calculated between <i>in vivo</i> and <i>ex vivo</i> images for the LV cavity (0.93 ± 0.01), right ventricle (RV) cavity (0.80 ± 0.05), and the myocardium (0.72 ± 0.04). The <i>R</i> <sup><i>2</i></sup> coefficient between <i>in vivo</i> and <i>ex vivo</i> LV and RV cavity volumes were 0.95 and 0.91, respectively. These results suggest that this method adequately restores <i>ex vivo</i> geometry to match <i>in vivo</i> geometry. This approach permits a more precise incorporation of high-resolution <i>ex vivo</i> anatomical and microstructural data into computational models that use <i>in vivo</i> data for simulation of cardiac mechanics and electrophysiology. |
2,328,703 | MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats. | Conditioned medium derived from ischemic myocardium improves rodent cardiac function after myocardial infarction. Exosomal miRNA-mediated intercellular communication is considered to mediate the protective effect of conditioned medium against ischemic injury. Oxygen-glucose-deprivation (OGD)-treated cardiac cells and a rat model with acute myocardial infarction (AMI) were applied. The expression profiles of myocardial-disease-associated miRNAs in cardiomyocytes, cardiac fibroblasts, ventricular myocardium, and conditioned medium derived from cardiomyocytes under ischemic stresses were analyzed. Primary cultured cell model and a rat model with myocardial infarction were applied to examine the role of miRNA in regulating cardiomyocyte apoptosis, fibroblast activation, immune cell infiltration, and myocardial infarction. Results showed that expression levels of miR-21 in cardiomyocytes, cardiac fibroblasts, and conditioned medium (CM) derived from cardiomyocytes were up-regulated with OGD treatment. With the depletion of miR-21, the protective effect of CM on cardiomyocytes against oxidative stress, enhanced fibroblast activation, and promotion of angiogenesis in endothelial cells were reduced. Administration of CM reduced the infarcted size and immune cell infiltration in myocardium of rats with AMI, while depletion of miR-21 reduced the effect of CM. In conclusion, miR-21 plays a role in intercellular communication among ischemic cardiac cells. The expression of miR-21 is important for the protective effect of conditioned medium against myocardial infarction. |
2,328,704 | Complete Free-breathing Adenosine Stress Cardiac MRI Using Compressed Sensing and Motion Correction: Comparison of Functional Parameters, Perfusion, and Late Enhancement with the Standard Breath-holding Examination. | To compare free-breathing (FB) stress cardiac MRI examinations with the reference standard breath-holding (BH) examination.</AbstractText>A total of 40 consecutive patients were enrolled prospectively and were examined with 3-T MRI. Functional imaging, perfusion, and late gadolinium enhancement (LGE) sequences were performed in BH and FB by using compressed sensing and in-line motion correction. Left ventricle (LV) and right ventricle (RV) functional parameters in BH and FB examinations were compared by using Bland-Altman plots and linear mixed models. Subjective image quality was assessed with a five-point scale (1 = nondiagnostic, 5 = very good). For perfusion and LGE imaging, diagnostic confidence was rated with a three-point scale (1 = low, 3 = high), and image quality was rated with a five-point scale (1 = nondiagnostic, 5 = very good). The Wilcoxon test was used to compare image quality and diagnostic confidence.</AbstractText>Bland-Altman plots showed good agreement for LV and RV functional parameters in BH and FB sequences. Subjective image quality was significantly better with the BH sequences in the LV (P</i> < .01) but was comparable in the RV (P</i> > .99). Scanning time was 218 seconds (range, 130-385 seconds) for cine BH and 16 seconds (range, 11-27 seconds) for cine FB. Extent of perfusion defects, LGE, and diagnostic confidence was comparable between groups. Scanning time was 371 seconds (range, 239-502 seconds) for the LGE BH sequence and 189 seconds (range, 122-286 seconds) for the LGE FB sequence.</AbstractText>FB adenosine stress cardiac MRI delivers diagnostic image quality and could represent an alternative for use in patients who are unable to meet the demands of multiple BHs and long examination times.© RSNA, 2019.</AbstractText>2019 by the Radiological Society of North America, Inc.</CopyrightInformation> |
2,328,705 | Primary Malignant Pericardial Mesothelioma: A Clinical Case Series Illustrating the Necessity of a Multidisciplinary Approach. | Primary malignant pericardial mesothelioma is a rare cardiac neoplasm. The authors evaluated risk factors, clinical presentation, and outcomes by reviewing all biopsy-confirmed cases at one institution. The use of multimodality imaging, detailed hemodynamic assessment for the presence of an effusive-constrictive profile, and cytology evaluation can support the diagnosis. (<b>Level of Difficulty: Advanced.</b>). |
2,328,706 | Left-Sided Intracardiac Tumors in a Case of Widespread Vulvar Cancer. | Metastatic cardiac tumors associated with gynecological malignancies are rare. This report describes the case of stage-4 vulvar carcinoma that metastasized to the left ventricle of the heart. (<b>Level of Difficulty: Intermediate.</b>). |
2,328,707 | Bcl2-Expressing Quiescent Type B Neural Stem Cells in the Ventricular-Subventricular Zone Are Resistant to Concurrent Temozolomide/X-Irradiation. | The ventricular-subventricular zone (V-SVZ) of the mammalian brain is a site of adult neurogenesis. Within the V-SVZ reside type B neural stem cells (NSCs) and type A neuroblasts. The V-SVZ is also a primary site for very aggressive glioblastoma (GBM). Standard-of-care therapy for GBM consists of safe maximum resection, concurrent temozolomide (TMZ), and X-irradiation (XRT), followed by adjuvant TMZ therapy. The question of how this therapy impacts neurogenesis is not well understood and is of fundamental importance as normal tissue tolerance is a limiting factor. Here, we studied the effects of concurrent TMZ/XRT followed by adjuvant TMZ on type B stem cells and type A neuroblasts of the V-SVZ in C57BL/6 mice. We found that chemoradiation induced an apoptotic response in type A neuroblasts, as marked by cleavage of caspase 3, but not in NSCs, and that A cells within the V-SVZ were repopulated given sufficient recovery time. 53BP1 foci formation and resolution was used to assess the repair of DNA double-strand breaks. Remarkably, the repair was the same in type B and type A cells. While Bax expression was the same for type A or B cells, antiapoptotic Bcl2 and Mcl1 expression was significantly greater in NSCs. Thus, the resistance of type B NSCs to TMZ/XRT appears to be due, in part, to high basal expression of antiapoptotic proteins compared with type A cells. This preclinical research, demonstrating that murine NSCs residing in the V-SVZ are tolerant of standard chemoradiation therapy, supports a dose escalation strategy for treatment of GBM. Stem Cells 2019;37:1629-1639. |
2,328,708 | Potential synaptic plasticity-based Shenzhiling oral liquid for a SAD Mouse Model. | Synaptic plasticity is the basis of memory formation. The pathological manifestations of abnormal glucose metabolism in the nervous system of sporadic Alzheimer's disease (SAD) may affect synaptic plasticity, thus causing memory damage. As a traditional Chinese medicine compound preparation, the mechanism by which Shenzhiling (SZL) oral liquid can alleviate the cognitive impairment of SAD by improving synaptic plasticity remains unclear.</AbstractText>This article mainly discusses whether SZL can exert a protective synaptic effect as mediated by glutamate receptors and glycogen synthesis kinase 3β (GSK3β); further, it discusses whether SZL can improve cognitive function in SAD.</AbstractText>C57BL/6 mice were used as a SAD model after injection with streptozotocin (STZ) into the bilateral lateral ventricles; mice of the same background were injected with artificial cerebrospinal fluid into bilateral ventricles and were used as a control group. After 3 months of exposure to the intervention, the step-down test was carried out. Western blot was used to detect the levels of NMDAR2B, p-NMDAR2B, mGlu5, GSK3β, and p-GSK3β in the hippocampus of mice. Immunohistochemical analysis was used to observe the number of GSK3β-positive cells in the CA1 region of mouse hippocampus.</AbstractText>The memory retention ability of mice was significantly improved after 3 months of SZL treatment, and the expression levels of NMDAR2B, mGlu5, and GSK3β were significantly changed.</AbstractText>Shenzhiling provides a potential for the treatment for SAD with traditional Chinese medicine.</AbstractText>© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.</CopyrightInformation> |
2,328,709 | Absolute and relative estimates of genetic and environmental variance in brain structure volumes. | Comparing estimates of the amount of genetic and environmental variance for different brain structures may elucidate differences in the genetic architecture or developmental constraints of individual brain structures. However, most studies compare estimates of relative genetic (heritability) and environmental variance in brain structure, which do not reflect differences in absolute variance between brain regions. Here we used a population sample of young adult twins and singleton siblings of twins (n = 791; M = 23 years, Queensland Twin IMaging study) to estimate the absolute genetic and environmental variance, standardised by the phenotypic mean, in the size of cortical, subcortical, and ventricular brain structures. Mean-standardised genetic variance differed widely across structures [23.5-fold range 0.52% (hippocampus) to 12.28% (lateral ventricles)], but the range of estimates within cortical, subcortical, or ventricular structures was more moderate (two to fivefold range). There was no association between mean-standardised and relative measures of genetic variance (i.e., heritability) in brain structure volumes. We found similar results in an independent sample (n = 1075, M = 29 years, Human Connectome Project). These findings open important new lines of enquiry: namely, understanding the bases of these variance patterns, and their implications regarding the genetic architecture, evolution, and development of the human brain. |
2,328,710 | Primary central nervous system small lymphocytic lymphoma in the bilateral ventricles: two case reports. | Primary central nervous system (CNS) small lymphocytic lymphoma (SLL), as a type of low-grade lymphoma, is extremely rare. The diagnosis of CNS SLL is challenging due to its variable clinical and radiological features, which may overlap with those of diffuse large B-cell lymphoma (DLBCL). Primary CNS SLL differs from DLBCL in that it has an indolent clinical course and a good prognosis. Thus, it is important to distinguish SLL from DLBCL. By reviewing the literature, only two cases of low-grade SLL, primarily located in the CNS and involving the brain parenchyma and dura, have been reported. To our knowledge, primary CNS SLL in the bilateral ventricles has never been reported. Interestingly, the two cases in our report are identical in terms of the clinical presentations, magnetic resonance imaging (MRI) features, pathological results and prognoses.</AbstractText>Both patients presented with headaches. MRI suggested solid lesions located in the bilateral ventricles that were isointense on T1-weighted images and hypointense on T2-weighted images. After the injection of contrast agent (gadolinium, Gd), the intraventricular lesions were homogeneously enhanced and hyperperfused. CSF cytology revealed malignant cells. Brain biopsy revealed diffuse proliferation of small lymphocytes with positive labelling of B-cell immunomarkers. The primary origin in the CNS was confirmed with no evidence of systemic lymphoma. Two patients were given high doses of methotrexate-based chemotherapy and were free from symptoms and progression for more than 1-year of follow-up.</AbstractText>The presence of homogeneously enhanced intraventricular MRI lesions should raise the suspicion of primary CNS SLL.</AbstractText> |
2,328,711 | Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice. | Cilia are evolutionarily conserved hair-like structures with a wide spectrum of key biological roles, and their dysfunction has been linked to a growing class of genetic disorders, known collectively as ciliopathies. Many strides have been made towards deciphering the molecular causes for these diseases, which have in turn expanded the understanding of cilia and their functional roles. One recently-identified ciliary gene is ARL2BP, encoding the ADP-Ribosylation Factor Like 2 Binding Protein. In this study, we have identified multiple ciliopathy phenotypes associated with mutations in ARL2BP in human patients and in a mouse knockout model. Our research demonstrates that spermiogenesis is impaired, resulting in abnormally shaped heads, shortened and mis-assembled sperm tails, as well as in loss of axonemal doublets. Additional phenotypes in the mouse included enlarged ventricles of the brain and situs inversus. Mouse embryonic fibroblasts derived from knockout animals revealed delayed depolymerization of primary cilia. Our results suggest that ARL2BP is required for the structural maintenance of cilia as well as of the sperm flagellum, and that its deficiency leads to syndromic ciliopathy. |
2,328,712 | Transcriptomic analysis of left ventricle myocardium in an SHR congenic line with ameliorated cardiac fibrosis. | Metabolic syndrome and one of its manifestations, essential hypertension, is an important cause of worldwide morbidity and mortality. Morbidity and mortality associated with hypertension are caused by organ complications. Previously we revealed a decrease of blood pressure and an amelioration of cardiac fibrosis in a congenic line of spontaneously hypertensive rats (SHR), in which a short segment of chromosome 8 (encompassing only 7 genes) was exchanged for a segment of normotensive polydactylous (PD) origin. To unravel the genetic background of this phenotype we compared heart transcriptomes between SHR rat males and this chromosome 8 minimal congenic line (PD5). We found 18 differentially expressed genes, which were further analyzed using annotations from Database for Annotation, Visualization and Integrated Discovery (DAVID). Four of the differentially expressed genes (Per1, Nr4a1, Nr4a3, Kcna5) belong to circadian rhythm pathways, aldosterone synthesis and secretion, PI3K-Akt signaling pathway and potassium homeostasis. We were also able to confirm Nr4a1 2.8x-fold upregulation in PD5 on protein level using Western blotting, thus suggesting a possible role of Nr4a1 in pathogenesis of the metabolic syndrome. |
2,328,713 | Opioid and endocannabinoid system in orofacial pain. | Orofacial pain disorders are frequent in the general population and their pharmacological treatment is difficult and controversial. Therefore, the search for novel, safe and efficient analgesics is an important but still elusive goal for contemporary medicine. In the recent years, the antinociceptive potential of endocannabinoids and opioids has been emphasized. However, concerns for the safety of their use limit their clinical applications. the possibility of modulating the activity of endocannabinoids by regulation of their synthesis and/or degradation offers an innovative approach to the treatment of pain. A rat model of trigeminal pain, utilizing tongue jerks evoked by electrical tooth pulp stimulation during perfusion of the cerebral ventricles with various neurotransmitter solutions can be used in the pharmacological studies of nociception in the orofacial area. The aim of this review is to present the effects of pharmacological activity of opioids and endocannabinoids affecting the transmission of the sensory information from the orofacial area on the example of trigemino-hypoglossal reflex in rats. |
2,328,714 | Cerebral cysts of ependymal or ventricular origin in a juvenile rhesus macaque (Macaca mulatta) with neurologic signs. | Naturally occurring neurologic disease in non-human primates may be attributable to a wide-range of causes, including infectious agents, congenital or acquired malformations, degenerative diseases, and, rarely, neoplasia. We report a case of ataxia and paresis in a juvenile rhesus macaque with ependymal-lined cerebral cysts. |
2,328,715 | Chordoid glioma: an entity occurring not exclusively in the third ventricle. | Chordoid gliomas are extremely rare entities, which are generally considered occurring exclusively in the third ventricle. Despite the low-grade histological grade, aggressive behaviors have been reported in literatures. Due to the low morbidity, the origins, clinical, and radiological features, management and prognosis are still yet to be well elucidated. We retrospectively reviewed the clinical profiles from a series of 6 patients with chordoid gliomas. All patients underwent surgical treatment, and the diagnoses were based on histopathological examinations. Magnetic resonance imaging (MRI) was performed perioperatively. Follow-up outcomes were presented. This case series consisted of three male and three female patients (age range 27-67 years; mean age 43.3 years). MRI results showed tumors in the third ventricle (4/6), temporal-parietal-occipital lobe involving the lateral ventricle (1/6), and cerebellar hemisphere (1/6). Three tumors were solid, and the others were cystic-solid. Hydrocephalus was present in one patient. The T1-weighted imaging showed hypo- to isointensity, and T2-weighted imaging showed iso- to hyperintensity; enhancement was homogeneous (4/6) or heterogeneous (2/6). Diffusion-weighted imaging showed no evidence of restricted diffusion. Magnetic resonance spectrum showed an elevated choline value and reduced N-acetylaspartate value. Gross total resection was achieved in all patients, and during an average follow-up period of 35.8 months, no recurrence was noted. Chordoid gliomas can occur outside the third ventricle with a great diagnostic challenge. The MRI characteristics suggest a low-grade tumor, and the accurate diagnosis depends on pathological criteria. Complete surgical resection is associated with a favorable outcome. |
2,328,716 | Changes in one-carbon metabolism and DNA methylation in the hearts of mice exposed to space environment-relevant doses of oxygen ions (<sup>16</sup>O). | Cardiovascular disease constitutes an important threat to humans after space missions beyond the Earth's magnetosphere. Epigenetic alterations have an important role in the etiology and pathogenesis of cardiovascular disease. Previous research in animal models has shown that protons and <sup>56</sup>Fe ions cause long-term changes in DNA methylation and expression of repetitive elements in the heart. However, astronauts will be exposed to a variety of ions, including the smaller fragmented products of heavy ions after they interact with the walls of the space craft. Here, we investigated the effects of <sup>16</sup>O on the cardiac methylome and one-carbon metabolism in male C57BL/6 J mice. Left ventricles were examined 14 and 90 days after exposure to space-relevant doses of 0.1, 0.25, or 1 Gy of <sup>16</sup>O (600 MeV/n). At 14 days, the two higher radiation doses elicited global DNA hypomethylation in the 5'-UTR of Long Interspersed Nuclear Elements 1 (LINE-1) compared to unirradiated, sham-treated mice, whereas specific LINE-1 elements exhibited hypermethylation at day 90. The pericentromeric major satellites were affected both at the DNA methylation and expression levels at the lowest radiation dose. DNA methylation was elevated, particularly after 90 days, while expression showed first a decrease followed by an increase in transcript abundance. Metabolomics analysis revealed that metabolites involved in homocysteine remethylation, central to DNA methylation, were unaffected by radiation, but the transsulfuration pathway was impacted after 90 days, with a large increase in cystathione levels at the lowest dose. In summary, we observed dynamic changes in the cardiac epigenome and metabolome three months after exposure to a single low dose of oxygen ions. |
2,328,717 | Prediction of amyloid pathology in cognitively unimpaired individuals using voxel-wise analysis of longitudinal structural brain MRI. | Magnetic resonance imaging (MRI) has unveiled specific alterations at different stages of Alzheimer's disease (AD) pathophysiologic continuum constituting what has been established as "AD signature". To what extent MRI can detect amyloid-related cerebral changes from structural MRI in cognitively unimpaired individuals is still an area open for exploration.</AbstractText>Longitudinal 3D-T1 MRI scans were acquired from a subset of the ADNI cohort comprising 403 subjects: 79 controls (Ctrls), 50 preclinical AD (PreAD), and 274 MCI and dementia due to AD (MCI/AD). Amyloid CSF was used as gold-standard measure with established cutoffs (< 192 pg/mL) to establish diagnostic categories. Cognitively unimpaired individuals were defined as Ctrls if were amyloid negative and PreAD otherwise. The MCI/AD group was amyloid positive. Only subjects with the same diagnostic category at baseline and follow-up visits were considered for the study. Longitudinal morphometric analysis was performed using SPM12 to calculate Jacobian determinant maps. Statistical analysis was carried out on these Jacobian maps to identify structural changes that were significantly different between diagnostic categories. A machine learning classifier was applied on Jacobian determinant maps to predict the presence of abnormal amyloid levels in cognitively unimpaired individuals. The performance of this classifier was evaluated using receiver operating characteristic curve analysis and as a function of the follow-up time between MRI scans. We applied a cost function to assess the benefit of using this classifier in the triaging of individuals in a clinical trial-recruitment setting.</AbstractText>The optimal follow-up time for classification of Ctrls vs PreAD was Δt > 2.5 years, and hence, only subjects within this temporal span are used for evaluation (15 Ctrls, 10 PreAD). The longitudinal voxel-based classifier achieved an AUC = 0.87 (95%CI 0.72-0.97). The brain regions that showed the highest discriminative power to detect amyloid abnormalities were the medial, inferior, and lateral temporal lobes; precuneus; caudate heads; basal forebrain; and lateral ventricles.</AbstractText>Our work supports that machine learning applied to longitudinal brain volumetric changes can be used to predict, with high precision, the presence of amyloid abnormalities in cognitively unimpaired subjects. Used as a triaging method to identify a fixed number of amyloid-positive individuals, this longitudinal voxel-wise classifier is expected to avoid 55% of unnecessary CSF and/or PET scans and reduce economic cost by 40%.</AbstractText> |
