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2,329,100 | Acylated ghrelin prevents doxorubicin-induced cardiac intrinsic cell death and fibrosis in rats by restoring IL-6/JAK2/STAT3 signaling pathway and inhibition of STAT1. | This study investigated if JAK/STAT signaling pathway mediates doxorubicin (DOX)-induced cell death and fibrosis in left ventricles (LVs) of rats and examined if acylated ghrelin affords protection by modulating this pathway. Male rats (120 ± 5 g) were divided into 6 groups (10 rats each) as follows: control; control + AG (10 ng/kg, s.c.); DOX (an accumulative dose 15 mg/kg, i.p.); DOX + AG, DOX + AG + AG490, a JAK2 inhibitor (5 mg/kg, i.p.); and DOX + AG + [D-Lys3]-GHRP-6; an AG receptor antagonist (3.75 mg/kg, i.p.). All treatments were carried out for 35 days. In rats' LVs, DOX significantly impaired the systolic and diastolic functions, enhanced levels of ROS and MDA, reduced levels of GSH and Bcl-2, and increased mRNA and protein levels of collagen I/III and TGF-β and cleaved caspase-3. In addition, although DOX did not affect JAK1 or JAK2 activity, it significantly increased protein levels of IL-6, decreased STAT3 and p-STAT3 (Tyr701&Ser727), and increased STAT1 and p-STAT1 (Tyr701&Ser727) levels, with a concomitant decrease in ERK1/2 activity and an increase in P38 activity. However, without affecting IL-6 and JAK1/2, AG reversed all of the observed alterations with a significant increase in the levels and activities of JAK2. Similar effects of AG were also seen in control rats. Interestingly, all the beneficial effects afforded by AG were abolished by AG490 and AG + [D-Lys3]-GHRP-6. In conclusion, DOX-induced cardiac toxicity involves stimulation of IL-6, P38, and STAT1 signaling levels whereas the protective effect afforded by AG involves the activation of ERK1/2 and JAK2/STAT3 and inhibition of STAT1. |
2,329,101 | Progenitors from the central nervous system drive neurogenesis in cancer. | Autonomic nerve fibres in the tumour microenvironment regulate cancer initiation and dissemination, but how nerves emerge in tumours is currently unknown. Here we show that neural progenitors from the central nervous system that express doublecortin (DCX<sup>+</sup>) infiltrate prostate tumours and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX<sup>+</sup> neural progenitors in the subventricular zone-a neurogenic area of the central nervous system-are associated with disruption of the blood-brain barrier, and with the egress of DCX<sup>+</sup> cells into the circulation. These cells then infiltrate and reside in the tumour, and can generate new adrenergic neurons. Selective genetic depletion of DCX<sup>+</sup> cells inhibits the early phases of tumour development in our mouse models of prostate cancer, whereas transplantation of DCX<sup>+</sup> neural progenitors promotes tumour growth and metastasis. In humans, the density of DCX<sup>+</sup> neural progenitors is strongly associated with the aggressiveness and recurrence of prostate adenocarcinoma. These results reveal a unique crosstalk between the central nervous system and prostate tumours, and indicate neural targets for the treatment of cancer. |
2,329,102 | [Aquaporin4 (AQP4) in brain disorder]. | Two third of our body is composed of water molecules. Regulation of water and electrolytes is indeed the most important homeostatic functions. Many diseases, such as heart failure, are associated with disturbance in fluid homeostasis. Surprisingly, water dynamics inside the brain is still largely unknown. In 2012, a new concept referred as "glymphatic system" was proposed by Nedergaard's group, where aquaporin4 (AQP4) may play an important role as well as sleep. AQP4 is mainly expressed in the central nervous system, especially in the foot processes of astrocytes; surrounding the capillary, beneath pia matter and lining the ventricles. The unique distribution of AQP4 suggest that AQP4 might play a role in brain water homeostasis. The concept of "glymphatic system" is still controversial, and needs to be clarified with new experimental data. This approach will lead to the better understanding of roles of astrocytes in neurodegenerative diseases and pharmacokinetics inside the brain, and eventually will facilitate the development of new drugs for sleep or mental disorders. It has been accumulating evidence that sleep disturbance is related to several kinds of chronic diseases such as hypertension and diabetes. In addition, the number of patients with dementia are significantly increasing. It is therefore critical to understand the physiological and pathological mechanisms of brain lymphatic system from the medical and social point of views. Here I will discuss about the roles of AQP4 in neurodegenerative diseases and introduce new knowledge regarding to "glymphatic system". |
2,329,103 | Role of RF-amid Related Peptide-3 (RFRP-3) in Inhibitory Effect of Orexin A on Reproductive Function in the Animal Model of Male Wistar Rats. | The aim of the present study is to examine the orexin A (OXA) signaling can leave any impact on the hypothalamic-pituitary-gonadal (HPG) axis and this impact can be relayed through the pathway of RF amide-related peptide-3 (RFRP-3, the mammalian ortholog of the avian gonadotropin-inhibitory hormone)/G-protein coupled receptor (GPR)-147 (RFRP-3 receptor) as a novel target for controlling of HPG axis in the male rats.</AbstractText>Male rats were categorized randomly into experimental groups including control vehicle, OXA, and its antagonists' group and went through to surgical cannulation into the third ventricle. After the intracerebroventricular injection of each solution, blood samples were collected for measurements of the LH and testosterone using radioimmunoassay method. Hypothalamus of the animals were isolated for analysis of the relative expression of Rfrp-3</i>/Gpr</i>-147 along with Gnrh</i> gene by Real time-PCR. Also, in the different cohort of animal sexual behavior test was done.</AbstractText>It was shown that OXA significantly decreases the mean serum level of the LH and testosterone and, at the same time, its antagonists neutralize this impact. Moreover, we demonstrated that OXA has reduced the hypothalamic gene expression of Gnrh and increased the expression of Rfrp-3 and Gpr-147 genes</i>. While OXA antagonists neutralize this impact.</AbstractText>The results of this study are related to the impact of orexin on the HPG axis. It is recommended that RFRP-3/GPR-147 system as the interneural pathway relay the data of orexin to the neurons of GnRH.</AbstractText>© Georg Thieme Verlag KG Stuttgart · New York.</CopyrightInformation> |
2,329,104 | Altered K<sup>+</sup> current profiles underlie cardiac action potential shortening in hyperkalemia and β-adrenergic stimulation. | Hyperkalemia is known to develop in various conditions including vigorous physical exercise. In the heart, hyperkalemia is associated with action potential (AP) shortening that was attributed to altered gating of K<sup>+</sup> channels. However, it remains unknown how hyperkalemia changes the profiles of each K<sup>+</sup> current under a cardiac AP. Therefore, we recorded the major K<sup>+</sup> currents (inward rectifier K<sup>+</sup> current, <i>I</i><sub>K1</sub>; rapid and slow delayed rectifier K<sup>+</sup> currents, <i>I</i><sub>Kr</sub> and <i>I</i><sub>Ks</sub>, respectively) using AP-clamp in rabbit ventricular myocytes. As K<sup>+</sup> may accumulate at rapid heart rates during sympathetic stimulation, we also examined the effect of isoproterenol on these K<sup>+</sup> currents. We found that <i>I</i><sub>K1</sub> was significantly increased in hyperkalemia, whereas the reduction of driving force for K<sup>+</sup> efflux dominated over the altered channel gating in case of <i>I</i><sub>Kr</sub> and <i>I</i><sub>Ks</sub>. Overall, the markedly increased <i>I</i><sub>K1</sub> in hyperkalemia overcame the relative decreases of <i>I</i><sub>Kr</sub> and <i>I</i><sub>Ks</sub> during AP, resulting in an increased net repolarizing current during AP phase 3. β-Adrenergic stimulation of <i>I</i><sub>Ks</sub> also provided further repolarizing power during sympathetic activation, although hyperkalemia limited <i>I</i><sub>Ks</sub> upregulation. These results indicate that facilitation of <i>I</i><sub>K1</sub> in hyperkalemia and β-adrenergic stimulation of <i>I</i><sub>Ks</sub> represent important compensatory mechanisms against AP prolongation and arrhythmia susceptibility.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hegyi</LastName><ForeName>Bence</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>a Department of Pharmacology, University of California, Davis, CA 95616, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen-Izu</LastName><ForeName>Ye</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>a Department of Pharmacology, University of California, Davis, CA 95616, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>b Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>c Department of Internal Medicine/Cardiology, University of California, Davis, CA 95616, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Izu</LastName><ForeName>Leighton T</ForeName><Initials>LT</Initials><AffiliationInfo><Affiliation>a Department of Pharmacology, University of California, Davis, CA 95616, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bányász</LastName><ForeName>Tamás</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>a Department of Pharmacology, University of California, Davis, CA 95616, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>d Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 HL090880</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 HL123526</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 HL141460</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>05</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>Canada</Country><MedlineTA>Can J Physiol Pharmacol</MedlineTA><NlmUniqueID>0372712</NlmUniqueID><ISSNLinking>0008-4212</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000318">Adrenergic beta-Agonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>L628TT009W</RegistryNumber><NameOfSubstance UI="D007545">Isoproterenol</NameOfSubstance></Chemical><Chemical><RegistryNumber>RWP5GA015D</RegistryNumber><NameOfSubstance UI="D011188">Potassium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000200" MajorTopicYN="N">Action Potentials</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000318" MajorTopicYN="N">Adrenergic beta-Agonists</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006947" MajorTopicYN="N">Hyperkalemia</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007545" MajorTopicYN="N">Isoproterenol</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D032383" MajorTopicYN="N">Myocytes, Cardiac</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011188" MajorTopicYN="N">Potassium</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011817" MajorTopicYN="N">Rabbits</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="fre">On sait que l’hyperkaliémie se produit dans diverses situations, y compris pendant l’exercice physique vigoureux. Dans le cœur, l’hyperkaliémie est associée avec une diminution de la durée du potentiel d’action (PA), qui est attribuée à des canaux K<sup>+</sup> dont les propriétés de « gating » sont altérées. Toutefois, on ne sait toujours pas comment l’hyperkaliémie entraîne des variations dans le profil de chacun des courants K<sup>+</sup> à la base du PA cardiaque. Par conséquent, nous avons enregistré les principaux courants K<sup>+</sup> (courant à rectification entrante (<i>I</i><sub>K1</sub>); courants à rectification rapide et lente (<i>I</i><sub>Kr</sub> et <i>I</i><sub>Ks</sub>, respectivement)) à l’aide de la technique de clampage du PA dans des myocytes ventriculaires de lapin. Comme les ions K<sup>+</sup> peuvent s’accumuler à des fréquences cardiaques élevées pendant une stimulation sympathique, nous avons aussi étudié l’effet de l’isoprotérénol sur ces courants K<sup>+</sup>. Nous avons observé qu’<i>I</i><sub>K1</sub> était nettement augmenté en hyperkaliémie, tandis que la diminution de la force motrice de l’efflux de K<sup>+</sup> dominait comparativement au défaut de « gating » des canaux dans le cas d’<i>I</i><sub>Kr</sub> et d’<i>I</i><sub>Ks</sub>. Dans l’ensemble, l’augmentation marquée d’<i>I</i><sub>K1</sub> en hyperkaliémie parvenait à contrer la diminution relative d’IK<sub>r</sub> et d’I<sub>Ks</sub> pendant le PA, entraînant une augmentation nette des courants de repolarisation pendant la phase 3 du PA. La stimulation β-adrénergique d’I<sub>Ks</sub> fournissait aussi une puissance de repolarisation supplémentaire pendant l’activation sympathique, même si l’hyperkaliémie limitait la régulation à la hausse d’<i>I</i><sub>Ks</sub>. Ces résultats montrent que la facilitation d’<i>I</i><sub>K1</sub> en hyperkaliémie et la stimulation β-adrénergique d’<i>I</i><sub>Ks</sub> représentent des modes d’action compensatoires importants contre l’augmentation de la durée du PA et la susceptibilité aux arythmies. [Traduit par la Rédaction] |
2,329,105 | HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development. | Coordinated transcriptional and epigenetic mechanisms that direct development of the later differentiating second heart field (SHF) progenitors remain largely unknown. Here, we show that a novel zebrafish histone deacetylase 1 (hdac1) mutant allele cardiac really gone (crg) has a deficit of ventricular cardiomyocytes (VCs) and smooth muscle within the outflow tract (OFT) due to both cell and non-cell autonomous loss in SHF progenitor proliferation. Cyp26-deficient embryos, which have increased retinoic acid (RA) levels, have similar defects in SHF-derived OFT development. We found that nkx2.5+ progenitors from Hdac1 and Cyp26-deficient embryos have ectopic expression of ripply3, a transcriptional co-repressor of T-box transcription factors that is normally restricted to the posterior pharyngeal endoderm. Furthermore, the ripply3 expression domain is expanded anteriorly into the posterior nkx2.5+ progenitor domain in crg mutants. Importantly, excess ripply3 is sufficient to repress VC development, while genetic depletion of Ripply3 and Tbx1 in crg mutants can partially restore VC number. We find that the epigenetic signature at RA response elements (RAREs) that can associate with Hdac1 and RA receptors (RARs) becomes indicative of transcriptional activation in crg mutants. Our study highlights that transcriptional repression via the epigenetic regulator Hdac1 facilitates OFT development through directly preventing expression of the RA-responsive gene ripply3 within SHF progenitors. |
