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2,330,900 | Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome. | This case documents the co-occurrence of the fragile X-associated tremor ataxia syndrome (FXTAS) and Alzheimer-type neuropathology in a 71-year-old premutation carrier with 85 CGG repeats in the fragile X mental retardation 1 (<i>FMR1)</i> gene, in addition to an apolipoprotein E (<i>APOE)</i> ε4 allele. FXTAS and Alzheimer's Disease (AD) are late-onset neurodegenerative diseases that share overlapping cognitive deficits including processing speed, working memory and executive function. The prevalence of coexistent FXTAS-AD pathology remains unknown. The clinical picture in this case was marked with rapid cognitive decline between age 67 and 71 years in addition to remarkable MRI changes. Over the 16 months between the two clinical evaluations, the brain atrophied 4.12% while the lateral ventricles increased 26.4% and white matter hyperintensities (WMH) volume increased 15.6%. Other regions atrophied substantially faster than the whole brain included the thalamus (-6.28%), globus pallidus (-10.95%), hippocampus (-6.95%), and amygdala (-7.58%). A detailed postmortem assessment included an MRI with confluent WMH and evidence of cerebral microbleeds (CMB). The histopathological study demonstrated FXTAS inclusions in neurons and astrocytes, a widespread presence of phosphorylated tau protein and, amyloid β plaques in cortical areas and the hippocampus. CMBs were noticed in the precentral gyrus, middle temporal gyrus, visual cortex, and brainstem. There were high amounts of iron deposits in the globus pallidus and the putamen consistent with MRI findings. We hypothesize that coexistent FXTAS-AD neuropathology contributed to the steep decline in cognitive abilities. |
2,330,901 | Metabolic profiles identify circulating biomarkers associated with heart failure in young single ventricle patients. | Children and young adults with single ventricle (SV) heart disease frequently develop heart failure (HF) that is intractable and difficult to treat. Our understanding of the molecular and biochemical reasons underlying this is imperfect. Thus, there is an urgent need for biomarkers that predict outcome and provide a rational basis for treatment, and advance our understanding of the basis of HF.</AbstractText>We sought to determine if a metabolomic approach would provide biochemical signatures of HF in SV children and young adults. If significant, these analytes might serve as biomarkers to predict outcome and inform on the biological mechanism(s) of HF.</AbstractText>We applied a multi-platform metabolomics approach composed of mass spectrometry (MS) and nuclear magnetic resonance (NMR) which yielded 495 and 26 metabolite measurements respectively. The plasma samples came from a cross-sectional set of young SV subjects, ages 2-19 years with ten control (Con) subjects and 16 SV subjects. Of the SV subjects, nine were diagnosed as congestive HF (SVHF), and 7 were not in HF. Metabolomic data were correlated with clinical status to determine if there was a signature associated with HF.</AbstractText>There were no differences in age, height, weight or sex between the 3 cohorts. However, statistical analysis of the metabolomic profiles using ANOVA revealed 44 metabolites with significant differences between cohorts including 41 profiled by MS and 3 by NMR. These metabolites included acylcarnitines, amino acids, and bile acids, which distinguished Con from all SV subjects. Furthermore, metabolite profiles could distinguish between SV and SVHF subjects.</AbstractText>These are the first data to demonstrate a clear metabolomic signature associated with HF in children and young adults with SV. Larger studies are warranted to determine if these findings are predictive of progression to HF in time to provide intervention.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,330,902 | Dual activation of Shh and Notch signaling induces dramatic enlargement of neocortical surface area. | The expansion of the neocortex represents a characteristic event over the course of mammalian evolution. Gyrencephalic mammals that have the larger brains with many folds (gyri and sulci) seem to have acquired higher intelligence, reflective of the enlargement of the neocortical surface area. In this process, germinal layers containing neural stem cells (NSCs) and neural progenitors expanded in number, leading to an increase in the total number of cortical neurons. In this study, we sought to expand neural stem/progenitor cells and enlarge the neocortical surface area by the dual activation of Shh and Notch signaling in transgenic (Tg) mice, promoting the proliferation of neural stem/progenitor cells by the Shh signaling effector while maintaining the undifferentiated state of NSCs by the Notch signaling effector. In the neocortical region of the Tg embryos, NSCs increased in number, and the ventricles, ventricular zone, and neocortical surface area were dramatically expanded. Furthermore, we observed that folds/wrinkles on the neocortical surface were progressively formed, accompanied by the vascular formation. These findings suggest that Shh and Notch signaling may be key regulators of mammalian brain evolution. |
2,330,903 | Ventricular wall stress and wall shear stress homeostasis predicts cardiac remodeling during pregnancy: A modeling study. | Pregnancy is a unique and dynamic process characterized by significant changes in the maternal cardiovascular system that are required to satisfy the increased maternal and fetal metabolic demands. Profound structural and hemodynamic adaptations occur during healthy pregnancy that allows the mother to maintain healthy hemodynamics and provide an adequate uteroplacental blood circulation to ensure physiological fetal development. Investigating these adaptations is crucial for understanding the physiology of pregnancy and may provide important insights for the management of high-risk pregnancies. However, no previous modeling studies have investigated the maternal cardiac structural changes that occur during gestation. This study, therefore, had two aims. The first was to develop a lumped parameter model of the whole maternal circulation that is suitable for studying global hemodynamics and cardiac function at different stages of gestation. The second was to test the hypothesis that myofiber stress and wall shear stress homeostasis principles can be used to predict cardiac remodeling that occurs during normal pregnancy. Hemodynamics and cardiac variables predicted from simulations with and without controlled cardiac remodeling algorithms were compared and evaluated with reference clinical data. While both models reproduced the hemodynamic variations that arise in pregnancy, importantly, we show that the structural changes that occur with pregnancy could be predicted by assuming invariant homeostatic "target" values of myocardial wall stress and chamber wall shear stress. |
2,330,904 | Cell proliferation fate mapping reveals regional cardiomyocyte cell-cycle activity in subendocardial muscle of left ventricle. | Cardiac regeneration involves the generation of new cardiomyocytes from cycling cardiomyocytes. Understanding cell-cycle activity of pre-existing cardiomyocytes provides valuable information to heart repair and regeneration. However, the anatomical locations and in situ dynamics of cycling cardiomyocytes remain unclear. Here we develop a genetic approach for a temporally seamless recording of cardiomyocyte-specific cell-cycle activity in vivo. We find that the majority of cycling cardiomyocytes are positioned in the subendocardial muscle of the left ventricle, especially in the papillary muscles. Clonal analysis revealed that a subset of cycling cardiomyocytes have undergone cell division. Myocardial infarction and cardiac pressure overload induce regional patterns of cycling cardiomyocytes. Mechanistically, cardiomyocyte cell cycle activity requires the Hippo pathway effector YAP. These genetic fate-mapping studies advance our basic understanding of cardiomyocyte cell cycle activity and generation in cardiac homeostasis, repair, and regeneration. |
2,330,905 | Dinitramine induces cardiotoxicity and morphological alterations on zebrafish embryo development. | Dinitramine (DN), an herbicide in the dinitroaniline family, is used in agricultural areas to prevent unwanted plant growth. Dinitroaniline herbicides inhibit cell division by preventing microtubulin synthesis. They are strongly absorbed by the soil and can contaminate groundwater; however, the mode of action of these herbicides in non-target organisms remains unclear. In this study, we examined the developmental toxicity of DN in zebrafish embryos exposed to 1.6, 3.2, and 6.4 mg/L DN, compared to embryos exposed to DMSO (control) for 96 h. Visual assessments using transgenic zebrafish (fli1:eGFP) indicated abnormal cardiac development with enlarged ventricles and atria, decreased heartbeats, and impaired cardiac function. Along with cardiac development, vessel formation and angiogenesis were suppressed through activation of the inflammatory response. In addition, exposure to 6.4 mg/L DN for 96 h induced cell death, with upregulation of genes related to apoptosis. Our results showed that DN induced morphological changes and triggered an inflammatory response and apoptotic cell death that can impair embryonic growth and survival, providing an important mechanism of DN in aquatic organisms. |
2,330,906 | GSK-3β as a target for apigenin-induced neuroprotection against Aβ 25-35 in a rat model of Alzheimer's disease. | Glycogen synthase kinase-3 (GSK-3) is a critical molecule in Alzheimer's disease (AD) that modulates two histopathological hallmarks of AD: Amyloid beta (Aβ) plaques and neurofibrillary tangles composed of aberrant hyper-phosphorylation of tau protein. This study was performed to investigate the protective effect of flavone apigenin through inhibition of GSK-3 and the involvement of this kinase in the inhibition of BACE1 expression and hyperphosphorylation of tau protein in an AD rat model. 15 nM of aggregated amyloid-beta 25-35 was microinjected into the left lateral ventricle of an AD rat. Apigenin (50 mg/kg) was administered orally 45 min before the Aβ injection and continued daily for three weeks. Immunohistochemistry and western blot analysis showed that apigenin significantly reduced the hyperphosphorylation of tau levels in the hippocampus. Real-time PCR analysis revealed significant inhibition of the mRNA level of β secretase (BACE1) and GSK-3β, but Apigenin had no effect on the level of GSK-3α. The results demonstrate that apigenin has a protective effect against amyloid-beta 25-35 by decreasing the expression of GSK-3β with the consequence of lowering the hyperphosphorylation of tau protein and suppressing BACE1 expression. |
2,330,907 | Chronic <i>Porphyromonas gingivalis</i> lipopolysaccharide induces adverse myocardial infarction wound healing through activation of CD8<sup>+</sup> T cells. | Oral and gum health have long been associated with incidence and outcomes of cardiovascular disease. Periodontal disease increases myocardial infarction (MI) mortality by sevenfold through mechanisms that are not fully understood. The goal of this study was to evaluate whether lipopolysaccharide (LPS) from a periodontal pathogen accelerates inflammation after MI through memory T-cell activation. We compared four groups [no MI, chronic LPS, <i>day 1</i> after MI, and <i>day 1</i> after MI with chronic LPS (LPS + MI); <i>n</i> = 68 mice] using the mouse heart attack research tool 1.0 database and tissue bank coupled with new analyses and experiments. LPS + MI increased total CD8<sup>+</sup> T cells in the left ventricle versus the other groups (<i>P</i> < 0.05 vs. all). Memory CD8<sup>+</sup> T cells (CD44<sup> + </sup>CD27<sup>+</sup>) were 10-fold greater in LPS + MI than in MI alone (<i>P</i> = 0.02). Interleukin (IL)-4 stimulated splenic CD8<sup>+</sup> T cells away from an effector phenotype and toward a memory phenotype, inducing secretion of factors associated with the Wnt/β-catenin signaling that promoted monocyte migration and decreased viability. To dissect the effect of CD8<sup>+</sup> T cells after MI, we administered a major histocompatibility complex-I-blocking antibody starting 7 days before MI, which prevented effector CD8<sup>+</sup> T-cell activation without affecting the memory response. The reduction in effector cells diminished infarct wall thinning but had no effect on macrophage numbers or MertK expression. LPS + MI + IgG attenuated macrophages within the infarct without effecting CD8<sup>+</sup> T cells, suggesting these two processes were independent. Overall, our data indicate that effector and memory CD8<sup>+</sup> T cells at post-MI <i>day 1</i> are amplified by chronic LPS to potentially promote infarct wall thinning.<b>NEW & NOTEWORTHY</b> Although there is a well-documented link between periodontal disease and heart health, the mechanisms are unclear. Our study indicates that in response to circulating periodontal endotoxins, memory CD8<sup>+</sup> T cells are activated, resulting in an acceleration of macrophage-mediated inflammation after MI. Blocking activation of effector CD8<sup>+</sup> T cells had no effect on the macrophage numbers or wall thinning at post-MI <i>day 1</i>, indicating that this response was likely due in part to memory CD8<sup>+</sup> T cells. |
2,330,908 | Symptomatic bilateral choroid plexus xanthogranuloma in a pediatric patient. | Central nervous system xanthogranulomas are uncommon clinical entities, and symptomatic bilateral choroid plexus xanthogranulomas are rare.</AbstractText>We present the case of a 15-year-old male patient with bilateral choroid plexus xanthogranulomas with symptoms of increased intracranial pressure. Gross total resection of the tumor in the left lateral ventricle was performed. The patient improved, and asymptomatic right-sided tumor was monitored at follow-up.</AbstractText>The main treatment objective in these tumors is gross total resection. Asymptomatic tumors can be followed without intervention. However, surgery should be performed for symptomatic tumors that cause hydrocephalus or symptoms of increased intracranial pressure.</AbstractText>© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</CopyrightInformation> |
2,330,909 | Role of Exercise Testing and Speckle Tracking Echocardiography in Paradoxical Severe Aortic Stenosis. | Introduction The clinical behavior and prognosis of patients with asymptomatic paradoxical low-gradient aortic stenosis (PLGAS) still remain controversial. Some authors consider PLGAS as an echocardiographically poorly quantified moderate AS (MAS). We aimed to investigate the clinical behavior of PLGAS by comparing it with that of asymptomatic high-gradient aortic stenosis (HG-AS) and MAS using transthoracic echocardiography (TTE) with speckle tracking imaging (STI) and cardiopulmonary exercise testing (CPET). The hypothesis of our study is, unlike that described by other authors, to demonstrate the existence of clinical and echocardiographic differences between PLGAS and MAS. Methods A cohort of 113 patients was included and categorized into three groups according to AS type: MAS (n=63), HG-AS (n=29), and PLGAS (n=21). Patients' clinical data were obtained. Patients underwent 2D TTE with STI and CPET. Results There were no significant differences in the clinical variables between the three AS groups. In the multivariate multinomial logistic regression analysis, with PLGAS being the reference category, the most powerful variable for establishing a difference with HG-AS was the left ventricular mass (LVM) indexed by body-surface area (odds ratio [OR]=1.04, confidence interval (CI)=1.01-1.06, p<0.05). The MAS group showed less abnormal CPET (OR=0.198, CI=0.06-0.69, p<0.05), and higher left ventricle global longitudinal strain rate (GLSR) (OR=0.003, CI=0.00-0.35, p<0.05) than the PLGAS group. Conclusions TTE with STI and CPET established the clear differences between patients with asymptomatic PLGAS and those with asymptomatic MAS, as well as the similarities between patients with PLGAS and those with HG-AS. Our data identify PLGAS as a completely different entity from MAS. |
2,330,910 | Large Metastatic Cardiac Tumor from Ascending Colon Cancer with Autopsy. | A metastatic cardiac tumor from colon cancer is an exceedingly rare clinical feature associated with a poor prognosis without therapeutic intervention; however, such cases may be frequently encountered in clinical practice, especially among the elderly. We report a case of synchronous double cancer of the prostate and ascending colon with metastases to multiple organs, including a large cardiac tumor. A 71-year-old Japanese man had prostate cancer with neck and para-aortic metastasis. He visited our hospital with complaints of fatigue and a positive fecal occult blood test result. Colonoscopy findings revealed the presence of a tumor in the ascending colon, and contrast-enhanced CT revealed a tumor in the heart, which was possibly due to metastasis from the ascending colon. The patient received palliative care and declined anticancer treatment. He died due to respiratory failure 3 months after the first diagnosis but did not show critical arrhythmia until death. Autopsy revealed the presence of a large mass in the right ventricle with tumor embolism of the right coronary artery. The cardiac mass was pathologically consistent with metastasis from the colon. In case of colorectal cancer with cardiac metastasis involving poor prognosis or performance status, best supportive care without any therapeutic intervention could be the optimal treatment for the quality of the remaining time. |
2,330,911 | VCAM1 expression in the myocardium is associated with the risk of heart failure and immune cell infiltration in myocardium. | Ischemic heart disease (IHD) and dilated cardiomyopathy (DCM) are the two most common etiologies of heart failure (HF). Both forms share common characteristics including ventricle dilation in the final stage. Immune mechanisms in HF are increasingly highlighted and have been implicated in the pathogeneses of IHD and DCM. A better understanding of adhesion molecule expression and correlated immune cell infiltration could enhance disease detection and improve therapeutic targets. This study was performed to explore the common mechanisms underlying IHD and DCM. After searching the Gene Expression Omnibus database, we selected the GSE42955, GSE76701, GSE5406, GSE133054 and GSE57338 datasets for different expressed gene (DEGs) selection and new cohort establishment. We use xcell to calculate immune infiltration degree, ssGSEA and GSEA to calculate the pathway and biological enrichment score, consensus cluster to identify the m6A modification pattern, and LASSO regression to make risk predicting model and use new combined cohort to validate the results. The screening stage revealed that vascular cell adhesion molecule 1 (VCAM1) play pivotal roles in regulating DEGs. Subsequent analyses revealed that VCAM1 was differentially expressed in the myocardium and involved in regulating immune cell infiltration. We also found that dysregulated VCAM1 expression was associated with a higher risk of HF by constructing a clinical risk-predicting model. Besides, we also find a connection among the m6A RNA modification ,expression of VCAM1 and immune regulation. Those connection can be linked by the Wnt pathway enrichment alternation. Collectively, our results suggest that VCAM-1 have the potential to be used as a biomarker or therapy target for HF and the m6A modification pattern is associated with the VCAM1 expression and immune regulation. |
2,330,912 | Neuroendoscopic Management of Lateral Ventricular Neurocysticercosis Presenting as Brun's Syndrome. | Brun's syndrome is a phenomenon characterized by sudden onset of severe headache, vomiting associated to a vestibular syndrome triggered by an abrupt movement of the head.</AbstractText>We present a case of a 12-year-old female patient with headache, vertigo, and vomiting; magnetic resonance imaging (MRI) was suggestive of a cystic intraventricular mass in the frontal horn of the left lateral ventricle. The patient underwent endoscopic exploration for the excision of cyst with complete postoperative recovery and histopathology suggestive of intraventricular neurocysticercosis.</AbstractText>Brun's syndrome is caused by a mobile deformable intraventricular mass leading to an episodic obstructive hydrocephalus resulting from an intermittent or positional CSF obstruction with elevation of intracranial pressure due to the ball valve mechanism. Treatment is mainly surgical, preferably by the neuroendoscopic technique as it has an advantage of performing septostomies and third ventriculostomies in addition to cyst removal, making this procedure practical for most cases of ventricular cysticercosis even in emergencies.</AbstractText>Copyright: © 2021 Journal of Pediatric Neurosciences.</CopyrightInformation> |
2,330,913 | Cobiveco: Consistent biventricular coordinates for precise and intuitive description of position in the heart - with MATLAB implementation. | Ventricular coordinates are widely used as a versatile tool for various applications that benefit from a description of local position within the heart. However, the practical usefulness of ventricular coordinates is determined by their ability to meet application-specific requirements. For regression-based estimation of biventricular position, for example, a symmetric definition of coordinate directions in both ventricles is important. For the transfer of data between different hearts as another use case, the consistency of coordinate values across different geometries is particularly relevant. To meet these requirements, we compare different approaches to compute coordinates and present Cobiveco, a symmetric, consistent and intuitive biventricular coordinate system that builds upon existing coordinate systems, but overcomes some of their limitations. A novel one-way transfer error is introduced to assess the consistency of the coordinates. Normalized distances along bijective trajectories between two boundaries were found to be superior to solutions of Laplace's equation for defining coordinate values, as they show better linearity in space. Evaluation of transfer and linearity errors on 36 patient geometries revealed a more than 4-fold improvement compared to a state-of-the-art method. Finally, we show two application examples underlining the relevance for cardiac data processing. Cobiveco MATLAB code is available under a permissive open-source license. |