2,328,718 | Exclusive Endoscopic Occipital Transtentorial Approach for Pineal Region Tumors. | Removal of pineal region tumors, which are deeply placed and encircled by intricate neurovascular structures, is challenging to neurosurgeons. The aim of this study was to present our experience with the exclusive endoscopic occipital transtentorial approach (EEOTA) used for removal of pineal region tumors.</AbstractText>A retrospective review was performed of patients who underwent surgery using the EEOTA to remove pineal region tumors from May 2016 to August 2018. The details of the EEOTA procedure were confirmed.</AbstractText>Five patients underwent surgery via the EEOTA for treatment of pineal region tumors. In all cases, it was possible to perform the EEOTA less invasively through a keyhole craniotomy approximately 2.0-2.5 cm in size. The EEOTA produced an excellent view and provided natural and automatic orientation. There was essentially no blind spot in this procedure, even for the floor or ipsilateral wall of the third ventricle. Gross total resection was achieved in 4 cases. In the patient with atypical teratoid rhabdoid tumor, we abandoned gross total resection because of a hardened adhesion to the tectum and the great cerebral vein and its tributaries. Two patients presented with transient upper gaze palsy immediately after surgery but experienced complete recovery during the follow-up period.</AbstractText>The EEOTA is a very promising technique for removal of pineal region tumors and has the potential for extensive and routine application for surgeons familiar with endoscopic surgery.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,719 | Scalp-to-cortex distance of left primary motor cortex and its computational head model: Implications for personalized neuromodulation. | Non-invasive brain stimulation (NIBS) is increasingly used as a probe of function and therapeutics in experimental neuroscience and neurorehabilitation. Scalp-to-cortex distance (SCD), as a key parameter, has been shown to potentially impact on the electric field. This study aimed to examine the region-specific SCD and its relationship with cognitive function in the context of age-related brain atrophy.</AbstractText>We analyzed the SCD and cortical thickness (CT) of left primary motor cortex (M1) in 164 cognitively normal (CN) adults and 43 dementia patients drawn from the Open Access Series of Imaging Studies (OASIS). The degree of brain atrophy was measured by the volume of ventricular system. Computational head model was developed to simulate the impact of SCD on the electric field.</AbstractText>Increased SCD of left M1 was only found in dementia patients (P < .001). When considering CT, the ratio of SCD to CT (F = 27.41, P < .001) showed better differential value than SCD. The SCD of left M1 was associated with worse global cognition (r = -.207, P = .011) and enlarged third ventricle (r = .241, P < .001). The electric field was consequently reduced with the increased SCD across cognitively normal elderly and dementia groups.</AbstractText>Scalable distance measures, including SCD and CT, are markedly correlated with reduced electric field in dementia patients. The findings suggest that it is important to be aware of region-specific distance measures when conducting NIBS-based rehabilitation in individuals with brain atrophy.</AbstractText>© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.</CopyrightInformation> |
2,328,720 | Differential Effects of Directional Cyclic Stretching on the Functionalities of Engineered Cardiac Tissues.<Pagination><StartPage>3508</StartPage><EndPage>3519</EndPage><MedlinePgn>3508-3519</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/acsabm.9b00414</ELocationID><Abstract><AbstractText>Cardiac tissue engineering aims to regenerate functional cardiac tissues through recapitulating the native microenvironmental cues, where cardiomyocytes are highly oriented and rhythmically contract along their long-axis direction in the native myocardium. In addition, the different oriented layers of the left ventricle lead to a dynamic biaxial stretching on cardiomyocytes, which makes the mechanical microenvironment in the myocardium much more complex. Thus, it is important to investigate the effect of dynamic mechanical stimulation along different directions to preoriented cardiomyocytes on the functionalities of engineered cardiac tissues. In this study, we regenerate oriented cardiac tissues using electrospun silk fibroin scaffolds, followed by applying the dynamic mechanical stimulation parallel or perpendicular to the cell orientation. The design and utilization of nanofibrous scaffolds combining the aligned topography and random substrate ensure the realization of dynamic mechanical stimulation with a homogeneous strain along both directions. The results reveal that the parallel mechanical stretching promotes the alignment of cardiomyocytes and the formation of sarcomeres and gap junctions, while the perpendicular stimulation interferes with the cell alignment and gap junction formation. This study would provide guidance for promoting the functionalities of regenerated cardiac tissues through directional dynamic mechanical stimulation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Guoxu</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Material Science and Chemical Engineering, Xi'an Technological University, Xi'an 710021, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bao</LastName><ForeName>Xuejiao</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Guoyou</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Feng</ForeName><Initials>F</Initials><Identifier Source="ORCID">0000-0003-4351-0222</Identifier><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaohui</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>31</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>ACS Appl Bio Mater</MedlineTA><NlmUniqueID>101729147</NlmUniqueID><ISSNLinking>2576-6422</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">cardiac tissue engineering</Keyword><Keyword MajorTopicYN="N">cardiomyocytes</Keyword><Keyword MajorTopicYN="N">cell alignment</Keyword><Keyword MajorTopicYN="N">electrospun scaffolds</Keyword><Keyword MajorTopicYN="N">mechanical microenvironment</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>1</Month><Day>15</Day><Hour>1</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>8</Month><Day>19</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>8</Month><Day>19</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">35030738</ArticleId><ArticleId IdType="doi">10.1021/acsabm.9b00414</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">31693326</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK549365</ArticleId></ArticleIdList><Book><Publisher><PublisherName>Canadian Agency for Drugs and Technologies in Health</PublisherName><PublisherLocation>Ottawa (ON)</PublisherLocation></Publisher><BookTitle book="rc1163">Natriuretic Peptide Testing for Monitoring of Heart Failure Therapy: A Review of Clinical Effectiveness, Clinical Utility, Cost-Effectiveness, and Guidelines</BookTitle><PubDate><Year>2019</Year><Month>08</Month><Day>19</Day></PubDate><AuthorList Type="authors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Banerjee</LastName><ForeName>Srabani</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>McCormack</LastName><ForeName>Suzanne</ForeName><Initials>S</Initials></Author></AuthorList><CollectionTitle book="cadthrdcollect">CADTH Rapid Response Reports</CollectionTitle><Medium>Internet</Medium></Book><Language>eng</Language><PublicationType UI="D016454">Review</PublicationType><Abstract><AbstractText>Heart failure (HF) is a complex condition, in which the heart is unable to pump enough blood to meet all the needs of the body.<sup>,</sup> HF is mainly of two types: heart failure with a reduced ejection fraction (HFrEF) and heart failure with a preserved ejection fraction (HFpEF). HFrEF is caused by left ventricular systolic dysfunction because the left ventricle becomes weak and is unable to contract properly. In HFpEF, the left ventricle becomes stiff, making it difficult for the heart chamber to fill with blood. Typical symptoms include breathlessness, ankle swelling and fatigue. Heart failure is a costly health condition and is a major public health concern. In Canada, approximately 669,600 (3.6%) persons aged 40 years or older, live with diagnosed HF. The estimated cost resulting from hospital admissions for which HF was the primary diagnosis was $482 million in 2013; the number of HF patients admitted being 45,600. By 2030, the number of patients admitted with HF is expected to rise to 54,000 and the associated cost to increase to $2.8 billion. Pharmacological treatment for HF includes drugs such as angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist. It has been reported that it may be difficult to recognize the early signs of worsening HF and that sometimes sub-optimal doses of drugs are used for fear of adverse events such as renal dysfunction and hypotension. Biomarkers such as neuropeptides (NPs) may provide an objective assessment of HF severity and enable use of appropriate drug doses for HF therapy. The NPs, B-type natriuretic peptide (BNP) and N (or amino) terminal pro-B-type natriuretic peptide (NT-proBNP) are released by the myocardium in response to volume and pressure overload. In HF patients natriuretic peptide (NP) levels are elevated. Measurement of NP levels in plasma has been used for diagnosis and prognosis of HF patients, but its role. in guiding therapy for patients with HF appears uncertain.<sup>–</sup> The purpose of this report is to review the clinical effectiveness, clinical utility, and cost-effectiveness of. natriuretic peptide testing for monitoring of heart failure therapy. Additionally, this report aims to review the evidence-based guidelines regarding natriuretic peptide testing for monitoring of heart failure therapy.</AbstractText><CopyrightInformation>Copyright © 2019 Canadian Agency for Drugs and Technologies in Health.</CopyrightInformation></Abstract></BookDocument><PubmedBookData><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31693326</ArticleId></ArticleIdList></PubmedBookData></PubmedBookArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31419793</PMID><DateRevised><Year>2019</Year><Month>08</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0693</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Aug</Month><Day>16</Day></PubDate></JournalIssue><Title>Journal of neurosurgery</Title><ISOAbbreviation>J Neurosurg</ISOAbbreviation></Journal>Form follows function: estimation of CSF flow in the third ventricle-aqueduct-fourth ventricle complex modeled as a diffuser/nozzle pump. | Cardiac tissue engineering aims to regenerate functional cardiac tissues through recapitulating the native microenvironmental cues, where cardiomyocytes are highly oriented and rhythmically contract along their long-axis direction in the native myocardium. In addition, the different oriented layers of the left ventricle lead to a dynamic biaxial stretching on cardiomyocytes, which makes the mechanical microenvironment in the myocardium much more complex. Thus, it is important to investigate the effect of dynamic mechanical stimulation along different directions to preoriented cardiomyocytes on the functionalities of engineered cardiac tissues. In this study, we regenerate oriented cardiac tissues using electrospun silk fibroin scaffolds, followed by applying the dynamic mechanical stimulation parallel or perpendicular to the cell orientation. The design and utilization of nanofibrous scaffolds combining the aligned topography and random substrate ensure the realization of dynamic mechanical stimulation with a homogeneous strain along both directions. The results reveal that the parallel mechanical stretching promotes the alignment of cardiomyocytes and the formation of sarcomeres and gap junctions, while the perpendicular stimulation interferes with the cell alignment and gap junction formation. This study would provide guidance for promoting the functionalities of regenerated cardiac tissues through directional dynamic mechanical stimulation.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Guoxu</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Material Science and Chemical Engineering, Xi'an Technological University, Xi'an 710021, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bao</LastName><ForeName>Xuejiao</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Guoyou</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Feng</ForeName><Initials>F</Initials><Identifier Source="ORCID">0000-0003-4351-0222</Identifier><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaohui</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>31</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>ACS Appl Bio Mater</MedlineTA><NlmUniqueID>101729147</NlmUniqueID><ISSNLinking>2576-6422</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">cardiac tissue engineering</Keyword><Keyword MajorTopicYN="N">cardiomyocytes</Keyword><Keyword MajorTopicYN="N">cell alignment</Keyword><Keyword MajorTopicYN="N">electrospun scaffolds</Keyword><Keyword MajorTopicYN="N">mechanical microenvironment</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>1</Month><Day>15</Day><Hour>1</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>8</Month><Day>19</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>8</Month><Day>19</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">35030738</ArticleId><ArticleId IdType="doi">10.1021/acsabm.9b00414</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">31693326</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK549365</ArticleId></ArticleIdList><Book><Publisher><PublisherName>Canadian Agency for Drugs and Technologies in Health</PublisherName><PublisherLocation>Ottawa (ON)</PublisherLocation></Publisher><BookTitle book="rc1163">Natriuretic Peptide Testing for Monitoring of Heart Failure Therapy: A Review of Clinical Effectiveness, Clinical Utility, Cost-Effectiveness, and Guidelines</BookTitle><PubDate><Year>2019</Year><Month>08</Month><Day>19</Day></PubDate><AuthorList Type="authors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Banerjee</LastName><ForeName>Srabani</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>McCormack</LastName><ForeName>Suzanne</ForeName><Initials>S</Initials></Author></AuthorList><CollectionTitle book="cadthrdcollect">CADTH Rapid Response Reports</CollectionTitle><Medium>Internet</Medium></Book><Language>eng</Language><PublicationType UI="D016454">Review</PublicationType><Abstract>Heart failure (HF) is a complex condition, in which the heart is unable to pump enough blood to meet all the needs of the body.<sup>,</sup> HF is mainly of two types: heart failure with a reduced ejection fraction (HFrEF) and heart failure with a preserved ejection fraction (HFpEF). HFrEF is caused by left ventricular systolic dysfunction because the left ventricle becomes weak and is unable to contract properly. In HFpEF, the left ventricle becomes stiff, making it difficult for the heart chamber to fill with blood. Typical symptoms include breathlessness, ankle swelling and fatigue. Heart failure is a costly health condition and is a major public health concern. In Canada, approximately 669,600 (3.6%) persons aged 40 years or older, live with diagnosed HF. The estimated cost resulting from hospital admissions for which HF was the primary diagnosis was $482 million in 2013; the number of HF patients admitted being 45,600. By 2030, the number of patients admitted with HF is expected to rise to 54,000 and the associated cost to increase to $2.8 billion. Pharmacological treatment for HF includes drugs such as angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist. It has been reported that it may be difficult to recognize the early signs of worsening HF and that sometimes sub-optimal doses of drugs are used for fear of adverse events such as renal dysfunction and hypotension. Biomarkers such as neuropeptides (NPs) may provide an objective assessment of HF severity and enable use of appropriate drug doses for HF therapy. The NPs, B-type natriuretic peptide (BNP) and N (or amino) terminal pro-B-type natriuretic peptide (NT-proBNP) are released by the myocardium in response to volume and pressure overload. In HF patients natriuretic peptide (NP) levels are elevated. Measurement of NP levels in plasma has been used for diagnosis and prognosis of HF patients, but its role. in guiding therapy for patients with HF appears uncertain.<sup>–</sup> The purpose of this report is to review the clinical effectiveness, clinical utility, and cost-effectiveness of. natriuretic peptide testing for monitoring of heart failure therapy. Additionally, this report aims to review the evidence-based guidelines regarding natriuretic peptide testing for monitoring of heart failure therapy.<CopyrightInformation>Copyright © 2019 Canadian Agency for Drugs and Technologies in Health.</CopyrightInformation></Abstract></BookDocument><PubmedBookData><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31693326</ArticleId></ArticleIdList></PubmedBookData></PubmedBookArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31419793</PMID><DateRevised><Year>2019</Year><Month>08</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0693</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Aug</Month><Day>16</Day></PubDate></JournalIssue><Title>Journal of neurosurgery</Title><ISOAbbreviation>J Neurosurg</ISOAbbreviation></Journal><ArticleTitle>Form follows function: estimation of CSF flow in the third ventricle-aqueduct-fourth ventricle complex modeled as a diffuser/nozzle pump.</ArticleTitle><Pagination><StartPage>1</StartPage><EndPage>8</EndPage><MedlinePgn>1-8</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3171/2019.5.JNS19276</ELocationID><ELocationID EIdType="pii" ValidYN="Y">2019.5.JNS19276</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">In the last 20 years, researchers have debated cerebrospinal fluid (CSF) dynamics theories, commonly based on the classic bulk flow perspective. New hypotheses do not consider a possible hydraulic impact of the ventricular morphology. The present study investigates, by means of a mathematical model, the eventual role played by the geometric shape of the "third ventricle-aqueduct-fourth ventricle" complex in CSF circulation under the assumption that the complex behaves like a diffuser/nozzle (DN) pump.<AbstractText Label="METHODS" NlmCategory="METHODS">DN pumps are quite recent devices introduced as valveless micropumps in various industrial applications given their property of driving net flow when subjected to rhythmic pulsations. A novel peculiar DN pump configuration was adopted in this study to mimic the ventricular complex, with two reservoirs (the ventricles) and one tube provided with a conical reach (the aqueduct-proximal fourth ventricle). The flow was modeled according to the classic equations of laminar flow, and the external rhythmic pulsations forcing the system were reproduced as a pulsatile pressure gradient between the chambers. Several physiological scenarios were implemented with the integration of data acquired by MRI in 10 patients with no known pathology of CSF dynamics, and a quantitative analysis of the effect of geometric and hydraulic parameters (diverging angle, sizes, frequency of pulsations) on the CSF net flow was performed.<AbstractText Label="RESULTS" NlmCategory="RESULTS">The results showed a craniocaudal net flow in all the given values, consistent with the findings of cine MRI studies. Moreover, the net flow estimated for the analyzed cohort of patients ranged from 0.221 to 0.505 ml/min, remarkably close to the values found on phase contrast cine MRI in healthy subjects. Sensitivity analysis underlines the pivotal role of the DN configuration, as well as of the frequency of forcing pressure, which promotes a relevant net flow considering both the heart and respiration rate.<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">This work suggests that the geometry of the third ventricle-aqueduct-fourth ventricle complex, which resembles a diverter, appears to be functional in the generation of a net craniocaudal flow and potentially has an impact on CSF dynamics. These conclusions can be drawn by observing the analogies between the shape of the ventricles and the geometry of DN pumps and by recognizing the basis of the mathematical model of the simplified third ventricle-aqueduct-fourth ventricle complex proposed. |
2,328,721 | Associations between Skeletal Muscle and Myocardium in Aging: A Syndrome of "Cardio-Sarcopenia"? | The link between skeletal muscle and heart disease remains intriguing. It is unknown how skeletal muscle may be associated with aspects of myocardial structure and function, particularly in the presence of aging-related sarcopenia. We hypothesize that among aging adults with sarcopenia, alterations in myocardial structure and/or function may exist, resulting in a syndrome of "cardio-sarcopenia."</AbstractText>Participants derived from a community cohort study underwent same-day bioimpedance body composition analysis that measured skeletal muscle in sites such as the trunk, upper limb, and lower limb, and echocardiography for assessment of myocardial structure and function. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia criteria.</AbstractText>We studied a total of 378 participants, of whom 88 (23.3%) had sarcopenia. Participants with sarcopenia had smaller left ventricular (LV) sizes (lower LV internal diameter end diastole (4.1 ± .7 vs 4.5 ± .6 cm; P < .0001), lower LV internal diameter end systole (2.3 ± .5 vs 2.5 ± .4 cm; P = .010), lower LV posterior wall end diastole (.7 ± .1 vs .8 ± .1 cm; P = .0036), and lower LV posterior wall end systole (1.4 ± .3 vs 1.5 ± .2 cm; P = .0031). Sarcopenic participants also had lower LV mass (106 ± 35 vs 126 ± 53; P = .0014) and lower left atrial (LA) volume (33 ± 13 vs 36 ± 13; P = .033). Adjusting for age and diabetes mellitus, skeletal muscle mass was associated with LV diameter (β = .06; 95% confidence interval [CI] = .03-.09; P < .0001), LV mass (β = 4.04; 95% CI = 1.78-6.29; P = .001), LA diameter (β = .05; 95% CI = .01-.09; P = .007), and LA volume (β = 1.26; 95% CI = .38-2.13; P = .005). A positive linear correlation was observed between LV mass and handgrip strength (r = .25; P < .0001).</AbstractText>Among a community sample of older adults with preserved heart function, sarcopenia is associated with reductions in LV and LA sizes. Skeletal muscle mass was independently associated with specific indices of myocardial structure. J Am Geriatr Soc 67:2568-2573, 2019.</AbstractText>© 2019 The American Geriatrics Society.</CopyrightInformation> |