2,329,106 | Comparison of Left Ventricular Mass Calculation Methods via Two-Dimensional Echocardiogram in Children, Adolescents, and Young Adults With Systemic Hypertension. | Left ventricular (LV) mass is a major determining tool for myocardial injury in hypertensive patients. Issues with LV mass calculations exist given that there are multiple methods to assess mass, including from the parasternal long axis (PLA), parasternal short axis (PSA), and 2-dimensional (2D) volumetric methods. The aim of this study was to compare the agreement of LV mass calculations using the PLA, PSA, and 2D volumetric methods. This study retrospectively reviewed 200 consecutive, initial echocardiograms for the indication of hypertension. A single reader calculated the LV mass in each patient via the PLA, PSA, and 2D volumetric methods. Percent differences for each study were calculated. LV mass threshold cutoffs of 51 g/m<sup>2.7</sup> (cardiac organ injury) and 38.6 g/m<sup>2.7</sup> (elevated LV mass) were used to compare categorical differences between the different measurement methods. Paired comparisons demonstrated an absolute mean percent difference of 8.46% to 9.41% among the different methods. LV mass calculated by the 2D volumetric method was less compared with PLA and PSA methods (31.64 vs 33.90 vs 35.51 g/m<sup>2.7</sup>; p < 0.0001). Fewer patients were classified as having cardiac target organ injury or elevated LV mass via 2D volumetric calculation, compared with PLA and PSA methods (p = 0.02 and p = 0.03, respectively). In conclusion, there is a small but important difference in LV mass calculations for patients with hypertension. These results emphasize the need for consistency within echocardiography laboratories as surveillance studies are common in this patient population. |
2,329,107 | Cortical thickness, white matter hyperintensities, and cognition after stroke. | A thinner cerebral cortex is associated with higher white matter hyperintensity burden and cognitive impairment in community-dwelling and dementia cohorts. It is important to assess these associations in people with ischemic stroke because their cerebrovascular disease profiles are different to these cohorts.</AbstractText>We aimed to determine whether cortical thickness was related to white matter hyperintensity burden and cognition after ischemic stroke.</AbstractText>We measured cortical thickness using advanced normalization tools' "KellyKapowski" function in 244 patients with ischemic stroke or transient ischemic attack from the Virtual International Stroke Trials Archive. We measured white matter hyperintensity burden via quantitative volumes and Fazekas score. We extracted data on vascular risk factors at baseline and Mini Mental State Examination scores at one year. We assessed associations between imaging and clinical data using correlation and multiple linear regression.</AbstractText>Pairwise correlation showed that higher white matter hyperintensity Fazekas score was associated with a thinner cortex (rho = -0.284, P</i> < 0.0001). White matter hyperintensities were generally distributed adjacent to and above the lateral ventricles. Voxel-wise analyses showed statistically significant negative associations between cortical thickness and white matter hyperintensities across fronto-temporal and inferior parietal cortical regions. Mean cortical thickness was positively related to Mini Mental State Examination in pair-wise correlation (r = 0.167, P = 0.0088) but there was no independent association after adjustment for age and white matter hyperintensities (beta = 0.016, P = 0.7874).</AbstractText>Cortical thickness was not an independent predictor of cognition after ischemic stroke. Further work is required to understand how white matter hyperintensities are associated with a thinner cortex in temporal regions but less so in more superior regions where white matter hyperintensities are generally found in people with stroke.</AbstractText> |
2,329,108 | Focus on echocardiographic right ventricular strain analysis in cystic fibrosis adults without cardiovascular risk factors: a case-control study. | Strain echocardiography is able to detect subclinical ventricular systolic and diastolic dysfunction. Prolonged survival to cystic fibrosis favors heart and vessel involvement. The purpose of the present study was to compare clinically stable adult patients affected by cystic fibrosis without overt pulmonary hypertension with controls to evaluate right ventricular (RV) systolic and diastolic function by means of strain and tissue Doppler imaging (TDI), respectively. 22 adults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors or overt pulmonary hypertension. All people underwent blood pressure measurement and transthoracic echocardiography. Cystic fibrosis patients showed higher sPAP [median 25 (IQR 21-30) vs 22 (22-22) mmHg; p = 0.02] and more frequent RV diastolic dysfunction (p < 0.001). Among cases, some RV systolic parameters were significantly altered than controls, such as TAPSE [20 (18-24) vs. 23 (21-28) mm; p = 0.001], FAC [34 (26-44) vs. 49 (48-50)%; p < 0.001], midwall tissue strain [- 25.0 (- 31.3 to - 22.8) vs. - 30.5 (- 31.8 to - 29.3)%; p = 0.03], apical tissue strain [- 22 (- 29.3 to - 19.0) vs. - 30.5 (- 32.8 to - 28.3)%; p = 0.001] and 2D strain [- 22.0 (- 25.1 to - 19.0) vs. - 29.5 (- 31.8 to - 27.3)%; p < 0.001]. Finally, 2D strain correlated with spirometric FEV1 (ρ = - 0.463, p = 0.03) and nearly with FEF25-75% (ρ = - 0.393, p = 0.07). Our study confirmed a RV subclinical systo-diastolic dysfunction in clinically stable patients affected by cystic fibrosis without overt pulmonary hypertension nor cardiovascular risk factors. This may be due to systemic inflammation and temporary recurrent pulmonary hypertension. We retain that RV 2D strain and TDI echocardiography could become an important tool in the follow-up of these patients. |
2,329,109 | Overexpression of the HCN2 channel increases the arrhythmogenicity induced by hypokalemia. | Hypokalemia, an abnormally low level of potassium (K<sup>+</sup>), is a electrolyte imbalance that commonly occurs in heart failure patients. Hypokalemia is well known to induce lethal ventricular arrhythmia. However, the effects of hypokalemia in failing hearts that have undergone electrophysiological remodeling, i.e., the reactivation of fetal-type ion channels, remain unexplored. We have examined the effect of hypokalemia in the myocytes of transgenic mice overexpressing the hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) channel in the heart (HCN2-Tg mice). Perfusion with a mild hypokalemic solution containing 3 mM K<sup>+</sup> induced ectopic ventricular automaticity in 55.0% of HCN2-Tg mouse myocytes. In the remaining HCN2-Tg mouse myocytes, the resting membrane potential (RMP) was more depolarized than that of wild-type myocytes subjected to the same treatment and could also be hyperpolarized by an HCN channel blocker. We conclude that in hypokalemia in our mice model, the HCN2 channel was constitutively activated at the hyperpolarized RMP, thereby destabilizing the electrophysiological activity of ventricular myocytes. |
2,329,110 | Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory. | Regular exercise and dietary supplements with antioxidants each have the potential to improve cognitive function and attenuate cognitive decline, and, in some cases, they enhance each other. Our current results reveal that low-intensity exercise (mild exercise, ME) and the natural antioxidant carotenoid astaxanthin (AX) each have equivalent beneficial effects on hippocampal neurogenesis and memory function. We found that the enhancement by ME combined with AX in potentiating hippocampus-based plasticity and cognition is mediated by leptin (LEP) made and acting in the hippocampus. In assessing the combined effects upon wild-type (WT) mice undergoing ME with or without an AX diet for four weeks, we found that, when administrated alone, ME and AX separately enhanced neurogenesis and spatial memory, and when combined they were at least additive in their effects. DNA microarray and bioinformatics analyses revealed not only the up-regulation of an antioxidant gene, <i>ABHD3</i>, but also that the up-regulation of <i>LEP</i> gene expression in the hippocampus of WT mice with ME alone is further enhanced by AX. Together, they also increased hippocampal LEP (h-LEP) protein levels and enhanced spatial memory mediated through AKT/STAT3 signaling. AX treatment also has direct action on human neuroblastoma cell lines to increase cell viability associated with increased LEP expression. In LEP-deficient mice (<i>ob/ob</i>), chronic infusion of LEP into the lateral ventricles restored the synergy. Collectively, our findings suggest that not only h-LEP but also exogenous LEP mediates effects of ME on neural functions underlying memory, which is further enhanced by the antioxidant AX. |
2,329,111 | Hindbrain Estrogen Receptor Regulation of Ventromedial Hypothalamic Glycogen Metabolism and Glucoregulatory Transmitter Expression in the Hypoglycemic Female Rat. | Neural substrates for estrogen regulation of glucose homeostasis remain unclear. Female rat dorsal vagal complex (DVC) A2 noradrenergic neurons are estrogen- and metabolic-sensitive. The ventromedial hypothalamic nucleus (VMN) is a key component of the brain network that governs counter-regulatory responses to insulin-induced hypoglycemia (IIH). Here, the selective estrogen receptor-alpha (ERα) or -beta (ERβ) antagonists MPP and PHTPP were administered separately to the caudal fourth ventricle to address the premise that these hindbrain ER variants exert distinctive control of VMN reactivity to IIH in the female sex. Data show that ERα governs hypoglycemic patterns of VMN astrocyte glycogen metabolic enzyme, e.g. glycogen synthase and phosphorylase protein expression, whereas ERβ mediates local glycogen breakdown. DVC ERs also regulate VMN neurotransmitter signaling of energy sufficiency [γ-aminobutyric acid] or deficiency [nitric oxide, steroidogenic factor-1] during IIH. Neither hindbrain ER mediates IIH-associated diminution of VMN norepinephrine (NE) content. Both ERs oppose hypoglycemic hyperglucagonemia, while ERβ contributes to reduced corticosterone output. Outcomes reveal that input from the female hindbrain to the VMN is critical for energy reserve mobilization, metabolic transmitter signaling, and counter-regulatory hormone secretion during hypoglycemia, and that ERs control those cues. Evidence that VMN NE content is not controlled by hindbrain ERα or -β implies that these receptors may regulate VMN function via NE-independent mechanisms, or alternatively, that other neurotransmitter signals to the VMN may control local substrate receptivity to NE. |
2,329,112 | Neonatal treatment with cyclosporine A restores neurogenesis and spinogenesis in the Ts65Dn model of Down syndrome. | Down syndrome (DS), a genetic condition due to triplication of chromosome 21, is characterized by reduced proliferation of neural progenitor cells (NPCs) starting from early life stages. This defect is worsened by a reduction of neuronogenesis (accompanied by an increase in astrogliogenesis) and dendritic spine atrophy. Since this triad of defects underlies intellectual disability, it seems important to establish whether it is possible to pharmacologically correct these alterations. In this study, we exploited the Ts65Dn mouse model of DS in order to obtain an answer to this question. In the framework of an in vitro drug-screening campaign of FDA/EMA-approved drugs, we found that the immunosuppressant cyclosporine A (CSA) restored proliferation, acquisition of a neuronal phenotype, and maturation of neural progenitor cells (NPCs) from the subventricular zone (SVZ) of the lateral ventricle of Ts65Dn mice. Based on these findings, we treated Ts65Dn mice with CSA in the postnatal period P3-P15. We found that treatment fully restored NPC proliferation in the SVZ and in the subgranular zone of the hippocampal dentate gyrus, and total number of hippocampal granule cells. Moreover, CSA enhanced development of dendritic spines on the dendritic arbor of the granule cells whose density even surpassed that of euploid mice. In hippocampal homogenates from Ts65Dn mice, we found that CSA normalized the excessive levels of p21, a key determinant of proliferation impairment. Results show that neonatal treatment with CSA restores the whole triad of defects of the trisomic brain. In DS CSA treatment may pose caveats because it is an immunosuppressant that may cause adverse effects. However, CSA analogues that mimic its effect without eliciting immunosuppression may represent practicable tools for ameliorating brain development in individuals with DS. |
2,329,113 | Assessment of protein extraction and digestion efficiency of well-established shotgun protocols for heart proteomics. | Ischemic heart disease is the leading cause of deaths worldwide. Thus, understanding the molecular mechanisms underlying disease progression is needed. Due to heart importance and lack of studies evaluating different sample preparation methods for heart proteomics, we compared three well-established protocols in shotgun proteomics using dimethyl label quantitation to allow relative quantitation. The tested methods for the analysis of left ventricle (LV) tissue were: i) in-solution digestion (ISD); ii) on-pellet digestion (OPD); and iii) on-filter digestion (OFD). Protein extraction was done using SDS-containing buffer for OPD and OFD while this step was under urea-containing buffer for ISD. We used an optimized one-step reaction for reduction of disulfide bonds and alkylation of thiol groups in ISD and OPD. Using the same amount of tissue, we observed that OFD and ISD extracted significantly higher amount of protein than OPD. ISD outperformed OFD and OPD in the number of proteins identified. We did not observe significant bias related to physicochemical features of the identified proteins when comparing the three protocols. ISD was more efficient to identify low abundant proteins and yielded more proteins per protocol duration. Thus, we concluded that the optimized ISD suited better for heart proteomics than OFD and OPD. |