2,330,914 | A novel family illustrating the mild phenotypic spectrum of TUBB2B variants. | TUBB2B codes for one of the isotypes of β-tubulin and dominant negative variants in this gene result in distinctive malformations of cortical development (MCD), including dysgyria, dysmorphic basal ganglia and cerebellar anomalies. We present a novel family with a heterozygous missense variant in TUBB2B and an unusually mild phenotype. First, at 21 37 weeks of gestation ultrasonography revealed a fetus with a relatively small head, enlarged lateral ventricles, borderline hypoplastic cerebellum and a thin corpus callosum. The couple opted for pregnancy termination. Exome sequencing on fetal material afterwards identified a heterozygous maternally inherited variant in TUBB2B (NM_178012.4 (TUBB2B):c.530A > T, p.(Asp177Val)), not present in GnomAD and predicted as damaging. The healthy mother had only a language delay in childhood. This inherited TUBB2B variant prompted re-evaluation of the older son of the couple, who presented with a mild delay in motor skills and speech. His MRI revealed mildly enlarged lateral ventricles, a thin corpus callosum, mild cortical dysgyria, and dysmorphic vermis and basal ganglia, a pattern typical of tubulinopathies. This son finally showed the same TUBB2B variant, supporting pathogenicity of the TUBB2B variant. These observations illustrate the wide phenotypic heterogeneity of tubulinopathies, including reduced penetrance and mild expressivity, that require careful evaluation in pre- and postnatal counseling. |
2,330,915 | TLR4 deletion increases basal energy expenditure and attenuates heart apoptosis and ER stress but mitigates the training-induced cardiac function and performance improvement. | Strategies capable of attenuating TLR4 can attenuate metabolic processes such as inflammation, endoplasmic reticulum (ER) stress, and apoptosis in the body. Physical exercise has been a cornerstone in suppressing inflammation and dysmetabolic outcomes caused by TRL4 activation. Thus, the present study aimed to evaluate the effects of a chronic physical exercise protocol on the TLR4 expression and its repercussion in the inflammation, ER stress, and apoptosis pathways in mice hearts. Echocardiogram, RT-qPCR, immunoblotting, and histological techniques were used to evaluate the left ventricle of wild-type (WT) and Tlr4 knockout (TLR4 KO) mice submitted to a 4-week physical exercise protocol. Moreover, we performed a bioinformatics analysis to expand the relationship of Tlr4 mRNA in the heart with inflammation, ER stress, and apoptosis-related genes of several isogenic strains of BXD mice. The TLR4 KO mice had higher energy expenditure and heart rate in the control state but lower activation of apoptosis and ER stress pathways. The bioinformatics analysis reinforced these data. In the exercised state, the WT mice improved performance and cardiac function. However, these responses were blunted in the KO group. In conclusion, TLR4 has an essential role in the inhibition of apoptosis and ER stress pathways, as well as in the training-induced beneficial adaptations. |
2,330,916 | Comparative analysis of the potential of the secretomes of cardiac resident stromal cells and fibroblasts. | The secretome of different cell types has been applied on in vitro and in vivo assays, indicating considerable therapeutic potential. However, the choice of the ideal cell type and culture conditions for obtaining the best set of soluble factors, as well as the assays to assess specific effects, remain subjects of vigorous debate. In this study, we used mass spectrometry to characterize the secretomes of ventricle derived-cardiac resident stromal cells (vCRSC) and human dermal fibroblasts (HDFs) and evaluate them in an effort to understand the niche specificity of biological responses toward different cellular behaviors, such as cell proliferation, adhesion, migration, and differentiation. It was interesting to note that the HDF and vCRSC secretomes were both able to induce proliferation and cardiac differentiation of H9c2 cells, as well as to increase the adhesion activity of H9c2 cells and human umbilical vein endothelial cells. Analysis of the secretome composition showed that the vCRSCs derived from different donors secreted a similar set of proteins. Despite the differences, almost half of the proteins identified in conditioned medium were common to both HDF and vCRSC. Consequently, a high number of common biological processes were identified in the secretomes of the two cell types, which could help to explain the similar results observed in the in vitro assays. We show that soluble factors secreted by both HDF and vCRSC are able to promote proliferation and differentiation of cardiomyoblasts in vitro. Our study indicates the possible use of vCRSC or HDF secretomes in acellular therapies for regenerative medicine. |
2,330,917 | MICROSURGICAL MANAGEMENT OF A RARE INCIDENTAL INTRAVENTRICULAR MENINGIOMA: A CASE REPORT AND RELEVANT LITERATURE REVIEW. | Intraventricular meningiomas are rare and make up between 0.5% and 3% of all intracranial meningiomas, representing one of the most challenging tumors in neurosurgery due to their difficult location. Being initially asymptomatic, such tumors usually attain large size before clinical presentation and diagnostic detection. Available literature concerned with their surgical management remains scarce. Herein, we present a case of microsurgical resection of incidental intraventricular meningioma in a 32-year-old female patient who was admitted to the hospital due to the sudden loss of consciousness, retrograde amnesia, and nausea following a head trauma. Routine brain magnetic resonance imaging revealed an irregular expansive formation located in the occipital horn of the right lateral ventricle showing heterogeneous contrast enhancement. The patient underwent right-side temporal osteoplastic craniotomy with total tumor microsurgical resection followed by external ventricular drainage, and recovered fully afterwards. Histopathologic analysis of tumor tissue samples confirmed the tumor as meningioma WHO grade I. Postoperative brain computed tomography confirmed complete tumor resection. In conclusion, intraventricular meningiomas are rather rare extra-axial tumors and may present with various symptoms depending on their size and difficult location. The development of most modern neuroimaging methods offers the opportunity of their precise and accurate diagnosis, better surgical planning, and favorable outcome. Microsurgical gross resection utilizing intraoperative neuromonitoring and cutting-edge neurosurgical armamentarium remains the treatment of choice for these location-challenging and surgically demanding, predominantly benign intracranial tumors. |
2,330,918 | Structural Brain Volumes of Individuals at Clinical High Risk for Psychosis: A Meta-analysis. | Structural magnetic resonance imaging studies in individuals at clinical high risk (CHR) for psychosis have yielded conflicting results.</AbstractText>The aims of this study were to compare intracranial and structural brain volumes and variability of CHR individuals with those of healthy control (HC) subjects and to investigate brain volume differences and variability in CHR subjects with and without transition to psychosis. The PubMed and Embase databases were searched for relevant studies published before June 1, 2020.</AbstractText>A total of 34 studies were deemed eligible, which included baseline data of 2111 CHR and 1472 HC participants. In addition, data were included for 401 CHR subjects who subsequently transitioned to psychosis and 1023 nontransitioned CHR participants. Whole-brain and left, right, and bilateral hippocampal volume were significantly smaller in CHR subjects than in HC subjects. Cerebrospinal fluid and lateral ventricle volumes were significantly larger in CHR subjects than in HC subjects. Variability was not significantly different in CHR subjects compared with HC subjects. CHR individuals with and without subsequent transition to psychosis did not show significant differences in any of the volumetric assessments or in variability.</AbstractText>This meta-analysis demonstrates reduced whole-brain and hippocampal volumes and increased cerebrospinal fluid and lateral ventricle volumes in CHR individuals. However, no significant differences were observed in any of the volumetric assessments between CHR individuals with and without subsequent transition to psychosis. These findings suggest that although structural brain alterations are present before the onset of the disorder, they may not significantly contribute to the identification of CHR individuals at the highest risk for the development of psychosis.</AbstractText>© 2021 The Authors.</CopyrightInformation> |
2,330,919 | Third Ventricular Floor Bowing Indicates Surgical Success in Patients Undergoing Endoscopic Third Ventriculostomy-Systematic Review and Meta-Analysis. | This meta-analysis aimed to evaluate the prognostic performance of third ventricular floor bowing (TVFB) as a marker for surgical success in patients undergoing endoscopic third ventriculostomy (ETV).</AbstractText>We performed a comprehensive literature search for studies comparing ETV success in patients with TVFB compared with those without using PubMed, SCOPUS, Embase, and EuropePMC. TVFB was defined as inferior bowing or bulging deformation or convex third ventricular floor. Surgical success was defined as resolution of symptoms post surgery and requires no further intervention for hydrocephalus. The outcome was surgical success in patients with TVFB compared with those without TVFB. The effect estimate was reported as odds ratio (OR).</AbstractText>Five studies comprising 439 patients were included in this meta-analysis. The prevalence of overall surgical success was 42%. The prevalence of surgical success was 85% in patients with TVFB. TVFB was associated with increased success rates (OR 5.94 [95% confidence interval 3.07, 11.5], P < 0.001; I2</sup>: 26.04%, P = 0.248). TVFB was associated with sensitivity 0.83, specificity 0.54, positive likelihood ratio 1.8, negative likelihood ratio 0.32, diagnostic OR 6, and area under curve 0.81 (0.77-0.84) for surgical success. Presence of TVFB confers to a 56% rate of surgical success, and no TVFB confers to a rate of 19% surgical success. The association between TVFB and surgical success was not affected by age (coefficient: -0.03, P = 0.474) and aqueductal stenosis (P = -0.05, P = 0.237).</AbstractText>This meta-analysis showed that the presence of TVFB was associated with increased ETV success.</AbstractText>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,330,920 | From the inside out: oculocerebrocutaneous syndrome without dermatological manifestations. | Delleman-Oorthuys or oculocerebrocutaneous syndrome (OCCS) is an extremely rare condition which relies on three pillars of manifestations: ophthalmological, neurological, and dermatological. It was first described by Delleman and Oorthuys in 1981, and since then, very few other cases have been reported. We report the case of a 13-month-old boy, referred to an ophthalmological tertiary service for investigation of a microglobe with a cystic retrobulbar mass on translucency test. MRI revealed a left microphthalmia, with extensive retrobulbar cystic lesions occupying the remaining orbit and protruding anteriorly the microglobe. Cerebral findings included polymicrogyria, subependymal nodular heterotopia at the level of the left occipital horn of the lateral ventricle, and an importantly enlarged mesencephalic tectum observed in association with an absent cerebellar vermis. The ensemble of malformations met the criteria for definite OCCS. Being a tremendously rare syndrome, OCCS will always represent a diagnostic challenge. However, its emblematic cutaneous manifestations might be an important part of the road map leading to its correct interpretation. Thus, when absent, diagnosis can be harder than usual, and, on these cases, neurologists, ophthalmologists, and radiologists play a crucial role. |
2,330,921 | Three-Dimensional Global Left Ventricular Myocardial Strain Reduced in All Directions in Subclinical Diabetic Cardiomyopathy: A Systematic Review and Meta-Analysis. | Background Three-dimensional (3D) speckle tracking echocardiography can identify subclinical diabetic cardiomyopathy without geometric assumption and loss of speckle from out-of-plane motions. There is, however, significant heterogeneity among the previous reports. We performed a systematic review and meta-analysis to compare 3D strain values between adults with asymptomatic, subclinical diabetes mellitus (ie, patients with diabetes mellitus without known clinical manifestations of cardiac disease) and healthy controls. Methods and Results After systematic review of 5 databases, 12 valid studies (544 patients with diabetes mellitus and 489 controls) were eligible for meta-analysis. Pooled means and mean difference (MD) using a random-effects model for 3D global longitudinal, circumferential, radial, and area strain were calculated. Patients with diabetes mellitus had an overall 2.31 percentage points lower 3D global longitudinal strain than healthy subjects (16.6%, 95% CI, 15.7-17.6 versus 19.0; 95% CI, 18.2-19.7; MD, -2.31, 95% CI, -2.72 to -2.03). Similarly, 3D global circumferential strain (18.9%; 95% CI, 17.5-20.3 versus 20.5; 95% CI, 18.9-22.1; MD, -1.50; 95% CI, -2.09 to -0.91); 3D global radial strain (44.6%; 95% CI, 40.2-49.1 versus 48.2; 95% CI, 44.7-51.8; MD, -3.47; 95% CI, -4.98 to -1.97), and 3D global area strain (30.5%; 95% CI, 29.2-31.8 versus 32.4; 95% CI, 30.5-34.3; MD, -1.76; 95% CI, -2.74 to -0.78) were also lower in patients with diabetes mellitus. Significant heterogeneity was noted between studies for all strain directions (inconsistency factor [I<sup>2</sup>], 37%-78%). Meta-regression in subgroup analysis of studies using the most popular vendor found higher prevalence of hypertension as a significant contributor to worse 3D global longitudinal strain. Higher hemoglobulin A<sub>1c</sub> was the most significant contributor to worse 3D global circumferential strain in patients with diabetes mellitus. Conclusions Three-dimensional myocardial strain was reduced in all directions in asymptomatic diabetic patients. Hypertension and hemoglobin A<sub>1c</sub> were associated with worse 3D global longitudinal strain and 3D global circumferential strain, respectively. Registration URL: https://www.crd.york.ac.uk/prospero; unique identifier: CRD42020197825. |
2,330,922 | Programmed Multi-Level Ventilation: A Strategy for Ventilating Non-Homogenous Lungs. | Mechanical ventilation (MV) has been an integral method used in ICU care for decades. MV is typically viewed as a life-supporting intervention. However, it can also contribute to lung injury through stress and strain, as evidenced by ventilator-induced lung injury (VILI), even in previously healthy lungs. The negative impact may be worsened when significant lung non-homogeneity is present, eg. ALI and ARDS. Protective lung strategies to minimize VILI are to use low tidal volumes (Vt 4-6 mL/kg/PBW), plateau pressures (P<sub>plat</sub>) <30 cmH<sub>2</sub>O and relatively high positive end-expiratory pressures (PEEP). Yet, use of constantly high PEEP levels is well recognized to result in hemodynamic compromise of the right ventricle, increased stress and strain through high mechanical energy impact on the lung and overdistension of relatively healthy lung tissue. Taking these issues into consideration, a different approach to mechanical ventilation was developed specifically for patients with non-homogeneity. This review focuses on a feature called programmed multi-level ventilation (PMLV). It is not a ventilation mode per se, but rather a form of extension that adjusts and modifies any ventilation mode (eg PCV,PSV, VCV, SIMV, etc.). PMLV is based on measured time constants (Tau) of the whole respiratory system, including artificial airways, breathing circuits, humidification devices and mechanical ventilator. Using a physiology-based approach presents a method to ventilate non-homogenous lungs through cyclic changes of different PEEP levels; recruitment takes place in lung areas with long time constants but protects relatively healthy lung areas from overdistension thus minimizing excessive mechanical power to the lung tissue. |
2,330,923 | Dendrobium officinale polysaccharide-induced neuron-like cells from bone marrow mesenchymal stem cells improve neuronal function a rat stroke model. | Various methods have been used to induce the neuronal differentiation of marrow mesenchymal stem cells (MSCs). However, the limited induction efficiency of cells in vitro has restricted their use. Therefore, identifying a simple and efficient treatment method is necessary. Dendrobium officinale is an important traditional Chinese medicine, and its main component, polysaccharides, has many pharmacological activities. However, the effects of D. officinale polysaccharide (DOP) on the neuronal differentiation of bone marrow mesenchymal stem cells (BMSCs) and treatment of ischaemic stroke remain unknown. We found that DOP promoted the neuronal differentiation of BMSCs by increasing the expression levels of neural markers, and the optimal concentration of DOP was 25 μg/mL. Additionally, the Notch signalling pathway was inhibited during the neuronal differentiation of BMSCs induced by DOP, and this effect was strengthened using an inhibitor of this pathway. The Wnt signalling pathway was activated during the differentiation of BMSCs, and inhibition of the Wnt signalling pathway downregulated the expression of neuronal genes. Furthermore, the transplantation of neuron-like cells induced by DOP improved neuronal recovery, as the brain infarct volume, neurologic severity scores and levels of inflammatory factors were all significantly reduced in vivo. In conclusion, DOP is an effective inducer of the neuronal differentiation of BMSCs and treatment option for ischaemic stroke. |
2,330,924 | The Celsr3-Kif2a axis directs neuronal migration in the postnatal brain. | The tangential migration of immature neurons in the postnatal brain involves consecutive migration cycles and depends on constant remodeling of the cell cytoskeleton, particularly in the leading process (LP). Despite the identification of several proteins with permissive and empowering functions, the mechanisms that specify the direction of migration remain largely unknown. Here, we report that planar cell polarity protein Celsr3 orients neuroblasts migration from the subventricular zone (SVZ) to olfactory bulb (OB). In Celsr3-forebrain conditional knockout mice, neuroblasts loose directionality and few can reach the OB. Celsr3-deficient neuroblasts exhibit aberrant branching of LP, de novo LP formation, and decreased growth rate of microtubules (MT). Mechanistically, we show that Celsr3 interacts physically with Kif2a, a MT depolymerizing protein and that conditional inactivation of Kif2a in the forebrain recapitulates the Celsr3 knockout phenotype. Our findings provide evidence that Celsr3 and Kif2a cooperatively specify the directionality of neuroblasts tangential migration in the postnatal brain. |
2,330,925 | The Expanding Role of Posterior Vault Distraction Osteogenesis in Idiopathic Intracranial Hypertension and Slit Ventricle Syndrome. | The purpose of this study was to compare perioperative safety and efficacy of posterior vault distraction osteogenesis (PVDO) in patients with primary nonsynostotic cephalo-cranial disproportion, namely slit ventricle syndrome and idiopathic intracranial hypertension (IIH), to a cohort of patients with craniosynostosis (CS). A retrospective review of patients undergoing PVDO from 2009 to 2019 at our institution was performed. Craniosynostosis patients were matched by sex and age at PVDO to the nonsynostotic cohort. Operative details, perioperative outcomes, and distraction patterns were analyzed with appropriate statistics. Nine patients met inclusion criteria for the non-CS cohort. Six patients (67%) underwent PVDO for slit ventricle and the remaining 3 patients (33%) underwent PVDO for IIH. The majority of CS patients were syndromic (n = 6, 67%) and had multisuture synostosis (n = 7, 78%). The non-CS cohort underwent PVDO at a median 56.1 months old [Q1 41.1, Q3 86.6] versus the CS cohort at 55.7 months [Q1 39.6, Q3 76.0] (P = 0.931). Total hospital length of stay was longer in the non-CS patients (median days 5 [Q1 4, Q3 6] versus 3 [Q1 3, Q3 4], P = 0.021). Non-CS patients with ventriculoperitoneal shunts had significantly less shunt operations for ICP concerns post-PVDO (median rate: 1.74/year [Q1 1.30, Q3 3.00] versus median: 0.18/year [Q1 0.0, Q3 0.7]; P = 0.046). In this pilot study using PVDO to treat slit ventricle syndrome and IIH, safety appears similar to PVDO in the synostotic setting. The cohort lacks adequate follow-up to assess long term efficacy, although short-midterm follow-up demonstrates promising results with less need for shunt revision and symptomatic relief. Future studies are warranted to identify the preferred surgical approach in these complex patients. |
2,330,926 | The localization of amyloid precursor protein to ependymal cilia in vertebrates and its role in ciliogenesis and brain development in zebrafish. | Amyloid precursor protein (APP) is expressed in many tissues in human, mice and in zebrafish. In zebrafish, there are two orthologues, Appa and Appb. Interestingly, some cellular processes associated with APP overlap with cilia-mediated functions. Whereas the localization of APP to primary cilia of in vitro-cultured cells has been reported, we addressed the presence of APP in motile and in non-motile sensory cilia and its potential implication for ciliogenesis using zebrafish, mouse, and human samples. We report that Appa and Appb are expressed by ciliated cells and become localized at the membrane of cilia in the olfactory epithelium, otic vesicle and in the brain ventricles of zebrafish embryos. App in ependymal cilia persisted in adult zebrafish and was also detected in mouse and human brain. Finally, we found morphologically abnormal ependymal cilia and smaller brain ventricles in appa<sup>-/-</sup>appb<sup>-/-</sup> mutant zebrafish. Our findings demonstrate an evolutionary conserved localisation of APP to cilia and suggest a role of App in ciliogenesis and cilia-related functions. |