2,328,722 | A primary third ventricle mixed germ cell tumor with leptomeningeal dissemination of immature teratoma component. | A 17-year-old male patient presented to the clinic with a headache, nausea, and vomiting. Magnetic resonance imaging demonstrated a fat-containing and -enhancing heterogeneous tumor in the third ventricle, and fat droplets within the ventricles and the subarachnoid space. Obstructive hydrocephalus was also present. Emergency subtotal removal of the mass was performed via interhemispheric transcallosal approach. The histopathological diagnosis was a mixed germ cell tumor that was composed of embryonal carcinoma, yolk-sac tumor, germinoma, and immature teratoma containing a large amount of mature elements. The patient was referred for postoperative chemoradiotherapy. A mixed germ cell tumor is a rare type of nongerminomatous germ cell tumor that is made up of at least two different types of germ cell tumors. These may include germinoma, choriocarcinoma, embryonal carcinoma, yolk sac tumor, mature teratoma, immature teratoma, or teratoma with malignant degeneration. As far as we know, this is the first reported case of a primary third ventricle mixed germ cell tumor with leptomeningeal dissemination of the immature teratoma component that contains grossly visible mature elements at admission. |
2,328,723 | The transcallosal transchoroidal approach to the diencephalic-mesencephalic junction: how I do it. | Different approaches have to be considered for lesions of the diencephalic-mesencephalic junction based on the localization, extension of the lesion, and relationship to the ventricular system.</AbstractText>We present the case of a young lady who presented with a cavernoma of the junction of midbrain and diencephalon after an episode of hemorrhage. The microsurgical anatomy of the trans-callosal trans-choroidal approach for this lesion is described along with its advantages and limitations.</AbstractText>The trans-choroidal approach allows adequate access to lesions of the diencephalic-mesencephalic junction that project into the third ventricle.</AbstractText> |
2,328,724 | Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Management of Patients With Myelomeningocele: Whether Persistent Ventriculomegaly Adversely Impacts Neurocognitive Development. | Myelomeningocele (MM) is the most common congenital anomaly to affect the nervous system and affects 1500-2000 newborn infants per year in the United States. It is accompanied by symptomatic hydrocephalus in approximately 70%-80% of patients. Different treatment strategies for hydrocephalus characteristically result in different effects on the size of the ventricles.</AbstractText>The objective of this systematic review was to determine whether persistent ventricular enlargement adversely impacts neurocognitive development in patients with MM.</AbstractText>The PubMed National Library of Medicine Medline database and Embase were queried using MeSH headings and keywords relevant to neurocognitive or intellectual development and ventricular size or morphology. Abstracts were reviewed by the authors to identify which studies met strict inclusion criteria. An evidence table was constructed that summarized the included studies and reflected the quality of evidence (Classes I-III) that each represented. A recommendation was made that is based on the quality of the evidence.</AbstractText>An initial abstract review utilizing strict inclusion/exclusion criteria yielded 48 studies, 9 of which underwent full-text review. There is limited and conflicting Class III evidence from 2 studies.</AbstractText>Currently, there is insufficient data to conclude that ventricular size and morphology impact neurocognitive development.The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-5.</AbstractText>Copyright © 2019 by the Congress of Neurological Surgeons.</CopyrightInformation> |
2,328,725 | Aqueductal Developmental Venous Anomaly Presenting with Mimic Symptoms of Idiopathic Normal Pressure Hydrocephalus in an Elderly Patient: A Case Report. | Developmental venous anomalies (DVAs) are generally asymptomatic; however, they can sometimes cause central nervous disorders. Aqueductal stenosis caused by DVAs is so rare that only 14 cases have been reported to date. Moreover, most patients are children or young adults, presenting with headaches or consciousness disturbances, associated with raised intracranial pressure. Here, we report on an 83-year-old man presenting with mimic symptoms of idiopathic normal pressure hydrocephalus (cognitive disorder, gait disturbance, and urinary urgency: Hakim's triad) because of obstructive hydrocephalus caused by a DVA located in the aqueduct. Endoscopic third ventriculostomy (ETV) was performed to relieve his symptoms, and the opening pressure of the lateral ventricle was recorded to be 10 cm-H<sub>2</sub>O. Endoscopic examination of the intraventricular system clearly revealed a vein within the aqueduct converging with the adjacent subependymal vessels. These findings were compatible with the characteristics of DVAs. His symptoms improved after the ETV. This case suggested that DVAs within the aqueduct, despite of their congenital nature, could give rise to decompensated obstructive hydrocephalus even in elderly patients, resulting in Hakim's triad. |
2,328,726 | Early LV remodelling patterns in overweight and obesity: Feasibility of cardiac CT to detect early geometric left ventricular changes. | Obesity is an in independent risk factor for cardiovascular disease.</AbstractText>To describe the early LV remodelling pattern in patients with overweight and obesity and structurally normal hearts.</AbstractText>Consecutive patients (n = 2374), with structurally normal hearts and BMI ≥ 18.5 kg/m2</sup>, undergoing prospective mid-diastolic ECG gated CTCA were selected. Left ventricular mass (LVM) and Left ventricular mid-diastolic volume (LVMDV) were measured. The concentricity index (LVM/LVMDV) were calculated. According to the definitions of the World Health Organization (WHO), the patients were divided into weight categories.</AbstractText>The mean LVM ± Std. deviation in the subgroups according to WHO classification was 101.68 ± 28.99 g (normal weight), 115.79 ± 29.14 g (overweight), 123.8 ± 33.44 g (class I obesity), 125.85 ± 32.89 g (class II obesity) and 132.45 ± 37.85 g (class III obesity). (p < 0.001) The mean LVMDV progressed with increasing WHO weight category from 112.37 ± 36.46 in patients with normal BMI to 140.26 ± 43.78 in patients with class III obesity. (p < 0.001) The concentricity index was 0.935 ± 0.216 g/ml in patients with normal BMI, 0.979 ± 0.253 g/ml, 1.058 ± 0.635 g/ml, 0.996 ± 0.284 g/ml and 0.9768 ± 0.244 g/ml in patients with BMI categories 25-29.99, 30-34.99, 35-39.99 and ≥40 kg/m2</sup>, respectively.</AbstractText>Our study demonstrates a non-linear (inverse U-shape) relationship between increasing BMI class and concentricity index, reaching its maximum at a BMI of 30-34.99 kg/m2</sup>. Further increase in BMI results in LV dilation.</AbstractText>Copyright © 2019 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation> |
2,328,727 | White Matter Relationships Examined by Transillumination Technique Using a Lateral Transcortical Parietal Approach to the Atrium: Three-Dimensional Images and Surgical Considerations. | Numerous lesions are found in the ventricular atrium (VA). Access is gained through many white matter tracts with great relevance and specific neurologic functions. It is important to understand the configuration of the most relevant structures surrounding this zone and, thus, select the safest entry zone on the lateral cerebral surface.</AbstractText>We studied the white matter layers traversed in the lateral transcortical parietal approach through the intraparietal sulcus (IPS), adding a transillumination technique. With this knowledge, we selected the safest highway to improve this particular approach.</AbstractText>An in-depth study of the white matter tracts was performed on 24 cerebral hemispheres (12 human whole brains). The Klingler technique and microsurgical dissection techniques were used under ×6 to ×40 magnification. The transillumination technique (torch illuminating the ventricular cavity) was used to expose the layers surrounding the VA and, thus, guide the dissection.</AbstractText>Taking the IPS on the cerebral surface as a reference, we identified the following white matter layers ordered from the surface to the ependyma: U fibers, superior longitudinal fascicle, arcuate fascicle, vertical occipital fascicle, sagittal stratum with the optic radiations, and tapetum fibers. The transillumination technique allowed for the easier identification of the white matter deep periventricular layers.</AbstractText>Knowledge of the main fascicles in the path and neighborhood of the VA allowed us to understand how certain neurologic functions can be affected by lesions at this level and to select the most appropriate way to avoid damaging relevant fascicles.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,728 | Variation in brain structure volumes in schizophrenia: A commentary. | Recently, Kuo and Pogue-Geile (2019) quantitatively reviewed Magnetic Resonance Imaging (MRI) findings in patients with schizophrenia demonstrating, besides altered volume of several brain structures significantly greater structural variability in patients relative to controls as for intracranial, lateral and third ventricles volumes. We believe that additional points could be usefully included in the discussion of the conceptual meaning of these findings. In this commentary, first we highlight the role of potential confounding factors such as antipsychotic medication intake and duration of illness when interpreting MRI data in schizophrenia. Second, we discuss the finding of greater variability of cerebral structure volumes in the broader context of the pathophysiology and time course of brain abnormalities in the disease. |
2,328,729 | Semi-automated speckle-tracking for quantitative right ventricular assessment in children and adolescents. | Assessment of right ventricular size and function is an important part of the clinical cardiac evaluation; however, these quantitative measures are challenging by echocardiography. Automated software could be useful in place of manual measurements and qualitative assessment. This study evaluates a semi-automated software by comparing automated to manual measures in normal children.</AbstractText>Neonates to adolescents with normal echocardiograms were prospectively enrolled. Measurements were performed using manual techniques and semi-automated software (EchoInsight®, Epsilon Imaging, Ann Arbor, Michigan, United States of America). Right ventricular measurements included end-diastolic and end-systolic area, fractional area change, chamber dimensions, and tricuspid annular plane systolic excursion. Agreement between manual and semi-automated measures was compared.</AbstractText>Echocardiograms for 233 patients were included in the analysis. Intra- and inter-observer reliabilities for semi-automated measures were good with intraclass correlation coefficients all over 0.9 and 0.85, respectively. There was very strong correlation between manual and semi-automated methods for areas and dimensions (r = 0.93-0.99) and low bias (1.4-10.8%). For functional measures, tricuspid annular plane systolic excursion measures correlated well (r = 0.84), but fractional area change did not (r = 0.50). Both demonstrated significant bias (33.5-43.0%). The semi-automated method consistently underestimated fractional area change with a mean of 26.6% versus a manual mean of 36.1%.</AbstractText>The semi-automated software is capable of generating quantitative right ventricular measures in children with good reliability. The software demonstrates very good correlation and low bias when compared to manual methods for right ventricular areas and dimensions. There is a significant difference between manual and semi-automated techniques for the functional measures.</AbstractText> |
2,328,730 | Cytokine and inflammatory mediator effects on TRPV4 function in choroid plexus epithelial cells. | The choroid plexus (CP), composed of capillaries surrounded by a barrier epithelium, is the main producer of cerebrospinal fluid (CSF). The CP epithelium regulates the transport of ions and water between the blood and the ventricles, contributing to CSF production and composition. Several studies suggest a connection between the cation channel transient receptor potential vanilloid-4 (TRPV4) and transepithelial ion movement. TRPV4 is a nonselective, calcium-permeable cation channel present in CP epithelia reported to be activated by cytokines and inflammatory mediators. Utilizing the PCP-R (porcine choroid plexus-Riems) cell line, we investigated the effects of various cytokines and inflammatory mediators on TRPV4-mediated activity. Select proinflammatory cytokines (TNF-α, IL-1β, TGF-β1) had inhibitory effects on TRPV4-stimulated transepithelial ion flux and permeability changes, whereas anti-inflammatory cytokines (IL-10, IL-4, and IL-6) had none. Quantitative mRNA analysis showed that these cytokines had no effect on TRPV4 transcription levels. Inhibition of the transcription factor NF-κB, involved in the production and regulation of several inflammatory cytokines, inhibited TRPV4-mediated activity, suggesting a link between TRPV4 and cytokine production. Contrary to published studies, the proinflammatory mediator arachidonic acid (AA) had inhibitory rather than stimulatory effects on TRPV4-mediated responses. However, inhibition of AA metabolism also caused inhibitory effects on TRPV4, suggesting a complex interaction of AA and its metabolites in the regulation of TRPV4 activity. Together these data imply that TRPV4 activity is involved in the inflammatory response; it is negatively affected by proinflammatory mediators. Furthermore, arachidonic acid metabolites, but not arachidonic acid itself, are positive regulators of TRPV4. |
2,328,731 | Alpha-Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring. | Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 mol/L NaCl for 20 days before and during pregnancy. α-Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post-weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca<sup>2+</sup> -ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α-Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of Cr<sub>Cl</sub> , which was sensitized for a sharp decrease after α-Tocopherol. In conclusion, the combination of maternal saline overload and high α-Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome. |
2,328,732 | Endocardial biventricular pacing for chronic heart failure patients: Effect on transmural dispersion of repolarization. | Conventional epicardial cardiac resynchronization therapy (CRT) can cause fatal arrhythmia associated with increased transmural dispersion of repolarization (TDR). It is unknown whether endocardial biventricular pacing in various locations will decrease TDR and hence the occurrence of fatal arrhythmia. This study aimed to find out the most effective location of endocardial biventricular pacing resulting in the shortest homogenous TDR.</AbstractText>A before-and-after study on adult chronic heart failure (CHF) patients undergoing endocardial biventricular pacing in several defined locations. The changes in TDR from baseline were compared among various pacing locations.</AbstractText>Fourteen subjects were included with age ranged 36-74 years old, of which 10 were males. Location revealed the highest post biventricular pacing TDR (113.4 (SD 13.8) ms) was the outlet septum of right ventricle in combination with lateral wall of left ventricle (RVOTseptum-LVlateral) while the lowest one (106.1 (SD 11.6) ms) was of the right ventricular apex and posterolateral left ventricle (RVapex-LVposterolateral). Two CRT locations resulted in the most homogenous TDR, that is the right ventricular apex - left ventricular lateral wall (RVapex-LVlateral, mean difference -9.43; 95% CI (-19.72;0.87) ms, P</i> = 0.07) and right ventricular apex - left ventricle posterolateral wall (RVapex-LVposterolateral, mean difference -6.85; 95% CI (-13.93;0.22) ms, P</i> = 0.056).</AbstractText>Endocardial biventricular pacing on right ventricular apex and left ventricular lateral/posterolateral walls results in the most homogenous TDR.</AbstractText> |
2,328,733 | Stimulatory effect of dopamine derivative, salsolinol, on pulsatile luteinizing hormone secretion in seasonally anestrous sheep: Focus on dopamine, kisspeptin and gonadotropin-releasing hormone. | In the present study, there was testing of the hypothesis that a centrally administered dopamine (DA) derivative, salsolinol, could affect pulsatile luteinizing hormone (LH) secretion in seasonally anestrous sheep by affecting the neuronal components of the estradiol (E2) negative feedback. In two experiments performed during early spring (increasing day length - March/April), salsolinol or Ringer-Locke solution (control) were administered into the third brain ventricle (IIIv): 1) in several injections for three consecutive days; and 2) in several hour-long infusions. In addition to determining the LH concentration (in both experiments), the abundances of gonadotropin-releasing hormone (GnRH) and kisspeptin mRNA were examined in the hypothalamus and LHβ subunit mRNA in the pituitary (Experiment 1). In Experiment 2, concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in perfusates collected from the infundibular nucleus/median eminence (IN/ME) by the push-pull method. In both experiments, salsolinol increased both LH pulse frequency (P < 0.05) and plasma LH concentration (P < 0.001) compared to controls. The injected salsolinol also increased (P < 0.05) the abundance of GnRH mRNA in the mediobasal hypothalamus and kisspeptin mRNA in the arcuate nucleus. The two doses of infused salsolinol decreased DA to undetectable concentrations and DOPAC concentration by 60% in perfusates collected from the IN/ME. In conclusion, exogenous salsolinol functioning centrally stimulates pulsatile LH secretion in sheep during seasonal anestrus. It is suggested that salsolinol may have this effect by reducing the activity of the hypothalamic neuroendocrine dopaminergic system, which results in an increase in both kisspeptin and GnRH neurons activity. |
2,328,734 | The senses of the choroid plexus. | The composition of cerebrospinal and brain interstitial fluids is ensured by barriers between the blood and the brain parenchyma (the blood-brain barrier) and between the blood and the cerebrospinal fluid (the blood-cerebrospinal fluid barrier). Barrier function results from the combination of tight junctions between cells that impair solute flux via the paracellular pathway, cell membrane transporters that enable selective transcellular solute passage, and intracellular metabolizing enzymes that transform molecules in transit. Collectively, they comprise a chemical surveillance system, essential to protect the brain from toxicants, microorganisms, and other harmful compounds. Conversely, this chemical surveillance system compromises the brain delivery of many pharmacologic agents against brain cancer and brain metastasis, neurodegenerative diseases, and brain infections. Despite their importance, the mechanisms underlying the regulation of the components of this chemical surveillance system in response to alterations in the composition of blood and brain fluids are still poorly understood. We propose that odorant receptors, vomeronasal receptors and taste receptors, recently identified at brain barriers might be upstream components of this surveillance system. These chemosensory receptors are strategically placed to monitor the composition of blood, cerebrospinal and brain interstitial fluids. Upon ligand-binding, they may deploy the action of transporters and detoxifying enzymes or other unprecedented functions in brain barrier cells, to cope with alterations in the composition of blood and brain cerebrospinal and interstitial fluids, working as guardians of the central nervous system. |
2,328,735 | N-cadherin (Cdh2) Maintains Migration and Postmitotic Survival of Cortical Interneuron Precursors in a Cell-Type-Specific Manner. | The multiplex role of cadherin-based adhesion complexes during development of pallial excitatory neurons has been thoroughly characterized. In contrast, much less is known about their function during interneuron development. Here, we report that conditional removal of N-cadherin (Cdh2) from postmitotic neuroblasts of the subpallium results in a decreased number of Gad65-GFP-positive interneurons in the adult cortex. We also found that interneuron precursor migration into the pallium was already delayed at E14. Using immunohistochemistry and TUNEL assay in the embryonic subpallium, we excluded decreased mitosis and elevated cell death as possible sources of this defect. Moreover, by analyzing the interneuron composition of the adult somatosensory cortex, we uncovered an unexpected interneuron-type-specific defect caused by Cdh2-loss. This was not due to a fate-switch between interneuron populations or altered target selection during migration. Instead, potentially due to the migration delay, part of the precursors failed to enter the cortical plate and consequently got eliminated at early postnatal stages. In summary, our results indicate that Cdh2-mediated interactions are necessary for migration and survival during the postmitotic phase of interneuron development. Furthermore, we also propose that unlike in pallial glutamatergic cells, Cdh2 is not universal, rather a cell type-specific factor during this process. |
2,328,736 | Rare cause of pulmonary hypertension - pulmonary tumour thrombotic microangiopathy. | Pulmonary tumour thrombotic microangiopathy (PTTA) is a rare but lethal cause of pulmonary hypertension (PHT). Its underlying mechanism is believed to be fibrocellular intimal proliferation and microthrombosis. It has been reported in association with gastric adenocarcinoma and breast, pancreatic and lung cancers. The diagnosis is often made on postmortem examination due to the absence of diagnostic criteria and its rare occurrence. We describe the case of a middle-aged man who presented with rapidly progressive PHT. He deteriorated into multiorgan failure despite aggressive medical therapy and died 4 weeks after his initial presentation. A postmortem examination confirmed the diagnosis of PTTA in addition to the finding of signet cell gastric adenocarcinoma. This case highlights the lethal nature of this rare condition, the ongoing challenges in making an antemortem diagnosis, and the importance of postmortem examination in determining the cause of death to provide closure for both, the treating physician and the family. |
2,328,737 | Profiles of brain oxidative damage, ventricular alterations, and neurochemical metabolites in the striatum of PINK1 knockout rats as functions of age and gender: Relevance to Parkinson disease. | Parkinson disease (PD) is the second most common neurodegenerative disease associated with aging. Dopaminergic neuronal degeneration and α-synuclein aggregation are commonly found in PD brain. Oxidative damage and inflammation often are considered as etiological factors of PD, although the detailed mechanisms still remain unknown. Gender and aging are two important risk factors to PD, and gene mutations and certain environmental factors have been implicated in this disease. The current study employed PTEN-induced putative kinase -1 (PINK1) knockout (KO) rats, since mutations in PINK-1 lead to familial PD. We evaluated the oxidative damage in the brain of PINK1 KO rats, and we used MRI and MRS to measure the ventricle sizes and neurochemical metabolite profiles in these rats as a function of age and gender. Distinct gender- and age-related alterations were found. The results are discussed with respect to the suitabililty of this unique rat as a faithful model of known characteristics of PD. |