2,329,114 | Location of Neutrophils in Different Compartments of the Damaged Mouse Brain After Severe Ischemia/Reperfusion. | Background and Purpose- Ischemia attracts neutrophils to the injured brain. However, neutrophil location and access to the damaged brain tissue is not yet entirely understood. We aimed to investigate neutrophil location in a mouse model of cerebral ischemia/reperfusion. Methods- Adult male C57BL/6 mice (n=52) received 45-minute intraluminal middle cerebral artery occlusion followed by 14, 24, 48, or 96 hours of reperfusion. Sham-operated mice (n=9) were subjected to the entire surgical procedure. We used wild-type mice and Catchup<sup>IVM</sup> mice expressing a red fluorescent protein in neutrophils. In addition, fluorescent neutrophils obtained from reporter DsRed (discosoma red fluorescent protein) mice were transferred intravenously to wild-type mice after ischemia. Mice received transcardial paraformaldehyde perfusion, the brain was cryoprotected, frozen, and cryostat sections were studied by immunofluorescence and confocal microscopy. Results- Ischemia induced a time-dependent increase in brain neutrophil numbers versus sham operation. We detected neutrophils in the leptomeninges, ventricles, capillary lumen, perivascular spaces, and parenchyma within the infarcted core. Most ischemic mice showed neutrophils in the leptomeninges and perivascular spaces, whereas the presence and number of neutrophils in the parenchyma was variable among ischemic mice. During the first 24 hours, only a few mice showed parenchymal neutrophils, but the frequency of mice showing neutrophils in the parenchyma and neutrophil numbers increased at 48 and 96 hours. We also detected signs of basement membrane disruption and hints of occasional neutrophil degranulation and formation of neutrophil extracellular traps. Conclusions- After ischemia/reperfusion, neutrophils accumulate in the leptomeninges and perivascular spaces, and eventually can reach the infarcted brain parenchyma. |
2,329,115 | [Speckle Tracking Echocardiography - a New Tool for the Intensive Care Unit?]. | The noninvasive evaluation of cardiac morphology and function by echocardiography is an essential part of modern intensive care therapy. However, this procedure can be challenging and beginners often lack the ability to objectively state the correct global and regional myocardial function. Recent developments allow a semi-automatic deformation (strain) analysis by a couple of more objective respective parametric techniques. Strain describes the change in length of a myocardial segment during the cardiac cycle. While this is primarily a regional analysis, an insight into the global left ventricular deformation is possible by averaging all relevant segments. Speckle tracking echocardiography (STE) is actually the only clinically relevant technique and is well scientifically and clinically approved. The advantages of STE are the angle-independency, the ease and fastness of its use, the availability at the bedside and low costs. Through proven good reproducibility it should be a good method for repeated analysis even by different echocardiographers. However, actually the greatest disadvantage is the variation of measures between different vendors of ultrasound machines and software-packages. At the moment, a task force of leading echocardiography experts and industry personal is working on a solution. Normal values have been published for healthy collectives and STE has been in use in the majority of cardiac diseases. Besides from a few research studies, the usage in critically ill patients actually is still limited.<CopyrightInformation>Georg Thieme Verlag KG Stuttgart · New York.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Reckefuß</LastName><ForeName>Norbert</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Heuer</LastName><ForeName>Jan Florian</ForeName><Initials>JF</Initials></Author><Author ValidYN="Y"><LastName>Butz</LastName><ForeName>Thomas</ForeName><Initials>T</Initials></Author></AuthorList><Language>ger</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Speckle-Tracking-Echokardiografie – ein neues Tool für die Intensivstation?</VernacularTitle><ArticleDate DateType="Electronic"><Year>2019</Year><Month>05</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Anasthesiol Intensivmed Notfallmed Schmerzther</MedlineTA><NlmUniqueID>9109478</NlmUniqueID><ISSNLinking>0939-2661</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D004452" MajorTopicYN="Y">Echocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006331" MajorTopicYN="Y">Heart Diseases</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007362" MajorTopicYN="Y">Intensive Care Units</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015203" MajorTopicYN="N">Reproducibility of Results</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="ger">Die Beurteilung der kardialen Funktion kritisch kranker Patienten ist eine wichtige diagnostische Maßnahme auf Intensivstationen. Jedoch kann die meist angewandte detaillierte echokardiografische Untersuchung gerade Ungeübte rasch an ihre Grenzen bringen. Zusätzliche Informationen vermag die myokardiale Deformationsanalyse mittels Speckle-Tracking-Echokardiografie zu liefern – ein innovatives Verfahren, das in diesem Beitrag vorgestellt wird. |
2,329,116 | A novel model for minimally invasive left ventricular assist device implantation training.<Pagination><StartPage>194</StartPage><EndPage>201</EndPage><MedlinePgn>194-201</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/13645706.2019.1616559</ELocationID><Abstract><AbstractText><b>Background:</b> Significant advances in minimally invasive implantation of mechanical circulatory support devices have been made. These approaches are technically challenging and associated with a learning curve. Simulation and training opportunities in these techniques are limited. We developed a high-fidelity novel model for minimally invasive left ventricular assist device implantation.<b>Material and methods:</b> Using a modified inanimate simulator (LSI SOLUTIONS<sup>®</sup>) and an animal tissue model, a hybrid simulator was created, with a porcine ex vivo heart secured within the inanimate simulator in the normal anatomic position. Key components of the minimally invasive left ventricular assist device implantation were performed, including left ventricular apical coring, attachment of the apical ring, attachment of the assist device, and creation of the aortic-outflow graft anastomosis.<b>Results:</b> A novel composite inanimate and tissue model for minimally invasive left ventricular assist device implantation was successfully developed. These simulation techniques were reproducible, and the model demonstrated ability to successfully simulate key components of the procedure.<b>Conclusions:</b> This high-fidelity, reproducible hybrid model allows for crucial components of minimally invasive LVAD implantation to be performed. This model has the potential to be used as an adjunct to surgical training, providing a safe and controlled learning environment for trainees to acquire skills in minimally invasive LVAD implantation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Robinson</LastName><ForeName>Davida</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fitzsimmons</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>LSI SOLUTIONS®, Victor, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Waters</LastName><ForeName>Kenneth</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>LSI SOLUTIONS®, Victor, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mohiuddin</LastName><ForeName>Farrukh</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>LSI SOLUTIONS®, Victor, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Knight</LastName><ForeName>Peter</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sauer</LastName><ForeName>Jude</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>LSI SOLUTIONS®, Victor, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jr</LastName><ForeName>Carl Johnson</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gosev</LastName><ForeName>Igor</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>05</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Minim Invasive Ther Allied Technol</MedlineTA><NlmUniqueID>9612996</NlmUniqueID><ISSNLinking>1364-5706</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000714" MajorTopicYN="N">Anastomosis, Surgical</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006353" MajorTopicYN="Y">Heart-Assist Devices</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019060" MajorTopicYN="N">Minimally Invasive Surgical Procedures</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008953" MajorTopicYN="N">Models, Anatomic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019919" MajorTopicYN="N">Prosthesis Implantation</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013552" MajorTopicYN="N">Swine</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Cardiac surgery</Keyword><Keyword MajorTopicYN="N">cardiothoracic surgery</Keyword><Keyword MajorTopicYN="N">minimally invasive surgery</Keyword><Keyword MajorTopicYN="N">simulation</Keyword><Keyword MajorTopicYN="N">training</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>5</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>10</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>5</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31082283</ArticleId><ArticleId IdType="doi">10.1080/13645706.2019.1616559</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">31081820</PMID><DateCompleted><Year>2020</Year><Month>03</Month><Day>20</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>20</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>146</Issue><PubDate><Year>2019</Year><Month>Apr</Month><Day>27</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse. | <b>Background:</b> Significant advances in minimally invasive implantation of mechanical circulatory support devices have been made. These approaches are technically challenging and associated with a learning curve. Simulation and training opportunities in these techniques are limited. We developed a high-fidelity novel model for minimally invasive left ventricular assist device implantation.<b>Material and methods:</b> Using a modified inanimate simulator (LSI SOLUTIONS<sup>®</sup>) and an animal tissue model, a hybrid simulator was created, with a porcine ex vivo heart secured within the inanimate simulator in the normal anatomic position. Key components of the minimally invasive left ventricular assist device implantation were performed, including left ventricular apical coring, attachment of the apical ring, attachment of the assist device, and creation of the aortic-outflow graft anastomosis.<b>Results:</b> A novel composite inanimate and tissue model for minimally invasive left ventricular assist device implantation was successfully developed. These simulation techniques were reproducible, and the model demonstrated ability to successfully simulate key components of the procedure.<b>Conclusions:</b> This high-fidelity, reproducible hybrid model allows for crucial components of minimally invasive LVAD implantation to be performed. This model has the potential to be used as an adjunct to surgical training, providing a safe and controlled learning environment for trainees to acquire skills in minimally invasive LVAD implantation.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Robinson</LastName><ForeName>Davida</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fitzsimmons</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>LSI SOLUTIONS®, Victor, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Waters</LastName><ForeName>Kenneth</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>LSI SOLUTIONS®, Victor, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mohiuddin</LastName><ForeName>Farrukh</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>LSI SOLUTIONS®, Victor, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Knight</LastName><ForeName>Peter</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sauer</LastName><ForeName>Jude</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>LSI SOLUTIONS®, Victor, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jr</LastName><ForeName>Carl Johnson</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gosev</LastName><ForeName>Igor</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>05</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Minim Invasive Ther Allied Technol</MedlineTA><NlmUniqueID>9612996</NlmUniqueID><ISSNLinking>1364-5706</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000714" MajorTopicYN="N">Anastomosis, Surgical</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006353" MajorTopicYN="Y">Heart-Assist Devices</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019060" MajorTopicYN="N">Minimally Invasive Surgical Procedures</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008953" MajorTopicYN="N">Models, Anatomic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019919" MajorTopicYN="N">Prosthesis Implantation</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013552" MajorTopicYN="N">Swine</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Cardiac surgery</Keyword><Keyword MajorTopicYN="N">cardiothoracic surgery</Keyword><Keyword MajorTopicYN="N">minimally invasive surgery</Keyword><Keyword MajorTopicYN="N">simulation</Keyword><Keyword MajorTopicYN="N">training</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>5</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>10</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>5</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31082283</ArticleId><ArticleId IdType="doi">10.1080/13645706.2019.1616559</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">31081820</PMID><DateCompleted><Year>2020</Year><Month>03</Month><Day>20</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>20</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>146</Issue><PubDate><Year>2019</Year><Month>Apr</Month><Day>27</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal><ArticleTitle>Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.3791/58021</ELocationID><Abstract>Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV diastolic function is rarely quantified in experimental studies. This might be due to technical difficulties in the visualization of the RV in the apical four-chamber view in rodents. Here we describe two positions facilitating the visualization of the apical four-chamber view in mice to assess the RV diastolic function. The apical four-chamber view is enabled by tilting the mouse fixation platform to the left and caudally (LeCa) or to the right and cranially (RiCr). Both positions provide images of comparable quality. The results of the RV diastolic function obtained from two positions are not significantly different. Both positions are comparably easy to perform. This protocol can be incorporated into published protocols and enables detailed investigations of the RV function. |