2,330,927 | Architecture and Composition Dictate Viscoelastic Properties of Organ-Derived Extracellular Matrix Hydrogels. | The proteins and polysaccharides of the extracellular matrix (ECM) provide architectural support as well as biochemical and biophysical instruction to cells. Decellularized, ECM hydrogels replicate in vivo functions. The ECM's elasticity and water retention renders it viscoelastic. In this study, we compared the viscoelastic properties of ECM hydrogels derived from the skin, lung and (cardiac) left ventricle and mathematically modelled these data with a generalized Maxwell model. ECM hydrogels from the skin, lung and cardiac left ventricle (LV) were subjected to a stress relaxation test under uniaxial low-load compression at a 20%/s strain rate and the viscoelasticity determined. Stress relaxation data were modelled according to Maxwell. Physical data were compared with protein and sulfated GAGs composition and ultrastructure SEM. We show that the skin-ECM relaxed faster and had a lower elastic modulus than the lung-ECM and the LV-ECM. The skin-ECM had two Maxwell elements, the lung-ECM and the LV-ECM had three. The skin-ECM had a higher number of sulfated GAGs, and a highly porous surface, while both the LV-ECM and the lung-ECM had homogenous surfaces with localized porous regions. Our results show that the elasticity of ECM hydrogels, but also their viscoelastic relaxation and gelling behavior, was organ dependent. Part of these physical features correlated with their biochemical composition and ultrastructure. |
2,330,928 | Genetic and Epigenetic Factors of Takotsubo Syndrome: A Systematic Review. | Takotsubo syndrome (TTS), recognized as stress's cardiomyopathy, or as left ventricular apical balloon syndrome in recent years, is a rare pathology, described for the first time by Japanese researchers in 1990. TTS is characterized by an interindividual heterogeneity in onset and progression, and by strong predominance in postmenopausal women. The clear causes of these TTS features are uncertain, given the limited understanding of this intriguing syndrome until now. However, the increasing frequency of TTS cases in recent years, and particularly correlated to the SARS-CoV-2 pandemic, leads us to the imperative necessity both of a complete knowledge of TTS pathophysiology for identifying biomarkers facilitating its management, and of targets for specific and effective treatments. The suspect of a genetic basis in TTS pathogenesis has been evidenced. Accordingly, familial forms of TTS have been described. However, a systematic and comprehensive characterization of the genetic or epigenetic factors significantly associated with TTS is lacking. Thus, we here conducted a systematic review of the literature before June 2021, to contribute to the identification of potential genetic and epigenetic factors associated with TTS. Interesting data were evidenced, but few in number and with diverse limitations. Consequently, we concluded that further work is needed to address the gaps discussed, and clear evidence may arrive by using multi-omics investigations. |
2,330,929 | Teriflunomide Inhibits JCPyV Infection and Spread in Glial Cells and Choroid Plexus Epithelial Cells. | Several classes of immunomodulators are used for treating relapsing-remitting multiple sclerosis (RRMS). Most of these disease-modifying therapies, except teriflunomide, carry the risk of progressive multifocal leukoencephalopathy (PML), a severely debilitating, often fatal virus-induced demyelinating disease. Because teriflunomide has been shown to have antiviral activity against DNA viruses, we investigated whether treatment of cells with teriflunomide inhibits infection and spread of JC polyomavirus (JCPyV), the causative agent of PML. Treatment of choroid plexus epithelial cells and astrocytes with teriflunomide reduced JCPyV infection and spread. We also used droplet digital PCR to quantify JCPyV DNA associated with extracellular vesicles isolated from RRMS patients. We detected JCPyV DNA in all patients with confirmed PML diagnosis (<i>n</i> = 2), and in six natalizumab-treated (<i>n</i> = 12), two teriflunomide-treated (<i>n</i> = 7), and two nonimmunomodulated (<i>n</i> = 2) patients. Of the 21 patients, 12 (57%) had detectable JCPyV in either plasma or serum. CSF was uniformly negative for JCPyV. Isolation of extracellular vesicles did not increase the level of detection of JCPyV DNA versus bulk unprocessed biofluid. Overall, our study demonstrated an effect of teriflunomide inhibiting JCPyV infection and spread in glial and choroid plexus epithelial cells. Larger studies using patient samples are needed to correlate these in vitro findings with patient data. |
2,330,930 | Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus. | Aquaporin-4 (AQP4) is the principal water channel in the brain being expressed in astrocytes and ependymal cells. AQP4 plays an important role in cerebrospinal fluid (CSF) homeostasis, and alterations in its expression have been associated with hydrocephalus. AQP4 contributes to the development of hydrocephalus by hypoxia in aged mice, reproducing such principal characteristics of the disease. Here, we explore whether these alterations associated with the hydrocephalic state are permanent or can be reverted by reexposure to normoxia. Alterations such as ventriculomegaly, elevated intracranial pressure, and cognitive deficits were reversed, whereas deficits in CSF outflow and ventricular distensibility were not recovered, remaining impaired even one month after reestablishment of normoxia. Interestingly, in AQP4<sup>-/-</sup> mice, the impairment in CSF drainage and ventricular distensibility was completely reverted by re-normoxia, indicating that AQP4 has a structural role in the chronification of those alterations. Finally, we show that aged mice subjected to two hypoxic episodes experience permanent ventriculomegaly. These data reveal that repetitive hypoxic events in aged cerebral tissue promote the permanent alterations involved in hydrocephalic pathophysiology, which are dependent on AQP4 expression. |
2,330,931 | Multi-Systemic Alterations by Chronic Exposure to a Low Dose of Bisphenol A in Drinking Water: Effects on Inflammation and NAD<sup>+</sup>-Dependent Deacetylase Sirtuin1 in Lactating and Weaned Rats. | Bisphenol A (BPA) is largely used as a monomer in some types of plastics. It accumulates in tissues and fluids and is able to bypass the placental barrier, affecting various organs and systems. Due to huge developmental processes, children, foetuses, and neonates could be more sensitive to BPA-induced toxicity. To investigate the multi-systemic effects of chronic exposure to a low BPA dose (100 μg/L), pregnant Wistar rats were exposed to BPA in drinking water during gestation and lactation. At weaning, newborn rats received the same treatments as dams until sex maturation. Free and conjugated BPA levels were measured in plasma and adipose tissue; the size of cerebral ventricles was analysed in the brain; morpho-functional and molecular analyses were carried out in the liver with a focus on the expression of inflammatory cytokines and Sirtuin 1 (Sirt1). Higher BPA levels were found in plasma and adipose tissue from BPA treated pups (17 PND) but not in weaned animals. Lateral cerebral ventricles were significantly enlarged in lactating and weaned BPA-exposed animals. In addition, apart from microvesicular steatosis, liver morphology did not exhibit any statistically significant difference for morphological signs of inflammation, hypertrophy, or macrovesicular steatosis, but the expression of inflammatory cytokines, Sirt1, its natural antisense long non-coding RNA (<i>Sirt1-AS LncRNA</i>) and histone deacetylase 1 (Hdac1) were affected in exposed animals. In conclusion, chronic exposure to a low BPA dose could increase the risk for disease in adult life as a consequence of higher BPA circulating levels and accumulation in adipose tissue during the neonatal period. |
2,330,932 | Pathophysiology of Takotsubo Syndrome as A Bridge to Personalized Treatment. | Takotsubo syndrome (TTS) consists of transient dysfunction of the left and/or right ventricle in the absence of ruptured plaque; thrombus or vessel dissection. TTS may be divided into two categories. Primary TTS occurs when the cause of hospitalization is the symptoms resulting from damage to the myocardium usually preceded by emotional stress. Secondary TTS occurs in patients hospitalized for other medical; surgical; anesthetic; obstetric or psychiatric conditions who have activation of their sympathetic nervous system and catecholamines release- they develop TTS as a complication of their primary condition or its treatment. There are several hypotheses concerning the cause of the disease. They include a decrease in estrogen levels; microcirculation dysfunction; endothelial dysfunction and the hypothesis based on the importance of the brain-heart axis. More and more research concerns the importance of genetic factors in the development of the disease. To date; no effective treatment or prevention of recurrent TTS has been found. Only when the pathophysiology of the disease is fully known; then personalized treatment will be possible. |
2,330,933 | Pediatric Extraspinal Sacrococcygeal Ependymoma: Report of Two Cases and Literature Review. | Primary central nervous system (CNS) tumors represent the most common solid tumors in childhood. Ependymomas arise from ependymal cells lining the wall of ventricles or central canal of spinal cord and their occurrence outside the CNS is extremely rare, published in the literature as case reports or small case series. We present two cases of extra-CNS myxopapillary ependymomas treated at our institution in the past three years; both cases originate in the sacrococcygeal region and were initially misdiagnosed as epidermoid cyst and germ cell tumor, respectively. The first case, which arose in a 9-year-old girl, was treated with a surgical excision in two stages, due to the non-radical manner of the first operation; no recurrence was observed after two years of follow-up. The other case was a 12-year-old boy who was treated with a complete resection and showed no evidence of recurrence at one-year follow-up. In this paper, we report our experience in treating an extremely rare disease that lacks a standardized approach to diagnosis, treatment and follow-up; in addition, we perform a literature review of the past 35 years. |
2,330,934 | CSF Secretion Is Not Altered by NKCC1 Nor TRPV4 Antagonism in Healthy Rats. | Cerebrospinal fluid (CSF) secretion can be targeted to reduce elevated intracranial pressure (ICP). Sodium-potassium-chloride cotransporter 1 (NKCC1) antagonism is used clinically. However, supporting evidence is limited. The transient receptor potential vanilloid-4 (TRPV4) channel may also regulate CSF secretion and ICP elevation. We investigated whether antagonism of these proteins reduces CSF secretion.</AbstractText>We quantified CSF secretion rates in male Wistar rats. The cerebral aqueduct was blocked with viscous mineral oil, and a lateral ventricle was cannulated. Secretion rate was measured at baseline and after antagonist administration. Acetazolamide was administered as a positive control to confirm changes in CSF secretion rates.</AbstractText>Neither NKCC1, nor TRPV4 antagonism altered CSF secretion rate from baseline, n</i> = 3, t(2) = 1.14, p</i> = 0.37, and n</i> = 4, t(3) = 0.58, p</i> = 0.6, respectively. Acetazolamide reduced CSF secretion by ~50% across all groups, n</i> = 7, t(6) = 4.294, p</i> = 0.005.</AbstractText>Acute antagonism of NKCC1 and TRPV4 proteins at the choroid plexus does not reduce CSF secretion in healthy rats. Further investigation of protein changes and antagonism should be explored in neurological disease where increased CSF secretion and ICP are observed before discounting the therapeutic potential of protein antagonism at these sites.</AbstractText> |
2,330,935 | Development and Validation of an HPLC Method for Analysis of Topotecan in Human Cerebrospinal Fluid and Its Application in Elimination Evaluation of Topotecan after Intraventricular Injection. | Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient's topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs. |
2,330,936 | The Structure of the Spinal Cord Ependymal Region in Adult Humans Is a Distinctive Trait among Mammals. | In species that regenerate the injured spinal cord, the ependymal region is a source of new cells and a prominent coordinator of regeneration. In mammals, cells at the ependymal region proliferate in normal conditions and react after injury, but in humans, the central canal is lost in the majority of individuals from early childhood. It is replaced by a structure that does not proliferate after damage and is formed by large accumulations of ependymal cells, strong astrogliosis and perivascular pseudo-rosettes. We inform here of two additional mammals that lose the central canal during their lifetime: the Naked Mole-Rat (NMR, <i>Heterocephalus glaber</i>) and the mutant hyh (<i>hydrocephalus with hop gait</i>) mice. The morphological study of their spinal cords shows that the tissue substituting the central canal is not similar to that found in humans. In both NMR and hyh mice, the central canal is replaced by tissue reminiscent of normal lamina X and may include small groups of ependymal cells in the midline, partially resembling specific domains of the former canal. However, no features of the adult human ependymal remnant are found, suggesting that this structure is a specific human trait. In order to shed some more light on the mechanism of human central canal closure, we provide new data suggesting that canal patency is lost by delamination of the ependymal epithelium, in a process that includes apical polarity loss and the expression of signaling mediators involved in epithelial to mesenchymal transitions. |
2,330,937 | Does the Heart Want What It Wants? A Case for Self-Adapting, Mechano-Sensitive Therapies After Infarction. | There is a critical need for interventions to control the development and remodeling of scar tissue after myocardial infarction. A significant hurdle to fibrosis-related therapy is presented by the complex spatial needs of the infarcted ventricle, namely that collagenous buildup is beneficial in the ischemic zone but detrimental in the border and remote zones. As a new, alternative approach, we present a case to develop self-adapting, mechano-sensitive drug targets in order to leverage local, microenvironmental mechanics to modulate a therapy's pharmacologic effect. Such approaches could provide self-tuning control to either promote fibrosis or reduce fibrosis only when and where it is beneficial to do so. |
2,330,938 | Atypical metastatic lung cancer of the right ventricle on FDG PET/CT. | Although primary cardiac tumours are extremely uncommon, secondary tumours or cardiac metastasis are not. We present a 68-year-old gentleman with squamous cell carcinoma of the right lower lobe with bony metastasis to the right clavicle who was treated with radiotherapy to the lung and clavicle as well as combination immunotherapy (Pembrolizumab) and chemotherapy (Carboplatin/Paclitaxel). Despite completing the above treatment regime, <sup>18</sup>F-FDG PET/CT scan showed progression with two new sites of metastasis including a focus in the lateral wall of the right ventricle which correlate to a soft tissue density mass on CT as well as a FDG avid mass in the left masseter. Identification of cardiac lesions with <sup>18</sup>F-FDG PET/CT maybe challenging with routine preparation due high physiological FDG uptake in the myocardium and significant variability, nevertheless, focal FDG uptake in the heart should be carefully assessed for the possibility of cardiac metastasis. |
2,330,939 | Primary intracranial extra-skeletal myxoid chondrosarcoma of right lateral ventricle with EWSR1 gene fusion: a case report and review of literature. | Primary intracranial malignancies with extra-skeletal myxoid chondrosarcoma (EMC) features are extremely rare. EMC constitutes a distinct genomic entity characterised by reciprocal translocation of fusion genes, most commonly EWS RNA Binding Protein 1 (EWSR1) in 22q12 with Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) in 9q2-q31.1. It is reported to have a high propensity for local recurrence and has potential for metastasis. So far in 28 years since its first description, only 17 cases of primary intracranial EMC were reported in literature. This would be the second case of intraventricular origin and first case from lateral ventricle.</AbstractText>A 27-year-old male presenting with complaints of headache, seizures and pain in neck was diagnosed to have a mass lesion in right lateral ventricle in Magnetic Resonance Imaging of brain. He underwent right parieto-occipital craniotomy with total excision of the lesion. Initial histopathological examination was reported as Ependymoma, WHO grade II. However, blocks and slides review with immunohistochemistry (IHC) markers revealed neoplastic aetiology with extensive myxoid changes. Hence, fluorescent in-situ hybridisation (FISH) testing was done with EWSR1 break apart probe, which demonstrated EWSR1 break apart signals. Therefore, correlating the clinical findings with morphology, IHC and FISH, the diagnosis of primary intracranial EMC was rendered. Patient received adjuvant external beam radiation of 54 Gy in 30 fractions to the post-op region. At 29-month follow-up, there was no evidence of disease recurrence.</AbstractText>Owing to the rarity of the condition, there are no standard treatment guidelines available for primary intracranial EMC. A combined treatment approach with surgery followed by adjuvant radiotherapy provides good local control with less morbidity.</AbstractText>© the authors; licensee ecancermedicalscience.</CopyrightInformation> |
2,330,940 | Ornidazole-Induced Recurrent Encephalopathy in a Chinese Man: A Rare Case Report and Literature Review. | Ornidazole-induced encephalopathy (OIE) is seldom seen in the clinic. In this study, we report a new case of a patient who had taken 1,000 mg ornidazole daily for nearly 4 years because of suspected diarrhea and proctitis and presented with subacute symptoms such as unsteady gait, slurred speech, and psychiatric disorder. These symptoms were significantly relieved 3 days after the patient stopped taking ornidazole. When he took this medicine again, however, similar symptoms occurred 4 months later, which were again reduced after 4 days of drug discontinuation. After the second onset, abnormal signals were identified around the aqueduct of the midbrain, around the fourth ventricle, and in the dentate nuclei of the cerebellum bilaterally. After 9 days of drug discontinuation, lesions disappeared in the magnetic resonance imaging (MRI) results. According to the clinical manifestations, imaging features, and the reduced symptoms after drug withdrawal, we clinically diagnosed the patient with OIE. This paper also reviews the literature on OIE. Only five cases (including our case) have been reported, all of whom presented with cerebellar ataxia and dysarthria and three with additional mental symptoms such as agitation and irritability. All five patients had abnormal lesions in the dentate nucleus of the cerebellum bilaterally, among whom four also had lesions in the corpus callosum and three around the periaqueduct of the midbrain. After withdrawal of ornidazole, the symptoms in all patients vanished or were alleviated, and three of them showed reduced or disappeared lesions in a head MRI reexamination. Overall, OIE has rarely been reported. Our case report and literature review show that the lesions in the cerebellum, corpus callosum, and brainstem can be reversed. The main manifestations of the lesions-cerebellar ataxia, dysarthria, and mental symptoms-quickly weaken or disappear after drug withdrawal, with good prognosis. Nevertheless, clear pathogenesis has yet to be further investigated. |
2,330,941 | [A case of hydrocephalus during the course of sporadic Blau syndrome]. | Blau syndrome (BS) is a rare granulomatous inflammatory disease presenting in early childhood as dermatitis, arthritis, and uveitis. Here, we describe a case of hydrocephalus in a patient with sporadic BS. A 36-year-old female, with mutations in the NOD2 gene on chromosome 16, who had been diagnosed with BS at the age of 19 years, had visual impairment and required support when walking for a long time. She was admitted to our hospital due to deterioration in her walking ability and an inability to stand by herself. We diagnosed an obstructive hydrocephalus based on head MRI. The aqueductal stenosis and obstructive hydrocephalus associated with granulomatous lesions were considered in this case. After third ventricle fenestration, her standing movement and walking improved immediately. |