2,328,738 | Choroid plexus papilloma of the third ventricle. A case report. | Choroid plexus papilloma is an uncommon tumour of the central nervous system, accounting for less than 1% of all intracranial neoplasm. The usual locations are the lateral ventricle in infants and children and the fourth ventricle in adults. The third ventricle is a rare location, with few cases reported in the literature. We describe the case of a 3-month-old boy who was admitted to our centre with signs of raised intracranial pressure. Neuroimaging studies showed a third ventricular mass with associated hydrocephalus. The patient underwent complete tumour removal through a transfrontal approach and ventriculo-peritoneal shunt surgery. Postoperative course of the child was uneventful and follow-up magnetic resonance imaging revealed no residual tumour. Histopathology of the resected lesion confirmed the diagnosis of choroid plexus papilloma. We discuss the clinical, radiological and histological features of this infrequent type of tumours. |
2,328,739 | A Novel Simple Puncture Positioning and Guidance System for Intracerebral Hematoma. | Minimally invasive surgical techniques may have beneficial effects on spontaneous intracerebral hemorrhage. Accurate localization of the hematoma and real-time guided puncture are more important in minimally invasive surgical procedures than in traditional craniotomy. Here, we introduce a novel simple puncture positioning and guidance system for intracerebral hematoma and demonstrate its utility for hematoma puncture surgery in a simulation experiment and series of patients.</AbstractText>We describe the device and use of the technique for hematoma puncture surgery in basal ganglia hematomas and report on the precision of the simulation experiments compared to that of freehand puncture, as well as its clinical application in 16 cases.</AbstractText>The accuracy of this technique was superior to that of freehand puncture. All 16 patients underwent successful puncturing of the hematoma cavity or ventricles only once without any related complications.</AbstractText>We demonstrate a novel simple puncture positioning and guidance system that has the advantages of simplicity, low-cost, device availability, and individual real-time guidance. We believe this system may be useful in resource-limited centers where navigation is not available.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,740 | Abnormal anisotropic diffusion properties in pediatric myelomeningocele patients treated with fetal surgery: an initial DTI study. | To investigate white matter microstructural abnormality based on diffusion tensor imaging (DTI) in pediatric patients with fetal repair for myelomeningocele (MMC).</AbstractText>This was a retrospective analysis of DTI data from 8 pediatric patients with prenatal MMC repair (age range 1.64-33.70 months; sex 3F/5M) and 8 age-matched controls (age 2.24-31.20 months; sex 5F/2M). All participants were scanned on 1.5T GE Signa MR scanner (GE Healthcare, Milwaukee, WI) with the same sequence specifications. Two DTI measures, including fractional anisotropy (FA) and mean diffusivity (MD), were calculated from the genu of corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). DTI values and fronto-occipital horn ratio (FOHR) were tested for group difference based on two-tailed paired t test.</AbstractText>The ventricle size based on FOHR in patients with prenatal MMC repair was significantly larger than that in the age-matched control group (p < 0.001). Statistically significant group difference in DTI (lower FA and higher MD in patient group) was found in gCC (p = 0.007 and 0.003, respectively). A trend level increase in MD was also found (p = 0.065) in PLIC in patients when compared with the age-matched controls.</AbstractText>Our data showed white matter abnormality based on DTI in pediatric patient with fetal repair for MMC. The sensitivity of DTI in detecting white matter abnormality, as shown in the present study, may help to serve as an imaging biomarker for assessing hydrocephalus and improve and optimize decision making for the treatment of hydrocephalus in this patient population.</AbstractText> |
2,328,741 | Bilateral Serous Retinal Detachment from Neonatal-Onset Multisystemic Inflammatory Disorder. | Neonatal-onset Multisystem Inflammatory Disorder (NOMID) is a systemic syndrome characterized by rash, large joint osteoarthropathies and chronic meningitis. Ocular manifestations include optic disc edema, corneal opacities and uveitis. We report the novel finding of serous retinal detachments (RD) in NOMID.</AbstractText>Case report.</AbstractText>An eight-month-old girl was referred to the ED for work-up of optic disc edema. Physical exam revealed flat fontanelles; macrocephaly and frontal bossing; diffuse urticarial rash; and swollen joints; WBC count and inflammatory markers were elevated. Ophthalmology exam revealed decreased visual acuity, optic disc edema and bilateral serous RD. MRI revealed bilateral enhancement of the ocular choroid and enlargement of the third and fourth ventricles secondary to aqueductal webbing. After infectious testing returned negative, the patient was treated with anakinra, an interleukin-1 receptor antagonist. Three months later, the serous RDs resolved.</AbstractText>Physicians should consider NOMID in infants presenting with diffuse rash, bilateral disc edema and serous retinal detachments.</AbstractText> |
2,328,742 | AQP4-IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD) coexisting with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis: A case report and literature review. | Neuromyelitis optica spectrum disorder (NMOSD) can coexist with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Patients with overlapping Aquaporin 4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD and anti-NMDAR encephalitis with positive NMDAR antibodies in the cerebrospinal fluid (CSF) are rare but should not be ignored.</AbstractText>A unique case of NMOSD coexisting with anti-NMDAR encephalitis is presented. Case reports of AQP4-IgG-seropositive NMOSD overlapping with anti-NMDAR encephalitis with positive NMDAR antibodies in the CSF were reviewed.</AbstractText>A 61-year-old female presented with headache, blurred vision, dysuria, limb weakness, coma, respiratory failure, and hypotension. Brain magnetic resonance imaging (MRI) showed abnormal signals in the left temporal lobe, white matter around the bilateral ventricles, midbrain, medulla oblongata, cervical, and upper thoracic medulla. AQP4-IgG antibodies were positive in the serum and CSF. NMDAR antibodies were positive in the CSF. The patient's condition was stable following intravenous gamma globulin, corticosteroids, immunosuppressants, and symptomatic support treatments. Only a single met the criteria of NMOSD simultaneously coexisting with anti-NMDAR encephalitis in addition to our own case.</AbstractText>This case provides further evidence for the occurrence of NMOSD with AQP4-IgG-seropositive overlapping anti-NMDAR encephalitis in a Chinese patient. The mechanisms underlying the occurrence of double positive antibodies remains elusive. When NMOSD patients show unusual symptoms (abnormal behavior, prominent psychiatric manifestations, cognitive dysfunction, autonomic dysfunction), or atypical supratentorial lesions, the coexistence of anti-NMDAR encephalitis should be considered.</AbstractText>Copyright © 2019. Published by Elsevier B.V.</CopyrightInformation> |
2,328,743 | Multifactorial analysis of local control and survival in patients with early glottic cancer. | The purpose of this study is to determine the effects of various prognostic factors for early glottic cancer patients who underwent radiotherapy.</AbstractText>We retrospectively reviewed the all patients who were treated at our hospital for early glottic squamous cell carcinoma from 2004 to 2016. Data included patient's age, sex, T classification, tumor size, pathological grade, anterior commissure involvement, subglottic extension, laryngeal ventricle involvement, and restriction of vocal cord movement.</AbstractText>There were 74 patients with T1 tumors and 31 with T2 tumors. Recurrence was found in four patients with T1 and eight patients with T2. There were 99 males and six females enrolled, and the mean age was 67.5 ± 9.2 years for T1a, 67.3 ± 11.2 years for T1b, and 67.4 ± 7.9 years for T2. One patient with recurrence after 1 month was thought to have a residual tumor. The 5-year overall survival (OS) rate and the 5-year disease-specific survival (DSS) rate for T1-T2 patients were both 100%. The rate of larynx preservation was 94.6% for T1 and 74.2% for T2. A univariate analysis showed that the effective factors were age, T, size, SE. A multivariate logistic regression analysis showed that age influenced the recurrence status. Size is also suspected to be a prognostic factor.</AbstractText>This study revealed that the effective factors were age, T, size, and SE.</AbstractText>4 Laryngoscope, 130:1701-1706, 2020.</AbstractText>© 2019 The American Laryngological, Rhinological and Otological Society, Inc.</CopyrightInformation> |
2,328,744 | Analysis of magnetic resonance spectroscopy relative metabolite ratios in mild traumatic brain injury and normative controls. | We evaluated magnetic resonance spectroscopy (MRS) in United States military personnel with persistent symptoms after mild traumatic brain injury (mTBI), comparing over time two groups randomized to receive hyperbaric oxygen or sham chamber sessions and a third group of normative controls.</AbstractText>Active-duty or veteran military personnel and normative controls underwent MRS outcome measures at baseline, 13 weeks (mTBI group only), and six months. Participants received 3.0 Tesla brain MRS for analysis of water-suppressed two-dimensional (2D) multivoxel 1H-MRS of the brain using point resolved spectroscopy (PRESS) with volume selection localized above the lateral ventricles and within the brain parenchyma, of which one voxel was chosen in each hemisphere without artifact. Script-based automatic data processing was used to assess N-acetylaspartate (NAA), creatine (Cr), and choline (Cho). Metabolite ratios for white matter were then calculated for NAA/Cr (Area), Cho/Cr (Area), and Cho/NAA (Area). These ratios were compared using standard analysis methodology.</AbstractText>There were no observable differences between participants with mTBI and normative controls nor any observable changes over time in the NAA/Cr (area), Cho/Cr (area), and Cho/NAA (area) ratios. Similarly, the control and injured participants were indistinguishable.</AbstractText>While participants with mild TBI showed no difference in MRS compared to normative controls, our results are limited by the few voxels chosen and potentially by less sensitive MRS markers.</AbstractText>Copyright© Undersea and Hyperbaric Medical Society.</CopyrightInformation> |
2,328,745 | Cardiac neural crest contributes to cardiomyocytes in amniotes and heart regeneration in zebrafish. | Cardiac neural crest cells contribute to important portions of the cardiovascular system including the aorticopulmonary septum and cardiac ganglion. Using replication incompetent avian retroviruses for precise high-resolution lineage analysis, we uncover a previously undescribed neural crest contribution to cardiomyocytes of the ventricles in <i>Gallus gallus</i>, supported by <i>Wnt1-Cre</i> lineage analysis in <i>Mus musculus</i>. To test the intriguing possibility that neural crest cells contribute to heart repair, we examined <i>Danio rerio</i> adult heart regeneration in the neural crest transgenic line, <i>Tg(-4.9sox10:eGFP)</i>. Whereas the adult heart has few <i>sox10+</i> cells in the apex, <i>sox10</i> and other neural crest regulatory network genes are upregulated in the regenerating myocardium after resection. The results suggest that neural crest cells contribute to many cardiovascular structures including cardiomyocytes across vertebrates and to the regenerating heart of teleost fish. Thus, understanding molecular mechanisms that control the normal development of the neural crest into cardiomyocytes and reactivation of the neural crest program upon regeneration may open potential therapeutic approaches to repair heart damage in amniotes. |
2,328,746 | Cell-specific ablation of Hsp47 defines the collagen-producing cells in the injured heart. | Collagen production in the adult heart is thought to be regulated by the fibroblast, although cardiomyocytes and endothelial cells also express multiple collagen mRNAs. Molecular chaperones are required for procollagen biosynthesis, including heat shock protein 47 (Hsp47). To determine the cell types critically involved in cardiac injury–induced fibrosis theHsp47 gene was deleted in cardiomyocytes, endothelial cells, or myofibroblasts. Deletion ofHsp47 from cardiomyocytes during embryonic development or adult stages, or deletion from adult endothelial cells, did not affect cardiac fibrosis after pressure overload injury. However, myofibroblast-specific ablation of Hsp47; blocked fibrosis and deposition of collagens type I, III, and V following pressure overload as well as significantly reduced cardiac hypertrophy. Fibroblast-specific Hsp47-deleted mice showed lethality after myocardial infarction injury, with ineffective scar formation and ventricular wall rupture. Similarly, only myofibroblast-specific deletion of Hsp47reduced fibrosis and disease in skeletal muscle in a mouse model of muscular dystrophy. Mechanistically, deletion of Hsp47 from myofibroblasts reduced mRNA expression of fibrillar collagens and attenuated their proliferation in the heart without affecting paracrine secretory activity of these cells. The results show that myofibroblasts are the primary mediators of tissue fibrosis and scar formation in the injured adult heart, which unexpectedly affects cardiomyocyte hypertrophy. |
2,328,747 | SLC12A ion transporter mutations in sporadic and familial human congenital hydrocephalus. | Congenital hydrocephalus (CH) is a highly morbid disease that features enlarged brain ventricles and impaired cerebrospinal fluid homeostasis. Although early linkage or targeted sequencing studies in large multigenerational families have localized several genes for CH, the etiology of most CH cases remains unclear. Recent advances in whole exome sequencing (WES) have identified five new bona fide CH genes, implicating impaired regulation of neural stem cell fate in CH pathogenesis. Nonetheless, in the majority of CH cases, the pathological etiology remains unknown, suggesting more genes await discovery.</AbstractText>WES of family members of a sporadic and familial form of severe L1CAM mutation-negative CH associated with aqueductal stenosis was performed. Rare genetic variants were analyzed, prioritized, and validated. De novo copy number variants (CNVs) were identified using the XHMM algorithm and validated using qPCR. Xenopus oocyte experiments were performed to access mutation impact on protein function and expression.</AbstractText>A novel inherited protein-damaging mutation (p.Pro605Leu) in SLC12A6, encoding the K+</sup> -Cl-</sup> cotransporter KCC3, was identified in both affected members of multiplex kindred CHYD110. p.Pro605 is conserved in KCC3 orthologs and among all human KCC paralogs. The p.Pro605Leu mutation maps to the ion-transporting domain, and significantly reduces KCC3-dependent K+</sup> transport. A novel de novo CNV (deletion) was identified in SLC12A7, encoding the KCC3 paralog and binding partner KCC4, in another family (CHYD130) with sporadic CH.</AbstractText>These findings identify two novel, related genes associated with CH, and implicate genetically encoded impairments in ion transport for the first time in CH pathogenesis.</AbstractText>© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.</CopyrightInformation> |
2,328,748 | MRI of Whole Rat Brain Perivascular Network Reveals Role for Ventricles in Brain Waste Clearance. | Investigating the mechanisms by which metabolic wastes are cleared from nervous tissue is important for understanding natural function and the pathophysiology of several neurological disorders including Alzheimer's disease. Recent evidence suggests clearance may be the function of annular spaces around cerebral blood vessels, called perivascular spaces (PVS), through which cerebrospinal fluid (CSF) is transported from the subarachnoid space into brain parenchyma to exchange with interstitial fluid (also known as the glymphatic system). In this work, an MRI-based methodology was developed to reconstruct the PVS network in whole rat brain to better elucidate both PVS uptake and clearance pathways. MR visible tracer (Gd-albumin) was infused in vivo into the CSF-filled lateral ventricle followed by ex vivo high-resolution MR imaging at 17.6 T with an image voxel volume two orders of magnitude smaller than previously reported. Imaged tracer distribution patterns were reconstructed to obtain a more complete brain PVS network. Several PVS connections were repeatedly highlighted across different animals, and new PVS connections between ventricles and different parts of the brain parenchyma were revealed suggesting a possible role for the ventricles as a source or sink for solutes in the brain. In the future, this methodology may be applied to understand changes in the PVS network with disease. |
2,328,749 | Magnetic resonance imaging measures of brain atrophy from the EXPEDITION3 trial in mild Alzheimer's disease. | Solanezumab is a humanized monoclonal antibody that preferentially binds to soluble amyloid β and promotes its clearance from the brain in preclinical studies. The objective of this study was to assess the effect of solanezumab in slowing global and anatomically localized brain atrophy as measured by volumetric magnetic resonance imaging (MRI).</AbstractText>In the EXPEDITION3 phase 3 trial, participants with mild Alzheimer's disease were randomized to receive intravenous infusions of either 400 mg of solanezumab or placebo every 4 weeks for 76 weeks. Volumetric MRI scans were acquired at baseline and at 80 weeks from 275 MRI facilities using a standardized imaging protocol. A subset of 1462 patients who completed both MRI and 14-item Alzheimer's Disease Assessment Scale-Cognitive Subscale assessments at both time points were selected for analysis. Longitudinal MRI volume changes were analyzed centrally by tensor-based morphometry with a standard FreeSurfer brain parcellation. Prespecified volumetric measures, including whole brain and ventricles, along with anatomically localized regions in the temporal, parietal, and frontal lobes were evaluated in those participants.</AbstractText>Group-mean differences in brain atrophy rates were directionally consistent across a number of brain regions but small in magnitude (1.3-6.9% slowing) and not statistically significant when corrected for multiple comparisons. The annualized rates of change of the volumetric measures and the correlation of these changes with cognitive changes in placebo-treated subjects were similar to those reported previously.</AbstractText>In the EXPEDITION3 trial, solanezumab did not significantly slow down rates of global or anatomically localized brain atrophy. Brain volume changes and their relationship to cognition were consistent with previous reports.</AbstractText> |
2,328,750 | Hydrocephalus associated with multiple Tarlov cysts. | Tarlov cysts (TCs) consist of dilated nerve root sheaths filled with cerebrospinal fluid (CSF) and are most frequently found in the sacrum. It is estimated that 25% of detected TCs cause chronic pain and intestinal and urogenital symptoms due to compression of the sacral nerve root fibers inside the TC. Unfortunately, symptomatic TCs are frequently overlooked. It is assumed that TCs result from pathologically increased hydrostatic pressure (HP) in the dural sac that forces CSF into the nerve root sheaths. We hypothesize that in patients with TCs, increased spinal hydrostatic pressure is always associated with increased intracranial pressure. This hypothesis of increased cerebrospinal pressure might explain why patients with sacral TCs frequently report distant symptoms, such as headaches and pain in the neck and arms. In this paper, we describe a case report that provides evidence for this hypothesis. A 30-year-old man presented for the first time in our clinic complaining of lower back, leg, thoracic, neck, and arm pain; headaches; and bladder, bowel, and sphincter symptoms. He was born prematurely and suffered cerebral intraventricular bleeding followed by progressive hydrocephalus. Progression was stabilized with acetazolamide and lumbar punctures. At 19 years of age, his head circumference had further increased and he reported back pain and headaches. Fundoscopy showed no papilledema, and lumbar puncture for CSF evacuation improved the headaches and back pain. The former medical team chose not to insert a ventriculo-external shunt. Brain magnetic resonance imaging (MRI) showed significant dilation of all the ventricles. No CSF flow obstruction between the ventricles was observed. Surprisingly, MRI of the lumbar and sacral spine showed multiple large TCs. This case report indicates that hydrocephalus with a patent aqueduct may be associated with TCs because the increased intracranial pressure is transferred to the spinal canal. While increased intracranial pressure causes dilation of the ventricles, the associated increased spinal pressure may cause dilation of multiple spinal nerve root sheaths to form TCs. Furthermore, while the increased volume of the ventricles gradually compresses the neurons and axons of the brain against the bony skull, simultaneously, the increased pressure inside the nerve sheaths may also gradually compress the neurons and axons located inside the dorsal root ganglia and spinal nerves, resulting in neuropathic pain, sensory abnormalities, and neurogenic bladder and bowel symptoms. Hydrocephalus patients reporting neuropathic pain should be screened for the presence of TCs. |