2,329,117 | First clinical experience with the new noninvasive transfontanelle ICP monitoring device in management of children with premature IVH. | We previously introduced a novel noninvasive technique of intracranial pressure (ICP) monitoring in children with open fontanelles. Within this study, we describe the first clinical implementation and results of this new technique in management of children with hydrocephalus caused by intraventricular hemorrhage (IVH). In neonates with posthemorrhagic hydrocephalus (PHH), an Ommaya reservoir was implanted for initial treatment of hydrocephalus. The ICP obtained noninvasively with our new device was measured before and after CSF removal and correlated to cranial ultra-sonographies. Six children with a mean age of 27.3 weeks and mean weight of 1082.3 g suffering from PHH were included in this study. We performed an overall of 30 aspirations due to ventricular enlargement. Before CSF removal, the mean ICP was 15.3 mmHg and after removal of CSF the mean ICP measured noninvasively decreased to 3.4 mmHg, p = 0.0001. The anterior horn width (AHW), which reflects early expansion of the ventricles, was before and after CSF removal 15.1 mm and 5.5 mm, respectively, p < 0.0006. There was a strong correlation between noninvasively measured ICP values and sonographically obtained AHW, r = 0.81. Ultimately, all children underwent ventriculoperitoneal shunt procedures. This is the first study providing proof for a noninvasively ICP-based approach for management of posthemorrhagic hydrocephalus in newborn children. |
2,329,118 | Significance of isolated borderline ventriculomegaly. | Foetal ventriculomegaly (VM) is one of the most commonly diagnosed brain abnormalities. The aims of this study were to assess cases with isolated VM, describe the prenatal course and assess short- and long-term follow-up at the age of 2 years.</AbstractText>We performed a retrospective analysis from our prenatal data base and included all children that were prenatally diagnosed with VM in our unit between 2008 and 2013 (n = 250). Prenatal management, postnatal outcome and neurologic development at the age of 2 years were evaluated.</AbstractText>A total of 106 children were born at our institution and were diagnosed prenatally with isolated borderline VM. A total of 1.9% (n = 2/106) was transferred to the neonatal unit. A total of 0.9% (n = 1/106) showed abnormal findings in postnatal brain ultrasound. A total of 1.9% (n = 2/106) showed mild neurologic abnormalities after birth, but none had to be seen by a neuropediatrician. At the follow-up at 2 years, 2.5% (n = 1/40) had an insertion of a shunt.</AbstractText>Based on our analysis, the majority of isolated borderline VM do not show short- or long-term neurological abnormalities. However, all cases of VM should be referred to a detailed prenatal ultrasound exam by a specialist.</AbstractText> |
2,329,119 | Behaviour and neuropathology in mice injected with human contactin-associated protein 2 antibodies. | Serum antibodies that bind to the surface of neurons or glia are associated with a wide range of rare but treatable CNS diseases. In many, if not most instances, the serum levels are higher than CSF levels yet most of the reported attempts to reproduce the human disease in mice have used infusion of antibodies into the mouse cerebral ventricle(s) or intrathecal space. We used the intraperitoneal route and injected purified plasma IgG from either a CASPR2-antibody-positive patient (n = 10 mice) or healthy individual (n = 9 mice) daily for 8 days. Lipopolysaccharide was injected intraperitoneally on Day 3 to cause a temporary breach in the blood brain barrier. A wide range of baseline behaviours, including tests of locomotion, coordination, memory, anxiety and social interactions, were established before the injections and tested from Day 5 until Day 11. At termination, brain tissue was analysed for human IgG, CASPR2 and c-fos expression, lymphocyte infiltration, and neuronal, astrocytic and microglial markers. Mice exposed to CASPR2-IgG, compared with control-IgG injected mice, displayed reduced working memory during the continuous spontaneous alternation test with trends towards reduced short-term and long-term memories. In the open field tests, activities were not different from controls, but in the reciprocal social interaction test, CASPR2-IgG injected mice showed longer latency to start interacting, associated with more freezing behaviour and reduced non-social activities of rearing and grooming. At termination, neuropathology showed more IgG deposited in the brains of CASPR2-IgG injected mice, but a trend towards increased CASPR2 expression; these results were mirrored in short-term in vitro experiments where CASPR2-IgG binding to hippocampal neurons and to CASPR2-transfected HEK cells led to some internalization of the IgG, but with a trend towards higher surface CASPR2 expression. Despite these limited results, in the CASPR2-IgG injected mouse brains there was increased c-fos expression in the piriform-entorhinal cortex and hypothalamus, and a modest loss of Purkinje cells. There was also increased microglia density, morphological changes in both microglia and astrocytes and raised complement C3 expression on astrocytes, all consistent with glial activation. Patients with CASPR2 antibodies can present with a range of clinical features reflecting central, autonomic and peripheral dysfunction. Although the behavioural changes in mice were limited to social interactions and mild working-memory defects, the neuropathological features indicate potentially widespread effects of the antibodies on different brain regions. |
2,329,120 | Solitary Metastasis of Adenocarcinoma of Submandibular Gland to Choroid Plexus in Cerebellopontine Angle: First Case Reported in Literature. | Adenocarcinoma of the salivary gland (AdCASG) is a rare and malignant tumor of the salivary glands. Albeit, metastatic lesions occur anecdotally in the choroid plexus and most rarely in the cerebellopontine angle (CPA). We report the first case of metastatic AdCASG to the choroid plexus of the lateral recess of the fourth ventricle located in CPA, emphasizing the clinical presentation and neuroradiologic findings.</AbstractText>A 40-year-old man was referred with signs of increased intracranial pressure and a unilateral hearing problem. Magnetic resonance imaging showed a pear-shaped, vividly enhancing tumor in the left CPA. The tumor was a metastatic AdCASG. Gross total resection of the lesion was followed by a conventional radiotherapy lead in a 5-year tumor-free control interval.</AbstractText>Metastatic lesions to the choroid plexus may show a pedunculated shape in magnetic resonance imaging. It is hypothesized that tumor seeding may occur through the veins, lymphatics, and nerve sheaths in the skull base region. Tissue specimen is necessary to confirm such rare pathology.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,121 | Role of intra-ventricular vortex in left ventricular ejection elucidated by echo-dynamography. | From the correlation between the blood flow dynamics and wall dynamics in the left ventriocle (LV) analyzed using echo-dynamography, the ejection mechanisms and role of the intra-ventricular vortex in the LV were elucidated in detail during the pre-ejection transitional period (pre-ETP), the very short period preceding LV ejection.</AbstractText>The study included 10 healthy volunteers. Flow structure was analyzed using echo-dynamography, and LV wall dynamics were measured using both high-frame-rate two-dimensional echocardiography and a phase difference tracking method we developed.</AbstractText>A large accelerated vortex occurred at the central basal area of the LV during this period. The main flow axis velocity line of the LV showed a linearly increasing pattern. The slope of the velocity pattern reflected the deformity of the flow route induced by LV contraction during the pre-ETP. The centrifugal force of the vortex at its junction with the main outflow created a stepwise increase of about 50% of the ejection velocity.</AbstractText>Ejection of blood from the LV was accomplished by the extruding action of the ventricular wall and the centrifugal force of the accelerated vortex during this period. During ejection, acceralated outflow was considered to create a spiral flow in the aorta with help from the spherical structure of the Valsalva sinus.</AbstractText> |
2,329,122 | Anterior third ventricular height and infundibulochiasmatic angle: two novel measurements to predict clinical success of endoscopic third ventriculostomy in the early postoperative period. | The authors sought to develop a set of parameters that reliably predict the clinical success of endoscopic third ventriculostomy (ETV) when assessed before and after the operation, and to establish a plan for MRI follow-up after this procedure.</AbstractText>This retrospective study involved 77 patients who had undergone 78 ETV procedures for obstructive hydrocephalus between 2010 and 2015. Constructive interference in steady-state (CISS) MRI evaluations before and after ETV were reviewed, and 4 parameters were measured. Two well-known standard parameters, fronto-occipital horn ratio (FOHR) and third ventricular index (TVI), and 2 newly defined parameters, infundibulochiasmatic (IC) angle and anterior third ventricular height (TVH), were measured in this study. Associations between preoperative measurements of and postoperative changes in the 4 variables and the clinical success of ETV were analyzed.</AbstractText>Of the 78 ETV procedures, 70 (89.7%) were successful and 8 (10.3%) failed. On the preoperative MR images, the mean IC angle and anterior TVH were significantly larger in the successful procedures. On the 24-hour postoperative MR images of the successful procedures, the mean IC angle declined significantly from 114.2° to 94.6° (p < 0.05) and the mean anterior TVH declined significantly from 15 to 11.2 mm (p < 0.05). The mean percentage reduction of the IC angle was 17.1%, and that of the anterior TVH was 25.5% (both p < 0.05). On the 1-month MR images of the successful procedures, the mean IC angle declined significantly from 94.6° to 84.2° (p < 0.05) and the mean anterior TVH declined significantly from 11.2 to 9.3 mm (p < 0.05). The mean percentage reductions in IC angle (11%) and anterior TVH (16.9%) remained significant at this time point but were smaller than those observed at 24 hours. The 6-month and 1-year postoperative MR images of the successful group showed no significant changes in mean IC angle or mean anterior TVH. Regarding the unsuccessful procedures, there were no significant changes observed in IC angle or anterior TVH at any of the time points studied. Reduction of IC angle and reduction of anterior TVH on 24-hour postoperative MR images were significantly associated with successful ETV. However, no clinically significant association was found between FOHR, TVI, and ETV success.</AbstractText>Assessing the IC angle and anterior TVH on preoperative and 24-hour postoperative MR images is useful for predicting the clinical success of ETV. These 2 measurements could also be valuable as radiological follow-up parameters.</AbstractText> |
2,329,123 | VEGF- and PDGF-dependent proliferation of oligodendrocyte progenitor cells in the medulla oblongata after LPC-induced focal demyelination. | The myelin sheath is critical in maintaining normal functions of the adult central nervous system (CNS) and the loss of the myelin sheath results in various neurological diseases. Although remyelination is the intrinsic repair system against demyelination that new myelin sheath is formed around axons in the adult CNS, little has been reported on remyelination system in the medulla oblongata. In the present study, we showed that the proliferation of oligodendrocyte progenitor cells (OPCs) was increased in the medulla oblongata by lysophosphatidylcholine (LPC)-induced focal demyelination, but that of NSCs was not changed. The inhibition of vascular endothelial growth factor (VEGF)- and platelet-derived growth factor (PDGF)-signaling suppressed the proliferation of OPCs by LPC-induced demyelination. Thus, the present study indicates that resident OPCs contribute to focal remyelination and VEGF and PDGF signaling is required for the proliferation of OPCs in the medulla oblongata of the adult mouse. |
2,329,124 | Shape and Mobility of a Left Ventricular Thrombus Are Predictors of Thrombus Resolution. | Left ventricular (LV) apical thrombi are usually present with LV dilatation, and oral anticoagulants reduce embolic risk in these patients. However, echocardiographic data regarding thrombus resolution remain limited. We studied its echocardiographic features that were associated with early resolution (within 1 month).</AbstractText>We performed a retrospective observational study by reviewing baseline and follow-up echocardiographic images and medical records in patients with LV apical thrombi.</AbstractText>Between January 2005 and December 2017, 77 patients (59 males, mean 61±12 years old) were enrolled. Patients were classified into 2 groups based on duration of thrombus resolution: group 1 showing resolution within 1 month (n=23) and group 2 with persistence after 1 month (n=54). Thrombus size was significantly smaller in group 1 (10.7±4.2 vs. 12.1±5.5 mm, p=0.046). Grade 1 mobility (partially mobile; odds ratio [OR], 7.800; p=0.012) and grade 2 mobility (highly mobile; OR, 14.625; p=0.002) were significantly associated with the early resolution. Round thrombi were associated with early resolution than mural form (OR, 3.187; p=0.026). Multivariate analysis showed that the mobility was the most important parameter, and a highly mobile (grade 2 mobility) LV apical thrombi showed earlier resolution (OR, 12.525; p=0.013). During the follow-up over 62±44 months, 25 patients (32.5%) had ≥1 adverse clinical events. The late resolution of thrombi was associated with poor long-term clinical outcomes (hazard ratio, 5.727; p=0.020).</AbstractText>Mobility of LV apical thrombi was the most important parameter associated with early thrombus resolution. Late resolution of LV apical thrombi was associated with poor long-term clinical outcomes.</AbstractText>Copyright © 2019. The Korean Society of Cardiology.</CopyrightInformation> |