2,330,942 | Electroacupuncture improves repeated social defeat stress-elicited social avoidance and anxiety-like behaviors by reducing Lipocalin-2 in the hippocampus. | Post-traumatic stress disorder (PTSD) is a trauma-related disorder that is associated with pro-inflammatory activation and neurobiological impairments in the brain and leads to a series of affective-like behaviors. Electroacupuncture (EA) has been proposed as a clinically useful therapy for several brain diseases. However, the potential role of EA treatment in PTSD and its molecular and cellular mechanisms has rarely been investigated.</AbstractText>We used an established preclinical social defeat stress mouse model to study whether EA treatment modulates PTSD-like symptoms and understand its underlying mechanisms. To this end, male C57BL/6 mice were subjected to repeated social defeat stress (RSDS) for 6 consecutive days to induce symptoms of PTSD and treated with EA at Baihui (GV 20) and Dazhui (GV 14) acupoints.</AbstractText>The stimulation of EA, but not needle insertion at Baihui (GV 20) and Dazhui (GV 14) acupoints effectively improved PTSD-like behaviors such as, social avoidance and anxiety-like behaviors. However, EA stimulation at the bilateral Tianzong (SI11) acupoints did not affect the PTSD-like behaviors obtained by RSDS. EA stimulation also markedly inhibited astrocyte activation in both the dorsal and ventral hippocampi of RSDS-treated mice. Using next-generation sequencing analysis, our results showed that EA stimulation attenuated RSDS-enhanced lipocalin 2 expression in the hippocampus. Importantly, using double-staining immunofluorescence, we observed that the increased lipocalin 2 expression in astrocytes by RSDS was also reduced by EA stimulation. In addition, intracerebroventricular injection of mouse recombinant lipocalin 2 protein in the lateral ventricles provoked social avoidance, anxiety-like behaviors, and the activation of astrocytes in the hippocampus. Interestingly, the overexpression of lipocalin 2 in the brain also altered the expression of stress-related genes, including monoamine oxidase A, monoamine oxidase B, mineralocorticoid receptor, and glucocorticoid receptor in the hippocampus.</AbstractText>This study suggests that the treatment of EA at Baihui (GV 20) and Dazhui (GV 14) acupoints improves RSDS-induced social avoidance, anxiety-like behaviors, astrocyte activation, and lipocalin 2 expression. Furthermore, our findings also indicate that lipocalin 2 expression in the brain may be an important biomarker for the development of PTSD-related symptoms.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,330,943 | Chronic thinner inhalation alters olfactory behaviors in adult mice. | Volatile solvents exposure can result in various behavioral impairments that have been partly associated to altered adult hippocampal neurogenesis. Despite recent evidence supporting this association, few studies have been devoted to examine the impact on olfactory functioning and olfactory bulb (OB) neurogenesis, although olfactory system is directly in contact with volatile molecules. Thus, this study was designed to evaluate in adult mice the potential modifications of the olfactory functioning after acute (1 day), subchronic (6 weeks) and chronic (12 weeks) exposure to thinner vapor at both behavioral and cellular levels. Firstly, behavioral evaluations showed that chronic thinner exposure impacts on odor detection ability of treated mice but does not affect mice ability to efficiently discriminate between two different odors. Moreover, chronic thinner exposure produces impairment in the olfactory-mediated associative memory. Secondly, analysis of the effects of thinner exposure in the subventricular zone (SVZ) of the lateral ventricle and in the OB revealed that thinner treatments do not induce apoptosis nor glial activation. Thirdly, immunohistochemical quantification of different markers of adult olfactory neurogenesis showed that inhalant treatments do not change the number of proliferating progenitors in the SVZ and the rostral migratory stream (RMS), as well as the number of newborn cells reaching and integrating in the OB circuitry. Altogether, our data highlight that the impaired olfactory performances in chronically-exposed mice are not associated to an alteration of adult neurogenesis in the SVZ-OB system. |
2,330,944 | The role of tractography in the localisation of the Vim nucleus of the thalamus and the dentatorubrothalamic tract for the treatment of tremor. | The ventralis intermedius (VIM) nucleus of the thalamus is the usual surgical target for tremor. However, locating the structure may be difficult as it is not visible with conventional imaging methods; therefore, surgical procedures typically use indirect calculations correlated with clinical and intraoperative neurophysiological findings. Current ablative surgical procedures such as Gamma-Knife thalamotomy and magnetic resonance-guided focused ultrasound require new alternatives for locating the VIM nucleus. In this review, we compare VIM nucleus location for the treatment of tremor using stereotactic procedures versus direct location by means of tractography.</AbstractText>The most widely used cytoarchitectonic definition of the VIM nucleus is that established by Schaltenbrand and Wahren. There is a well-defined limit between the motor and the sensory thalamus; VIM neurons respond to passive joint movements and are synchronous with peripheral tremor. The most frequently used stereotactic coordinates for the VIM nucleus are based on indirect calculations referencing the mid-commissural line and third ventricle, which vary between patients. Recent studies suggest that the dentato-rubro-thalamic tract is an optimal target for controlling tremor, citing a clinical improvement; however, this has not yet been corroborated.</AbstractText>Visualisation of the cerebello-rubro-thalamic pathway by tractography may help in locating the VIM nucleus. The technique has several limitations, and the method requires standardisation to obtain more precise results. The utility of direct targeting by tractography over indirect targeting for patients with tremor remains to be demonstrated in the long-term.</AbstractText>Copyright © 2019 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.</CopyrightInformation> |
2,330,945 | The first pediatric case of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) associated with Neisseria meningitidis. | Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinic-radiological syndrome characterized by neurological deficiencies and reversible magnetic resonance imaging findings in the splenium of the corpus callosum. Usually, it has a good prognosis, and patients recover without any sequelae. A viral infection has caused most MERS cases, and bacterial agents have rarely been reported as a cause of MERS.</AbstractText>A 5-month-old male was admitted to the hospital with fever, poor feeding, decreased activity and groaning. He had focal seizures and required mechanical ventilation. A lumbar puncture was performed, and nucleic acid amplification tests (NAATs) of cerebral spinal fluid was positive for non-typeable serogroup of Neisseria meningitidis. Cranial magnetic resonance imaging (MRI) performed on day 3 of admission showed T2 hyperintensity and diffusion restriction at the splenium of corpus callosum (SCC). Diffusion restriction in the occipital horn of the left ventricular compatible with empyema was also obvious. According to the findings on cranial MRI, this clinical course was diagnosed as MERS associated with meningitis. His fever resolved in one week, cefotaxime was discontinued after 14 days, and the patient completely recovered. A follow-up MRI performed after three weeks of admission showed complete resolution of the signal intensity changes in the SCC and the occipital horn of the left lateral ventricle.</AbstractText>To the best of our knowledge, this is the first report of MERS associated with Neisseria meningitidis in children. Bacterial agents as a cause of MERS should be kept in mind, and we should avoid unnecessary treatment strategies due to the good prognosis of MERS in children.</AbstractText>Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,330,946 | A multiphase texture-based model of active contours assisted by a convolutional neural network for automatic CT and MRI heart ventricle segmentation. | Left and right ventricle automatic segmentation remains one of the more important tasks in computed aided diagnosis. Active contours have shown to be efficient for this task, however they often require user interaction to provide the initial position, which drives the tool substantially dependent on a prior knowledge and a manual process.</AbstractText>We propose to overcome this limitation with a Convolutional Neural Network (CNN) to reach the assumed target locations. This is followed by a novel multiphase active contour method based on texture that enhances whole heart patterns leading to an accurate identification of distinct regions, mainly left (LV) and right ventricle (RV) for the purposes of this work.</AbstractText>Experiments reveal that the initial location and estimated shape provided by the CNN are of great concern for the subsequent active contour stage. We assessed our method on two short data sets with Dice scores of 93% (LV-CT), 91% (LV-MRI), 0.86% (RV-CT) and 0.85% (RV-MRI).</AbstractText>Our approach overcomes the performance of other techniques by means of a multiregion segmentation assisted by a CNN trained with a limited data set, a typical issue in medical imaging.</AbstractText>Copyright © 2021. Published by Elsevier B.V.</CopyrightInformation> |
2,330,947 | Estimation of the time of death by measuring the variation of lateral cerebral ventricle volume and cerebrospinal fluid radiodensity using postmortem computed tomography. | Using postmortem CT (PMCT), changes in the volume of the lateral cerebral ventricles (LCVs) and modifications of the radiodensity of cerebrospinal fluid (CSF) have been examined to identify a possible relationship between these changes and the time of death. Subsequent periodical CT scans termed "sequential scans" for ten corpses at known time of death were obtained, and a 3D segmentation of the entire LCV was carried out to measure its volume and radiodensity over time from ~ 5.5- h up to 273-h postmortem. A linear decrease of the LCV volume for all the cases was observed in the investigated time range, together with an overall logarithmic increase of radiodensity. Although a larger sampling should be performed to improve the result reliability, our finding suggests that the postmortem variation of CSF radiodensity can be a potentially useful tool in determining postmortem interval, a finding that is worthy of further investigation. |
2,330,948 | Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor: a prospective study with comparison to a historical cohort. | The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation (DBS) to control symptoms related to essential tremor. The VIM is typically targeted using indirect methods, although studies have reported visualization of the VIM on proton density-weighted MRI. This study compares the outcomes between patients who underwent VIM DBS with direct and indirect targeting.</AbstractText>Between August 2013 and December 2019, 230 patients underwent VIM DBS at the senior author's institution. Of these patients, 92 had direct targeting (direct visualization on proton density 3-T MRI). The remaining 138 patients had indirect targeting (relative to the third ventricle and anterior commissure-posterior commissure line).</AbstractText>Coordinates of electrodes placed with direct targeting were significantly more lateral (p < 0.001) and anterior (p < 0.001) than those placed with indirect targeting. The optimal stimulation amplitude for devices measured in voltage was lower for those who underwent direct targeting than for those who underwent indirect targeting (p < 0.001). Patients undergoing direct targeting had a greater improvement only in their Quality of Life in Essential Tremor Questionnaire hobby score versus those undergoing indirect targeting (p = 0.04). The direct targeting group had substantially more symptomatic hemorrhages than the indirect targeting group (p = 0.04). All patients who experienced a postoperative hemorrhage after DBS recovered without intervention.</AbstractText>Patients who underwent direct VIM targeting for DBS treatment of essential tremor had similar clinical outcomes to those who underwent indirect targeting. Direct VIM targeting is safe and effective.</AbstractText> |
2,330,949 | Risk factors for unchanged ventricles during pediatric shunt malfunction. | Children whose ventricles do not change during shunt malfunction present a diagnostic dilemma. This study was performed to identify risk factors for unchanged ventricular size at shunt malfunction.</AbstractText>This retrospective 1:1 age-matched case-control study identified children with shunted hydrocephalus who underwent shunt revision with intraoperative evidence of malfunction at one of the three participating institutions from 1997 to 2019. Cases were defined as patients with a change of < 0.05 in the frontal-occipital horn ratio (FOR) between malfunction and baseline, and controls included patients with FOR changes ≥ 0.05. The presence of infection, abdominal pseudocyst, pseudomeningocele, or wound drainage and lack of baseline cranial imaging at the time of malfunction warranted exclusion.</AbstractText>Of 450 included patients, 60% were male, 73% were Caucasian, and 67% had an occipital shunt. The median age was 4.3 (IQR 0.97-9.21) years at malfunction. On univariable analysis, unchanged ventricles at malfunction were associated with a frontal shunt (41% vs 28%, p < 0.001), programmable valve (17% vs 9%, p = 0.011), nonsiphoning shunt (85% vs 66%, p < 0.001), larger baseline FOR (0.44 ± 0.12 vs 0.38 ± 0.11, p < 0.001), no prior shunt infection (87% vs 76%, p = 0.003), and no prior shunt revisions (68% vs 52%, p < 0.001). On multivariable analysis with collinear variables removed, patients with a frontal shunt (OR 1.67, 95% CI 1.08-2.70, p = 0.037), programmable valve (OR 2.63, 95% CI 1.32-5.26, p = 0.007), nonsiphoning shunt at malfunction (OR 2.76, 95% CI 1.63-4.67, p < 0.001), larger baseline FOR (OR 3.13, 95% CI 2.21-4.43, p < 0.001), and no prior shunt infection (OR 2.34, 95% CI 1.27-4.30, p = 0.007) were more likely to have unchanged ventricles at malfunction.</AbstractText>In a multicenter cohort of children with shunt malfunction, those with a frontal shunt, programmable valve, nonsiphoning shunt, baseline large ventricles, and no prior shunt infection were more likely than others to have unchanged ventricles at shunt failure.</AbstractText> |
2,330,950 | Effect of a single dose of pimobendan on right ventricular and right atrial function in 11 healthy cats. | The objective of this study was to investigate the effect of pimobendan on echocardiographic parameters of right ventricular and atrial function in healthy cats.</AbstractText>Eleven privately owned, healthy adult cats.</AbstractText>Each cat underwent five echocardiographic examinations: the first and second examinations were performed 1 h apart on day 0. On day 1, the third examination served as baseline, whereas the fourth and fifth examinations were performed one and 6 h after administration of a single oral dose of pimobendan (1.25 mg/cat), respectively. Parameters of right ventricular and atrial morphology and function were collected and compared among time points.</AbstractText>Pimobendan administration produced a change in some echocardiographic variables. Specifically, heart rate, right ventricular fractional shortening and peak velocity of systolic lateral tricuspid annular motion increased (P = 0.032, P = 0.002 and P < 0.001, respectively), whereas right ventricular end-systolic internal diameter and right atrial maximum and minimum internal diameters decreased (P = 0.004, P = 0.025 and P = 0.01, respectively). Right ventricular fractional area change and tricuspid annular plane systolic excursion did not change.</AbstractText>This novel study showed that pimobendan had positive effects on right ventricular and right atrial function in healthy cats. Further studies are needed to determine whether pimobendan has similar effects in cats with cardiac diseases.</AbstractText>Copyright © 2021 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,330,951 | Transependymal Edema as a Predictor of Endoscopic Third Ventriculostomy Success in Pediatric Hydrocephalus. | The Endoscopic Third Ventriculostomy Success Score (ETVSS) is based on the clinical features of hydrocephalus except for radiological findings. A previous study suggested that transependymal edema (TEE) as a radiological finding may be a reliable predictor of endoscopic third ventriculostomy (ETV) success in patients of all ages. We aimed to investigate whether TEE on preoperative magnetic resonance imaging can predict ETV success in pediatric patients.</AbstractText>Medical and radiological records of all pediatric patients with an initial ETV in our hospital between 2013 and 2019 were retrospectively reviewed.</AbstractText>This study included 32 patients with hydrocephalus. The median age at surgery was 10.0 years (interquartile range: 5.6-12.9 years). There were 20 patients in the high ETVSS (90-80) group and 12 patients in the moderate ETVSS (70-50) group. The median follow-up period was 29.0 months (interquartile range: 12.9-46.2 months). The ETV success rate at the final follow-up was 81%. Preoperative brain magnetic resonance imaging revealed TEE in 20 patients and third ventricle floor ballooning in 25 patients, of whom 19 (95%) and 22 (88%), respectively, achieved successful ETV. Patients with TEE had a significantly better outcome than patients without TEE (95% vs. 58%, P = 0.018). Multivariate analysis demonstrated that the presence of TEE (odds ratio 13.6, 95% confidence interval 1.3-137.5, P = 0.027) is a significant predictor of ETV success.</AbstractText>In our cohort with a high or moderate ETVSS, the ETV success rate in patients with TEE was significantly higher than in patients without TEE, suggesting that TEE may be a useful predictor of ETV success in pediatric hydrocephalus.</AbstractText>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,330,952 | Long-term changes in neuroimaging markers, cognitive function and psychiatric symptoms in an experimental model of Gulf War Illness. | Gulf War Illness (GWI) is a multi-symptom disease with debilitating cognitive and emotional impairments in veterans. GWI, like epilepsy, is caused by chemical neurotoxicity and manifests from disturbances in neuronal excitability. However, the mechanisms underlying such devastating neurological and psychiatric symptoms remain unclear. Here we investigated the long-term changes in neural behavior and brain structural abnormalities in a rat model of GWI. GWI is linked to exposure to GWI-related organophosphate chemicals (pyridostigmine bromide or PB and insecticide DEET, permethrin) during the stressful Gulf war.</AbstractText>To mimic GWI, we generated an experimental GWI prototype in rats by daily exposure to GWI-related chemicals with restraint stress (GWIR-CS) for 4 weeks. Changes in MRI scan and cognitive function were assessed at 5- and 10- months post-exposure.</AbstractText>In MRI scans, rats displayed significant increases in lateral ventricle T2 relaxation times at both 5- and 10-months after GWIR-CS, indicating alterations in the cerebrospinal fluid (CSF) density. Furthermore, at 10 months, there were significant decreases in the volumes of the hippocampus and thalamus and an increase in the lateral ventricle volume. At both time points, they exhibited impairments in multiple neurobehavioral tests, confirming substantial deficits in memory and mood function. GWI-CS rats also displayed aggressive behavior and a marked decrease in social interaction and forced swimming, indicating depression.</AbstractText>These results confirm that chronic GWIR-CS exposure led to cognitive and psychiatric symptoms with concurrent neuroimaging abnormalities in CSF, with morphological neural lesions, demonstrating the role of divergent etiological mechanisms in GWI and its comorbidities.</AbstractText>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,330,953 | Characteristics and optimal ablation settings of a novel, contact-force sensing and local impedance-enabled catheter in an ex vivo perfused swine ventricle model. | Local impedance (LI) has emerged as a new technology that informs on electrical catheter-tissue coupling during radiofrequency (RF) ablation. Recently, IntellaNav StablePoint, a novel LI-enabled catheter that equips contact force (CF) sensing, has been introduced. Although StablePoint and its predecessor IntellaNav MiFi OI share the common technology that reports LI, distinct mechanics for LI sensing between the two products raise a concern that the LI-RF lesion formation relationship may differ.</AbstractText>In an ex vivo swine cardiac tissue model, we investigated the initial level and range of a reduction in LI during a 60-s RF ablation and the resultant lesion characteristics at nine combinations of three energy power (30, 40, and 50 W) and CF (10, 30, and 50 g) steps. Correlations and interactions between CF, LI, wattage, and formed lesions were analyzed. Incidence of achieving LI drop plateau and that of a steam pop were also determined.</AbstractText>Positive correlations existed between CF and initial LI, CF and absolute/relative LI drop, CF and lesion volume, and LI drop and lesion volume. At the same LI drop, wattage-dependent gain in lesion volume was observed. Steam pops occurred in all CF steps and the prevalence was highest at 50 W. LI drop predicted a steam pop with a cutoff value at 89Ω.</AbstractText>In StablePoint, wattage crucially affects LI drop and lesion volume. Because 30 W ablation may by underpowered for intramural lesion formation and 50 W often resulted in a steam pop, 40 W appears to achieve the balance between the safety and efficacy.</AbstractText>© 2021 Wiley Periodicals LLC.</CopyrightInformation> |
2,330,954 | Fetal myocardial deformation measured with two-dimensional speckle-tracking echocardiography: longitudinal prospective cohort study of 124 healthy fetuses. | Two-dimensional speckle-tracking echocardiography (2D-STE) is a promising technique which allows assessment of fetal cardiac function, and can be used in the evaluation of cardiac and non-cardiac diseases in pregnancy. However, reliable fetal reference values for deformation parameters measured using 2D-STE are needed before it can be introduced into clinical practice. This study aimed to obtain reference values for fetal global longitudinal strain (GLS) and GLS rate (GLSR) measured using 2D-STE and compare right and left ventricular values.</AbstractText>This was a prospective longitudinal cohort study of uncomplicated pregnancies that underwent echocardiography every 4 weeks from inclusion at 18-21 weeks until delivery to obtain four-chamber loops of the fetal heart. Left and right ventricular GLS and GLSR were measured using 2D-STE at each examination. Using Bayesian mixed-effects models, reference values with lower and upper 5% prediction limits were calculated according to gestational age. Right and left ventricular GLS values according to gestational age were compared using the Wilcoxon signed-rank test.</AbstractText>A total of 592 left ventricular and 566 right ventricular GLS and GLSR measurements were obtained from 124 women with uncomplicated pregnancy and non-anomalous, appropriately grown fetuses. Reference values were obtained for both fetal ventricles according to gestational week. GLS and GLSR values of both ventricles increased (i.e. became less negative) significantly during pregnancy. Right ventricular GLS values were significantly higher (i.e. less negative) than the respective left ventricular values at every gestational week.</AbstractText>Reference values were obtained for fetal GLS and GLSR measured using 2D-STE. GLS and GLSR values increased significantly for both ventricles from the second trimester until delivery. GLS values were significantly higher for the right ventricle compared with the left ventricle. Future studies are needed to assess whether the obtained reference values are helpful in clinical practice in the assessment of pregnancy complications, such as fetal growth restriction or cardiac anomaly. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.</AbstractText>© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.</CopyrightInformation> |