2,328,751 | Effect of miR-124 on neuronal apoptosis in rats with cerebral infarction through Wnt/β-catenin signaling pathway. | The aim of this study was to observe the influence of micro ribonucleic acid (miR)-124 on neuronal apoptosis in rats with cerebral infarction (CI), and to further investigate the underlying mechanism of miR-124 in CI occurrence and development.</AbstractText>A total of 60 adult male Wistar rats were randomly divided into the Sham group, the CI group and the CI + miR-124 mimics group using a random number table. The focal CI model was established using the suture-occluded method. After successful modeling, miR-124 mimics were stereotactically injected into the lateral ventricle of rats. 24 h after operation, the neurological function of rats in each group was scored using modified neurological severity score (mNSS). Meanwhile, the infarction area of brain tissues was evaluated by the triphenyl tetrazolium chloride (TTC) method. The protein expression levels of apoptosis-related genes, including B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), C-Caspase and T-Caspase, were detected via Western blotting. The expression and location of caspase-3 in brain tissues were detected via immunofluorescence staining. Moreover, the level of apoptosis in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. In addition, the expression levels of the Wnt/β-catenin signaling pathway-related proteins were detected via Western blotting.</AbstractText>Polymerase Chain Reaction (PCR) results revealed that the expression level of miR-124 in the CI group was significantly decreased when compared with that of the Sham group (p<0.05). The mNSS and TTC staining results manifested that injection of miR-124 mimics could significantly reduce the CI-induced neurological deficits and CI area (p<0.05). At the same time, the levels of Bax and C-caspase/T-Caspase were significantly decreased, whereas the expression of Bcl-2 was remarkably increased after the injection of miR-124 mimics (p<0.05). Besides, the number of apoptotic cells in the CI + miR-124 mimic group was remarkably decreased (p<0.05). In addition, miR-124 mimics significantly activated the expression levels of Wnt and β-catenin (p<0.05).</AbstractText>The inhibitory effect of miR-124 on neuronal apoptosis in CI rats is probably related to the activation of the Wnt/β-catenin signaling pathway. Furthermore, miR-124 is expected to be a target drug for the clinical treatment of CI.</AbstractText> |
2,328,752 | A new technique of endoscopic decompression of suprasellar craniopharyngioma cyst. | Craniopharyngiomas represent a unique management challenge. Aggressive surgical management has traditionally been associated with high rates of morbidity. Modern surgical techniques, and increasing practice of subtotal resection followed by radiosurgery, have reduced morbidity and mortality rates. One cause of postoperative morbidity, and indeed mortality, is aseptic meningitis from spill-out of craniopharyngioma cyst contents. We have developed a surgical technique for the management of large craniopharygngioma cysts extending into the third ventricle, to reduce this risk.</AbstractText>We describe a technique of using an epidural catheter, inserted into the working channel of a neuroendoscope, to decompress the cystic portion of a craniopharyngioma cyst before opening the cyst wall widely, preventing spill-out of large volumes of cyst content into the ventricular system.</AbstractText>We have had no cases of aseptic meningitis, nor any complications, from use of the described technique.</AbstractText>We believe that this is a safe and effective technique of decompression and fenestration of large suprasellar craniopharyngioma cysts that reduces rates of aseptic meningitis and the associated morbidity and mortality from this.</AbstractText> |
2,328,753 | Repeated Intraperitoneal Administration of Low-Concentration Methylcellulose Leads to Systemic Histologic Lesions Without Loss of Preclinical Phenotype. | Methylcellulose (MC; 0.5% concentration) is commonly used when evaluating investigational agents for efficacy in preclinical models of disease. When administered by the oral (PO) route, MC is considered a Food and Drug Administration "generally recognized as safe" compound. Yet, there is limited data pertaining to the tolerability and impact on model fidelity of repeated intraperitoneal administration of 0.5% MC. Chronic administration of high-concentration MC (2%-2.5%) has been used to induce anemia, splenomegaly, and lesions in multiple organ systems in several preclinical species. Histopathological findings from a diagnostic pathologic analysis of a single mouse from our laboratory with experimentally induced chronic seizures that had received repeated intraperitoneal administration of antiseizure drugs delivered in MC revealed similar widespread lesions. This study thus tested the hypothesis that chronic administration of intraperitoneal, but not PO, MC incites histologic lesions without effects on preclinical phenotype. Male CF-1 mice (<i>n</i> = 2-14/group) were randomized to receive either 6 weeks of twice weekly 0.5% MC or saline (intraperitoneal or PO) following induction of chronic seizures. Histology of a subset of mice revealed lesions in kidney, liver, mediastinal lymph nodes, mesentery, aorta, and choroid plexus only in intraperitoneal MC-treated mice (<i>n</i> = 7/7). Kindled mice that received MC PO (<i>n</i> = 5) or saline (intraperitoneal <i>n</i> = 6, PO <i>n</i> = 3) had no lesions. There were no effects of intraperitoneal MC treatment on body weight, appearance, seizure stability, or behavior. Nonetheless, our findings suggest that repeated intraperitoneal, but not PO, MC elicits systemic organ damage without impacting the model phenotype, which may confound interpretation of investigational drug-induced histologic lesions. SIGNIFICANCE STATEMENT: Methylcellulose (0.5% concentration) is commonly used when evaluating investigational agents for efficacy in preclinical models of disease. Herein, we demonstrate that repeated administration of 0.5% methylcellulose by the intraperitoneal, but not oral, route results in systemic inflammation and presence of foam-laden macrophages but does not impact the behavioral phenotype of a rodent model of neurological disease. |
2,328,754 | Left ventricular myxoma: A contractile mass causing intracavitary obstruction and severe pulmonary hypertension.<Pagination><StartPage>1127</StartPage><EndPage>1129</EndPage><MedlinePgn>1127-1129</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/jocs.14195</ELocationID><Abstract><AbstractText>Cardiac myxomas can be fatal and left ventricular (LV) myxomas with papillary muscle and mitral valve (MV) involvement are rare. The following case is that of a 55-year-old woman who developed signs and symptoms of pulmonary hypertension. Imaging revealed a contractile mass in the LV that was in continuum with the papillary muscles and affected MV function. Her clinical course, radiologic, and hemodynamic findings are discussed. Finally, her surgical extraction technique is described in addition to potential complications encountered.</AbstractText><CopyrightInformation>© 2019 Wiley Periodicals, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Orozco-Hernandez</LastName><ForeName>Erik J</ForeName><Initials>EJ</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Argueta-Sosa</LastName><ForeName>Erwin E</ForeName><Initials>EE</Initials><Identifier Source="ORCID">0000-0002-5583-6193</Identifier><AffiliationInfo><Affiliation>Division of Cardiovascular Diseases, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mauchley</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Rongbing</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mitchell</LastName><ForeName>Chace B</ForeName><Initials>CB</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Self</LastName><ForeName>Dwight M</ForeName><Initials>DM</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davies</LastName><ForeName>James E</ForeName><Initials>JE</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>08</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Card Surg</MedlineTA><NlmUniqueID>8908809</NlmUniqueID><ISSNLinking>0886-0440</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D004452" MajorTopicYN="N">Echocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006338" MajorTopicYN="N">Heart Neoplasms</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006976" MajorTopicYN="N">Hypertension, Pulmonary</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019028" MajorTopicYN="N">Magnetic Resonance Imaging, Cine</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008943" MajorTopicYN="N">Mitral Valve</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009232" MajorTopicYN="N">Myxoma</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010210" MajorTopicYN="N">Papillary Muscles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049268" MajorTopicYN="N">Positron-Emission Tomography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014057" MajorTopicYN="N">Tomography, X-Ray Computed</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">cardiac mass</Keyword><Keyword MajorTopicYN="N">cardiovascular pathology</Keyword><Keyword MajorTopicYN="N">myxoma</Keyword><Keyword MajorTopicYN="N">ventricular mass resection</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>8</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>2</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>8</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31374579</ArticleId><ArticleId IdType="doi">10.1111/jocs.14195</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31374555</PMID><DateRevised><Year>2020</Year><Month>06</Month><Day>05</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0693</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Aug</Month><Day>02</Day></PubDate></JournalIssue><Title>Journal of neurosurgery</Title><ISOAbbreviation>J Neurosurg</ISOAbbreviation></Journal>Neural and vascular architecture of the septum pellucidum: an anatomical study and considerations for safe endoscopic septum pellucidotomy. | Cardiac myxomas can be fatal and left ventricular (LV) myxomas with papillary muscle and mitral valve (MV) involvement are rare. The following case is that of a 55-year-old woman who developed signs and symptoms of pulmonary hypertension. Imaging revealed a contractile mass in the LV that was in continuum with the papillary muscles and affected MV function. Her clinical course, radiologic, and hemodynamic findings are discussed. Finally, her surgical extraction technique is described in addition to potential complications encountered.<CopyrightInformation>© 2019 Wiley Periodicals, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Orozco-Hernandez</LastName><ForeName>Erik J</ForeName><Initials>EJ</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Argueta-Sosa</LastName><ForeName>Erwin E</ForeName><Initials>EE</Initials><Identifier Source="ORCID">0000-0002-5583-6193</Identifier><AffiliationInfo><Affiliation>Division of Cardiovascular Diseases, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mauchley</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Rongbing</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mitchell</LastName><ForeName>Chace B</ForeName><Initials>CB</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Self</LastName><ForeName>Dwight M</ForeName><Initials>DM</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davies</LastName><ForeName>James E</ForeName><Initials>JE</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Surgery, University of Alabama at Birmingham Hospital, Birmingham, Alabama.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>08</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Card Surg</MedlineTA><NlmUniqueID>8908809</NlmUniqueID><ISSNLinking>0886-0440</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D004452" MajorTopicYN="N">Echocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006338" MajorTopicYN="N">Heart Neoplasms</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006976" MajorTopicYN="N">Hypertension, Pulmonary</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019028" MajorTopicYN="N">Magnetic Resonance Imaging, Cine</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008943" MajorTopicYN="N">Mitral Valve</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009232" MajorTopicYN="N">Myxoma</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010210" MajorTopicYN="N">Papillary Muscles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049268" MajorTopicYN="N">Positron-Emission Tomography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014057" MajorTopicYN="N">Tomography, X-Ray Computed</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">cardiac mass</Keyword><Keyword MajorTopicYN="N">cardiovascular pathology</Keyword><Keyword MajorTopicYN="N">myxoma</Keyword><Keyword MajorTopicYN="N">ventricular mass resection</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>8</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>2</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>8</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31374579</ArticleId><ArticleId IdType="doi">10.1111/jocs.14195</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31374555</PMID><DateRevised><Year>2020</Year><Month>06</Month><Day>05</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0693</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Aug</Month><Day>02</Day></PubDate></JournalIssue><Title>Journal of neurosurgery</Title><ISOAbbreviation>J Neurosurg</ISOAbbreviation></Journal><ArticleTitle>Neural and vascular architecture of the septum pellucidum: an anatomical study and considerations for safe endoscopic septum pellucidotomy.</ArticleTitle><Pagination><StartPage>1</StartPage><EndPage>10</EndPage><MedlinePgn>1-10</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3171/2019.5.JNS19754</ELocationID><ELocationID EIdType="pii" ValidYN="Y">2019.5.JNS19754</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">The septum pellucidum is a bilateral thin membranous structure representing the border between the frontal horns of the lateral ventricles. Its most examined components are the septal veins due to their surgical importance during endoscopic septum pellucidotomy (ESP), which is a well-accepted method for surgical treatment of unilateral hydrocephalus. It is widely accepted that the septum pellucidum contains nerve fibers as well, but interestingly, no anatomical study has been addressed to its neural components before. The aim of the present study was to identify these elements as well as their relations to the septal veins and to define major landmarks within the ventricular system for neurosurgical use.<AbstractText Label="METHODS" NlmCategory="METHODS">Nine formalin-fixed human cadaveric brains (18 septa pellucida) were involved in this study. A central block containing both septa pellucida was removed and frozen at -30°C for 2 weeks in 7 cases. The fibers of the septum pellucidum and the adjacent areas including the venous elements were dissected under magnification by using homemade wooden spatulas and microsurgical instruments. In 2 cases a histological technique was used to validate the findings of the dissections. The blocks were sliced, embedded in paraffin, cut in 7-µm-thick slices, and then stained as follows: 1) with H & E, 2) with Luxol fast blue combined with cresyl violet, and 3) with Luxol fast blue combined with Sirius red.<AbstractText Label="RESULTS" NlmCategory="RESULTS">The septum pellucidum and the subjacent septum verum form the medial wall of the frontal horn of the lateral ventricle. Both structures contain nerve fibers that were organized in 3 groups: 1) the precommissural fibers of the fornix; 2) the inferior fascicle; and 3) the superior fascicle of the septum pellucidum. The area directly rostral to the postcommissural column of the fornix consisted of macroscopically identifiable gray matter corresponding to the septal nuclei. The histological examinations validated the findings of the authors' fiber dissections.<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">The nerve elements of the septum pellucidum as well as the subjacent septum verum were identified with fiber dissection and verified with histology for the first time. The septal nuclei located just anterior to the fornix and the precommissural fibers of the fornix should be preserved during ESP. Considering the venous anatomy as well as the neural architecture of the septum pellucidum, the fenestration should ideally be placed above the superior edge of the fornix and preferably dorsal to the interventricular foramen. |
2,328,755 | The right ventricular fibroblast secretome drives cardiomyocyte dedifferentiation. | In virtually all models of heart failure, prognosis is determined by right ventricular (RV) function; thus, understanding the cellular mechanisms contributing to RV dysfunction is critical. Whole organ remodeling is associated with cell-specific changes, including cardiomyocyte dedifferentiation and activation of cardiac fibroblasts (Cfib) which in turn is linked to disorganization of cytoskeletal proteins and loss of sarcomeric structures. However, how these cellular changes contribute to RV function remains unknown. We've previously shown significant organ-level RV dysfunction in a large animal model of pulmonary hypertension (PH) which was not mirrored by reduced function of isolated cardiomyocytes. We hypothesized that factors produced by the endogenous Cfib contribute to global RV dysfunction by generating a heterogeneous cellular environment populated by dedifferentiated cells.</AbstractText>To determine the effect of Cfib conditioned media (CM) from the PH calf (PH-CM) on adult rat ventricular myocytes (ARVM) in culture.</AbstractText>Brief exposure (<2 days) to PH-CM results in rapid, marked dedifferentiation of ARVM to a neonatal-like phenotype exhibiting spontaneous contractile behavior. Dedifferentiated cells maintain viability for over 30 days with continued expression of cardiomyocyte proteins including TnI and α-actinin yet exhibit myofibroblast characteristics including expression of α-smooth muscle actin. Using a bioinformatics approach to identify factor(s) that contribute to dedifferentiation, we found activation of the PH Cfib results in a unique transcriptome correlating with factors both in the secretome and with activated pathways in the dedifferentiated myocyte. Further, we identified upregulation of periostin in the Cfib and CM, and demonstrate that periostin is sufficient to drive cardiomyocyte dedifferentiation.</AbstractText>These data suggest that paracrine factor(s) released by Cfib from the PH calf signal a phenotypic transformation in a population of cardiomyocytes that likely contributes to RV dysfunction. Therapies targeting this process, such as inhibition of periostin, have the potential to prevent RV dysfunction.</AbstractText> |
2,328,756 | Value of computerized shunt infusion study in assessment of pediatric hydrocephalus shunt function-a two center cross-sectional study. | Hydrocephalus shunt malfunction can-also in children-occur insidiously without clear symptoms of raised intracranial pressure (ICP) or changes in ventricular size, imposing a diagnostic challenge. Computerized shunt infusion studies enable quantitative shunt function assessment. We report on feasibility and results of this technique in children in a two center cross-sectional study.</AbstractText>Shunt infusion study (SIS) is performed with two needles inserted into a pre-chamber for ICP recording and CSF infusion. After baseline ICP recording, constant rate infusion is started until a new ICP plateau (ICPpl) is reached. Dedicated software containing the shunt's resistance characteristics calculates ICP and its amplitude outflow resistance and critical shunt pressure (CSP). Overall, 203 SIS were performed in 166 children. Shunts were defined as functional if ICPpl was <CSP and obstructed if ICPpl was > 5 mmHg above CSP and borderline in between.</AbstractText>Forty-one shunts (20.2%) were found obstructed, 26 (12.8%) had borderline characteristics, and 136 (67%) were functional. Baseline ICP in obstructed shunts was significantly above shunt operating pressure. CSF outflow resistance (Rout</sub>) and ∆ICP plateau were significantly elevated in obstructed shunts, with cut-off thresholds of 8.07 mmHg min/ml and 11.74 mmHg respectively. Subgroup analysis showed smaller ventricles in 69% of revised cases.</AbstractText>SIS is a feasible, reliable, and radiation-free technique for quantitative shunt assessment to rule out or prove shunt malfunction. Dedicated software containing shunt hydrodynamic characteristics is necessary and small children may need short-term sedation. Due to the clinical and inherent economic advantages, SIS should be more frequently used in pediatric neurosurgery.</AbstractText> |
2,328,757 | Plasma neurofilament light chain concentration is increased in anorexia nervosa. | Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality and, to a large extent, unknown pathophysiology. Structural brain differences, such as global or focal reductions in grey or white matter volumes, as well as enlargement of the sulci and the ventricles, have repeatedly been observed in individuals with AN. However, many of the documented aberrances normalize with weight recovery, even though some studies show enduring changes. To further explore whether AN is associated with neuronal damage, we analysed the levels of neurofilament light chain (NfL), a marker reflecting ongoing neuronal injury, in plasma samples from females with AN, females recovered from AN (AN-REC) and normal-weight age-matched female controls (CTRLS). We detected significantly increased plasma levels of NfL in AN vs CTRLS (median<sub>AN</sub> = 15.6 pg/ml, IQR<sub>AN</sub> = 12.1-21.3, median<sub>CTRL</sub> = 9.3 pg/ml, IQR<sub>CTRL</sub> = 6.4-12.9, and p < 0.0001), AN vs AN-REC (median<sub>AN-REC</sub> = 11.1 pg/ml, IQR<sub>AN-REC</sub> = 8.6-15.5, and p < 0.0001), and AN-REC vs CTRLS (p = 0.004). The plasma levels of NfL are negatively associated with BMI overall samples (β (±se) = -0.62 ± 0.087 and p = 6.9‧10<sup>-12</sup>). This indicates that AN is associated with neuronal damage that partially normalizes with weight recovery. Further studies are needed to determine which brain areas are affected, and potential long-term sequelae. |
2,328,758 | 3D bioprinting of collagen to rebuild components of the human heart. | Collagen is the primary component of the extracellular matrix in the human body. It has proved challenging to fabricate collagen scaffolds capable of replicating the structure and function of tissues and organs. We present a method to 3D-bioprint collagen using freeform reversible embedding of suspended hydrogels (FRESH) to engineer components of the human heart at various scales, from capillaries to the full organ. Control of pH-driven gelation provides 20-micrometer filament resolution, a porous microstructure that enables rapid cellular infiltration and microvascularization, and mechanical strength for fabrication and perfusion of multiscale vasculature and tri-leaflet valves. We found that FRESH 3D-bioprinted hearts accurately reproduce patient-specific anatomical structure as determined by micro-computed tomography. Cardiac ventricles printed with human cardiomyocytes showed synchronized contractions, directional action potential propagation, and wall thickening up to 14% during peak systole. |