2,329,125 | Aging and Brain Atrophy in Multiple Sclerosis. | Brain atrophy accelerates at the age of 60 in healthy individuals (HI) and at disease onset in multiple sclerosis (MS) patients. Whether there is an exacerbating effect of aging superimposed on MS-related brain atrophy is unknown. We estimated the aging effect on lateral ventricular volume (LVV) and whole brain volume (WBV) changes in MS patients.</AbstractText>1,982 MS patients (mean follow-up: 4.8 years) and 351 HI (mean follow-up: of 3.1 years), aged from 20 to 79 years old (yo), were collected retrospectively. Percent LVV change (PLVVC) and percent brain volume change (PBVC) on 1.5T and 3T MRI scanners (median of 3.9 scans per subject) were calculated. These were determined between all-time points and subjects were divided in six-decade age groups. MRI differences between age groups were calculated using analysis of covariance (ANCOVA).</AbstractText>Compared to HI, at first MRI, MS patients had significantly increased LVV in the age groups: 30-39 yo, 40-49 yo, 50-59 yo, 60-69 yo (all P < .0001), and 70-79 yo (P = .029), and decreased WBV in the age groups: 20-29 yo (P = .024), 30-39 yo (P = .031), 40-49 yo, and 50-59 yo (all P < .0001). Annualized PLVVC was significantly different between the age groups 20-59 and 60-79 yo in MS patients (P = .005) and HI (P < .0001), as was for PBVC in MS patients (P = .001), but not for HI (P = .521). There was a significant aging interaction effect in the annualized PLVVC (P = .001) between HI and MS patients, which was not observed for the annualized PBVC (P = .380).</AbstractText>Development of brain atrophy manifests progressively in MS patients, and occurs with a different pattern, as compared to aging HI. PLVVC increased across age in HI as compared to MS, while PBVC decreased across ages in both HI and MS.</AbstractText>© 2019 by the American Society of Neuroimaging.</CopyrightInformation> |
2,329,126 | Prior endoscopic third ventriculostomy does not increase ventriculoperitoneal shunt failure rate. | To determine whether prior endoscopic third ventriculostomy (ETV) influences the failure rate of subsequently placed ventriculoperitoneal (VP) shunts.</AbstractText>Our institution's operative database and patient records were reviewed retrospectively to identify all paediatric patients who had undergone a first VP shunt or ETV at our institution between January 2012 and December 2015. Data was analysed using the Microsoft Excel, GraphPad Prism v7 and SPSS statistics. The literature on this topic to date was also reviewed.</AbstractText>Eighty-six children were included in the study: 61 patients had a primary VP shunt inserted during the study period and 25 had a VP shunt inserted following failed ETV. There was no significant difference in the underlying aetiology or age of the patients in each group. In the primary VP shunt group, 47.5% (29 patients) required shunt removal at an average of 274 days post-insertion (range 7 days to 3.4 years). The 1-year revision rate was 34.4%. In the shunt post-ETV group, 48% (12 patients) required shunt removal at an average of 207 days post-insertion (range 2 days to 2.7 years). The 1-year revision rate was 36%. The most common reason for revision in both groups was blockage.</AbstractText>We found no significant difference in failure rate or pattern between primarily inserted VP shunts and those inserted following an endoscopic third ventriculostomy. On the basis of this study and the small number of previously reported studies, we would advocate a trial of ETV where feasible to allow a chance at shunt independence.</AbstractText> |
2,329,127 | Rapid Involution of Large Cardiac Rhabdomyomas With Everolimus Therapy. | Rhabdomyoma of the fetal heart is a rare disease accounting for about 1% of all fetal cardiac structural anomalies. They are often found in association with tuberous sclerosis complex. Large cardiac rhabdomyomas can compromise the cardiac function. We report a case of multiple large rhabdomyomas of the right and left ventricles, affecting the cardiac function, which was successfully treated with the chemotherapeutic and immunosuppressive medication everolimus, in a neonate with genetically confirmed tuberous sclerosis complex with multisystem manifestations. There was rapid involution of the tumors in response to everolimus therapy in this infant. |
2,329,128 | Multiple Remote Sequential Supratentorial Epidural Hematomas-An Unusual and Rare Complication After Posterior Fossa Surgery. | Postoperative hemorrhage is a serious complication of intracranial surgery. Epidural hematomas (EDHs) are one of the common forms of bleeding after surgery, with ≤12% of patients requiring re-exploration. However, distant or remote site EDHs have been rare, in particular, those in a supratentorial location after infratentorial surgery.</AbstractText>We report an unusual complication of surgery for fourth ventricular outlet obstruction. A young male patient developed multiple sequential supratentorial EDHs after posterior fossa surgery. He required 2 re-explorations after the primary surgery for evacuation of the EDHs within 24 hours. In the available data, we found only 28 such reported cases previously. Only 2 additional cases have been reported to have sequential EDHs after surgery. Various theories have been postulated, ranging from sudden intracranial pressure decompression, pin site hematoma, and shunt site bleeding due to dural stripping. None has been proven to definitively explain the complication.</AbstractText>We wished to highlight this unusual complication of posterior fossa surgery, with an emphasis on rapid computed tomography scanning of the brain for patients in the early postoperative period with any neurological deterioration. Early radiological detection and timely intervention can be lifesaving.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,129 | Endoscope-assisted microsurgical evacuation versus external ventricular drainage for the treatment of cast intraventricular hemorrhage: results of a comparative series. | Cast intraventricular hemorrhage (IVH) is associated to high morbidity/mortality rates. External ventricular drainage (EVD), the most common treatment adopted in these patients, may be unsuccessful due to short-term drain obstruction and requires weeks for cerebrospinal fluid (CSF) clearing, increasing the risks of ventriculits. Administration of intraventricular fibrinolytic agents and endoscopic evacuation have been proposed as alternative treatments, but with equally poor results. We present a retrospective analysis of two groups of patients who respectively underwent endoscope-assisted microsurgical evacuation versus EVD for the treatment of cast IVH. In a 10-year time, 25 patients with cast IVH underwent microsurgical, endoscope-assisted evacuation. Twenty-seven were instead treated by EVD. The two groups were compared in terms of hematoma evacuation, CSF clearing time, infection rates, need for permanent shunting, short/long-term survival, and functional outcome. In endoscope-assisted surgeries, full CSF clearance required 14 ± 3 days in 20 patients and 21 ± 3 days in 5; in the EVD group, 21 ± 3 days were needed in 12 patients, 28 ± 3 days in 11, and 35 ± 3 days in 4. Permanent shunting was inserted respectively in 19 endoscopic and 23 EVD patients. Final mRs score was 0-3 in 13 endoscopic cases, 4-5 in the remaining 12. In the EVD group, 7 subjects scored mRs 0-3, 16 scored 4-5; 4 died. In our experience, endoscope-assisted evacuation of cast IVH reduced ICU staying and CSF clearance times. It also seemed to improve neurological outcome, but without affecting the need for permanent shunt. On the counterside, it increases the number of severely disabled survivors. |
2,329,130 | Is endoscopic third ventriculostomy safe and efficient in the treatment of obstructive chronic hydrocephalus in adults? A prospective clinical and MRI study. | In case of suspected normal pressure hydrocephalus, MRI is performed systematically and can sometimes highlight an obstruction of the flow pathways of the CSF (aqueductal stenosis or other downstream obstruction). It seems legitimate for these patients to ask the question of a treatment with endoscopic third ventriculostomy (ETV), even if the late decompensation of an obstruction may suggest an association with a CSF resorption disorder. The aim of this study was to evaluate clinical and radiological evolution after ETV in a group of elderly patients with an obstructive chronic hydrocephalus (OCH).</AbstractText>ETV was performed in 15 patients with OCH between 2012 and 2017. Morphometric (callosal angle, ventricular surface, third ventricular width, and Evans' index) and velocimetric parameters (stroke volume of the aqueductal (SVa) CSF) parameters were measured prior and after surgery with brain MRI. The clinical score (mini-mental status examination (MMSE) and the modified Larsson's score, evaluating walking, autonomy, and incontinence) were performed pre- and postoperatively.</AbstractText>SVa was less than 15 μL/R-R in 12 out of the 15 patients; in the other three cases, the obstruction was located at a distance from the middle part of the aqueduct. Fourteen out of 15 patients were significantly improved: mean Larsson's score decreased from 3.8 to 0.6 (P ≤ 0.01) and mean MMSE increased from 25.7 to 28 (P = 0.084). Evans' index and ventricular area decreased postoperatively and the callosal angle increased (P ≤ 0.01). The mean follow-up lasted 17.9 months. No postoperative complications were observed.</AbstractText>ETV seems to be a safe and efficient alternative to shunt for chronic hydrocephalus with obstruction; the clinical improvement is usual and ventricular size decreases slightly.</AbstractText> |
2,329,131 | Neuronal Migration Generates New Populations of Neurons That Develop Unique Connections, Physiological Properties and Pathologies. | Central nervous system neurons become postmitotic when radial glia cells divide to form neuroblasts. Neuroblasts may migrate away from the ventricle radially along glia fibers, in various directions or even across the midline. We present four cases of unusual migration that are variably connected to either pathology or formation of new populations of neurons with new connectivities. One of the best-known cases of radial migration involves granule cells that migrate from the external granule cell layer along radial Bergman glia fibers to become mature internal granule cells. In various medulloblastoma cases this migration does not occur and transforms the external granule cell layer into a rapidly growing tumor. Among the ocular motor neurons is one unique population that undergoes a contralateral migration and uniquely innervates the superior rectus and levator palpebrae muscles. In humans, a mutation of a single gene ubiquitously expressed in all cells, induces innervation defects only in this unique motor neuron population, leading to inability to elevate eyes or upper eyelids. One of the best-known cases for longitudinal migration is the facial branchial motor (FBM) neurons and the overlapping inner ear efferent population. We describe here molecular cues that are needed for the caudal migration of FBM to segregate these motor neurons from the differently migrating inner ear efferent population. Finally, we describe unusual migration of inner ear spiral ganglion neurons that result in aberrant connections with disruption of frequency presentation. Combined, these data identify unique migratory properties of various neuronal populations that allow them to adopt new connections but also sets them up for unique pathologies. |
2,329,132 | Transcription factor TAp73 and microRNA-449 complement each other to support multiciliogenesis. | Motile cilia serve vital functions in development, homeostasis, and regeneration. We recently demonstrated that TAp73 is an essential transcriptional regulator of respiratory multiciliogenesis. Here, we show that TAp73 is expressed in multiciliated cells (MCCs) of diverse tissues. Analysis of TAp73 mutant animals revealed that TAp73 regulates Foxj1, Rfx2, Rfx3, axonemal dyneins Dnali1 and Dnai1, plays a pivotal role in the generation of MCCs in male and female reproductive ducts, and contributes to fertility. However, the function of MCCs in the brain appears to be preserved despite the loss of TAp73, and robust activity of cilia-related networks is maintained in the absence of TAp73. Notably, TAp73 loss leads to distinct changes in ciliogenic microRNAs: miR34bc expression is reduced, whereas the miR449 cluster is induced in diverse multiciliated epithelia. Among different MCCs, choroid plexus (CP) epithelial cells in the brain display prominent miR449 expression, whereas brain ventricles exhibit significant increase in miR449 levels along with an increase in the activity of ciliogenic E2F4/MCIDAS circuit in TAp73 mutant animals. Conversely, E2F4 induces robust transcriptional response from miR449 genomic regions. To address whether increased miR449 levels in the brain maintain the multiciliogenesis program in the absence of TAp73, we deleted both TAp73 and miR449 in mice. Although loss of miR449 alone led to a mild ciliary defect in the CP, more pronounced ciliary defects and hydrocephalus were observed in the brain lacking both TAp73 and miR449. In contrast, miR449 loss in other MCCs failed to enhance ciliary defects associated with TAp73 loss. Together, our study shows that, in addition to the airways, TAp73 is essential for generation of MCCs in male and female reproductive ducts, whereas miR449 and TAp73 complement each other to support multiciliogenesis and CP development in the brain. |