2,330,955 | HOXA11-AS aggravates microglia-induced neuroinflammation after traumatic brain injury. | Long noncoding RNAs (lncRNAs) participate in many pathophysiological processes after traumatic brain injury by mediating neuroinflammation and apoptosis. Homeobox A11 antisense RNA (HOXA11-AS) is a member of the lncRNA family that has been reported to participate in many inflammatory reactions; however, its role in traumatic brain injury remains unclear. In this study, we established rat models of traumatic brain injury using a weight-drop hitting device and injected LV-HOXA11-AS into the right lateral ventricle 2 weeks before modeling. The results revealed that overexpression of HOXA11-AS aggravated neurological deficits in traumatic brain injury rats, increased brain edema and apoptosis, promoted the secretion of proinflammatory factors interleukin-1β, interleukin-6, and tumor necrosis factor α, and promoted the activation of astrocytes and microglia. Microglia were treated with 100 ng/mL lipopolysaccharide for 24 hours to establish in vitro cell models, and then transfected with pcDNA-HOXA11-AS, miR-124-3p mimic, or sh-MDK. The results revealed that HOXA11-AS inhibited miR-124-3p expression and boosted MDK expression and TLR4-nuclear factor-κB pathway activation. Furthermore, lipopolysaccharide enhanced potent microglia-induced inflammatory responses in astrocytes. Forced overexpression of miR-124-3p or downregulating MDK repressed microglial activation and the inflammatory response of astrocytes. However, the miR-124-3p-mediated anti-inflammatory effects were reversed by HOXA11-AS. These findings suggest that HOXA11-AS can aggravate neuroinflammation after traumatic brain injury by modulating the miR-124-3p-MDK axis. This study was approved by the Animal Protection and Use Committee of Southwest Medical University (approval No. SMU-2019-042) on February 4, 2019. |
2,330,956 | An epileptic seizure and haemorrhage into the ventricular system of the brain as the first manifestations of acquired haemophilia A - Case report. | Acquired haemophilia (AH) is a suddenly occurring severe blood diathesis that affects both males and females and is caused by autoantibodies which inhibit coagulation factor VIII. The report describes an unusual case of acquired haemophilia in which an epileptic seizure and haemorrhage into the ventricular system of the brain were the first manifestations of the disease. In addition, APTT was prolonged to 94.6 seconds and the factor VIII level was as low as 1.5%. The level of anti-FVIII antibody was extremely high - 272BU/ml. The patient did not undergo invasive diagnostic procedure or an operation. Recombinant factor VIIa was used to control the bleeding. In order to eradicate the inhibitor, the patient received prednisone and cyclophosphamide. Complete remission was achieved after 5.5 weeks of treatment. |
2,330,957 | Ependymosarcoma harboring C11orf95:RELA fusion transcript: Report of two cases and review of the literature. | Ependymoma is a relatively rare glial tumor of the central nervous system that arise from the cells lining the ventricles and central canal of the spinal cord. Ependymosarcoma (ES) is a newly introduced tumor entity of uncertain prognosis characterized by a rare phenomenon of a malignant mesenchymal transition arising within an ependymoma. ESs are surgically challenging tumors for diagnosis and therapy with a high incidence of morbidity and mortality. Here, we report two diagnostically challenging cases of primary ES in a 25-year-old female and a 17-year-old male. Both the cases presented with progressive and sequential neurological deficits over a period of five to eight months, and histological examination revealed a biphasic gliomesenchymal architecture comprised of anaplastic ependymomatous and sarcomatous components. Molecular genetic analysis revealed the presence of type 1 C11orf95:RELA fusion transcript. To date, 22 cases of ES have been reported in the literature, and only one case harbored type 1 C11orf95:RELA fusion transcript. |
2,330,958 | Advancing Our Understanding of Brain Disorders: Research Using Postmortem Brain Tissue. | It is thought that proliferative potential of neural progenitor cells, from postmortem tissue obtained from idiopathic PD patients, present in the substantia nigra (SN) as well as other brain regions can be maintained in vitro. While they might be lacking in factors required for differentiation into mature neurons, their regenerative potential is undeniable and suggestive that progenitor cells are found endogenously in the diseased brain. Adult stem/progenitor cells exist in several regions within the PD brain and are likely a valuable source of progenitor cells for understanding disease course, as well as useful tools for generating potential cellular and pharmacologic therapies. One successful therapy for some PD patients is deep brain stimulation (DBS) and has been used for more than a decade to treat PD; however its mechanism of action remains unknown. Given the close proximity of the electrode trajectory to areas of the brain known as the "germinal niches" and the Parkinsonian brain's regenerative potential, it is possible that DBS influences neural stem cell proliferation locally, as well as distally. A study of banked brain tissue from idiopathic PD patients treated with DBS, compared to 12 control brains without CNS disease, identified a significant increase in the number of proliferating precursor cells in the subventricular zone (SVZ) of the lateral ventricles, the third ventricle, and the tissue surrounding the DBS lead. Our studies with banked human tissues from the aforementioned regions demonstrate the importance of studying brain-banked tissue from germinal niches and DBS perielectrode tissue. We reveal in these studies the presence of proliferative potential in diseased brains as well as an increase in cellular plasticity in the brain as a consequence of DBS. |
2,330,959 | Distribution of Aldh1L1-CreER<sup>T2</sup> Recombination in Astrocytes Versus Neural Stem Cells in the Neurogenic Niches of the Adult Mouse Brain. | In the adult central nervous system, neural stem cells (NSCs) reside in two discrete niches: the subependymal zone (SEZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG). Here, NSCs represent a population of highly specialized astrocytes that are able to proliferate and give rise to neuronal and glial progeny. This process, termed adult neurogenesis, is extrinsically regulated by other niche cells such as non-stem cell astrocytes. Studying these non-stem cell niche astrocytes and their role during adult neuro- and gliogenesis has been hampered by the lack of genetic tools to discriminate between transcriptionally similar NSCs and niche astrocytes. Recently, Aldh1L1 has been shown to be a pan-astrocyte marker and that its promoter can be used to specifically target astrocytes using the Cre-loxP system. In this study we explored whether the recently described Aldh1L1-CreER<sup>T2</sup> mouse line (Winchenbach et al., 2016) can serve to specifically target niche astrocytes without inducing recombination in NSCs in adult neurogenic niches. Using short- and long-term tamoxifen protocols we revealed high recombination efficiency and specificity in non-stem cell astrocytes and little to no recombination in NSCs of the adult DG. However, in the SEZ we observed recombination in ependymal cells, astrocytes, and NSCs, the latter giving rise to neuronal progeny of the rostral migratory stream and olfactory bulb. Thus, we recommend the here described Aldh1L1-CreER<sup>T2</sup> mouse line for predominantly studying the functions of non-stem cell astrocytes in the DG under physiological and pathological conditions. |
2,330,960 | Is Image Guidance Essential for External Ventricular Drain Insertion? | This study aimed to compare the external ventricular drain (EVD) placement accuracy and complication rates, between neuronavigation-guided, ultrasound-guided, and freehand techniques in our single-center cohort, and through an additional meta-analysis of the currently available literature.</AbstractText>A retrospective review of patients who underwent EVD insertion from January 2016 to April 2019 was conducted. Information regarding demographics, indication, Evans index, use of image guidance, accuracy of catheter tip placement, and procedural complications was extracted from electronic records and imaging systems. The accuracy of the EVD tip placement was classified according to the Kakarla grading system into optimal, or suboptimal based on its proximity to the Foramen of Monro and involvement of noneloquent/eloquent structures.</AbstractText>In total, 294 patients (median age of 54 years) underwent EVD insertion during the study period. A total of 183 catheters were placed freehand, 66 neuronavigation-guided, and 45 ultrasound-guided; the mean Evans ratios were 0.33, 0.29, and 0.31, respectively. Whilst there was a tendency for lower rates of suboptimal placement were guidance was used, with rates of 10.6% and 15.6% for neuronavigation- and ultrasound-guidance, respectively, compared to 20.8% in freehand placement, this did not reach statistical significance (P = 0.168). However, pooling this data with two additional studies on meta-analysis found a significant reduction in the risk of suboptimal placement for image-guided vs. freehand EVDs (odds ratio: 0.50, 95% CI: 0.32-0.77, P = 0.002). Surgeon seniority and other procedure-related factors had no significant impact on EVD placement accuracy or complications.</AbstractText>Our results, pooled with those of previous studies, suggest image-guided EVD placement significantly reduced the rate of suboptimally placed EVDs. We conclude in appropriately selected cases that image-guided EVD insertions may improve accuracy of catheter placements and reduce associated complications of the procedure.</AbstractText>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,330,961 | Transcallosal-Transchoroidal Approach for a Symptomatic Third Ventricular Cavernous Malformation in a Pediatric Patient: Surgical Video. | Cavernous malformations of the third ventricle are rare, deep-seated lesions that pose a formidable surgical challenge due to the rich, surrounding anatomy. Despite the potential morbidity of surgical treatment, the possibility of catastrophic, spontaneous hemorrhage in this location is even more feared and aggressive treatment is warranted, especially if the patient had suffered previous hemorrhages and is currently symptomatic. We demonstrate this approach (Video 1) on a 16-year-old boy who presented with right-sided hemiparesis (power grade 4), intense headaches, difficulties with learning and concentration, and memory loss, mainly affecting short-term memory. The patient had a previous unsuccessful excision at another center 3 months after initial hemorrhage. The absence of hydrocephalus and medial thalamic location favored a modified transcallosal transchoroidal (or subchoroidal) approach. Due to the anatomy of the lesion, no other microsurgical approaches were considered. The surgery at our center (second attempt) was performed 5 months after initial hemorrhage. The head was placed in neutral position, with a slight elevation of the vertex and the midline in a vertical position. A callosotomy had already been performed during the patient's first excision attempt at another center. Although dissection through the tela choroidea is commonly performed medially to the choroidal fissure when one wants to enter the third ventricle, we chose to carefully dissect through this structure laterally, because this thalamic lesion extended almost into the ependymal surface of the third ventricle. This way, the choroidal plexus became a protective cushion for the fornix. On entering the third ventricle, a mulberry-like lesion was readily identified and the cavernoma was located. The central contents of the cavernoma were dissected initially, causing relative deflation of the lesion and more maneuverability to dissect it away from the surrounding structures. Neuromonitoring was used to avoid brainstem injury. Postoperative magnetic resonance imaging showed complete resection with no signs of hemorrhage or ischemia. The patient was discharged on postoperative day 5 with no new neurologic deficits. The patient was also able to return to school after 1 month and showed complete recovery. Unfortunately, neuropsychologic evaluation was unavailable to understand his improvement better. Microsurgical dissection images in this video are a courtesy of the Rhoton Collection, American Association of Neurological Surgeons (AANS)/Neurosurgical Research and Education Foundation (NREF). |
2,330,962 | Expanding role of vitamin E in protection against metabolic dysregulation: Insights gained from model systems, especially the developing nervous system of zebrafish embryos. | This review discusses why the embryo requires vitamin E (VitE) and shows that its lack causes metabolic dysregulation and impacts morphological changes at very early stages in development, which occur prior to when a woman knows she is pregnant. VitE halts the chain reactions of lipid peroxidation (LPO). Metabolomic analyses indicate that thiols become depleted in E- embryos because LPO generates products that require compensation using limited amino acids and methyl donors that are also developmentally relevant. Thus, VitE protects metabolic networks and the integrated gene expression networks that control development. VitE is critical especially for neurodevelopment, which is dependent on trafficking by the α-tocopherol transfer protein (TTPa). VitE-deficient (E-) zebrafish embryos initially appear normal, but by 12 and 24 h post-fertilization (hpf) E- embryos are developmentally abnormal with expression of pax2a and sox10 mis-localized in the midbrain-hindbrain boundary, neural crest cells and throughout the spinal neurons. These patterning defects indicate cells that are especially in need of VitE-protection. They precede obvious morphological abnormalities (cranial-facial malformation, pericardial edema, yolksac edema, skewed body-axis) and impaired behavioral responses to locomotor activity tests. The TTPA gene (ttpa) is expressed at the leading edges of the brain ventricle border. Ttpa knockdown using morpholinos is 100% lethal by 24 hpf, while E- embryo brains are often over- or under-inflated at 24 hpf. Further, E- embryos prior to 24 hpf have increased expression of genes involved in glycolysis and the pentose phosphate pathway, and decreased expression of genes involved in anabolic pathways and transcription. Combined data from both gene expression and the metabolome in E- embryos at 24 hpf suggest that the activity of the mechanistic Target of Rapamycin (mTOR) signaling pathway is decreased, which may impact both metabolism and neurodevelopment. Further evaluation of VitE deficiency in neurogenesis and its subsequent impact on learning and behavior is needed. |
2,330,963 | Anatomical Organization of the Rat Subfornical Organ. | The subfornical organ (SFO) is a sensory circumventricular organ located along the anterodorsal wall of the third ventricle. SFO lacks a complete blood-brain barrier (BBB), and thus peripherally-circulating factors can penetrate the SFO parenchyma. These signals are detected by local neurons providing the brain with information from the periphery to mediate central responses to humoral signals and physiological stressors. Circumventricular organs are characterized by the presence of unique populations of non-neuronal cells, such as tanycytes and fenestrated endothelium. However, how these populations are organized within the SFO is not well understood. In this study, we used histological techniques to analyze the anatomical organization of the rat SFO and examined the distribution of neurons, fenestrated and non-fenestrated vasculature, tanycytes, ependymocytes, glia cells, and pericytes within its confines. Our data show that the shell of SFO contains non-fenestrated vasculature, while fenestrated capillaries are restricted to the medial-posterior core region of the SFO and associated with a higher BBB permeability. In contrast to non-fenestrated vessels, fenestrated capillaries are encased in a scaffold created by pericytes and embedded in a network of tanycytic processes. Analysis of c-Fos expression following systemic injections of angiotensin II or hypertonic NaCl reveals distinct neuronal populations responding to these stimuli. Hypertonic NaCl activates ∼13% of SFO neurons located in the shell. Angiotensin II-sensitive neurons represent ∼35% of SFO neurons and their location varies between sexes. Our study provides a comprehensive description of the organization of diverse cellular elements within the SFO, facilitating future investigations in this important brain area. |
2,330,964 | Surgical strategy for symptomatic pineal cyst: is endoscopit third ventriculostomy necessary in addition to cyst fenestration? | Symptomatic large pineal cyst (PC) remains a rare entity. The stable natural course of asymptomatic PCs is well established. However, large cysts may cause pressure-related symptoms necessitating surgical intervention. The surgical strategy for symptomatic PCs is still controversial. Regardless of the approach, total resection of the cyst is not mandatory. The endoscopic approach allows cyst fenestration in patients with associated obstructive hydrocephalus. On the other hand, the necessity of simultaneous endoscopic third ventriculostomy (ETV) is still debatable. Here, we report a case of a woman who underwent endoscopic cyst fenestration, biopsy, and third ventriculostomy for a large symptomatic PC and discuss the surgical strategy. A 30-year-old woman presented with headache and diplopia, MRI showed a large PC and accompanying obstructive hydrocephalus. Simultaneous cyst fenestration, biopsy and ETV with endoscopy was successfully completed. She had an uneventful recovery period with immediate relief of symptoms. Although, the aqueduct was communicated due to cyst shrinkage, the patency of the third ventricular stoma was demonstrated in long-term follow-up scans. Based on clinical course of the present case, we concluded that ETV in addition to cyst fenestration should be considered necessary and beneficial in cases of large symptomatic PC with associated hydrocephalus whenever an endoscopic intraventricular approach is considered. |
2,330,965 | Application of developmental principles for spinal cord repair after injury. | The superiority of the mammalian central nervous system (CNS) compared with other vertebrates does not involve an advanced capacity for regeneration, and any insult results in irreversible functional loss. Spinal cord injury (SCI) is one example of CNS trauma affecting thousands of individuals, mostly young, each year. Despite enormous progress in our comprehension of the molecular and cellular mechanisms underlying the pathophysiology after SCI, also providing targets for therapeutic interventions, no efficient therapy exists as yet, emphasizing the need for further research. A breadth of studies have demonstrated that, after SCI, principles of development come into play either to promote or to prohibit spontaneous regeneration, and their appropriate manipulation has the potential to contribute towards functional recovery. In this overview, some of the most recent and important studies are discussed.These offer explicitly novel input from the field of development to the field of CNS repair regarding the modification of the inhibitory environment of the injured spinal cord - mainly referring to the glial scar - the activation of endogenous cell populations such as ependymal stem cells and oligodendrocyte precursor cells, and the developmental transcriptional program that is transiently activated in neurons after injury. Furthermore, current advances in stem cell technology are highlighted in terms of refinement and precise design of the appropriate stem cell population to be transplanted, not only for cell replacement but also for modulation of the host environment. As single-dimension applications have not yet proved clinically successful, it is suggested that combinatorial strategies tackling more than one target might be more effective. |
2,330,966 | Right Ventricular Shape Feature Quantification for Evaluation of Pulmonary Hypertension: Feasibility and Preliminary Associations With Clinical Outcome Submitted for Publication. | This study aimed to demonstrate feasibility of statistical shape analysis techniques to identify distinguishing features of right ventricle (RV) shape as related to hemodynamic variables and outcome data in pulmonary hypertension (PH). Cardiovascular magnetic resonance images were acquired from 50 patients (33 PH, 17 non-PH). Contemporaneous right heart catheterization data were collected for all individuals. Outcome was defined by all-cause mortality and hospitalization for heart failure. RV endocardial borders were manually segmented, and three-dimensional surfaces reconstructed at end diastole and end systole. Registration and harmonic mapping were then used to create a quantitative correspondence between all RV surfaces. Proper orthogonal decomposition was performed to generate modes describing RV shape features. The first 15 modes captured over 98% of the total modal energy. Two shape modes, 8 (free wall expansion) and 13 (septal flattening), stood out as relating to PH state (mode 13: r = 0.424, p = 0.002; mode 8: r = 0.429, p = 0.002). Mode 13 was significantly correlated with outcome (r = 0.438, p = 0.001), more so than any hemodynamic variable. Shape analysis techniques can derive unique RV shape descriptors corresponding to specific, anatomically meaningful features. The modes quantify shape features that had been previously only qualitatively related to PH progression. Modes describing relevant RV features are shown to correlate with clinical measures of RV status, as well as outcomes. These new shape descriptors lay the groundwork for a noninvasive strategy for identification of failing RVs, beyond what is currently available to clinicians. |