2,328,759 | New and expanding ventricular hemorrhage predicts poor outcome in acute intracerebral hemorrhage. | To describe the relationship between intraventricular hemorrhage (IVH) expansion and long-term outcome and to use this relationship to select and validate clinically relevant thresholds of IVH expansion in 2 separate intracerebral hemorrhage (ICH) populations.</AbstractText>We used fractional polynomial analysis to test linear and nonlinear models of 24-hour IVH volume change and clinical outcome with data from the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT)-ICH study. The primary outcome was poor clinical outcome (modified Rankin Scale [mRS] score 4-6) at 90 days. We derived dichotomous thresholds from the selected model and calculated diagnostic accuracy measures. We validated all thresholds in an independent single-center ICH cohort (Massachusetts General Hospital).</AbstractText>Of the 256 patients from PREDICT, 127 (49.6%) had an mRS score of 4 to 6. Twenty-four-hour IVH volume change and poor outcome fit a nonlinear relationship, in which minimal increases in IVH were associated with a high probability of an mRS score of 4 to 6. IVH expansion ≥1 mL (n = 53, sensitivity 33%, specificity 92%, adjusted odds ratio [aOR] 2.68, 95% confidence interval [CI] 1.11-6.46) and development of any new IVH (n = 74, sensitivity 43%, specificity 85%, aOR 2.53, 95% CI 1.22-5.26) strongly predicted poor outcome at 90 days. The dichotomous thresholds reproduced well in a validation cohort of 169 patients.</AbstractText>IVH expansion as small as 1 mL or any new IVH is strongly predictive of poor outcome. These findings may assist clinicians with bedside prognostication and could be incorporated into definitions of hematoma expansion to inform future ICH treatment trials.</AbstractText>© 2019 American Academy of Neurology.</CopyrightInformation> |
2,328,760 | [Dandy-Walker malformation. The CRIT protocol. A propos of a case]. | Dandy-Walker malformation is characterised by hypoplasia of the cerebellar vermis and cystic dilation of the fourth ventricle. Some of the clinical manifestations of this malformation are hydrocephalus, delayed motor development, hypotonia, and ataxia. Treatment aims to improve the individual's overall functioning and enhance quality of life through a multidisciplinary team. This case report describes the outcome of a patient diagnosed with Dandy-Walker malformation, after the intervention of the medical model at Centro de Rehabilitación e Inclusión Infantil Teletón Guanajuato (CRIT), which focuses on rehabilitating the patient and the family, covering each of the areas encompassing the patient. |
2,328,761 | N-acetylcysteine alleviated paraquat-induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells. | The developing brain is uniquely vulnerable to toxic chemical exposures. Studies indicate that neural stem cell (NSC) self-renewal is susceptible to oxidative stress caused by xenobiotics. However, the impact of antioxidants on NSC self-renewal and the potential mechanisms remain elusive. In this study, primary murine neural progenitor cells (mNPCs) from the subventricular zone were used as a research model. In addition, paraquat (PQ) was used to elicit oxidative stress and N-acetylcysteine (NAC) was used as a powerful antioxidant. mNPCs were treated with 80 μm PQ for 24 hours with or without 4 hours of NAC pretreatment. Our results showed that PQ treatment increased intracellular reactive oxygen species production, decreased cell viability and DNA synthesis, and promoted cell apoptosis. Meanwhile, pretreatment with NAC alleviated PQ-induced cytotoxicity in mNPCs. To elucidate the mechanisms further, we found that NAC pretreatment prevented PQ-induced reactive oxygen species production, mitochondrial fragmentation and autophagy in mNPCs. NAC-pretreated cells showed increased anti-apoptotic protein Bcl-2 and decreased pro-apoptotic protein Bax expression. Similarly, NAC pretreatment increased p-mTOR and decreased LC3B-II protein expression. Moreover, NAC decreased mitophagy related mRNA Pink1 and Parkin expression. Taken together, our results suggested that the antioxidant NAC treatment significantly attenuated PQ-induced mNPC self-renewal disruption through decreasing autophagy and salvaging mitochondrial morphology. These findings revealed a potential mechanism for neurological treatment relating to antioxidant and suggested potentially relevant implications for PQ-related neurodegenerative disorders. Thus, our study also provided insight into therapeutic strategies for the neurotoxic effects of oxidative stress-associated toxicants. |
2,328,762 | Biodegradation of injectable silk fibroin hydrogel prevents negative left ventricular remodeling after myocardial infarction. | In the present study, we investigated the optimal material properties of a tunable hydrogel for the treatment of myocardial infarction (MI) along with the therapeutic mechanism. We developed silk fibroin (SF) hydrogels with the same physical properties (e.g., stiffness) but different biodegradation rates via a peptide modification and evaluated the effect of hydrogel biodegradation on the prevention of negative left ventricular (LV) remodeling in a rat model of MI. LV enlargement was attenuated to a greater extent by injection of a slowly degrading unmodified SF hydrogel as compared to a rapidly degrading peptide-modified SF (SF + Pep) hydrogel for up to 12 weeks post-injection. This could not be explained by the mechanical stabilization of the LV wall by the injectant since the SF and SF + Pep hydrogels degraded completely within 4 weeks and the two groups showed no difference in LV wall thickness at 12 weeks. The SF group had dense randomly aligned collagen fibers whereas the SF + Pep group had sparse fibers surrounding the LV. These results suggest that randomly aligned fibrous tissues formed during/after biodegradation of a slowly degrading SF hydrogel may be more resistant to LV pressure and thus prevent LV enlargement. |
2,328,763 | Chemotherapy-Induced Cardiotoxicity in Adolescent After Heart Transplant: Do Not Forget the Right Ventricle. | The evaluation of oncologic patients at risk of chemotherapy-induced cardiotoxicity usually focuses on left ventricular function. However, recent studies have demonstrated that right ventricle impairment often coexists (and in some cases precedes) left-side affectation. We present the case of a 19-year-old heart transplant recipient who developed severe right ventricular dysfunction secondary to treatment of an abdominal lymphoma. |
2,328,764 | Left Ventricular Speckle Tracking Echocardiography Changes Among Early-stage Breast Cancer Patients Three Years After Radiotherapy. | <AbstractText Label="BACKGROUND/AIM" NlmCategory="OBJECTIVE">Chest radiotherapy (RT) doubles late cardiac mortality. This study aimed to evaluate the evolution of cardiac changes in speckle tracking echocardiography during a three-year follow-up.</AbstractText>This prospective study included 81 chemotherapy-naïve early-stage breast cancer patients who were evaluated at baseline, immediately after RT and three years after RT. Sixty-one patients had left-sided (LSBC) and 20 right-sided breast cancer (RSBC).</AbstractText>Global longitudinal strain (GLS) declined from baseline -18.0±3.3% to -17.0±3.0% (p=0.015) at the three-year follow-up examination. A decline over 15% (GLS15) was observed in 19 (27%) patients. GLS15 was independently associated with aromatase inhibitor use (β=-1.977, p=0.001). In regional analysis, patients with LSBC had apical strain decline by 3.2±5.5% (p<0.001) and patients with RSBC showed basal rotation decline by 1.8° (-0.2°, 3.8°) (p=0.030).</AbstractText>Even contemporary RT induced progressive global and regional decline in speckle tracking analysis. The regional changes complied with RT fields.</AbstractText>Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</CopyrightInformation> |
2,328,765 | Impaired redox homeostasis in the heart left ventricles of aged rats experiencing fast-developing severe hypobaric hypoxia. | Despite its rare occurrence, humans and animals have been prone to getting fast developing severe hypobaric hypoxia. Understanding the redox homeostasis related response of an aging heart to this type of hypoxia are crucially important, since the metabolism of myocardial tissue depends on the redox status of proteins. Rodents can tolerate hypoxic stress better than human subjects. This study was aimed at investigating the effects of fast developing severe hypobaric hypoxia on redox status biomarkers; such as, advanced oxidation protein products (AOPP), lipid hydroperoxides (LHPs), protein carbonyl groups (PCO), protein thiol groups (P-SH), and total thiol groups (T-SH) on the myocardial left ventricles of young and aged Wistar rats. The rats were gradually ascended and exposed to an 8000-meter hypobaric hypoxia. While AOPP levels showed no difference, the TSH and PSH concentrations decreased, and the PCO and LHP increased in both of the hypoxic groups than the controls. The TSH and PSH were lower, and AOPP, PCO and LHP were found to be higher in the elderly hypoxic groups than in the young ones. The significant outcome of the study represents that an 8000-meter hypobaric hypoxia could be considered as a severe hypoxic stress, but not life-treating for the rats and would affect both the young and aged left ventricles similarly in respect to impaired redox status. However, if the percentage increases are taken into consideration, it seems that the higher rate of protein oxidation occurs in young hearts; meanwhile aged hearts are more prone to T-SH oxidation. |
2,328,766 | Mild Parkinsonian Signs in a Hospital-based Cohort of Mild Cognitive Impairment Types: A Cross-sectional Study. | Mild Parkinsonian Signs (MPS) have been associated with Mild Cognitive Impairment (MCI) types with conflicting results.</AbstractText>To investigate the association of individual MPS with different MCI types using logistic ridge regression analysis, and to evaluate for each MCI type, the association of MPS with caudate atrophy, global cerebral atrophy, and the topographical location of White Matter Hyperintensities (WMH), and lacunes.</AbstractText>A cross-sectional study was performed among 1,168 subjects with different types of MCI aged 45-97 (70,52 ± 9,41) years, who underwent brain MRI. WMH were assessed through two visual rating scales. The number and location of lacunes were also rated. Atrophy of the caudate nuclei and global cerebral atrophy were assessed through the bicaudate ratio, and the lateral ventricles to brain ratio, respectively. Apolipoprotein E (APOE) genotypes were also assessed. Using the items of the motor section of the Unified Parkinson's Disease Rating Scale, tremor, rigidity, bradykinesia, and gait/balance/axial dysfunction were evaluated.</AbstractText>Bradykinesia, and gait/balance/axial dysfunction were the MPS more frequently encountered followed by rigidity, and tremor. MPS were present in both amnestic and non-amnestic MCI types, and were associated with WMH, lacunes, bicaudate ratio, and lateral ventricles to brain ratio.</AbstractText>MPS are present in both amnestic and non-amnestic MCI types, particularly in those multiple domain, and carrying the APOE ε4 allele. Cortical and subcortical vascular and atrophic processes contribute to MPS. Long prospective studies are needed to disentangle the contribution of MPS to the conversion from MCI to dementia.</AbstractText>Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.</CopyrightInformation> |
2,328,767 | Cerebrospinal Fluid Fistula in the Frontal Sinus Secondary to Obstructive Hydrocephalus. | In some rare cases, long-standing hydrocephalus can cause "high-pressure" cerebrospinal fluid fistulas. We report the case of a young overweight woman with rhinorrhea secondary to hydrocephalus with a fistula into the frontal sinus. Brain imaging studies revealed aqueduct stenosis. Ventriculocisternostomy treated the hydrocephalus but did not cure the rhinorrhea, and additional multilayer surgical skull base repair was necessary. In these cases, the CSF leakage acts as a safety valve, and closure will worsen the patient's condition if the causative lesion has not been treated first. Moreover, identifying the exact location of the fistula can be challenging and will usually require high-resolution bone computed tomography. |
2,328,768 | Potent hERG channel inhibition by sarizotan, an investigative treatment for Rett Syndrome. | Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder associated with respiratory abnormalities and, in up to ~40% of patients, with prolongation of the cardiac QT<sub>c</sub> interval. QT<sub>c</sub> prolongation calls for cautious use of drugs with a propensity to inhibit hERG channels. The STARS trial has been undertaken to investigate the efficacy of sarizotan, a 5-HT<sub>1A</sub> receptor agonist, at correcting RTT respiratory abnormalities. The present study investigated whether sarizotan inhibits hERG potassium channels and prolongs ventricular repolarization. Whole-cell patch-clamp measurements were made at 37 °C from hERG-expressing HEK293 cells. Docking analysis was conducted using a recent cryo-EM structure of hERG. Sarizotan was a potent inhibitor of hERG current (I<sub>hERG</sub>; IC<sub>50</sub> of 183 nM) and of native ventricular I<sub>Kr</sub> from guinea-pig ventricular myocytes. 100 nM and 1 μM sarizotan prolonged ventricular action potential (AP) duration (APD<sub>90</sub>) by 14.1 ± 3.3% (n = 6) and 29.8 ± 3.1% (n = 5) respectively and promoted AP triangulation. High affinity I<sub>hERG</sub> inhibition by sarizotan was contingent upon channel gating and intact inactivation. Mutagenesis experiments and docking analysis implicated F557, S624 and Y652 residues in sarizotan binding, with weaker contribution from F656. In conclusion, sarizotan inhibits I<sub>Kr</sub>/I<sub>hERG</sub>, accessing key binding residues on channel gating. This action and consequent ventricular AP prolongation occur at concentrations relevant to those proposed to treat breathing dysrhythmia in RTT. Sarizotan should only be used in RTT patients with careful evaluation of risk factors for QT<sub>c</sub> prolongation. |
2,328,769 | Dynamic palmitoylation regulates trafficking of K channel interacting protein 2 (KChIP2) across multiple subcellular compartments in cardiac myocytes. | K channel interacting protein 2 (KChIP2), initially cloned as Kv4 channel modulator, is a multi-tasking protein. In addition to modulating several cardiac ion channels at the plasma membrane, it can also modulate microRNA transcription inside nuclei, and interact with presenilins to modulate Ca release through RyR2 in the cytoplasm. However, the mechanism regulating its subcellular distribution is not clear.</AbstractText>We tested whether palmitoylation drives KChIP2 trafficking and distribution in cells, and whether the distribution pattern of KChIP2 in cardiac myocytes is sensitive to cellular milieu.</AbstractText>We conducted imaging and biochemical experiments on palmitoylatable and unpalmitoylatable KChIP2 variants expressed in COS-7 cells and in cardiomyocytes, and on native KChIP2 in myocytes.</AbstractText>In COS-7 cells, palmitoylatable KChIP2 clustered to plasma membrane, while unpalmitoylatable KChIP2 exhibited higher cytoplasmic mobility and faster nuclear entry. The same differences in distribution and mobility were observed when these KChIP2 variants were expressed in cardiac myocytes, indicating that the palmitoylation-dependent distribution and trafficking are intrinsic properties of KChIP2. Importantly, acute stress in a rat model of cardiac arrest/resuscitation induced changes in native KChIP2 resembling those of KChIP2 depalmitoylation, promoting KChIP2 nuclear entry.</AbstractText>The palmitoylation status of KChIP2 determines its subcellular distribution in cardiac myocytes. Stress promotes nuclear entry of KChIP2, diverting it from ion channel modulation at the plasma membrane to other functions in the nuclear compartment.</AbstractText>Copyright © 2019 Elsevier Ltd. All rights reserved.</CopyrightInformation> |
2,328,770 | Leptin receptor-expressing neurons in ventromedial nucleus of the hypothalamus contribute to weight loss caused by fourth ventricle leptin infusions. | Leptin administration into the hindbrain, and specifically the nucleus of the solitary tract, increases phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin receptor activation, in hypothalamic nuclei known to express leptin receptors. The ventromedial nucleus of the hypothalamus (VMH) shows the greatest response, with a threefold increase in pSTAT3. This experiment tested the importance of VMH leptin receptor-expressing neurons in mediating weight loss caused by fourth ventricle (4V) leptin infusion. Male Sprague-Dawley rats received bilateral VMH 75-nL injections of 260 ng/μL of leptin-conjugated saporin (Lep-Sap) or blank-saporin (Blk-Sap). After 23 days they were fitted with 4V infusion cannulas and 1 wk later adapted to housing in a calorimeter before they were infused with 0.9 μg leptin/day for 14 days. There was no effect of VMH Lep-Sap on weight gain or glucose clearance before leptin infusion. Leptin inhibited food intake and respiratory exchange ratio in Blk-Sap but not Lep-Sap rats. Leptin had no effect on energy expenditure or brown adipose tissue temperature of either group. Inguinal and epididymal fat were significantly reduced in leptin-treated Blk-Sap rats, but the response was greatly attenuated in Lep-Sap rats. VMH pSTAT3 was increased in leptin-treated Blk-Sap but not Lep-Sap rats. These results support the concept that leptin-induced weight loss results from an integrated response across different brain areas. They also support previous reports that VMH leptin receptors do not play a significant role in maintaining energy balance in basal conditions but limit weight gain during positive energy balance. |
2,328,771 | Glioneuronal Tumor With Features of Ganglioglioma and Neurocytoma Arising in the Fourth Ventricle: A Report of 2 Unusual Cases and a Review of Infratentorial Gangliogliomas. | Infratentorial glioneuronal neoplasms are overall quite rare and are more commonly low-grade with surgical excision usually being curative. Multiple distinct histologic entities have been described including rosette-forming glioneuronal tumor, papillary glioneuronal tumor, neurocytoma, dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), cerebellar liponeurocytoma, and ganglioglioma. While each of these entities has distinct findings, in some instances a tumor may demonstrate overlapping histologic features with mixed components. Herein, we report 2 unusual adult cases of a fourth ventricular glioneuronal tumor with features of ganglioglioma and neurocytoma, with one coming from a surgical resection and one found incidentally at autopsy. To the best of our knowledge, this specific histologic combination has not previously been described. As such, the clinical significance is unknown although in both cases the neoplasms were circumscribed and appeared to be low grade. The presence of the gangliogliomatous component was of particular interest since these are extremely rare occurrences in the fourth ventricle and we provide a comprehensive review of infratentorial gangliogliomas. |
2,328,772 | Bilateral Laryngocele Causing Epiglottic Deformity and Upper Airway Obstruction. | Laryngocele is the cystic dilatation of laryngeal ventricle. Most cases are asymptomatic and incidentally diagnosed in radiologic examinations. Although the etiology is unclear, obstruction, laryngeal pressure, congenital defects are possible risk factors. Computed tomography is the best method for diagnosis. Endoscopic, external or combined approaches have been described in the surgical treatment. Laryngocele should be kept in mind in patients with acute upper airway obstruction. Such patients may require tracheostomy. Some patients with laryngocele can also have laryngeal cancer, in which case direct laryngoscopy must be performed. This report presents a case with respiratory distress associated with bilateral laryngocele, and his management in the light of the literature. |
2,328,773 | Lupus-like symptoms with anti-RNP/Sm and anti-nuclear antibodies positivity: An extremely rare adverse event of dasatinib. | Dasatinib is a potent tyrosine-kinase inhibitor which is used for chronic myeloid leukemia treatment. Pleural effusion is a frequent side effect in patients during dasatinib treatment. Pulmonary arterial hypertension is a rare and life-threatening adverse event of dasatinib. The relationship between dasatinib and autoimmune disorders is unclear, but there are reports of possible mechanisms that have triggered autoimmunity by dasatinib.</AbstractText>A 53-year-old male was diagnosed with chronic myeloid leukemia and initiated imatinib mesylate as a treatment. Imatinib was changed to dasatinib as the patient was unresponsive in the first year of treatment. In the fourth year of dasatinib when chronic myeloid leukemia was in both hematological and cytogenetical remission, the patient presented with bilateral massive exudative pleural effusion. Echocardiography was consistent with pericardial effusion with right ventricle enlargement and normal left-side cardiac function. Pulmonary arterial hypertension was diagnosed with high systolic pulmonary arterial pressure. When he had fever and arthralgia, further investigation showed positivity of anti-nuclear antibodies (1/160 titer) and anti-RNP/Sm, which have high specificity for the diagnosis of Systemic Lupus Erythematosus (SLE).</AbstractText>Dasatinib was discontinued and nilotinib was initiated. As the pleural effusion persisted despite diuretics and methylprednisolone, mycophenolate mofetil was initiated as a steroid-sparing immune-suppressive agent. The lupus-like symptoms disappeared, and antibodies became undetectable after dasatinib discontinuation. Pericardial effusion improved and pleural effusion did not relapse.</AbstractText>Screening for auto-antibodies may be recommended for patients with a history or symptoms of autoimmune disease before starting dasatinib. All patients who develop pleural effusion while on dasatinib treatment should be investigated for antibodies for lupus.</AbstractText> |
2,328,774 | Fat embolism in right internal jugular vein: incidental ultrasound finding during internal jugular vein cannulation. | We report a case study of fat embolism seen on ultrasound at right internal jugular vein during central venous cannulation in a patient diagnosed with fat embolism syndrome. This case demonstrates the importance of ultrasound for evaluation of trauma cases with suspicion of fat embolism.</AbstractText>A 23-year-old trauma patient with closed fracture of left femoral shaft and left humerus presented to our emergency department (ED). 11 h after admission to ED, patient became confused, hypoxic and hypotensive. He was then intubated for respiratory failure and mechanically ventilated. Transesophageal ultrasound revealed hyperdynamic heart, dilated right ventricle with no regional wall abnormalities and no major aorta injuries. Whole-body computed tomography was normal. During central venous cannulation of right internal jugular vein (IJV), we found free floating mobile hyperechoic spots, located at the anterior part of the vein. A diagnosis of fat embolism syndrome later was made based on the clinical presentation of long bone fractures and fat globulin in the blood. Despite aggressive fluid resuscitation, patient was a non-responder and needed vasopressor infusion for persistent shock. Blood aspirated during cannulation from the IJV revealed a fat globule. Patient underwent uneventful orthopedic procedures and was discharged well on day 5 of admission.</AbstractText>Point-of-care ultrasound findings of fat embolism in central vein can facilitate and increase the suspicion of fat embolism syndrome.</AbstractText> |