2,329,133 | Postnatal nectin-3 knockdown induces structural abnormalities of hippocampal principal neurons and memory deficits in adult mice. | The early postnatal stage is a critical period of hippocampal neurodevelopment and also a period of high vulnerability to adverse life experiences. Recent evidence suggests that nectin-3, a cell adhesion molecule, mediates memory dysfunction and dendritic alterations in the adult hippocampus induced by postnatal stress. But it is unknown whether postnatal nectin-3 reduction alone is sufficient to alter hippocampal structure and function in adulthood. Here, we down regulated hippocampal expression of nectin-3 and its heterophilic adhesion partner nectin-1, respectively, from early postnatal stage by injecting adeno-associated virus (AAV) into the cerebral lateral ventricles of neonatal mice (postnatal day 2). We found that suppression of nectin-3, but not nectin-1, expression from the early postnatal stage impaired hippocampus-dependent novel object recognition and spatial object recognition in adult mice. Moreover, AAV-mediated nectin-3 knockdown significantly reduced dendritic complexity and spine density of pyramidal neurons throughout the hippocampus, whereas nectin-1 knockdown only induced the loss of stubby spines in CA3. Our data provide direct evidence that nectins, especially nectin-3, are necessary for postnatal hippocampal development of memory functions and structural integrity. |
2,329,134 | Microsurgical Treatment of Ruptured Spetzler-Martin Grade 3 Right Hippocampal Arteriovenous Malformation: 3-Dimensional Operative Video. | We present a 14-yr-old male with a history of traumatic brain injury in March 2016, secondary to clonic tonic generalized seizures. CT scan showed hemorrhage at mesial temporal region in the body of right hippocampus, intraventricular hemorrhage at the level of lateral ventricles (right and left side) and fourth ventricle. After this the patient presented with pulsating right temporal headache of high intensity (VAS 10/10) that improved with common analgesics, dizziness, and clonic tonic generalized seizures despite taking Phenobarbital 100 mg/24 h. Neuropsychological assessment reveal major deficits regarding executive functions: working memory, verbal fluency, and planning abilities. Brain MRI and angiography showed AVM at the right level of hippocampus body. An intranidal aneurysm was also observed. Venous drainage was through the basal vein of Rosenthal. We planned for surgery and resection of the hippocampal AVM through the trans-T2 approach. Postoperatively, the patient was without medical complications. We present a 3-dimensional video of the microsurgical treatment for right hippocampal AVM performed through a trans-T2 approach. The patient signed the Institutional Consent Form, which allows the use of his/her images and videos for any type of medical publications in conferences and/or scientific articles. |
2,329,135 | Resection of Massive "Tarry" Intra/Extra-ventricular Prepontine Colloid Cyst: 2-Dimensional Operative Video. | Colloid cysts are typically slow-growing lesions that account for approximately 1% of primary intracranial neoplasms and predominantly exist intraventricularly. These benign lesions typically can exist symptom-free for years and do not require surgical intervention. However, if the location of the colloid cyst is symptomatic, surgical debulking may be indicated. In this intraoperative video, we illustrate the case of an 8 cm, intra/extra-ventricular colloid cyst that appeared as a craniopharyngioma on preoperative imaging, but upon resection via a trans-middle temporal gyrus approach, was found to be very atypically filled with a thick, "tarry" substance, which we hypothesize is due to serial, subacute lesional hemorrhages. After debulking and piecemeal resection of the majority of the mass with ultrasonic aspiration and microsurgical tools, a hard, calcified nodule was left tenaciously adherent to the superior cerebellar artery to prevent damage to this vascular structure. |
2,329,136 | Giant Choroid Plexus Papilloma Resection Utilizing a Transcollation System. | Large vascular brain tumors pose an exceptional challenge in young children. Choroid plexus papilloma (CPP) is an example of a rare, often large and especially vascular neuroepithelial tumor that most commonly arises in children under 5 yr old. Although patients may be cured by total resection, this tumor poses significant surgical risks and challenges related to intraoperative hemostasis.</AbstractText>To describe our experience using a transcollation system during brain tumor surgery in a child to achieve hemostasis and minimize blood loss while preserving normal brain tissue.</AbstractText>A 3-yr-old girl presented following a fall and was found to have a giant CPP growing from the right lateral ventricle. Given the vascularity of the tumor and the low intravascular reserve in a small child, a transcollation device was used to reduce blood loss intraoperatively.</AbstractText>Gross total resection was achieved with approximately 300 mL of blood loss without complications. The patient did well postoperatively. Imaging performed at 3 mo after resection revealed return of normal brain architecture.</AbstractText>Transcollation devices appear to be an effective and safe addition to the armamentarium of neurosurgical hemostatic options in intracranial tumor resection in which there is a high risk of intraoperative hemorrhage.</AbstractText>Copyright © 2019 by the Congress of Neurological Surgeons.</CopyrightInformation> |
2,329,137 | Predisposition of Wingless Subgroup Medulloblastoma for Primary Tumor Hemorrhage. | Primary intratumoral hemorrhage as a presenting sign is rare in children with medulloblastomas but may result in severe complications. Given the distinct properties of molecular medulloblastoma subgroups, the impact on neurosurgical practice has still to be defined.</AbstractText>To investigate both clinical and radiological presentation of intratumoral hemorrhage in medulloblastoma patients in the context of molecular subgroups.</AbstractText>Data of all consecutive medulloblastoma patients treated at our institution between 1993 and 2018 (n = 104) were retrospectively reviewed in respect of clinical and radiological presentation as well as molecular subgroups. For cases with available tumor tissue (n = 86), subgroups were assigned by either 450 K methylation array or immunohistochemistry and CTNNB1 sequencing. Available imaging at diagnosis (n = 62) was reviewed by an experienced neuroradiologist.</AbstractText>Within the entire cohort, 4 patients (4%) presented with massive spontaneous hemorrhage. Although no patient died as a direct consequence of hemorrhage, all suffered from serious sequelae. Moreover, 3 additional patients displayed radiological evidence of significant hemorrhage. Interestingly, all 7 cases belonged to the wingless (WNT) subgroup (n = 13), resulting in intratumoral hemorrhage in 54% (7/13) of pediatric WNT medulloblastomas. In contrast, significant hemorrhage was absent in all other molecular subgroups.</AbstractText>Our results suggest that a substantial proportion of pediatric WNT medulloblastomas display significant intratumoral hemorrhage at the time of diagnosis. Consequently, the presence of significant hemorrhage in fourth ventricle childhood tumors is suggestive of WNT medulloblastoma and should lead to a less aggressive attempt for total resection in this prognostically favorable tumor type.</AbstractText>© Congress of Neurological Surgeons 2019.</CopyrightInformation> |
2,329,138 | OTX2 Signals from the Choroid Plexus to Regulate Adult Neurogenesis. | Proliferation and migration during adult neurogenesis are regulated by a microenvironment of signaling molecules originating from local vasculature, from CSF produced by the choroid plexus, and from local supporting cells including astrocytes. Here, we focus on the function of OTX2 homeoprotein transcription factor in the mouse adult ventricular-subventricular zone (V-SVZ), which generates olfactory bulb neurons. We find that OTX2 secreted by choroid plexus is transferred to the supporting cells of the V-SVZ and rostral migratory stream. Deletion of <i>Otx2</i> in choroid plexus affects neuroblast migration and reduces the number of olfactory bulb newborn neurons. Adult neurogenesis was also decreased by expressing secreted single-chain antibodies to sequester OTX2 in the CSF, demonstrating the importance of non-cell-autonomous OTX2. We show that OTX2 activity modifies extracellular matrix components and signaling molecules produced by supporting astrocytes. Thus, we reveal a multilevel and non-cell-autonomous role of a homeoprotein and reinforce the choroid plexus and astrocytes as key niche compartments affecting adult neurogenesis. |
2,329,139 | The wide spectrum of ultrasound diagnosis of holoprosencephaly. | Holoprosencephaly (HPE) is the most common brain malformation. A wide spectrum of anatomical variants are characterized by a lack of midline separation of the cerebral hemispheres. The aim of this study was to assess the ultrasound diagnostic criteria for HPE.</AbstractText>A database of 175 fetuses with central nervous system anomalies identified by ultrasound was collected retrospectively from 2006 to 2016 in this multicenter, retrospective, observational study. Among them 18 cases (10.2%) with HPE were identified.</AbstractText>The prevalence of HPE was 2.5:10.000 with the sex distributionmale:female of 1:1.6. Six cases were alobar subtype, 3 were semilobar, 7 were lobar and 2 were middle interhemispheric variant. In the second trimester, we consider that the abnormal fusion of the lateral ventricles and the absence of the cavum septum pellucidum are the most important landmarks for HPE. Facial abnormalities varied considerably.</AbstractText>This study illustrates the heterogeneity of HPE with different cerebral and facial appearances.</AbstractText> |
2,329,140 | Choroid Plexus Carcinoma in Adults: Two Case Reports. | Choroid plexus tumors are uncommon brain tumors that primarily occur in children. Most of these tumors originate from the intraventricular area, and the most common clinicalpresentation is increased intracranial pressure. Dissemination through the cerebrospinal fluid space is the inevitable natural course of the disease. Here, we present 2 rare cases of adult choroid plexus carcinoma (CPC), each with distinct clinical presentation and progression. The first case was a 40-year-old male who presented with multiple intraventricular masses. After surgical biopsy, radiation and intrathecal chemotherapy failed to elicit any response. The patient progressed with spinal cord dissemination and expired 1 year later. The second case presented with visual disturbance, and brain MRI revealed a large ovoid juxtaventricular mass with peritumoral edema. This 49-year-old female patient underwent craniotomy for what was thought to be a high-grade glioma; however, the mass was connected to the choroid plexus at the operative field. Her pathology specimen was diagnosed as CPC, and adjuvant systemic chemotherapy was administered. She has now been free of recurrence for 10 months. The description of the presentation and progression of these rare adult-onset CPC provides insight for the diagnosis and treatment of other rare instances of choroid plexus tumors. |
2,329,141 | Running-Activated Neural Stem Cells Enhance Subventricular Neurogenesis and Improve Olfactory Behavior in p21 Knockout Mice. | In the subventricular zone (SVZ) of the adult brain, the neural stem cells (NSCs) ensure a continuous supply of new neurons to the olfactory bulb (OB), playing a key role in its plasticity and olfactory-related behavior. The activation and expansion of NSCs within the SVZ are finely regulated by environmental and intrinsic factors. Running represents one of the most powerful neurogenic stimuli, although is ineffective in enhancing SVZ neurogenesis. The cell cycle inhibitor p21 is an intrinsic inhibitor of NSCs' expansion through the maintenance of their quiescence and the restrain of neural progenitor proliferation. In this work, we decided to test whether running unveils the intrinsic neurogenic potential of p21-lacking NSCs. To test this hypothesis, we examined the effect of three different paradigms of voluntary running (5, 12, and 21 days) on SVZ neurogenesis of p21 knockout (KO) male mice at two different stages of development, 2 and 12 months of age. In vivo and in vitro data clearly demonstrate that physical activity is consistent with the activation and expansion of NSCs and with the enhancement of SVZ neurogenesis in p21 KO mice. We also found that 12 days of running contribute to the increase in the number of new neurons functionally active within the OB, which associates with an improvement in olfactory performance strictly dependent on adult SVZ neurogenesis, i.e., the odor detection threshold and short-term olfactory memory. These data suggest that in the adult SVZ of p21 KO mice, NSCs retain a high neurogenic potential, triggered by physical activity, with long-term consequences in olfactory-related behavior. |
2,329,142 | [Neuro-endoscopic Management of Intraparenchymal Arachnoid Cyst in Adults:Three Case Reports]. | We report 3 cases of symptomatic intraparenchymal arachnoid cysts in adults, including 2 in elderly patients. Case 1:An 81-year-old woman developed right-sided hemiparesis and hemianopsia due to the enlargement of left occipital arachnoid cyst, which had been incidentally diagnosed 3 years ago. Under the guidance of neuronavigation, we inserted a rigid endoscope into the cyst and perforated the cyst wall toward the posterior horn of the lateral ventricle, making a good communication between the cyst and the ventricle for cerebrospinal fluid. Her symptoms improved within 3 days after the surgery, and the cyst mass reduced. Case 2:A 57-year-old woman was incidentally found to have a right frontal arachnoid cyst. She had a 3-month long history of low mood and loss of interest in work. We perforated the transparent septum via the cyst wall toword the left lateral ventricle in a neuro-endoscopic procedure. After the surgery, she regained interest in work, and her symptom was considered to be indicative of depression due to arachnoid cyst. Case 3:A 94-year-old woman in a geriatric facility developed left-sided hemiparesis due to the enlargement of a right temporal arachnoid cyst, which had been detected 10 years ago. Neuro-endoscopic perforation of the cyst wall toward the lateral ventricle remarkably improved her symptoms. Arachnoid cysts can become symptomatic in the long term, not only in the young but also in the elderly. Neuro-endoscopic fenestration is an effective treatment for symptomatic intraparenchymal cysts, especially in elderly patients. The neuronavigation system was useful in the planning of the trajectory and in the detection of the target point of fenestration. |