2,330,967 | The Acute Effect of Packed Red Blood Cell Transfusion in Mechanically Ventilated Children after the Norwood Operation. | Packed red blood cell (PRBC) transfusions are commonly administered in pediatric patients following the Norwood operation. This study was conducted to determine the effect of PRBC transfusions on hemodynamic parameters in pediatric patients with single-ventricle physiology and parallel circulation. A single-center, retrospective chart review was conducted. Pediatric patients admitted to the cardiac intensive care unit after Norwood operation between 2017 and 2018 were identified. Hemodynamic parameters were collected within a four-hour period before and after a PRBC transfusion. Univariate analyses using paired t tests were conducted to compare blood gas values before and after PRBC transfusion. Next, multivariate regression analyses were conducted to model the impact of transfusion volume, change in hemoglobin levels, and change in FiO2 on the change in PaO2 and PaCO2. These analyses included data from 33 eligible patients who received a PRBC transfusion following a Norwood operation. The hemoglobin levels (p < 0.01) and the PaO2/FiO2 ratio (p = 0.04) were significantly increased, while arterial lactate levels (p = 0.03) were significantly decreased following the transfusion. Transfusion for a pre-transfusion hemoglobin of 12.4 g/dL appears to provide greatest reduction in lactate, used as a surrogate marker for systemic oxygen delivery. No significant changes were found in arterial pH, PaO2, and PaCO2. PRBC transfusions following the Norwood operation may be a useful intervention to increase systemic oxygen delivery, improving PaO2/FiO2 ratio and improving serum lactate. The benefits of PRBC transfusions must be weighed against previously identified risks on a patient-specific basis. Further studies are warranted to further delineate the effects of such transfusions in this population. |
2,330,968 | Multi-omic Analysis of Non-human Primate Heart after Partial-body Radiation with Minimal Bone Marrow Sparing.<Pagination><StartPage>352</StartPage><EndPage>371</EndPage><MedlinePgn>352-371</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1097/HP.0000000000001478</ELocationID><Abstract><AbstractText>High-dose radiation exposure results in hematopoietic and gastrointestinal acute radiation syndromes followed by delayed effects of acute radiation exposure, which encompasses multiple organs, including heart, kidney, and lung. Here we sought to further characterize the natural history of radiation-induced heart injury via determination of differential protein and metabolite expression in the heart. We quantitatively profiled the proteome and metabolome of left and right ventricle from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Global proteome profiling identified more than 2,200 unique proteins, with 220 and 286 in the left and right ventricles, respectively, showing significant responses across at least three time points compared to baseline levels. High-throughput targeted metabolomics analyzed a total of 229 metabolites and metabolite combinations, with 18 and 22 in the left and right ventricles, respectively, showing significant responses compared to baseline levels. Bioinformatic analysis performed on metabolomic and proteomic data revealed pathways related to inflammation, energy metabolism, and myocardial remodeling were dysregulated. Additionally, we observed dysregulation of the retinoid homeostasis pathway, including significant post-radiation decreases in retinoic acid, an active metabolite of vitamin A. Significant differences between left and right ventricles in the pathology of radiation-induced injury were identified. This multi-omic study characterizes the natural history and molecular mechanisms of radiation-induced heart injury in NHP exposed to PBI with minimal bone marrow sparing.</AbstractText><CopyrightInformation>Copyright © 2021 Health Physics Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zalesak-Kravec</LastName><ForeName>Stephanie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Weiliang</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Pengcheng</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Jianshi</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Tian</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Defnet</LastName><ForeName>Amy E</ForeName><Initials>AE</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moise</LastName><ForeName>Alexander R</ForeName><Initials>AR</Initials><AffiliationInfo><Affiliation>Medical Sciences Division, Northern Ontario School of Medicine, Sudbury, ON, Canada; Departments of Chemistry and Biochemistry, and Biology and Biomolecular Sciences Program, Laurentian University, Sudbury, ON, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Farese</LastName><ForeName>Ann M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>MacVittie</LastName><ForeName>Thomas J</ForeName><Initials>TJ</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kane</LastName><ForeName>Maureen A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>HHSN272201000046C</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 GM066706</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>HHSN272201100013I</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Health Phys</MedlineTA><NlmUniqueID>2985093R</NlmUniqueID><ISSNLinking>0017-9078</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D054508" MajorTopicYN="Y">Acute Radiation Syndrome</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001853" MajorTopicYN="Y">Bone Marrow</DescriptorName><QualifierName UI="Q000528" MajorTopicYN="N">radiation effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011323" MajorTopicYN="Y">Primates</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D040901" MajorTopicYN="Y">Proteomics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011829" MajorTopicYN="N">Radiation Dosage</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011832" MajorTopicYN="Y">Radiation Injuries</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><CoiStatement>The authors declare no conflicts of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>9</Month><Day>21</Day><Hour>12</Hour><Minute>35</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>9</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>3</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34546217</ArticleId><ArticleId IdType="mid">NIHMS1716534</ArticleId><ArticleId IdType="pmc">PMC8554778</ArticleId><ArticleId IdType="doi">10.1097/HP.0000000000001478</ArticleId><ArticleId IdType="pii">00004032-202110000-00006</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Abdalla S, Fu X, Elzahwy SS, Klaetschke K, Streichert T, Quitterer U. 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Here we sought to further characterize the natural history of radiation-induced heart injury via determination of differential protein and metabolite expression in the heart. We quantitatively profiled the proteome and metabolome of left and right ventricle from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Global proteome profiling identified more than 2,200 unique proteins, with 220 and 286 in the left and right ventricles, respectively, showing significant responses across at least three time points compared to baseline levels. High-throughput targeted metabolomics analyzed a total of 229 metabolites and metabolite combinations, with 18 and 22 in the left and right ventricles, respectively, showing significant responses compared to baseline levels. Bioinformatic analysis performed on metabolomic and proteomic data revealed pathways related to inflammation, energy metabolism, and myocardial remodeling were dysregulated. Additionally, we observed dysregulation of the retinoid homeostasis pathway, including significant post-radiation decreases in retinoic acid, an active metabolite of vitamin A. Significant differences between left and right ventricles in the pathology of radiation-induced injury were identified. This multi-omic study characterizes the natural history and molecular mechanisms of radiation-induced heart injury in NHP exposed to PBI with minimal bone marrow sparing.<CopyrightInformation>Copyright © 2021 Health Physics Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zalesak-Kravec</LastName><ForeName>Stephanie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Weiliang</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Pengcheng</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Jianshi</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Tian</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Defnet</LastName><ForeName>Amy E</ForeName><Initials>AE</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moise</LastName><ForeName>Alexander R</ForeName><Initials>AR</Initials><AffiliationInfo><Affiliation>Medical Sciences Division, Northern Ontario School of Medicine, Sudbury, ON, Canada; Departments of Chemistry and Biochemistry, and Biology and Biomolecular Sciences Program, Laurentian University, Sudbury, ON, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Farese</LastName><ForeName>Ann M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>MacVittie</LastName><ForeName>Thomas J</ForeName><Initials>TJ</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kane</LastName><ForeName>Maureen A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>HHSN272201000046C</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 GM066706</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>HHSN272201100013I</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Health Phys</MedlineTA><NlmUniqueID>2985093R</NlmUniqueID><ISSNLinking>0017-9078</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D054508" MajorTopicYN="Y">Acute Radiation Syndrome</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001853" MajorTopicYN="Y">Bone Marrow</DescriptorName><QualifierName UI="Q000528" MajorTopicYN="N">radiation effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011323" MajorTopicYN="Y">Primates</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D040901" MajorTopicYN="Y">Proteomics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011829" MajorTopicYN="N">Radiation Dosage</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011832" MajorTopicYN="Y">Radiation Injuries</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><CoiStatement>The authors declare no conflicts of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>9</Month><Day>21</Day><Hour>12</Hour><Minute>35</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>9</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>3</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34546217</ArticleId><ArticleId IdType="mid">NIHMS1716534</ArticleId><ArticleId IdType="pmc">PMC8554778</ArticleId><ArticleId IdType="doi">10.1097/HP.0000000000001478</ArticleId><ArticleId IdType="pii">00004032-202110000-00006</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Abdalla S, Fu X, Elzahwy SS, Klaetschke K, Streichert T, Quitterer U. 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The objective of the study is to quantitatively assess and compare the exposure and microsurgical maneuverability of three absolutely endoscopic keyhole approaches, including interhemispheric transcallosal transchoroidal (TCTC), frontal transforminal transchoroidal (TFTC) and supraorbital subfrontal translamina terminalis (SFTL) approaches.<AbstractText Label="METHODS" NlmCategory="METHODS">Anatomical dissections and exposure of the important structures of the third ventricle were performed using six formalin-fixed cadaveric human heads (twelve sides) under endoscope. Tubular retractor system was used in the TFTC approach. Quantitative anatomical relationship between the important landmarks were obtained. Moreover, the exposure and surgical operability of three approaches were evaluated through applying the rating scale and accomplishing the quantitative anatomic analysis, area of surgical freedom and angle of attack.<AbstractText Label="RESULTS" NlmCategory="RESULTS">The mediolateral, anteroposterior (AM: between aqueduct and mammillary body; IM: between infundibular recess and mammillary body) and superoinferior distance of TCTC, TFTC and SFTL approaches were 4.0±1.0, 4.2±0.4, 4.1±1.1mm; 17.3±1.4, 17.6±0.5, 12.8±3.3mm (AM); 7.7±0.3, 7.8±0.5 mm, not measured (IM); and 5.6±0.3, 7.8±0.8, 7.8±1.5mm, respectively. Similar to TFTC, the exposed landmarks of TCTC were almost scored a "4" by three neurosurgeons except the infundibular recess scored a "3" according to the rating scale. During the SFTL approach, apart from the roof, the majority of the landmarks were scored a "4" except for the infundibular recess, which was scored a "3". The mean area of surgical freedom of TCTC (0° endoscope: 220±47; 30°: 247±56mm2) was not significantly different from that of TFTC approach (0° endoscope: 216±49; 30°: 245±53mm2) under same endoscope, P>0.05. Mean angle of attack of TCTC (0° endoscope: 21±4°; 30°: 26±4°) was significantly larger than that of TFTC approach (0° endoscope: 16±3°; 30°: 19±3°), P<0.05.<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Purely endoscopic TCTC and TFTC approaches offer brilliant exposure of the anterior, middle and posterior third ventricle. TCTC approach may have better surgical maneuverability than TFTC approach. Despite the long working distance, the whole third ventricle are exposed well except for the roof in the SFTL approach, and surgical manipulation can be accomplished smoothly. |
2,330,969 | Brain low-grade gliomas with high-grade spinal localization: report of a clinical case and systematic literature review. | Oncological aggressiveness and the ability to present distant localizations are known in high-grade gliomas (HGGs), but the knowledge about the possible aggressiveness of LGGs is scarce, especially concerning possible spinal localization.</AbstractText>A systematic search of low-grade gliomas (LGGs) with spinal localization on the three primary online databases (PubMed/MEDLINE, Embase, and Cochrane) was conducted. We included adult patients with histological diagnosis of intracranial LGG and specified WHO grade showing a remote spinal localization during follow-up. Additionally, we present a case of a left temporal LGG presenting a spinal localization fourteen years after the first appearance. We compared the survival rates of LGGs in our series with those of LGGs without spinal localizations.</AbstractText>Seven articles dealing with the subject and eight patients were considered (including our case), with a mean age at diagnosis of 42.25 years (range 26-69 years). The mean latency between a diagnosis of intracranial LGGs and a spinal localization occurrence was 7.37 years (range 2-14 years), and an increased WHO grade of the spinal localization compared to the brain LGG was observed in all patients. There was no sign of intracranial progression at the time of spinal glioma diagnosis in four cases, including ours. Survival at ten years was 28% against a 10-year survival rate of 65-71% for LGGs without distant localization, as reported in the literature.</AbstractText>Spinal metastasis of intracranial LGGs is an adverse prognostic factor. Surgical violation of ventricles can play a role in the pathophysiology of CSF spread of tumor cells in LGGs.</AbstractText> |
2,330,970 | An early analysis of Codman® CerebroFlo® Endexo coated ventricular catheters in the setting of intraventricular hemorrhage. | Intraventricular hemorrhages (IVH) are a potentially fatal diagnosis that must be managed properly to avoid devastating complications. While existing catheters have offered relative success, their reactive composition makes them prone to eventual obstruction and thrombotic activation. This problematic outcome has led to emergence of the Codman<sup>®</sup> CerebroFlo<sup>®</sup> EVD Catheter (Integra LifeSciences, Princeton, NJ, USA). This catheter is the first of its kind to incorporate the Endexo additive, a slightly reactive, surface modifying molecule that prevents protein adhesion and biomatter accumulation. Despite the promising early outcomes, there are no PubMed articles characterizing this device, with minimal literature highlighting its clinical value. Through a contemporary literature review, the authors will characterize the technological principles, indications, and advantages of this novel device. The authors reported the early findings of this catheter, with studies showing 99% reduction in thrombotic activity with an additional 89% reduction in catheter obstruction compared to its competitors. Areas of uncertainty regarding this device are discussed, with its lack of antibiotic coating being a possible area for clinical concern. In conclusion, the CerebroFlo<sup>®</sup> catheter is a novel and effective tool in the management of IVH that should be widely considered for the management of IVH. |
2,330,971 | Deciphering the role of nanoparticles for management of bacterial meningitis: an update on recent studies. | Meningitis is an inflammation of the protective membranes called meninges and fluid adjacent the brain and spinal cord. The inflammatory progression expands all through subarachnoid space of the brain and spinal cord and occupies the ventricles. The pathogens like bacteria, fungi, viruses, or parasites are main sources of infection causing meningitis. Bacterial meningitis is a life-threatening health problem that which needs instantaneous apprehension and treatment. Nesseria meningitidis, Streptococcus pneumoniae, and Haemophilus flu are major widespread factors causing bacterial meningitis. The conventional drug delivery approaches encounter difficulty in crossing this blood-brain barrier (BBB) and therefore are insufficient to elicit the desired pharmacological effect as required for treatment of meningitis. Therefore, application of nanoparticle-based drug delivery systems has become imperative for successful dealing with this deadly disease. The nanoparticles have ability to across BBB via four important transport mechanisms, i.e., paracellular transport, transcellular (transcytosis), endocytosis (adsorptive transcytosis), and receptor-mediated transcytosis. In this review, we reminisce distinctive symptoms of meningitis, and provide an overview of various types of bacterial meningitis, with a focus on its epidemiology, pathogenesis, and pathophysiology. This review describes conventional therapeutic approaches for treatment of meningitis and the problems encountered by them while transmitting across tight junctions of BBB. The nanotechnology approaches like functionalized polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, nanoemulsion, liposomes, transferosomes, and carbon nanotubes which have been recently evaluated for treatment or detection of bacterial meningitis have been focused. This review has also briefly summarized the recent patents and clinical status of therapeutic modalities for meningitis. |
2,330,972 | Olfactory receptor Olfr78 (prostate-specific G protein-coupled receptor PSGR) expression in arterioles supplying skeletal and cardiac muscles and in arterioles feeding some murine organs. | The olfactory receptor Olfr78 (prostate-specific G protein-coupled receptor PSGR) is a member of the G protein-coupled receptor family mediating olfactory chemosensation, but it is additionally expressed in other tissues. Olfr78 expressed in kidney participates in blood pressure regulation, and in prostate it plays a role in the development of cancer. We here screened many organs/tissues of transgenic mice co-expressing β-galactosidase with Olfr78. X-gal-positive cells were detectable in smooth muscle cells of numerous arterioles of striated muscles (heart ventricles and skeletal muscles of various embryological origin). In addition, in most organs where we found expression of Olfr78 mRNA, X-gal staining was restricted to smooth muscle cells of small blood vessels. The dominant expression of Olfr78 in arteriolar smooth muscle cells supports the concept of an important role in blood pressure regulation and suggests a participation in the fine tuning of blood supply especially of striated muscles. This should be considered when targeting Olfr78 in other contexts such as prostate cancer. |
2,330,973 | Lycopene-Loaded Microemulsion Regulates Neurogenesis in Rats with A<i>β</i>-Induced Alzheimer's Disease Rats Based on the Wnt/<i>β</i>-catenin Pathway. | To investigate the effects of lycopene-loaded microemulsion (LME) on the cognitive function and neurogenesis in the dentate gyrus (DG) of the hippocampus and subventricular (SVZ) region of rats with amyloid β</i>- (Aβ</i>-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/β</i>-catenin pathway.</AbstractText>Healthy Wistar rats were divided into four groups: the blank control (CON), AD control, traditional lycopene (LOO), and LME groups. The CON and AD groups were fed with normal saline, while the LOO group was fed with traditional lycopene, and the LME group was fed with lycopene-loaded microemulsion. Behavioral tests were performed after three weeks of gastric administration. Immunofluorescence-labeled cells were used to observe the differentiation and maturation of new nerve cells in the DG of the hippocampus and SVZ region. qRT-PCR and Western blotting detected the expression of neurogenesis genes and Wnt/β</i>-catenin pathway-related proteins, respectively.</AbstractText>On the Morris water maze test, LME rats had significantly shortened movement trajectory on the searching platform, reduced escape latency time, and increased residence time on the original platform quadrant. In addition, more LME rats crossed the platform when it was removed. Thus, LME can improve the spatial learning and memory of Aβ</i>-induced AD rats. On qRT-PCR, LME significantly increased Reelin, Nestin, and Pax6 gene expressions, which regulate neurogenesis. Immunofluorescence showed that LME could significantly increase BrdU+</sup>, Dcx+</sup>, BrdU+</sup>/Neun+</sup>, BrdU+</sup>/Dcx+</sup> cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1+</sup> and Iba1+</sup>/BrdU+</sup> cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/β</i>-catenin pathway by upregulating Wnt3a, β</i>-catenin, Disheveled (Dvl), and p-GSK3β</i> and downregulating p-β</i>-catenin and GSK3β</i>.</AbstractText>LME attenuates cognitive impairment in Aβ</i>-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/β</i>-catenin pathway.</AbstractText>Copyright © 2021 Wen-jing Ning et al.</CopyrightInformation> |