2,328,775 | Right Ventricle Function in Patients with Acute Coronary Syndrome and Concomitant Undiagnosed Chronic Obstructive Pulmonary Disease. | Chronic obstructive pulmonary disease (COPD) is frequently undiagnosed in patients with ischemic heart disease. Nowadays, it is still unknown whether undiagnosed concomitant COPD is related to early structural changes of the heart, as detectable by trans-thoracic echocardiography (TTE). Starting from the study population of the Screening for COPD in ACS Patients (SCAP) trial, we sought to investigate potential differences in echocardiographic parameters in patients with acute coronary syndromes (ACS), with or without undiagnosed concomitant COPD. Overall, 137 patients were included. Undiagnosed COPD was detected by spirometry in 39 (29%) patients. TTE was performed at inclusion (before hospital discharge) and after six months. Several echocardiographic parameters including fractional area change (FAC) and RV strain (RVS), were measured. Patients with undiagnosed COPD, as compared to those without COPD, showed lower FAC and reduced RVS both at inclusion (37 ± 6% vs. 44 ± 9%, <i>p</i> < 0.001; -15 ± -4 vs. -20 ± -5, <i>p</i> < 0.001, respectively) and after six months (38 ± 7% vs. 45 ± 9%, <i>p</i> < 0.001; -16 ± -4 vs. -20 ± -5, <i>p</i> < 0.001, respectively). After multivariate analysis undiagnosed COPD was independently associated with lower FAC and reduced RVS at baseline and at TTE after six months. Early impairment of RV function can be detected in ACS patients with concomitant undiagnosed COPD. If these alterations may be changed by an early diagnosis and an early treatment, should be evaluated in future studies. <b>Clinical trial registration:</b> NCT02324660. |
2,328,776 | Fetal and infant growth patterns and left and right ventricular measures in childhood assessed by cardiac MRI. | Early life is critical for cardiac development. We examined the associations of longitudinal fetal and childhood growth patterns with childhood right and left ventricular structures measured by cardiac magnetic resonance imaging.</AbstractText>In a population-based prospective cohort study among 2827 children, we measured growth at 20 and 30 weeks of pregnancy, at birth, 0.5, 1, 2, 6 and 10 years. At 10 years, we measured right ventricular end-diastolic volume, left ventricular end-diastolic volume, left ventricular mass and left ventricular mass-to-volume ratio by cardiac magnetic resonance imaging.</AbstractText>Small size for gestational age at birth was associated with smaller right and left ventricular end-diastolic volume relative to current body surface area, but with larger left ventricular mass-to-volume ratio (P</i> < 0.05). Children in the upper 25% of right and left ventricular end-diastolic volume and left ventricular mass at age 10 years were larger at birth and became taller and leaner in childhood (P</i> < 0.05). In contrast, children in the lower 25% of right and left ventricular end-diastolic volume and left ventricular mass were smaller at birth and became shorter and heavier in childhood (P</i> < 0.05). Both fetal and childhood growth were independently of each other associated with childhood right and left ventricular end-diastolic volume and left ventricular mass.</AbstractText>Children who are larger at birth and grow taller and leaner in childhood have larger hearts relative to body surface area. Small size at birth children, who grow shorter and heavier in childhood, have relatively smaller hearts with larger left ventricular mass-to-volume ratio. Both fetal and childhood growth are important for the development of cardiac dimensions.</AbstractText> |
2,328,777 | Intraaxial and Extraaxial Cavernous Malformation with Venous Linkage: Immune Cellular Inflammation Associated with Aggressiveness. | Intraorbital and intracerebral cavernous malformation (CM) lesions are considered independent entities. Purely cerebral CMs have variable biology with recent evidence depicting inflammation as an important player and a risk factor for aggressiveness. We describe a case of concomitant left intraaxial and extraaxial CMs, linked by the ipsilateral basal vein, where the extraaxial component has developed an aggressive behavior.</AbstractText>A 35-year-old female patient presented with a rapid and progressive exophthalmos and loss of vision on the left eye. Cranial magnetic resonance and angiography examinations demonstrated a left craniofacial CM and large intraorbital component. The lesion was connected through a large basal vein to a cerebral intraventricular CM. Transconjunctival resection showed typical findings of CM. A complete histopathology and immunostaining analysis was performed and revealed a clear acute lymphomononuclear reaction with a predominant immune cellular inflammation.</AbstractText>A case of intraorbital and extracranial cavernomatous mass, connected to a cerebral intraventricular CM through a large basal vein, has presented with an aggressive course. A complete histopathologic and immunohistochemical analysis of the orbital mass has pictured a clear immune-cellular inflammatory reaction adding to the amounting evidence of association between inflammation and site aggressiveness in the setting of CMs.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,778 | Melatonin from slow-release implants upregulates claudin-2 in the ovine choroid plexus. | In ewes, the turnover rate of cerebrospinal fluid (CSF), mainly produced by choroid plexus (ChP), is photoperiodically modulated and is higher during short days (SDs) than long days (LDs). We demonstrated that, melatonin from continuous slow-release implants increases the expression of aquaporins, water channel-forming proteins engaged in transcellular water transport (across the plasma membrane of the cells), in the ovine ChP. This study evaluated the effect of slow-release melatonin implants on the expression of claudin-2 (CLDN2), a pore-forming protein that allows the paracellular passage (between the cells) of select inorganic cations and water, in the ovine ChP. The studies were conducted on ovariectomized, estradiol-implanted ewes during seasonal anestrus (May/June). The ewes were implanted with slow-release-melatonin implants (n = 6, Melovine 18 mg) or sham-implanted (n = 6). Blood samples were collected for melatonin and prolactin measurements. The ewes were sacrificed 40 days after the melatonin/sham implantation, and the ChPs from the brain ventricles were collected for real-time PCR and Western blot analyses. Plasma melatonin concentration reached the median value of 120.4 pg/ml (range: min/max = 29.6/447.0) or was below the detection limit 40 days after the melatonin/sham implantation, respectively. The area under the curve of the plasma prolactin concentration was significantly (P < 0.05) higher in sham-implanted ewes than in melatonin-implanted ewes. CLDN2 expression in the ChP was significantly (P < 0.05) higher in melatonin-implanted ewes than in sham-implanted ewes at both the mRNA and protein levels. This is the first evidence for the photoperiodic regulation of CLDN2 expression in the ovine ChP, since it has been shown that slow-release melatonin implants during LDs, mimicking SDs, increased the expression of CLDN2. This may partially explain the higher turnover rate of CSF observed in ewes during SDs. |
2,328,779 | [Surgical treatment of laryngocele]. | Laryngocele is a unilateral or bilateral dilation of the saccule or appendix of the laryngeal ventricle. It is a benign lesion, often without any specific symptom, diagnosed unintentionally, but it can cause life-threatening airway obstruction, needing emergency tracheotomy. The authors present three cases of laryngocele and the related surgical methods. Orv Hetil. 2019; 160(31): 1235-1240.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kiricsi</LastName><ForeName>Ágnes</ForeName><Initials>Á</Initials><AffiliationInfo><Affiliation>Fül-Orr-Gégészeti és Fej-Nyaksebészeti Klinika, Szegedi Tudományegyetem, Általános Orvostudományi Kar Szeged, Tisza Lajos krt. 11., 7626.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fazekas</LastName><ForeName>Piroska</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Fül-Orr-Gégészeti és Fej-Nyaksebészeti Klinika, Szegedi Tudományegyetem, Általános Orvostudományi Kar Szeged, Tisza Lajos krt. 11., 7626.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nagy</LastName><ForeName>Attila</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Fül-Orr-Gégészeti és Fej-Nyaksebészeti Klinika, Szegedi Tudományegyetem, Általános Orvostudományi Kar Szeged, Tisza Lajos krt. 11., 7626.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tóbiás</LastName><ForeName>Zoltán</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Fül-Orr-Gégészeti és Fej-Nyaksebészeti Klinika, Szegedi Tudományegyetem, Általános Orvostudományi Kar Szeged, Tisza Lajos krt. 11., 7626.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bella</LastName><ForeName>Zsolt</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Fül-Orr-Gégészeti és Fej-Nyaksebészeti Klinika, Szegedi Tudományegyetem, Általános Orvostudományi Kar Szeged, Tisza Lajos krt. 11., 7626.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rovó</LastName><ForeName>László</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Fül-Orr-Gégészeti és Fej-Nyaksebészeti Klinika, Szegedi Tudományegyetem, Általános Orvostudományi Kar Szeged, Tisza Lajos krt. 11., 7626.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Csanády</LastName><ForeName>Miklós</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Fül-Orr-Gégészeti és Fej-Nyaksebészeti Klinika, Szegedi Tudományegyetem, Általános Orvostudományi Kar Szeged, Tisza Lajos krt. 11., 7626.</Affiliation></AffiliationInfo></Author></AuthorList><Language>hun</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Laryngokeleeseteink műtéti megoldásai.</VernacularTitle></Article><MedlineJournalInfo><Country>Hungary</Country><MedlineTA>Orv Hetil</MedlineTA><NlmUniqueID>0376412</NlmUniqueID><ISSNLinking>0030-6002</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000402" MajorTopicYN="N">Airway Obstruction</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001065" MajorTopicYN="N">Appendix</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059608" MajorTopicYN="N">Laryngocele</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007828" MajorTopicYN="N">Laryngoscopy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007830" MajorTopicYN="N">Larynx</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013517" MajorTopicYN="N">Otorhinolaryngologic Surgical Procedures</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014057" MajorTopicYN="N">Tomography, X-Ray Computed</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014140" MajorTopicYN="N">Tracheotomy</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="hun">Absztrakt: A laryngokele, azaz gégelégsérv a Morgagni-tasakok egy- vagy kétoldali kiboltosulásának következménye. Jóindulatú elváltozás, mely gyakran tünetszegény, és mellékleletként fedezik fel, azonban akár életet veszélyeztető légúti obstrukciót okozhat, mely azonnali sürgősségi gégemetszést tesz szükségessé. A szerzők három esetet és annak műtéti megoldásait mutatják be. Orv Hetil. 2019; 160(31): 1235–1240. |
2,328,780 | Prevention of non-response to cardiac resynchronization therapy: points to remember. | Cardiac resynchronization therapy (CRT) is an important and effective therapy for end-stage heart failure. Non-response to CRT is one of the main obstacles to its application in clinical practice. There is no uniform consensus or definition of CRT "response." Clinical symptoms, ventricular remodeling indices, and cardiovascular events have been reported to be associated with non-responders. To prevent non-response to CRT, three aspects should be thoroughly considered: preoperative patient selection, electrode implantation, and postoperative management. Preoperative selection of appropriate patients for CRT treatment is an important step in preventing non-response. Currently, the CRT inclusion criteria are mainly based on the morphology of QRS waves in deciding ventricular dyssynchrony. Echocardiography and cardiac magnetic resonance are being explored to predict nonresponse to CRT. The location of left ventricular electrode implantation is a current hot spot of research; it is important to identify the location of the latest exciting ventricular segment and avoid scars. Cardiac magnetic resonance and ultrasonic spot tracking are being progressively developed in this field. Some new techniques such as His Bundle pacing, endocardial electrodes, and novel sensors are also being investigated. Postoperative management of patients is another essential step towards preventing non-response; it mainly focuses on the treatment of the disease itself and CRT program control optimization. CRT treatment is just one part of the overall treatment of heart failure, and multidisciplinary efforts are needed to improve the overall outcome. |
2,328,781 | Bitter taste signaling mediated by Tas2r144 is down-regulated by 17β-estradiol and progesterone in the rat choroid plexus. | The blood-cerebrospinal fluid barrier is constituted by choroid plexus epithelial cells (CPEC) that regulate molecular trafficking between the blood and the cerebrospinal fluid. We hypothesize that taste receptors expressed in CPEC monitor the composition of these body fluids in a sex hormone dependent way. Thus, we compared the expression of taste related genes in the choroid plexus of sham and ovariectomized female rats, and then studied the effect of 17β-estradiol and progesterone in their expression and function. We found that the bitter receptors Tas2r109, Tas2r144, and the taste-related genes Plcb2 and Trpm5 were down-regulated by ovarian hormones in vivo and ex vivo with functional implications. Knocking-down Tas2r144 with a specific siRNA in a CPEC line (Z310) effectively reduced the Ca<sup>2+</sup> response to the bitter compound denatonium benzoate, in a similar manner to female sex hormones alone, suggesting that female sex hormones downregulated the responses of CPEC to chemical stimuli by reducing Tas2r144. |
2,328,782 | Anatomic Study on Neuroendoportal Transcortical Approach to Lateral Ventricles. | Resection of intraventricular lesions remains a challenge for modern neurosurgery. Endoscopy has provided great advantages in ventricular surgery, even if limited in terms of operability, due to the restricted working channel and impossibility for bimanual surgical manipulation. Tubular approaches have been considered as an option, enabling the use of microsurgical techniques, minimizing violation of brain tissue. The aim of our study was to describe and critically evaluate the use of portal surgery to access lateral ventricles in terms of surgical exposure and operability.</AbstractText>A microanatomic laboratory cadaver study was conducted with a stepwise description of the surgical technique. The operability score was applied for quantitative analysis of surgical operability, and an illustrative case is reported.</AbstractText>Through the anterior approach, the neuroport provides maximal operability at the foramen of Monro and the posterior aspect of the frontal horn, while through the posterior approach maximal operability is achieved in the paratrigonal area. Endoscopic assistance does not affect operability but provides adjunctive exposure in blind spots, as the roof of the frontal horn, the most anterior aspect of the temporal and occipital horn.</AbstractText>Ventricular tubular systems provide adequate visualization, with minimal brain retraction, improving operability as compared with endoscopy. Endoscopic assistance critically widens surgical exposure in blind spots without providing concomitant significant advantage in terms of surgical operability.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,783 | IL-17A exacerbates neuroinflammation and neurodegeneration by activating microglia in rodent models of Parkinson's disease. | Neuroinflammation has been involved in pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disease characterized neuropathologically by progressive dopaminergic neuronal loss in the substantia nigra (SN). We recently have shown that helper T (Th)17 cells facilitate dopaminergic neuronal loss in vitro. Herein, we demonstrated that interleukin (IL)-17A, a proinflammatory cytokine produced mainly by Th17 cells, contributed to PD pathogenesis depending on microglia. Mouse and rat models for PD were prepared by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or striatal injection of 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>), respectively. Both in MPTP-treated mice and MPP<sup>+</sup>-treated rats, blood-brain barrier (BBB) was disrupted and IL-17A level increased in the SN but not in cortex. Effector T (Teff) cells that were adoptively transferred via tail veins infiltrated into the brain of PD mice but not into that of normal mice. The Teff cell transfer aggravated nigrostriatal dopaminergic neurodegeneration, microglial activation and motor impairment. Contrarily, IL-17A deficiency alleviated BBB disruption, dopaminergic neurodegeneration, microglial activation and motor impairment. Anti-IL-17A-neutralizing antibody that was injected into lateral cerebral ventricle in PD rats ameliorated the manifestations mentioned above. IL-17A activated microglia but did not directly affect dopaminergic neuronal survival in vitro. IL-17A exacerbated dopaminergic neuronal loss only in the presence of microglia, and silencing IL-17A receptor gene in microglia abolished the IL-17A effect. IL-17A-treated microglial medium that contained higher concentration of tumor necrosis factor (TNF)-α facilitated dopaminergic neuronal death. Further, TNF-α-neutralizing antibody attenuated MPP<sup>+</sup>-induced neurotoxicity. The findings suggest that IL-17A accelerates neurodegeneration in PD depending on microglial activation and at least partly TNF-α release. |
2,328,784 | Prenatal and postnatal MRI findings in open spinal dysraphism following intrauterine repair via open versus fetoscopic surgical techniques. | The purpose of the study is to examine MRI findings of the brain and spine on prenatal and postnatal MRI following intrauterine repair of open spinal dysraphism (OSD) by open hysterotomy and fetoscopic approaches.</AbstractText>This study is a single-center HIPAA-compliant and IRB-approved retrospective analysis of fetal MRIs with open spinal dysraphism from January 2011 through December 2018 that underwent subsequent prenatal repair of OSD.</AbstractText>Sixty-two patients met inclusion criteria: 47 underwent open repair, and 15 underwent fetoscopic repair, with an average gestational age of 22.6 ± 1.4 weeks at initial MRI. On postnatal MRI, spinal cord syrinx was seen in 34% (16/47) of patients undergoing open versus 33.3% (5/15) undergoing fetoscopic repair (P = 0.96). Postnatally, there was no significant difference in hindbrain herniation between the open versus fetoscopic repair groups (P = 0.28). Lateral ventricular size was significantly larger in the open (20.9 ± 6.7 mm) versus the fetoscopic repair (16.1 ± 4.9 mm) group (P = 0.01).</AbstractText>Though lateral ventricular size in the open repair group was larger than the fetoscopic repair group, this can likely be explained by initial selection criteria used for fetoscopic repair. Other postoperative imaging parameters on postnatal MRI were not significantly different between the two groups.</AbstractText>© 2019 John Wiley & Sons, Ltd.</CopyrightInformation> |
2,328,785 | Fully automated intracranial ventricle segmentation on CT with 2D regional convolutional neural network to estimate ventricular volume. | Hydrocephalus is a clinically significant condition which can have devastating consequences if left untreated. Currently available methods for quantifying this condition using CT imaging are unreliable and prone to error. The purpose of this study is to investigate the clinical utility of using convolutional neural networks to calculate ventricular volume and explore limitations.</AbstractText>A two-dimensional convolutional neural network was designed to perform fully automated ventricular segmentation on CT images. A total of 300 head CTs were collected and used in this exploration. Two hundred were used to train the network, 50 were used for validation, and 50 were used for testing.</AbstractText>Dice scores for the left lateral, right lateral, and third ventricle segmentations were 0.92, 0.92, and 0.79, respectively; the coefficients of determination were r2</sup> = 0.991, r2</sup> = 0.994, and r2</sup> = 0.976; the average volume differences between manual and automated segmentation were 0.821 ml, 0.587 ml, and 0.099 ml.</AbstractText>Two-dimensional convolutional neural network architectures can be used to accurately segment and quantify intracranial ventricle volume. While further refinements are necessary, it is likely these networks could be used as a clinical tool to quantify hydrocephalus accurately and efficiently.</AbstractText> |
2,328,786 | The molecular mechanism of LncRNA34a-mediated regulation of bone metastasis in hepatocellular carcinoma. | Bone metastasis (BM) has long been recognized as a major threat to the quality of life of hepatocellular cancer (HCC) patients. While LncRNA34a (Lnc34a) has been shown to regulate colon cancer stem cell asymmetric division, its effect on HCC BM remains unknown.</AbstractText>In situ hybridization and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of Lnc34a in HCC tissues and cell lines. Ventricle injection model was constructed to explore the effect of Lnc34a on BM in vivo. The methylation of miR-34a promoter and histones deacetylation were examined by using bisulfate-sequencing PCR and chromatin immunoprecipitation assays. RNA pull down and RNA immunoprecipitation were performed to investigated the interaction between Lnc34a and epigenetic regulators. Dual-luciferase reporter assay was conducted to find miR-34a target. The involvement of TGF-β pathway in the BM from HCC was determined by qRT-PCR, western, and elisa assays.</AbstractText>We found that Lnc34a was significantly overexpressed in HCC tissues and associated with BM. Both in vitro and in vivo experiments indicate that the restoration or knockdown of Lnc34a expression in HCC cells had a marked effect on cellular migration, invasion, and metastasis. Mechanistic analyses suggested that Lnc34a epigenetically suppresses miR-34a expression through recruiting DNMT3a via PHB2 to methylate miR-34a promoter and HDAC1 to promote histones deacetylation. On the other hand, miR-34a targets Smad4 via the TGF-β pathway, followed by altering the transcription of the downstream genes (i.e., CTGF and IL-11) that are associated with BM.</AbstractText>Our study is the first to document the pro-bone metastatic role of Lnc34a in BM of HCC and reveal a novel mechanism for the activation of the TGF-β signaling pathway in HCC BM, providing evidence of a potential therapeutic strategy in HCC BM.</AbstractText> |