2,329,143 | Brain ventricular volume changes induced by long-duration spaceflight. | Long-duration spaceflight induces detrimental changes in human physiology. Its residual effects and mechanisms remain unclear. We prospectively investigated the changes in cerebrospinal fluid (CSF) volume of the brain ventricular regions in space crew by means of a region of interest analysis on structural brain scans. Cosmonaut MRI data were investigated preflight (<i>n</i> = 11), postflight (<i>n</i> = 11), and at long-term follow-up 7 mo after landing (<i>n</i> = 7). Post hoc analyses revealed a significant difference between preflight and postflight values for all supratentorial ventricular structures, i.e., lateral ventricle (mean % change ± SE = 13.3 ± 1.9), third ventricle (mean % change ± SE = 10.4 ± 1.1), and the total ventricular volume (mean % change ± SE = 11.6 ± 1.5) (all <i>P</i> < 0.0001), with higher volumes at postflight. At follow-up, these structures did not quite reach baseline levels, with still residual increases in volume for the lateral ventricle (mean % change ± SE = 7.7 ± 1.6; <i>P</i> = 0.0009), the third ventricle (mean % change ± SE = 4.7 ± 1.3; <i>P</i> = 0.0063), and the total ventricular volume (mean % change ± SE = 6.4 ± 1.3; <i>P</i> = 0.0008). This spatiotemporal pattern of CSF compartment enlargement and recovery points to a reduced CSF resorption in microgravity as the underlying cause. Our results warrant more detailed and longer longitudinal follow-up. The clinical impact of our findings on the long-term cosmonauts' health and their relation to ocular changes reported in space travelers requires further prospective studies. |
2,329,144 | Visualization of spatiotemporal dynamics of human glioma stem cell invasion. | Glioblastoma exhibits phenotypic and genetic heterogeneity, aggressive invasiveness, therapeutic resistance, and tumor recurrence, which can be explained by the existence of glioma stem cells (GSCs). In this study, we visualized the spatiotemporal dynamics of invasion of human GSCs in an orthotopic xenograft mouse model using time-lapse imaging of organotypic brain slice cultures and three-dimensional imaging of optically cleared whole brains. GSCs implanted in the striatum exhibited directional migration toward axon bundles, perivascular area, and the subventricular zone around the inferior horn of the lateral ventricle. GSCs migrated in a helical pattern around axon bundles in the striatum and invaded broadly in both the rostral and caudal directions. GSCs in the corpus callosum migrated more rapidly and unidirectionally toward the contralateral side with pseudopod extension. These characteristics of GSC invasion shared histological features observed in glioblastoma patients. Spatiotemporal visualization techniques can contribute to the elucidation of the mechanisms underlying GSC invasion that may lead to the development of effective therapy for glioblastoma. |
2,329,145 | Neurofibromatosis Type 1-Related Hydrocephalus: Treatment Options and Considerations. | Neurofibromatosis type I (NF1) will be associated with hydrocephalus in ≤13% of cases. Currently, very little data are available describing the actual etiologies and treatment options of NF1-associated hydrocephalus. We, therefore, have described our experience in treating NF1-associated hydrocephalus.</AbstractText>We completed a retrospective data analysis of 1020 patients with NF1 treated at the Gilbert's Israeli International Neurofibromatosis Center during a period of 20 years. The patients presenting with, and treated for, related hydrocephalus were included. The clinical, radiological, and surgical data are presented.</AbstractText>We included 22 patients (2.1% of the entire NF1 patient cohort), with 17 aged <19 years. Twenty patients had obstructive hydrocephalus. The most common etiologies included aqueductal or third ventricular obstruction. Of the 22 patients, 15 had underwent endoscopic procedures (14 third ventriculostomies) and 7 had undergone shunt procedures. The corresponding failure rates (including the need for additional cerebrospinal fluid procedures) were 60% and 71%.</AbstractText>Hydrocephalus in the context of NF1 has been caused mostly by obstructive etiologies. A tailored treatment approach is recommended to address the specific etiology. Regardless of the treatment approach, a relatively high rate of failure has been described.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,146 | Toll-like receptor 4 regulates subventricular zone proliferation and neuroblast migration after experimental stroke. | Ischemic stroke is one of the leading causes of death and disability with an urgent need for innovative therapies, especially targeting the chronic phase. New evidence has emerged showing that Toll-Like Receptor 4 (TLR4), a key mediator of brain damage after stroke, may be involved in brain repair by neurogenesis modulation. The aim of this study is to analyze the role of TLR4 in the different stages of neurogenesis initiated in the subventricular zone (SVZ) over time after stroke in mice. Wildtype and TLR4-deficient mice underwent experimental ischemia, and neural stem/progenitor cells (NSPCs) proliferation and migration were analyzed by using FACS analysis, fluorescence densitometry, RT-qPCR and in vitro assays. Our results show that both groups, wildtype and knock-out animals, present a similar pattern of bilateral cell proliferation at the SVZ, with a decrease in NSPCs proliferation in the acute phase of stroke. We also show that TLR4 activation, very likely mediated by ligands such as HMGB1 released to CSF after stroke, is necessary to keep an increased proliferation of NSCs as well as to promote differentiation from type C cells into neuroblasts promoting their migration. TLR4 activation was also implicated in earlier expression of SDF-1α and faster recovery of BDNF expression after stroke. These results support TLR4 as an important therapeutic target in the modulation of neurogenesis after stroke. |
2,329,147 | An integrative view of mammalian seasonal neuroendocrinology. | Seasonal neuroendocrine cycles that govern annual changes in reproductive activity, energy metabolism and hair growth are almost ubiquitous in mammals that have evolved at temperate and polar latitudes. Changes in nocturnal melatonin secretion regulating gene expression in the pars tuberalis (PT) of the pituitary stalk are a critical common feature in seasonal mammals. The PT sends signal(s) to the pars distalis of the pituitary to regulate prolactin secretion and thus the annual moult cycle. The PT also signals in a retrograde manner via thyroid-stimulating hormone to tanycytes, which line the ventral wall of the third ventricle in the hypothalamus. Tanycytes show seasonal plasticity in gene expression and play a pivotal role in regulating local thyroid hormone (TH) availability. Within the mediobasal hypothalamus, the cellular and molecular targets of TH remain elusive. However, two populations of hypothalamic neurones, which produce the RF-amide neuropeptides kisspeptin and RFRP3 (RF-amide related peptide 3), are plausible relays between TH and the gonadotrophin-releasing hormone-pituitary-gonadal axis. By contrast, the ways by which TH also impinges on hypothalamic systems regulating energy intake and expenditure remain unknown. Here, we review the neuroendocrine underpinnings of seasonality and identify several areas that warrant further research. |
2,329,148 | Assessment of cardiac function in donor and recipient fetuses during a 7-day follow-up after selective laser photocoagulation of communicating vessels due to TTTS. | The aim of the study was to analyze the changes in cardiac function and myocardial contractility of donor and recipient fetuses with twin-to-twin transfusion syndrome (TTTS) subjected to selective laser photocoagulation of the communicating vessels (SLPCV), between and after the procedure. Finally, we verified if fetuses with Quintero's stage I TTTS presented with early impairment of myocardial contractility.</AbstractText>We selected 77 consecutive women with twin pregnancies, whose both fetuses survived at least seven days post-SLPCV. Myocardial contractility of both fetuses was evaluated ultrasonographically, and their myocardial performance indices (Tei-Index values) and shortening fractions (SF) were determined.</AbstractText>In donor fetuses, the Tei-Index values for both right and left ventricle remained within the respective reference ranges both before the procedure and during a 7-day follow-up. A significant change in shortening fraction values for the left ventricle in recipient fetuses and the right ventricle of in the donors was observed during a 7-day follow-up.</AbstractText>Comparison of the cardiac parameters of donors and recipients revealed significant differences in Tei-indices during the entire follow-up period. The group with Quintero's I stage TTTS included 74% of recipient fetuses with abnormal Tei-Index values for the right ventricle (mean 0.53).</AbstractText> |
2,329,149 | Comparative Analysis of Subventricular Zone Glioblastoma Contact and Ventricular Entry During Resection in Predicting Dissemination, Hydrocephalus, and Survival. | Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes.</AbstractText>To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients.</AbstractText>Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation).</AbstractText>Surgical ventricular entry, SVZ-contacting glioblastoma, hydrocephalus, leptomeningeal dissemination, and distant recurrences were observed in 85 (36.6%), 114 (49.1%), 19 (8.2%), 78 (33.6%), and 59 (25.4%) patients, respectively. Multivariate, adjusted analysis revealed SVZ tumor contact-but not ventricular entry-associated with hydrocephalus (hazard ratio, HR, 4.20 [1.13-15.7], P = .03), leptomeningeal dissemination (HR 1.93 [1.14-3.28], P = .01), PFS (HR 2.10 [1.53-2.88], P < .001), and OS (HR 1.90 [1.35-2.67], P < .001). Distant recurrences were not associated with either. No interaction between the 2 variables was statistically noted.</AbstractText>SVZ contact by glioblastoma was independently associated with the development of hydrocephalus, leptomeningeal dissemination, and decreased survival. SVZ tumor contact was associated with ventricular entry during surgical resections, which did not independently correlate with these outcomes.</AbstractText>Copyright © 2019 by the Congress of Neurological Surgeons.</CopyrightInformation> |
2,329,150 | Sensing Glucose in the Central Melanocortin Circuits of Rainbow Trout: A Morphological Study. | In mammals, glucosensing markers reside in brain areas known to play an important role in the control of food intake. The best characterized glucosensing mechanism is that dependent on glucokinase (GK) whose activation by increased levels of glucose leads in specific hypothalamic neurons to decreased or increased activity, ultimately leading to decreased food intake. In fish, evidence obtained in recent years suggested the presence of GK-like immunoreactive cells in different brain areas related to food intake control. However, it has not been established yet whether or not those neuronal populations having glucosensing capacity are the same that express the neuropeptides involved in the metabolic control of food intake. Therefore, we assessed through dual fluorescent <i>in situ</i> hybridization the possible expression of GK in the melanocortinergic neurons expressing proopiomelanocortin (POMC) or agouti-related protein (AGRP). POMC and AGRP expression localized exclusively in the rostral hypothalamus, in the ventral pole of the lateral tuberal nucleus, the homolog of the mammalian arcuate nucleus. Hypothalamic GK expression confined to the ependymal cells coating the ventral pole of the third ventricle but some expression level occurred in the AGRP neurons. GK expression seems to be absent in the hypothalamic POMC neurons. These results suggest that AGRP neurons might sense glucose directly through a mechanism involving GK. In contrast, POMC neurons would not directly respond to glucose through GK and would require presynaptic inputs to sense glucose. Ependymal cells could play a critical role relying glucose metabolic information to the central circuitry regulating food intake in fish, especially in POMC neurons. |
2,329,151 | Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body Weight. | Despite the established comorbidity between mood disorders and abnormal eating behaviors, the underlying molecular mechanism and therapeutics remain to be resolved. Here, we show that a spexin-based galanin receptor type 2 agonist (SG2A) simultaneously normalized mood behaviors and body weight in corticosterone pellet-implanted (CORTI) mice, which are underweight and exhibit signs of anhedonia, increased anxiety, and depression. Administration of SG2A into the lateral ventricle produced antidepressive and anxiolytic effects in CORTI mice. Additionally, SG2A led to a recovery of body weight in CORTI mice while it induced significant weight loss in normal mice. In Pavlovian fear-conditioned mice, SG2A decreased contextual and auditory fear memory consolidation but accelerated the extinction of acquired fear memory without altering innate fear and recognition memory. The main action sites of SG2A in the brain may include serotonergic neurons in the dorsal raphe nucleus for mood control, and proopiomelanocortin/corticotropin-releasing hormone neurons in the hypothalamus for appetite and body weight control. Furthermore, intranasal administration of SG2A exerted the same anxiolytic and antidepressant-like effects and decreased food intake and body weight in a dose-dependent manner. Altogether, these results indicate that SG2A holds promise as a clinical treatment for patients with comorbid mood disorders and abnormal appetite/body weight. |