2,330,974 | Choroid plexus APP regulates adult brain proliferation and animal behavior. | Elevated amyloid precursor protein (APP) expression in the choroid plexus suggests an important role for extracellular APP metabolites such as sAPPα in cerebrospinal fluid. Despite widespread <i>App</i> brain expression, we hypothesized that specifically targeting choroid plexus expression could alter animal physiology. Through various genetic and viral approaches in the adult mouse, we show that choroid plexus APP levels significantly impact proliferation in both subventricular zone and hippocampus dentate gyrus neurogenic niches. Given the role of Aβ peptides in Alzheimer disease pathogenesis, we also tested whether favoring the production of Aβ in choroid plexus could negatively affect niche functions. After AAV5-mediated long-term expression of human mutated <i>APP</i> specifically in the choroid plexus of adult wild-type mice, we observe reduced niche proliferation, reduced hippocampus APP expression, behavioral defects in reversal learning, and deficits in hippocampal long-term potentiation. Our findings highlight the unique role played by the choroid plexus in regulating brain function and suggest that targeting APP in choroid plexus may provide a means to improve hippocampus function and alleviate disease-related burdens. |
2,330,975 | External Ventricular Drainage Complication Risks and Accuracy Analysis. | The setting of external ventricular drainage (EVD) is one of the most frequent procedures in the neurosurgical practice. However, complication risks of this procedure may grow from 5% to 39%. The number of publications concerning the advancement of ventricular drainage setting technique and complication risks identification is increasing year after year. We posed a question on the dependence of complication risks and catheter setting accuracy on the different factors of routine practice of the N. N. Burdenko National Medical Research Center for neurosurgery within the scope of this work.</AbstractText>The data on patients whose EVD was set in the premotor area in 2019 were collected retrospectively. The surgeons were divided into 3 groups according to their experience valued in years.</AbstractText>The result of drainage setting was considered satisfactory if its end was in the frontal horn or body of the ipsilateral ventricle. Generally, 122 patients passed EVD placement during 2019. According to computed tomography scans of the brain, the drainage position was satisfactory in 85 patients (75.9%) and unsatisfactory in 27 patients (24.1%).</AbstractText>The procedures were performed by surgeons with <2 years of experience in 16.1% of cases, 2-5 years of experience in 25% of cases, and >5 years of experience in 58.9% of cases. The complication risk and accuracy of drainage setting do not depend on surgeon experience, type of bone access, and position in the premotor area.</AbstractText>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,330,976 | A portable multi-sensor module for monitoring external ventricular drains. | External ventricular drains (EVDs) are used clinically to relieve excess fluid pressure in the brain. However, EVD outflow rate is highly variable and typical clinical flow tracking methods are manual and low resolution. To address this problem, we present an integrated multi-sensor module (IMSM) containing flow, temperature, and electrode/substrate integrity sensors to monitor the flow dynamics of cerebrospinal fluid (CSF) drainage through an EVD. The impedimetric sensors were microfabricated out of biocompatible polymer thin films, enabling seamless integration with the fluid drainage path due to their low profile. A custom measurement circuit enabled automated and portable sensor operation and data collection in the clinic. System performance was verified using real human CSF in a benchtop EVD model. Impedimetric flow sensors tracked flow rate through ambient temperature variation and biomimetic pulsatile flow, reducing error compared with previous work by a factor of 6.6. Detection of sensor breakdown using novel substrate and electrode integrity sensors was verified through soak testing and immersion in bovine serum albumin (BSA). Finally, the IMSM and measurement circuit were tested for 53 days with an RMS error of 61.4 μL/min. |
2,330,977 | DCE-MRI of Brain Fluid Barriers: <i>In Vivo</i> Water Cycling at the Human Choroid Plexus. | Metabolic deficits at brain-fluid barriers are an increasingly recognized feature of cognitive decline in older adults. At the blood-cerebrospinal fluid barrier, water is transported across the choroid plexus (CP) epithelium against large osmotic gradients via processes tightly coupled to activity of the sodium/potassium pump. Here, we quantify CP homeostatic water exchange using dynamic contrast-enhanced MRI and investigate the association of the water efflux rate constant (k<sub>co</sub>) with cognitive dysfunction in older individuals. Temporal changes in the longitudinal relaxation rate constant (R<sub>1</sub>) after contrast agent bolus injection were measured in a CP region of interest in 11 participants with mild cognitive dysfunction [CI; 73 ± 6 years] and 28 healthy controls [CN; 72 ± 7 years]. k<sub>co</sub> was determined from a modified two-site pharmacokinetic exchange analysis of the R<sub>1</sub> time-course. K<sup>trans</sup>, a measure of contrast agent extravasation to the interstitial space was also determined. Cognitive function was assessed by neuropsychological test performance. k<sub>co</sub> averages 5.8 ± 2.7 s<sup>-1</sup> in CN individuals and is reduced by 2.4 s<sup>-1</sup> [<i>ca</i>. 40%] in CI subjects. Significant associations of k<sub>co</sub> with global cognition and multiple cognitive domains are observed. K<sup>trans</sup> averages 0.13 ± 0.07 min<sup>-1</sup> and declines with age [-0.006 ± 0.002 min<sup>-1</sup> yr<sup>-1</sup>], but shows no difference between CI and CN individuals or association with cognitive performance. Our findings suggest that the CP water efflux rate constant is associated with cognitive dysfunction and shows an age-related decline in later life, consistent with the metabolic disturbances that characterize brain aging. |
2,330,978 | Proteomic Analysis of Cardiac Adaptation to Exercise by High Resolution Mass Spectrometry. | Regular exercise has many health benefits, among which is a significant reduction of cardiovascular risk. Although many beneficial effects of exercise are well described, the exact mechanisms by which exercise confers cardiovascular benefits are yet to be fully understood. In the current study, we have used high resolution mass spectrometry to determine the proteomic responses of the heart to exercise training in mice. The impact of exercise-induced oxidative stress on modifications of cardiomyocyte proteins with lipid peroxidation biomarker 4-hydroxynonenal (4-HNE) was examined as well. Fourteen male mice were randomized into the control (sedentary) group and the exercise group that was subjected to a swim exercise training program for 5 days a week for 5 months. Proteins were isolated from the left ventricular tissue, fractionated and digested for shotgun proteomics. Peptides were separated by nanoliquid chromatography and analyzed on an Orbitrap Fusion mass spectrometer using high-energy collision-induced dissociation and electron transfer dissociation fragmentation. We identified distinct ventricular protein signatures established in response to exercise training. Comparative proteomics identified 23 proteins that were upregulated and 37 proteins that were downregulated with exercise, in addition to 65 proteins that were identified only in ventricular tissue samples of exercised mice. Most of the proteins specific to exercised mice are involved in respiratory electron transport and/or implicated in glutathione conjugation. Additionally, 10 proteins were found to be modified with 4-HNE. This study provides new data on the effects of exercise on the cardiac proteome and contributes to our understanding of the molecular mechanisms underlying the beneficial effects of exercise on the heart. |
2,330,979 | Immersion pulmonary oedema in a triathlete - a diagnostic challenge in sports cardiology. | Immersion pulmonary oedema, also referred to as swimming-induced pulmonary oedema, is a form of pulmonary oedema which usually occurs during swimming in cold water. The condition is most common in triathlon athletes; it was first reported in military divers. The main symptoms include acute dyspnoea, cough, and occasionally haemoptysis, which usually subside within approximately 48 hours. The pathomechanism is not fully understood, but oedema is suspected to be due to an increased systemic vascular resistance that overloads the left ventricle. The diagnostic process can be challenging and require multiple stages to rule out a number of other possible conditions. In view of the circumstances in which incidents typically occur, immersion pulmonary oedema poses an immediate life threat to individuals involved in selected forms of physical activity, where survival is often determined by appropriate training of medical services. |
2,330,980 | The Impact of Bone Mineral Biomarkers on Cardiac Dysfunction in Predialysis Chronic Kidney Disease Children. | To evaluate the association of bone mineral biomarkers of calcium, phosphorus metabolism, and 25-hydroxy vitamin D with diastolic dysfunction of the left ventricle and left ventricle mass in predialysis chronic kidney children. Patients and Methods</i>. A cross-sectional observational study was conducted on 60 children with chronic kidney disease and treated by conservative treatment from October 2018 to September 2019 in the Pediatric Nephrology and Cardiology Department at our University Hospital.</AbstractText>The most common causes of CKD were congenital renal anomalies accounted for 22 (36.67%) of the studied cases. The mean age of children was 7.05 ± 2.74 years, and 32 (53.33%) were males. The children who had a normal diastolic function were 32 (53.33%), while those who had diastolic dysfunction were 28 (46.67%). There was a statistically significant in serum phosphorus (p</i> value = 0.03), serum PTH (p</i> value = 0.002), and hypertension (p</i> value = 0.03). There was a statistically significant positive correlation between LVMI and iPTH level (r</i> = 0.89, p</i> ≤ 0.0001), 25(OH) cholecalciferol (r</i> = -0.27, p</i> = 0.04), serum Ca (r</i> = -0.37, p</i> = 0.004), and serum phosphorus (r</i> = -0.45, p</i> = 0.0003).</AbstractText>Our results revealed that hyperparathyroidism, hyperphosphatemia, and hypertension were significantly associated with diastolic dysfunction while hypovitaminosis D was not significantly associated. Vitamin D deficiency was prevalent in all children with CKD. Biomarkers of mineral bone density were significantly associated with left ventricular hypertrophy and increased left ventricular mass index.</AbstractText>Copyright © 2021 Safaa Ali et al.</CopyrightInformation> |
2,330,981 | Microvessel stenosis, enlarged perivascular spaces, and fibrinogen deposition are associated with ischemic periventricular white matter hyperintensities. | Periventricular white matter hyperintensities (pvWMH) are neuroimaging abnormalities surrounding the lateral ventricles that are apparent on magnetic resonance imaging (MRI). They are associated with age, neurodegenerative disease, and cerebrovascular risk factors. While pvWMH ultimately represent a loss of white matter structural integrity, the pathological causes are heterogeneous in nature, and currently, cannot be distinguished using neuroimaging alone. pvWMH could occur because of a combination of small vessel disease (SVD), ependymal loss, blood-brain barrier dysfunction, and microgliosis. In this study we aimed to characterize microvascular stenosis, fibrinogen extravasation, and microgliosis within pvWMH with and without imaging evidence of periventricular infarction. Using postmortem neuroimaging of human brains (n = 20), we identified pvWMH with and without periventricular infarcts (PVI). We performed histological analysis of microvessel stenosis, perivascular spaces, microgliosis, and immunohistochemistry against fibrinogen as a measure of serum protein extravasation. Herein, we report distinctions between pvWMH with and without periventricular infarcts based on associations with microvessel stenosis, enlarged perivascular spaces, and fibrinogen IHC. Microvessel stenosis was significantly associated with PVI and with cellular deposition of fibrinogen in the white matter. The presence of fibrinogen was associated with PVI and increased number of microglia. These findings suggest that neuroimaging-based detection of infarction within pvWMH may help distinguish more severe lesions, associated with underlying microvascular disease and BBB dysfunction, from milder pvWMH that are a highly frequent finding on MRI. |
2,330,982 | Shape and volume changes of the superior lateral ventricle after electroconvulsive therapy measured with ultra-high field MRI. | The subventricular zone (SVZ) of the lateral ventricles harbors neuronal stem cells in adult mammals. Rodent studies report neurogenic effects in the SVZ of electroconvulsive stimulation. We hypothesize that if this finding translates to depressed patients undergoing electroconvulsive therapy (ECT), this would be reflected in shape changes at the SVZ. Using T1-weighted MR images acquired at ultra-high field strength (7T), the shape and volume of the ventricles were compared from pre to post ECT after 10 ECT sessions (in patients twice weekly) or 5 weeks apart (controls) using linear mixed models with age and gender as covariates. Ventricle shape significantly changed and volume significantly decreased over time in patients for the left ventricle, but not in controls. The decrease in volume of the ventricles was associated to a decrease in depression scores, and an increase in the left dentate gyrus, However, the shape changes of the ventricles were not restricted to the neurogenic niche in the lateral walls of the ventricles, providing no clear evidence for neurogenesis as sole explanation of volume changes in the ventricles after ECT. |
2,330,983 | 6-Gingerol protects against cerebral ischemia/reperfusion injury by inhibiting NLRP3 inflammasome and apoptosis via TRPV1 / FAF1 complex dissociation-mediated autophagy. | Our previous studies demonstrated that autophagy alleviates cerebral I/R injury by inhibiting NLRP3 inflammasome-mediated inflammation. 6-Gingerol, a phenolic compound extracted from ginger, was reported to possess potent antiapoptotic and anti-inflammatory activities and is associated with autophagy. However, the effects of 6-Gingerol in cerebral I/R injury have not been elucidated, and whether they involve autophagy-induced NLRP3 inflammasome inhibition remains unclear.</AbstractText>Adult male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, followed by reperfusion for 24 h. 6-Gingerol and 3-methyladenine (3-MA) were injected intraperitoneally, and si-TRPV1 was injected via the lateral ventricle. Cerebral infarct volume, brain edema, neurological deficits, HE and Nissl were used to evaluate the morphological and functional changes of brain tissue, respectively. TRPV1, FAF1, autophagy related (LC3II/I, P62, Beclin1), inflammation related (NLRP3, cleaved-caspase-1, caspase-1, cleaved-IL-1β, IL-1β, cleaved-IL-18, IL-18) and apoptosis related (Bcl-2, Bax, cleaved-caspase-3) proteins were assessed by Western blot, immunofluorescence staining and coimmunoprecipitation, respectively. Enzyme linked immunosorbent assay (ELISA) was used to evaluate the changes in the expression levels of interleukin-1 (IL-1β) and interleukin-18(IL-18), respectively. The degree of neuronal apoptosis was evaluated by TUNEL staining. Neuronal ultrastructure was examined by transmission electron microscopy.</AbstractText>6-Gingerol treatment significantly reduced cerebral infarct volume, improved brain edema and neurological scores, and reversed brain histomorphological damage after I/R injury. In addition, 6-Gingerol significantly reduced NLRP3 inflammasome-derived inflammation and neuronal apoptosis and upregulated autophagy. The autophagy inhibitor 3-MA rescued the effects of 6-Gingerol on the NLRP3 inflammasome and apoptosis. Moreover, the findings illustrated that 6-Gingerol inhibited autophagy-induced NLRP3 inflammasome activation and apoptosis through the dissociation of TRPV1 from FAF1.</AbstractText>In brief, 6-Gingerol exerts antiapoptotic and anti-inflammatory effects via TRPV1/FAF1 complex dissociation-mediated autophagy during cerebral I/R injury. Therefore, 6-Gingerol may be an effective drug for the treatment of I/R injury.</AbstractText>Copyright © 2021. Published by Elsevier B.V.</CopyrightInformation> |
2,330,984 | IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment. | Ependymal cells have multiple apical cilia that line the ventricular surfaces and the central canal of spinal cord. In cancer, the loss of ependymal cell polarity promotes the formation of different types of tumors, such as supratentorial anaplastic ependymomas, which are highly aggressive in children. IIIG9 (PPP1R32) is a protein restricted to adult ependymal cells located in cilia and in the apical cytoplasm and has unknown function. In this work, we studied the expression and localization of IIIG9 in the adherens junctions (cadherin/β-catenin-positive junctions) of adult brain ependymal cells using confocal and transmission electron microscopy. Through in vivo loss-of-function studies, ependymal denudation (single-dose injection experiments of inhibitory adenovirus) was observed, inducing the formation of ependymal cells with a "balloon-like" morphology. These cells had reduced cadherin expression (and/or delocalization) and cleavage of the cell death marker caspase-3, with "cilia rigidity" morphology (probably vibrational beating activity) and ventriculomegaly occurring prior to these events. Finally, after performing continuous infusions of adenovirus for 14 days, we observed total cell denudation and reactive parenchymal astrogliosis. Our data confirmed that IIIG9 is essential for the maintenance of adherens junctions of polarized ependymal cells. Eventually, altered levels of this protein in ependymal cell differentiation may increase ventricular pathologies, such as hydrocephalus or neoplastic transformation. |
2,330,985 | Intraparenchymal hemorrhage after serial ventricular reservoir taps in neonates with hydrocephalus and association with neurodevelopmental outcome at 2 years of age. | Decompressing the ventricles with a temporary device is often the initial neurosurgical intervention for preterm infants with hydrocephalus. The authors observed a subgroup of infants who developed intraparenchymal hemorrhage (IPH) after serial ventricular reservoir taps and sought to describe the characteristics of IPH and its association with neurodevelopmental outcome.</AbstractText>In this multicenter, case-control study, for each neonate with periventricular and/or subcortical IPH, a gestational age-matched control with reservoir who did not develop IPH was selected. Digital cranial ultrasound (cUS) scans and term-equivalent age (TEA)-MRI (TEA-MRI) studies were assessed. Ventricular measurements were recorded prior to and 3 days and 7 days after reservoir insertion. Changes in ventricular volumes were calculated. Neurodevelopmental outcome was assessed at 2 years corrected age using standardized tests.</AbstractText>Eighteen infants with IPH (mean gestational age 30.0 ± 4.3 weeks) and 18 matched controls were included. Reduction of the ventricular volumes relative to occipitofrontal head circumference after 7 days of reservoir taps was greater in infants with IPH (mean difference -0.19 [95% CI -0.37 to -0.004], p = 0.04). Cognitive and motor Z-scores were similar in infants with and those without IPH (mean difference 0.42 [95% CI -0.17 to 1.01] and 0.58 [95% CI -0.03 to 1.2]; p = 0.2 and 0.06, respectively). Multifocal IPH was negatively associated with cognitive score (coefficient -0.51 [95% CI -0.88 to -0.14], p = 0.009) and ventriculoperitoneal shunt with motor score (coefficient -0.50 [95% CI -1.6 to -0.14], p = 0.02) after adjusting for age at the time of assessment.</AbstractText>This study reports for the first time that IPH can occur after a rapid reduction of the ventricular volume during the 1st week after the initiation of serial reservoir taps in neonates with hydrocephalus. Further studies on the use of cUS to guide the amount of cerebrospinal fluid removal are warranted.</AbstractText> |
2,330,986 | Cognitive and gait outcomes after primary endoscopic third ventriculostomy in adults with chronic obstructive hydrocephalus. | The object of this study was to determine the short- and long-term efficacy of primary endoscopic third ventriculostomy (ETV) on cognition and gait in adults with chronic obstructive hydrocephalus.</AbstractText>Patients were prospectively accrued through the Adult Hydrocephalus Clinical Research Network patient registry. Patients with previously untreated congenital or acquired obstructive hydrocephalus were included in this study. Gait velocity was assessed using a 10-m walk test. Global cognition was assessed with the Montreal Cognitive Assessment (MoCA). Only patients with documented pre- and post-ETV gait analysis and/or pre- and post-ETV MoCA were included.</AbstractText>A total of 74 patients had undergone primary ETV, 42 of whom were analyzed. The remaining 32 patients were excluded, as they could not complete both pre- and post-ETV assessments. The mean age of the 42 patients, 19 (45.2%) of whom were female, was 51.9 ± 17.1 years (range 19-79 years). Most patients were White (37 [88.1%]), and the remainder were Asian. Surgical complications were minor. Congenital etiologies occurred in 31 patients (73.8%), with aqueductal stenosis in 23 of those patients (54.8%). The remaining 11 patients (26.2%) had acquired cases. The gait short-term follow-up cohort (mean 4.7 ± 4.1 months, 35 patients) had a baseline median gait velocity of 0.9 m/sec (IQR 0.7-1.3 m/sec) and a post-ETV median velocity of 1.3 m/sec (IQR 1.1-1.4 m/sec). Gait velocity significantly improved post-ETV with a median within-patient change of 0.3 m/sec (IQR 0.0-0.6 m/sec, p < 0.001). Gait velocity improvements were sustained in the long term (mean 14 ± 2.8 months, 12 patients) with a baseline median velocity of 0.7 m/sec (IQR 0.6-1.3 m/sec), post-ETV median of 1.3 m/sec (IQR 1.1-1.7 m/sec), and median within-patient change of 0.4 m/sec (IQR 0.2-0.6 m/sec, p < 0.001). The cognitive short-term follow-up cohort (mean 4.6 ± 4.0 months, 38 patients) had a baseline median MoCA total score (MoCA TS) of 24/30 (IQR 23-27) that improved to 26/30 (IQR 24-28) post-ETV. The median within-patient change was +1 point (IQR 0-2 points, p < 0.001). However, this change is not clinically significant. The cognitive long-term follow-up cohort (mean 14 ± 3.1 months, 15 patients) had a baseline median MoCA TS of 23/30 (IQR 22-27), which improved to 26/30 (IQR 25-28) post-ETV. The median within-patient change was +2 points (IQR 1-3 points, p = 0.007), which is both statistically and clinically significant.</AbstractText>Primary ETV can safely improve symptoms of gait and cognitive dysfunction in adults with chronic obstructive hydrocephalus. Gait velocity and global cognition were significantly improved, and the worsening of either was rare following ETV.</AbstractText> |