2,328,787 | Nonspecific dizziness as an unusual presentation of neurocysticercosis: A case report. | Neurocysticercosis (NCC) can cause lesions across the central nervous system, leading to varying clinical manifestations. While the presentation of nonspecific symptom is rare, they are easy to ignore. The present report documents a case of NCC that manifested as persistent dizziness.</AbstractText>A Chinese woman visited the hospital on account of dizziness, the severity of which had increased gradually over the month prior.</AbstractText>Head computed tomography and magnetic resonance imaging (MRI) revealed hydrocephalus. Cervical MRI revealed an abnormal object in the spinal canal at the junction of the medulla oblongata and C1, which blocked the circulation cerebrospinal fluid circulation and caused the enlargement of the ventricles.</AbstractText>The patient underwent surgical treatment. The abnormal object was removed, and a diagnosis of NCC was considered by pathological examination.</AbstractText>The patient's dizziness resolved after surgical treatment, and no other symptoms appeared thereafter.</AbstractText>Clinicians should not ignore nonspecific clinical symptoms, as they may indicate hydrocephalus.</AbstractText> |
2,328,788 | Store-Operated Calcium Entry in Mouse Cardiomyocytes. | The fluorescent dye fura-2 AM was employed to record activation of Ca<sup>2+</sup> entry in response to a decrease in Ca<sup>2+</sup> concentration in the endoplasmic reticulum. Using whole-cell voltage clamp technique, we revealed Ca<sup>2+</sup> currents with an amplitude of 0.46±0.13 pA/pF that passed through selective channels with current-voltage characteristics similar to those of classical store-operated CRAC channels. These currents were sensitive to 2-APB (50 μM), an inhibitor of store-operated channels. The data suggest that store-operated calcium entry is a characteristic feature of mature ventricular cardiomyocytes. Pathological alterations in store-operated Ca<sup>2+</sup> entry can be implicated in the development of heart diseases. |
2,328,789 | Magnetic Resonance Imaging in Assessment of Cardiac Remodeling in Rats with Experimental Arterial Hypertension. | Magnetic resonance imaging was employed to examine the morphofunctional status of myocardium in Wistar rats with multifactor cardiovasorenal model of arterial hypertension. In 3 months after the onset of experiment, the rats demonstrated a pronounced hypertrophy in left ventricular myocardium mostly due to thickening of the posterior and lateral walls against the background of relatively stable thickness of ventricular septum. The left ventricular endsystolic volume markedly increased in parallel with moderate increase of the end-diastolic volume. The standard calculated indices were used for precise assessment of the type of remodeling of individual myocardial structures. The study showed that multifactor arterial hypertension model was characterized by domination of hypertrophic mode of the left ventricular remodeling, whereas the concentric variant was observed more rarely by 2.5 times. The greatest alterations were observed in the posterior and lateral walls of the left ventricle, which could result from the hemodynamic effects of hypervolemic arterial hypertension. |
2,328,790 | Liposomal doxorubicin attenuates cardiotoxicity via induction of interferon-related DNA damage resistance. | The clinical application of doxorubicin (DOX) is severely compromised by its cardiotoxic effects, which limit the therapeutic index and the cumulative dose. Liposomal encapsulation of DOX (Myocet®) provides a certain protective effect against cardiotoxicity by reducing myocardial drug accumulation. We aimed to evaluate transcriptomic responses to anthracyclines with different cardiotoxicity profiles in a translational large animal model for identifying potential alleviation strategies.</AbstractText>We treated domestic pigs with either DOX, epirubicin (EPI), or liposomal DOX and compared the cardiac, laboratory, and haemodynamic effects with saline-treated animals. Cardiotoxicity was encountered in all groups, reflected by an increase of plasma markers N-terminal pro-brain-natriuretic peptide and Troponin I and an impact on body weight. High morbidity of EPI-treated animals impeded further evaluation. Cardiac magnetic resonance imaging with gadolinium late enhancement and transthoracic echocardiography showed stronger reduction of the left and right ventricular systolic function and stronger myocardial fibrosis in DOX-treated animals than in those treated with the liposomal formulation. Gene expression profiles of the left and right ventricles were analysed by RNA-sequencing and validated by qPCR. Interferon-stimulated genes (ISGs), linked to DNA damage repair and cell survival, were downregulated by DOX, but upregulated by liposomal DOX in both the left and right ventricle. The expression of cardioprotective translocator protein (TSPO) was inhibited by DOX, but not its liposomal formulation. Cardiac fibrosis with activation of collagen was found in all treatment groups.</AbstractText>All anthracycline-derivatives resulted in transcriptional activation of collagen synthesis and processing. Liposomal packaging of DOX-induced ISGs in association with lower cardiotoxicity, which is of high clinical importance in anticancer treatment. Our study identified potential mechanisms for rational development of strategies to mitigate anthracycline-induced cardiomyopathy.</AbstractText>© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.</CopyrightInformation> |
2,328,791 | Noncoding RNAs in Cardiac Autophagy following Myocardial Infarction. | Macroautophagy is an evolutionarily conserved process of the lysosome-dependent degradation of damaged proteins and organelles and plays an important role in cellular homeostasis. Macroautophagy is upregulated after myocardial infarction (MI) and seems to be detrimental during reperfusion and protective during left ventricle remodeling. Identifying new regulators of cardiac autophagy may help to maintain the activity of this process and protect the heart from MI effects. Recently, it was shown that noncoding RNAs (microRNAs and long noncoding RNAs) are involved in autophagy regulation in different cell types including cardiac cells. In this review, we summarized the role of macroautophagy in the heart following MI and we focused on the noncoding RNAs and their targeted genes reported to regulate autophagy in the heart under these pathological conditions. |
2,328,792 | [Fourth ventricle meningiomas. A case report and literature review]. | Intraventricular meningiomas are rare and account for approximately 0.5 to 3% of all meningiomas and 9.8 to 14% of all intraventricular tumors. Most rarely, intraventricular meningomas occur in the third and fourth ventricles. The article reviews the literature devoted to meningiomas of a rare localization, in the fourth ventricle. On the basis of published surgical procedures and neuroimaging data, we divided posterior cranial fossa meningiomas into tumors completely located in the fourth ventricle cavity and those with a partial intraventricular component, which are not associated with any structures outside the ventricle. The reason for this study was our own clinical observation.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Babichev</LastName><ForeName>K N</ForeName><Initials>KN</Initials><AffiliationInfo><Affiliation>Kirov Military Medical Academy, Saint Petersburg, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stanishevskiy</LastName><ForeName>A V</ForeName><Initials>AV</Initials><AffiliationInfo><Affiliation>Kirov Military Medical Academy, Saint Petersburg, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Svistov</LastName><ForeName>D V</ForeName><Initials>DV</Initials><AffiliationInfo><Affiliation>Kirov Military Medical Academy, Saint Petersburg, Russia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><VernacularTitle>Meningiomy IV zheludochka golovnogo mozga. Sluchaĭ iz praktiki i obzor literatury.</VernacularTitle></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Zh Vopr Neirokhir Im N N Burdenko</MedlineTA><NlmUniqueID>7809757</NlmUniqueID><ISSNLinking>0042-8817</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002551" MajorTopicYN="Y">Cerebral Ventricle Neoplasms</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020546" MajorTopicYN="N">Fourth Ventricle</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008577" MajorTopicYN="Y">Meningeal Neoplasms</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008579" MajorTopicYN="Y">Meningioma</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059906" MajorTopicYN="N">Neuroimaging</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="rus">Менингиомы внутрижелудочковой локализации встречаются редко, составляя примерно 0,5-3,0% всех менингиом и 9,8-14,0% всех внутрижелудочковых опухолей. Наиболее редкой локализацией внутрижелудочковых менингиом являются III и IV желудочки головного мозга. В статье представлен обзор литературы, касающийся менингиом IV желудочка. В ходе исследования мы подразделили ранее опубликованные данные о менингиомах задней черепной ямки, исходя из описания оперативного вмешательства и представленных в публикациях данных нейровизуализации, на менингиомы, полностью расположенные в полости IV желудочка, и менингиомы с частичным внутрижелудочковым компонентом, не связанные ни с какими структурами за его пределами. Поводом для работы явилось собственное клиническое наблюдение. |
2,328,793 | Identification of AV-1451 as a Weak, Nonselective Inhibitor of Monoamine Oxidase. | [<sup>18</sup>F]AV-1451 is one of the most widely used radiotracers for positron emission tomography (PET) imaging of tau protein aggregates in neurodegenerative disorders. While the radiotracer binds with high affinity to tau neurofibrillary tangles, extensive clinical studies have simultaneously revealed off-target tracer accumulation in areas of low tau burden such as the basal ganglia and choroid plexus. Though there are a number of possible reasons for this accumulation, it is often attributed to off-target binding to monoamine oxidase (MAO). In this paper, we investigate the association between [<sup>18</sup>F]AV-1451 and MAO through (i) enzyme inhibition assays, (ii) autoradiography with postmortem tissue samples, and (iii) nonhuman primate PET imaging. We confirm that [<sup>18</sup>F]AV-1451 is a weak inhibitor of MAO-A and -B and that MAO inhibitors can alter binding of [<sup>18</sup>F]AV-1451 in autoradiography and <i>in vivo</i> PET imaging. |
2,328,794 | Hypoxia drives cardiac miRNAs and inflammation in the right and left ventricle. | Alveolar and myocardial hypoxia may be causes or sequelae of pulmonary hypertension (PH) and heart failure. We hypothesized that hypoxia initiates specific epigenetic and transcriptional, pro-inflammatory programs in the right ventricle (RV) and left ventricle (LV). We performed an expression screen of 750 miRNAs by qPCR arrays in the murine RV and LV in normoxia (Nx) and hypoxia (Hx; 10% O<sub>2</sub> for 18 h, 48 h, and 5d). Additional validation included single qPCR analysis of miRNA and pro-inflammatory transcripts in murine and human RV/LV, and neonatal rat cardiomyocytes (NRCMs). Differential qPCR-analysis (Hx vs. Nx in RV, Hx vs. Nx in LV, and RV vs. LV in Hx) identified nine hypoxia-regulated miRNAs: let-7e-5p, miR-29c-3p, miR-127-3p, miR-130a-3p, miR-146b-5p, miR-197-3p, miR-214-3p, miR-223-3p, and miR-451. Hypoxia downregulated miR-146b in the RV (p < 0.01) and, less so, in the LV (trend; p = 0.28). In silico alignment showed significant binding affinity of miR-146b-5p sequence with the 3'UTR of TRAF6 known to be upstream of pro-inflammatory NF-kB. Consistently, hypoxia induced TRAF6, IL-6, CCL2(MCP-1) in the mouse RV and LV. Incubating neonatal rat cardiomyocytes with pre-miR-146b led to a downregulation of TRAF6, IL-6, and CCL2(MCP-1). TRAF6 mRNA expression was also increased by 3-fold in the RV and LV of end-stage idiopathic pulmonary arterial hypertension (PAH) patients vs. non-PAH controls. We identified hypoxia-regulated, ventricle-specific miRNA expression profiles in the adult mouse heart in vivo. Hypoxia suppresses miR-146b, thus de-repressing TRAF6, and inducing pro-inflammatory IL-6 and CCL2(MCP-1). This novel hypoxia-induced miR-146b-TRAF6-IL-6/CCL2(MCP-1) axis likely drives cardiac fibrosis and dysfunction, and may lead to heart failure. KEY MESSAGES: Chouvarine P, Legchenko E, Geldner J, Riehle C, Hansmann G. Hypoxia drives cardiac miRNAs and inflammation in the right and left ventricle. • Hypoxia drives ventricle-specific miRNA profiles, regulating cardiac inflammation. • miR-146b-5p downregulates TRAF6, known to act upstream of pro-inflammatory NF-κB. • Hypoxia downregulates miR-146b and induces TRAF6, IL-6, CCL2 (MCP-1) in the murine RV and LV. • The inhibitory regulatory effects of miR-146b are confirmed in primary rat cardiomyocytes (pre-miR, anti-miR) and human explant heart tissue (endstage pulmonary arterial hypertension). • A novel miR-146b-TRAF6-IL-6/CCL2(MCP-1) axis likely drives cardiac inflammation, fibrosis and ventricular dysfunction. |
2,328,795 | [Reference values (Z-score) of inlet and trabecular portion diameters of the right ventricle: First description in Spanish healthy children]. | Right ventricle (RV) measurements are crucial for certain congenital heart diseases and various cardiovascular conditions. Echocardiographic RV diameters are especially useful for its assessment. Paediatric echocardiographic data standardisation in normal subjects is complex, scarce, and heterogeneous. The aim of this study was to establish reliable and reproducible echocardiographic reference values (Z-score) of RV diameters in a healthy Spanish paediatric cohort.</AbstractText>A multicentre study was conducted on 661 healthy subjects (age range 0-18 years, 43.5% female). Several regression models were tested to examine the relationship between RV diameters and biometric variables. Heteroscedasticity and residual associations (Shapiro-Wilk and Breusch-Pagan tests) and confounding factors (gender, age, inter/intraobserver agreement) were considered for an unbiased standardisation.</AbstractText>Structured Z-scores were computed for each RV diameter. Predicted mean value for each diameter was determined according to age, weight, height, and different body surface area. The Haycock formula provided the best fit for basal, midcavity, and longitudinal diameters (R2</sup> 0.81; 0.82; 0.9). Confounders were not significant, and therefore not included in final models (inter/intraobserver agreement > 0.9).</AbstractText>This study reports reference values for echocardiographic RV diameters from a Spanish healthy paediatric cohort using a rigorous statistical design. These Z-scores partly cover a gap in current paediatric cardiology and represent a relevant diagnostic tool for clinical practice, as well as a useful guide to decision making at any paediatric stage.</AbstractText>Copyright © 2020 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.</CopyrightInformation> |
2,328,796 | Tissue damage in the heart after cardiac arrest induced by asphyxia and hemorrhage in newborn pigs. | Asphyxia of newborns is a severe and frequent challenge of the peri- and postnatal period.</AbstractText>Forty-four neonatal piglets underwent asphyxia and hemorrhage (AH), followed by resuscitation with blood or crystalloid transfusion. In this study, 15 piglets (blood n = 9, NaCl n = 6, mean age 31 h) were randomly chosen. Four hours after return of spontaneous circulation, heart tissue and blood were collected. Analyses of heart fatty acid binding protein (HFABP), cardiac troponin I (TnI) levels, and activation of the complement system were performed. Histological staining for connexin 43 (Cx43) and complement C5a receptor 1 (C5aR1) was performed.</AbstractText>Following AH, systemic elevation of cardiac TnI and HFABP revealed cardiac damage in both groups. Systemic activation of the complement system and the appearance of extracellular histones in plasma of the blood transfusion group were observed. The Cx43 was translocated from the intercalated discs to the cytosol after AH. Cardiac glycogen concentration was reduced in both groups. A significant reduction of C5aR1 in the left ventricle and a significant elevation of the heart injury score were investigated after blood transfusion.</AbstractText>AH leads to alteration of the heart, particularly in Cx43 and glycogen reserves, as well as local inflammation.</AbstractText> |
2,328,797 | A Transcriptomic Model of Postnatal Cardiac Effects of Prenatal Maternal Cortisol Excess in Sheep. | <i>In utero</i> treatment with glucocorticoids have been suggested to reprogram postnatal cardiovascular function and stress responsiveness. However, little is known about the effects of prenatal exposure to the natural corticosteroid, cortisol, on postnatal cardiovascular system or metabolism. We have demonstrated an increased incidence of stillbirth in sheep pregnancies in which there is mild maternal hypercortisolemia caused by infusion of 1 mg/kg/d cortisol. In order to model corticosteroid effects in the neonate, we created a second model in which cortisol was infused for 12 h per day for a daily infusion of 0.5 mg/kg/d. In this model we had previously found that neonatal plasma glucose was increased and plasma insulin was decreased compared to those in the control group, and that neonatal ponderal index and kidney weight were reduced and left ventricular wall thickness was increased in the 2 week old lamb. In this study, we have used transcriptomic modeling to better understand the programming effect of this maternal hypercortisolemia in these hearts. This is a time when both terminal differentiation and a shift in the metabolism of the heart from carbohydrates to lipid oxidation are thought to be complete. The transcriptomic model indicates suppression of genes in pathways for fatty acid and ketone production and upregulation of genes in pathways for angiogenesis in the epicardial adipose fat (EAT). The transcriptomic model indicates that RNA related pathways are overrepresented by downregulated genes, but ubiquitin-mediated proteolysis and protein targeting to the mitochondria are overrepresented by upregulated genes in the intraventricular septum (IVS) and left ventricle (LV). In IVS the AMPK pathway and adipocytokine signaling pathways were also modeled based on overrepresentation by downregulated genes. Peroxisomal activity is modeled as increased in EAT, but decreased in LV and IVS. Our results suggest that pathways for lipids as well as cell proliferation and cardiac remodeling have altered activity postnatally after the <i>in utero</i> cortisol exposure. Together, this model is consistent with the observed increase in cardiac wall thickness at necropsy and altered glucose metabolism observed <i>in vivo</i>, and predicts that <i>in utero</i> exposure to excess maternal cortisol will cause postnatal cardiac hypertrophy and altered responses to oxidative stress. |
2,328,798 | Data Quality and Optimal Background Correction Order of Respiratory-Gated k-Space Segmented Spoiled Gradient Echo (SGRE) and Echo Planar Imaging (EPI)-Based 4D Flow MRI. | A reduction in scan time of 4D Flow MRI would facilitate clinical application. A recent study indicates that echo-planar imaging (EPI) 4D Flow MRI allows for a reduction in scan time and better data quality than the recommended k-space segmented spoiled gradient echo (SGRE) sequence. It was argued that the poor data quality of SGRE was related to the nonrecommended absence of respiratory motion compensation. However, data quality can also be affected by the background offset compensation.</AbstractText>To compare the data quality of respiratory motion-compensated SGRE and EPI 4D Flow MRI and their dependence on background correction (BC) order.</AbstractText>Retrospective.</AbstractText>Eighteen healthy subjects (eight female, mean age 32 ± 5 years).</AbstractText>1.5 T. [Correction added on July 26, 2019, after first online publication: The preceding field strength was corrected.] SGRE and EPI-based 4D Flow MRI.</AbstractText>Data quality was investigated visually and by comparing flows through the cardiac valves and aorta. Measurements were obtained from transvalvular flow and pathline analysis.</AbstractText>Linear regression and Bland-Altman analysis were used. Wilcoxon test was used for comparison of visual scoring. Student's t-test was used for comparison of flow volumes.</AbstractText>No significant difference was found by visual inspection (P = 0.08). Left ventricular (LV) flows were strongly and very strongly associated with SGRE and EPI, respectively (R2</sup> = 0.86-0.94 SGRE; 0.71-0.79 EPI, BC0-4). LV and right ventricular (RV) outflows and LV pathline flows were very strongly associated (R2</sup> = 0.93-0.95 SGRE; 0.88-0.91 EPI, R2</sup> = 0.91-0.95 SGRE; 0.91-0.93 EPI, BC1-4). EPI LV outflow was lower than the short-axis-based stroke volume. EPI RV outflow and proximal descending aortic flow were lower than SGREs.</AbstractText>Both sequences yielded good internal data consistency when an adequate background correction was applied. Second and first BC order were considered sufficient for transvalvular flow analysis in SGRE and EPI, respectively. Higher BC orders were preferred for particle tracing. Level of Evidence 4 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2020;51:885-896.</AbstractText>© 2019 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.</CopyrightInformation> |
2,328,799 | Revisiting the rules for anatomical targeting of ventralis intermediate nucleus. | Indirect targeting of the Ventralis Intermedius Nucleus (Vim) is widely used for functional neurosurgical procedures to treat essential tremor (ET). Here, we review if the laterality of the Vim depends on the diameter of the third ventricle and if a targeting approach that incorporates this correlation can facilitate targeting and yields accurate lead placement. We analyzed 15 consecutive ET patients. Vim targeting was adapted according to the width of the third ventricle and the lateral distance to the internal capsule (IC). Postoperative outcome was assessed 12 months post-OP based on the Bain-Findley score. Application of this targeting approach resulted in mean target coordinates of LAT 12.8 ± 1.5; AP -3.6 ± 1.0 and VERT 0 ± 0 mm and which projected onto the Vim. The laterality of IC and Vim are correlated to the width of the third ventricle. The mean postoperative tremor reduction was 63.0%. In summary, adjusting the lateral coordinate according to the width of the third ventricle leads to accurate targeting and effective tremor reduction. |
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