2,330,987 | A diagnostic tree for differentiation of adult pilocytic astrocytomas from high-grade gliomas. | To develop a diagnostic tree analysis (DTA) model based on demographical information and conventional MRI for differential diagnosis of adult pilocytic astrocytomas (PAs) and high-grade gliomas (HGGs; World Health Organization grade III-IV).</AbstractText>A total of 357 adult patients with pathologically confirmed PA (n = 65) and HGGs (n = 292) who underwent conventional MRI were included. The patients were randomly divided into training (n = 250) and validation (n = 107) datasets to assess the diagnostic performance of the DTA model. The DTA model was created using a classification and regression tree algorithm on the basis of demographical and MRI findings.</AbstractText>In the DTA model, tumor location (on cerebellum, brainstem, hypothalamus, optic nerve, or ventricle), cystic mass with mural nodule appearance, presence of infiltrative growth, and major axis (cutoff value, 2.9 cm) were significant predictors for differential diagnosis of adult PAs and HGGs. The AUC, accuracy, sensitivity, and specificity were 0.94 (95% confidence interval 0.86-1.00), 96.2%, 89.5%, and 97.7%, respectively, in the test set. The accuracy of the DTA model was significantly higher than the no-information rate in the test (96.2 % vs 85.0%, P < 0.001) set.</AbstractText>The DTA model based on MRI findings may be useful for differential diagnosis of adult PA and HGGs.</AbstractText>Copyright © 2021 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,330,988 | Which bidomain conductivity is the most important for modelling heart and torso surface potentials during ischaemia? | Mathematical simulations using the bidomain model, which represents cardiac tissue as consisting of an intracellular and an extracellular space, are a key approach that can be used to improve understanding of heart conditions such as ischaemia. However, key inputs to these models, such as the bidomain conductivity values, are not known with any certainty. Since efforts are underway to measure these values, it would be useful to be able to quantify the effect on model outputs of uncertainty in these inputs, and also to determine, if possible, which are the most important values to focus on in experimental studies. Our previous work has systematically studied the sensitivity of heart surface potentials to the bidomain conductivity values, and this was performed using a half-ellipsoidal model of the left ventricle. This study uses a bi-ventricular heart in a torso model and this time looks at the sensitivity of the torso surface potentials, as well as the heart surface potentials, to various conductivity values (blood, torso and the six bidomain conductivities). We found that both epicardial and torso potentials are the most sensitive to the intracellular longitudinal (along the cardiac fibres) conductivity (g<sub>il</sub>) with more minor sensitivity to the torso conductivity, and that changes in g<sub>il</sub> have a significant effect on the surface potential distributions on both the torso and the heart. |
2,330,989 | Morphology of the papillary muscles and the chordae tendineae of the ventricles of adult human hearts. | The papillary muscles (PM) play a vital role in atrioventricular (AV) valve function. The PM and their chordae tendineae (CT) regulate the closure of the AV valve during systole. The present study was undertaken to categorize the PM based on their shapes and variant patterns and CT based on their types and the branching pattern.</AbstractText>This study included formalin-fixed ten adult cadaveric heart specimens. We observed the number, shape, length, breadth, pattern, and presence of extra PM. The number of chordae attached to the tip of each PM was quantified. We classified the types and branching patterns of the chordae and their pattern of attachment to the cusps.</AbstractText>In the right ventricle, conical, truncated, and flat-topped PM were observed. The anterior PM had 5.3 ± 1.9, the posterior PM had 2.7 ± 2.1, and the septal PM had 3.5 ± 2.3 CT attached to it. In the left ventricle, we observed conical, truncated, flat-topped, bifurcate, and trifurcate shapes of PM. The anterior and the posterior PM had 7.7 ± 2.8 and 7.7 ± 2.7 CT attached to them, respectively. The true CT were cusp, cleft, and commissural and the false CT were pillar-wall, inter-pillar, and strut. We also found 3 branching patterns for the chordae (single, fan-shaped, and web forming).</AbstractText>The study explored the comparative morphology of PM and chordae in the right and left ventricles. The knowledge of the morphological pattern of PM and CT would contribute to the valvular function and aid in diagnosing conditions such as valve prolapse or regurgitation.</AbstractText>Copyright © 2021. Published by Elsevier Inc.</CopyrightInformation> |
2,330,990 | Lumped parameter models for two-ventricle and healthy and failing extracardiac Fontan circulations. | Fontan circulations are surgical strategies to treat infants born with single ventricle physiology. Clinical and mathematical definitions of Fontan failure are lacking, and understanding is needed of parameters indicative of declining physiologies. Our objective is to develop lumped parameter models of two-ventricle and single-ventricle circulations. These models, their mathematical formulations and a proof of existence of periodic solutions are presented. Sensitivity analyses are performed to identify key parameters. Systemic venous and systolic left ventricular compliances and systemic capillary and pulmonary venous resistances are identified as key parameters. Our models serve as a framework to study the differences between two-ventricle and single-ventricle physiologies and healthy and failing Fontan circulations. |
2,330,991 | Organic bipolar disorder secondary to central neurocytoma resection: a case report. | entral neurocytoma is a neuroepithelial tumor described by Hassoun in 1982, predominantly located in the midline at the level of the septum pellucidum, or in the lateral ventricles wall1. They represent approximately 50% of intraventricular lesions in adults, and they are in total 0.25-0.5% of intracranial tumors. |
2,330,992 | High Central Venous Pressure and Right Ventricle Size Are Related to Non-decreased Left Ventricle Stroke Volume After Negative Fluid Balance in Critically Ill Patients: A Single Prospective Observational Study. | <b>Background:</b> Optimal adjustment of cardiac preload is essential for improving left ventricle stroke volume (LVSV) and tissue perfusion. Changes in LVSV caused by central venous pressure (CVP) are the most important concerns in the treatment of critically ill patients. <b>Objectives:</b> This study aimed to clarify the changes in LVSV after negative fluid balance in patients with elevated CVP, and to elucidate the relationship between the parameters of right ventricle (RV) filling state and LVSV changes. <b>Methods:</b> This prospective cohort study included patients with high central venous pressure (CVP) (≥8 mmHg) within 24 h of ICU admission in the Critical Medicine Department of Peking Union Medical College Hospital. Patients were classified into two groups based on the LVSV changes after negative fluid balance. The cutoff value was 10%. The hemodynamic and echo parameters of the two groups were recorded at baseline and after negative fluid balance. <b>Results:</b> A total of 71 patients included in this study. Forty in VI Group (LVOT VTI increased ≥10%) and 31 in VNI Group (LVOT VTI increased <10%). Of all patients, 56.3% showed increased LVSV after negative fluid balance. In terms of hemodynamic parameters at T0, patients in VI Group had a higher CVP (<i>p</i> < 0.001) and P(v-a)CO<sub>2</sub> (<i>p</i> < 0.001) and lower ScVO<sub>2</sub> (<i>p</i> < 0.001) relative to VNI Group, regarding the echo parameters at T0, the RV<sub>D</sub>/LV<sub>D</sub> ratio (<i>p</i> < 0.001), DIVC <sub>end-expiratory</sub> (<i>p</i> < 0.001), and ΔLVOT VTI (<i>p</i> < 0.001) were higher, while T0 LVOT VTI (<i>p</i> < 0.001) was lower, in VI Group patients. The multifactor logistic regression analysis suggested that a high CVP and RV<sub>D</sub>/LV<sub>D</sub> ratio ≥0.6 were significant associated with LVSV increase after negative fluid balance in critically patients. The AUC of CVP was 0.894. A CVP >10.5 mmHg provided a sensitivity of 87.5% and a specificity of 77.4%. The AUC of CVP combined with the RV<sub>D</sub>/LV<sub>D</sub> ratio ≥0.6 was 0.926, which provided a sensitivity of 92.6% and a specificity of 80.4%. <b>Conclusion:</b> High CVP and RV<sub>D</sub>/LV<sub>D</sub> ratio ≥0.6 were significant associated with RV stressed in critically patients. Negative fluid balance will not always lead to a decrease, even an increase, in LVSV in these patients. |
2,330,993 | Effect of Pravastatin as an Adjunctive Therapeutic for Mitral Insufficiency with Hyperlipidemia in a Dog. | Pravastatin (PS) has been found to increase left ventricle (LV) expansion capacity and decrease LV constriction and left atrial pressure in healthy dogs. To date, there are no available reports on the effects of PS in dogs with hypercholesterolemia with chronic heart failure (CHF). This case report demonstrates a successful long-term treatment plan using PS in a dog suffering from mitral insufficiency with hyperlipidemia. A 12-year-old, castrated male Chihuahua dog had mitral insufficiency with hyperlipidemia. The dog presented with symptoms of chronic coughing. PS was orally administered (1 mg/kg, SID) in addition to general treatment for mitral insufficiency. The follow-up period was 375 days. PS administration decreased the heart rate (HR), vertebral heart size (VHS), and N-terminal probrain natriuretic peptide (NT-proBNP) concentration of the dog. In addition, PS administration also improved chronic cardiac failure induced by mitral insufficiency and hyperlipidemia. This report suggests that PS can be useful as an adjunctive therapeutic for dogs with hypercholesterolemia with mitral insufficiency. |
2,330,994 | Neural network-based left ventricle geometry prediction from CMR images with application in biomechanics. | Combining biomechanical modelling of left ventricular (LV) function and dysfunction with cardiac magnetic resonance (CMR) imaging has the potential to improve the prognosis of patient-specific cardiovascular disease risks. Biomechanical studies of LV function in three dimensions usually rely on a computerized representation of the LV geometry based on finite element discretization, which is essential for numerically simulating in vivo cardiac dynamics. Detailed knowledge of the LV geometry is also relevant for various other clinical applications, such as assessing the LV cavity volume and wall thickness. Accurately and automatically reconstructing personalized LV geometries from conventional CMR images with minimal manual intervention is still a challenging task, which is a pre-requisite for any subsequent automated biomechanical analysis. We propose a deep learning-based automatic pipeline for predicting the three-dimensional LV geometry directly from routinely-available CMR cine images, without the need to manually annotate the ventricular wall. Our framework takes advantage of a low-dimensional representation of the high-dimensional LV geometry based on principal component analysis. We analyze how the inference of myocardial passive stiffness is affected by using our automatically generated LV geometries instead of manually generated ones. These insights will inform the development of statistical emulators of LV dynamics to avoid computationally expensive biomechanical simulations. Our proposed framework enables accurate LV geometry reconstruction, outperforming previous approaches by delivering a reconstruction error 50% lower than reported in the literature. We further demonstrate that for a nonlinear cardiac mechanics model, using our reconstructed LV geometries instead of manually extracted ones only moderately affects the inference of passive myocardial stiffness described by an anisotropic hyperelastic constitutive law. The developed methodological framework has the potential to make an important step towards personalized medicine by eliminating the need for time consuming and costly manual operations. In addition, our method automatically maps the CMR scan into a low-dimensional representation of the LV geometry, which constitutes an important stepping stone towards the development of an LV geometry-heterogeneous emulator. |
2,330,995 | A ketogenic diet affects brain volume and metabolome in juvenile mice. | Ketogenic diet (KD) is a high-fat and low-carbohydrate therapy for medically intractable epilepsy, and its applications in other neurological conditions, including those occurring in children, have been increasingly tested. However, how KD affects childhood neurodevelopment, a highly sensitive and plastic process, is not clear. In this study, we explored structural, metabolic, and functional consequences of a brief treatment of a strict KD (weight ratio of fat to carbohydrate plus protein is approximately 6.3:1) in naive juvenile mice of different inbred strains, using a multidisciplinary approach. Systemic measurements using magnetic resonance imaging revealed that unexpectedly, the volumes of most brain structures in KD-fed mice were about 90% of those in mice of the same strain but fed a standard diet. The reductions in volumes were nonselective, including different regions throughout the brain, the ventricles, and the white matter. The relative volumes of different brain structures were unaltered. Additionally, as KD is a metabolism-based treatment, we performed untargeted metabolomic profiling to explore potential means by which KD affected brain growth and to identify metabolic changes in the brain. We found that brain metabolomic profile was significantly impacted by KD, through both distinct and common pathways in different mouse strains. To explore whether the volumetric and metabolic changes induced by this KD treatment were associated with functional consequences, we recorded spontaneous EEG to measure brain network activity. Results demonstrated limited alterations in EEG patterns in KD-fed animals. In addition, we observed that cortical levels of brain-derived neurotrophic factor (BDNF), a critical molecule in neurodevelopment, did not change in KD-fed animals. Together, these findings indicate that a strict KD could affect volumetric development and metabolic profile of the brain in inbred juvenile mice, while global network activities and BDNF signaling in the brain were mostly preserved. Whether the volumetric and metabolic changes are related to any core functional consequences during neurodevelopment and whether they are also observed in humans need to be further investigated. In addition, our results indicate that certain outcomes of KD are specific to the individual mouse strains tested, suggesting that the physiological profiles of individuals may need to be examined to maximize the clinical benefit of KD. |
2,330,996 | Functional and structural alternations in the choroid plexus upon methamphetamine exposure. | Choroid plexus (CP) is the principal source of cerebrospinal fluid. CP can produce and release a wide range of materials including growth factors, neurotrophic factors, etc. all of which play an important role in the maintenance and proper functioning of the brain. Methamphetamine (METH) is a CNS neurostimulant that causes brain dysfunction. Herein, we investigated the potential effects of METH exposure on CP structure and function. Stereological analysis revealed a significant alteration in CP volume, epithelial cells and capillary number upon METH treatment. Electron microscopy exhibited changes in ultrastructure. Moreover, the upregulation of neurotrophic factors such as BDNF and VEGF as well as autophagy and apoptosis gene following METH administration were observed. We also identified several signaling cascades related to autophagy. In conclusion, gene expression changes coupled with structural alterations of the CP in response to METH suggested METH-induced autophagy in CP. |
2,330,997 | Virtual histology of an entire mouse brain from formalin fixation to paraffin embedding. Part 1: Data acquisition, anatomical feature segmentation, tracking global volume and density changes. | Micrometer-resolution neuroimaging with gold-standard conventional histology requires tissue fixation and embedding. The exchange of solvents for the creation of sectionable paraffin blocks modifies tissue density and generates non-uniform brain shrinkage.</AbstractText>We employed synchrotron radiation-based X-ray microtomography for slicing- and label-free virtual histology of the mouse brain at different stages of the standard preparation protocol from formalin fixation via ascending ethanol solutions and xylene to paraffin embedding. Segmentation of anatomical regions allowed us to quantify non-uniform tissue shrinkage. Global and local changes in X-ray absorption gave insight into contrast enhancement for virtual histology.</AbstractText>The volume of the entire mouse brain was 60%, 56%, and 40% of that in formalin for, respectively, 100% ethanol, xylene, and paraffin. The volume changes of anatomical regions such as the hippocampus, anterior commissure, and ventricles differ from the global volume change. X-ray absorption of the full brain decreased, while local absorption differences increased, resulting in enhanced contrast for virtual histology. These trends were also observed with laboratory microtomography measurements.</AbstractText>Microtomography provided sub-10 μm spatial resolution with sufficient density resolution to resolve anatomical structures at each step of the embedding protocol. The spatial resolution of conventional computed tomography and magnetic resonance microscopy is an order of magnitude lower and both do not match the contrast of microtomography over the entire embedding protocol. Unlike feature-to-feature or total volume measurements, our approach allows for calculation of volume change based on segmentation.</AbstractText>We present isotropic micrometer-resolution imaging to quantify morphology and composition changes in a mouse brain during the standard histological preparation. The proposed method can be employed to identify the most appropriate embedding medium for anatomical feature visualization, to reveal the basis for the dramatic X-ray contrast enhancement observed in numerous embedded tissues, and to quantify morphological changes during tissue fixation and embedding.</AbstractText>Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,330,998 | CyCoSeg: A Cyclic Collaborative Framework for Automated Medical Image Segmentation. | Deep neural networks have been tremendously successful at segmenting objects in images. However, it has been shown they still have limitations on challenging problems such as the segmentation of medical images. The main reason behind this lower success resides in the reduced size of the object in the image. In this paper we overcome this limitation through a cyclic collaborative framework, CyCoSeg. The proposed framework is based on a deep active shape model (D-ASM), which provides prior information about the shape of the object, and a semantic segmentation network (SSN). These two models collaborate to reach the desired segmentation by influencing each other: SSN helps D-ASM identify relevant keypoints in the image through an Expectation Maximization formulation, while D-ASM provides a segmentation proposal that guides the SSN. This cycle is repeated until both models converge. Extensive experimental evaluation shows CyCoSeg boosts the performance of the baseline models, including several popular SSNs, while avoiding major architectural modifications. The effectiveness of our method is demonstrated on the left ventricle segmentation on two benchmark datasets, where our approach achieves one of the most competitive results in segmentation accuracy. Furthermore, its generalization is demonstrated for lungs and kidneys segmentation in CT scans. |
2,330,999 | Paediatric atypical choroid plexus papilloma: is adjuvant therapy necessary? | Choroid Plexus Tumours (CPTs) account for 1-4% of all brain tumours in children. Atypical choroid plexus papillomas (aCPPs) are a subset of these tumours, defined over a decade ago, yet no consensus exists on the optimal approach to their management.</AbstractText>We conducted a retrospective analysis of all patients treated for CPTs at the Hospital for Sick Children between January 1, 2000, and December 31, 2018, and focused on patients with aCPP. Data extracted from the patient records for analysis included: demographic and clinical features, radiological imaging, surgical and adjuvant therapies, key pathological features, immunohistochemical staining for TP53 and tumour karyotype. Six of seven aCPP samples were profiled using Illumina HumanMethylationEPIC arrays and the top 10,000 most variably methylated probes were visualized using tSNE. Copy number inferencing was also performed.</AbstractText>Twenty-nine patients were diagnosed with CPT, seven of whom had a diagnosis of aCPP as confirmed by histological review. Methylation profiling demonstrated that aCPPs clustered with both choroid plexus papillomas (CPPs) and choroid plexus carcinomas (CPCs). Complete resection of the tumour was pursued in all cases of aCPP and no patient received adjuvant therapy. All aCPP patients were alive at last follow up.</AbstractText>This limited case series suggests that paediatric aCPP can be successfully managed with surgical resection alone, followed by a 'watch and wait' approach thus avoiding adjuvant therapies. A deeper understanding of the biology of aCPP is required to identify objective markers which can help provide robust risk stratification and inform treatment strategies.</AbstractText>© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</CopyrightInformation> |
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