2,329,152 | Primary intraventricular abscess of the third ventricle. | Intraventricular abscess is a rare pathology. We present a case of primary intraventricular abscess in an immunocompetent 22 year old male. We review the literature and discuss our management of this case with aspiration via neuroendoscopy. |
2,329,153 | Tissue oxygen saturation assessment of microvascular perfusion in adults with Fontan palliation and comparator groups using vascular optical spectrophotometry: a pilot study. | The Fontan operation greatly improves survival for single ventricle congenital heart disease patients but creates a physiology that leads to long-term multi-organ dysfunction. A non-invasive screening tool that can identify impending decline is sought. The objective of this pilot study was to assess the microcirculation in Fontan-palliated patients by measuring tissue oxygen saturation (StO2</sub>) in superficial and deeper tissues.</AbstractText>Three patient cohorts were studied: Fontan group (n  =  8) and two patient control groups, liver disease group (n  =  8) and tetralogy of Fallot group (n  =  9). 22 healthy controls were also examined. Superficial and deeper StO2</sub> was measured at the forearm, thenar eminence, index and ring fingers of both arms using the LEA O2C spectrophotometry device.</AbstractText>Superficial StO2</sub> was reduced in Fontan patients compared to healthy controls (p   =  0.002) and tetralogy patients (p   =  0.016), but not compared to the liver group (p   =  0.313). Deeper StO2</sub> was similar between groups (p   =  0.112). The gap between deeper and superficial StO2</sub> was raised in Fontan patients compared to healthy controls (p   =  0.001) and tetralogy patients (p   =  0.037), but not compared to the liver group (p   =  0.504). There was no clinically relevant difference in StO2</sub> between the left and right arms, and the variation in StO2</sub> according to measurement site was similar between the four groups.</AbstractText>Vascular optical spectrophotometry is a feasible non-invasive measure of micro-circulatory function that can easily be performed in the clinic setting and may have utility in patients with Fontan circulations. Further, we provide important normal range data in the healthy control population which can be used to design future studies.</AbstractText> |
2,329,154 | Wax Droplets Lining Ventricles. | Rupture of the spinal dermoid is rare. There may be intracranial deposition of fat secondary to it. We report a case of an adult male who presented with features of obstructive hydrocephalus secondary to ruptured lumbar dermoid. A 42-year-male presented with acute-onset headache and vomiting for 2 days. There was grade 3 papilledema on fundus examination. Magnetic resonance imaging showed ventriculomegaly with aqueductal obstruction. Multiple T1 and T2 hyperintense deposits were also noted along the ventricular wall. Magnetic resonance imaging of the spine showed a T1, T2 hyperintense intramedullary lesion at the lumbar region with multiple fat deposits along the spinal axis. He underwent endoscopic third ventriculostomy and is doing well at the 6-month follow-up. He is asymptomatic for the spinal lesion. Silent rupture of the spinal dermoid causing obstructive hydrocephalus is rare. These patients may remain asymptomatic for the spinal lesion and improves with cerebrospinal fluid diversion. |
2,329,155 | Weight loss enhances cardiac energy metabolism and function in heart failure associated with obesity. | Obesity is associated with high rates of cardiac fatty acid oxidation, low rates of glucose oxidation, cardiac hypertrophy and heart failure. Whether weight loss can lessen the severity of heart failure associated with obesity is not known. We therefore determined the effect of weight loss on cardiac energy metabolism and the severity of heart failure in obese mice with heart failure.</AbstractText>Obesity and heart failure were induced by feeding mice a high-fat (HF) diet and subjecting them to transverse aortic constriction (TAC). Obese mice with heart failure were then switched for 8 weeks to either a low-fat (LF) diet (HF TAC LF) or caloric restriction (CR) (40% caloric intake reduction, HF TAC CR) to induce weight loss.</AbstractText>Weight loss improved cardiac function (%EF was 38 ± 6% and 36 ± 6% in HF TAC LF and HF TAC CR mice vs 25 ± 3% in HF TAC mice, P < 0.05) and it decreased cardiac hypertrophy post TAC (left ventricle mass was 168 ± 7 and 171 ± 10 mg in HF TAC LF and HF TAC CR mice, respectively, vs 210 ± 8 mg in HF TAC mice, P < 0.05). Weight loss enhanced cardiac insulin signalling, insulin-stimulated glucose oxidation rates (1.5 ± 0.1 and 1.5 ± 0.1 μmol/g dry wt/min in HF TAC LF and HF TAC CR mice, respectively, vs 0.2 ± 0.1 μmol/g dry wt/min in HF TAC mice, P < 0.05) and it decreased pyruvate dehydrogenase phosphorylation. Cardiac fatty acid oxidation rates, AMPKTyr172</sup> /ACCSer79</sup> signalling and the acetylation of ß-oxidation enzymes, were attenuated following weight loss.</AbstractText>Weight loss is an effective intervention to improve cardiac function and energy metabolism in heart failure associated with obesity.</AbstractText>© 2019 John Wiley & Sons Ltd.</CopyrightInformation> |
2,329,156 | Relationship between Microcirculatory Perfusion and Arterial Elastance: A Pilot Study. | Arterial elastance (Ea) represents the total afterload imposed on the left ventricle, and it is largely influenced by systemic vascular resistance (SVR). Although one can expect that Ea is influenced by peripheral endothelial function, no data are available to support it in patients. The aim of this study was to investigate the relationship between Ea, SVR, and microvascular perfusion in critically ill patients undergoing the fluid challenge (FC).</AbstractText>A prospective study in patients receiving a fluid challenge. A pulse wave analysis system (MostCare, Vygon, France) was used to estimate Ea and an incident dark field (IDF) handheld device (Braedius Medical BV, The Netherlands) to evaluate the sublingual microcirculation. Microvascular perfusion was assessed using the proportion of small-perfused vessels (PPV). Relative changes in each variable were calculated before and after FC; fluid responsiveness was defined as an increase in the cardiac index by at least 10% from baseline.</AbstractText>We studied 20 patients requiring a fluid challenge (n</i>=10 for hypotension; n</i>=5 for oliguria; n</i>=3 for lactate values greater than 2 mmol/l; n</i>=2 for tachycardia), including 12 fluid responders. There was a strong correlation between Ea and SVR (r</i> 2</sup> = 0.75; p</i> < 0.001) and only a weak correlation between Ea and PPV at baseline (r</i> 2</sup> = 0.22; p</i>=0.04). Ea decreased from 1.4 [1.2-1.6] to 1.2 [1.1-1.4] mmHg/mL (p</i>=0.01), SVR from 1207 [1006-1373] to 1073 [997-1202] dyn ∗ s/cm5</sup> (p</i>=0.06), and PPV from 56 [51-64] % to 59 [47-73] % (p</i>=0.25) after fluid challenge. Changes in Ea were significantly correlated with changes in SVR, but not with changes in PPV.</AbstractText>The correlation between Ea and indexes of microvascular perfusion in the sublingual region is weak. The impact of microcirculatory perfusion on the arterial load is probably limited.</AbstractText> |
2,329,157 | Selective stimulation of central GABA<sub>A</sub>α2,3,5 receptors increases intake and motivation to consume sucrose solution in rats. | Benzodiazepines are one of the most commonly prescribed anxiolytic drugs in America, and between 2006 and 2015 prescription rates increased by an estimated 27.1%. Weight gain is a common side effect of these drugs and it may result from increased feeding caused by drug-enhanced food palatability. We investigated the role of specific GABA<sub>A</sub> receptor subtypes involved with benzodiazepine-induced food consumption through third ventricle injections of L-838,417, a partial agonist of GABA<sub>A</sub> α2, α3, and α5 subunits, and a full antagonist of the α1 receptor subunit. A microanalysis of the licking behavior of adult male rats to a sucrose solution was used to isolate drug effects on specific consummatory behaviors that include: hedonic taste evaluation, food approach behavior, and oromotor function. L-838,417 dose-dependently increased intake through increases in the motivation to approach the solution (shorter pause intervals between bouts of licking) and through enhancement of measures associated with hedonic taste evaluation. Oromotor depressant effects previously associated with broad-spectrum benzodiazepine receptor agonists were not observed. These results indicate that nuclei in proximity to the ventricles respond to GABA<sub>A</sub> α2, α3, or α5 activation to induce motivation to feed, absent of α1 receptor subunit activation. Furthermore, activation of the α1 subunit is not necessary for benzodiazepine hyperphagia and may instead contribute to the oromotor depressant and sedative properties of classic benzodiazepine agonists. Hypothalamic nuclei such as the paraventricular nucleus may be involved in the benzodiazepine-increased motivation to feed, while the parabrachial nucleus of the hindbrain could contribute to benzodiazepine-induced enhancement of taste palatability. |
2,329,158 | Aerodynamic impact of the ventricular folds in computational larynx models. | Ventricular folds (VeFs) act as passive, non-moving structures during normal phonation. According to the literature, VeFs potentially aid the flow-driven oscillations of the vocal folds (VFs) that produce the primary sound of human phonation. In this study, large eddy simulations were performed to analyze this influence in a numerical model with imposed VF motion as measured experimentally from a synthetic silicone vocal fold model. Model configurations with and without VeFs were considered. Furthermore, configurations with rectangular and elliptical glottis shapes were simulated to investigate the effects of three-dimensional glottal jet evolutions. Results showed that VeFs increased flow rate and transglottal pressure difference by a decrease in the pressure level in the ventricles immediately downstream of the VFs. This led to an increase in the glottal flow resistance, increased energy transfer rate between the flow and VFs, and a simultaneous decrease in the laryngeal flow resistance, which shows a higher amount of kinetic energy in the glottal flow. This enhancement was more pronounced in the rectangular glottis and varied with the subglottal pressure and VeF gap size. |
2,329,159 | Three-plane description of astroglial populations of OVLT subdivisions in rat: Tanycyte connections to distant parts of third ventricle. | This study demonstrates glial and gliovascular markers of organon vasculosum laminae terminalis (OVLT) in three planes. The distribution of glial markers displayed similarities to the subfornical organ. There was an inner part with vimentin- and nestin-immunopositive glia whereas GFAP and the water-channel aquaporin 4 were found at the periphery. This separation indicates different functions of the two regions. The presence of nestin may indicate stem cell-capabilities whereas aquaporin 4 has been reported to promote the osmoreceptor function. Glutamine synthetase immunoreactivity was sparse like in the area postrema and subfornical organ. The laminin and β-dystroglycan immunolabelings altered along the vessels such as in the subfornical organ indicating altering gliovascular relations. The different subdivisions of OVLT received glial processes of different origins. The posterior periventricular zone contained short vimentin-immunopositive processes from the ependyma of the adjacent surface of the third ventricle. The lateral periventricular zone received forceps-like process systems from the anterolateral part of the third ventricle. Most interestingly, the "dorsal cap" received a mixed group of long GFAP- and vimentin-immunopositive processes from a distant part of the third ventricle. The processes may have two functions: a guidance for newly produced cells like radial glia in immature brain and/or a connection between distant parts of the third ventricle and OVLT. |
2,329,160 | <i>De Novo</i> Duplication in the <i>CHD7</i> Gene Associated With Severe CHARGE Syndrome. | CHARGE syndrome is an autosomal dominant developmental disorder associated with a constellation of traits involving almost every organ and sensory system, in particular congenital anomalies, including choanal atresia and malformations of the heart, inner ear, and retina. Variants in <i>CHD7</i> have been shown to cause CHARGE syndrome. Here, we report the identification of a novel <i>de novo</i> p.Asp2119_Pro2120ins6 duplication variant in a conserved region of <i>CHD7</i> in a severely affected boy presenting with 3 and 5 of the CHARGE cardinal major and minor signs, respectively, combined with congenital umbilical hernia, congenital hernia at the linea alba, mildly hypoplastic inferior vermis, slight dilatation of the lateral ventricles, prominent metopic ridge, and hypoglycemic episodes. |
2,329,161 | Minimally Invasive Surgery for Spontaneous Cerebellar Hemorrhage: A Multicenter Study. | Spontaneous intracranial hemorrhage (ICH) of the cerebellum can be life threatening because of mass effect on the brainstem and fourth ventricle. Suboccipital craniectomy is currently the treatment of choice for cerebellar ICH evacuation. Minimally invasive surgery (MIS) is currently being investigated for the treatment of supratentorial ICH. However, its utility for cerebellar ICH is unknown. The aim of this multicenter, retrospective cohort study is to evaluate the outcomes of MIS for cerebellar ICH.</AbstractText>We retrospectively reviewed the records of all patients with cerebellar ICH who underwent MIS using either the Apollo or Artemis Neuro Evacuation Device (Penumbra Inc., Alameda, California, USA) at 3 institutions from May 2015 to July 2018. Data from each contributing center were deidentified and pooled for analysis.</AbstractText>The study cohort comprised 6 patients with a median age of 62.5 years. The median pre- and postoperative Glasgow Coma Scale scores were 10.5 and 15, respectively. The median degree of hematoma evacuation was 97.5% (range, 79%-100%). There were no procedural complications, but 1 patient required subsequent craniectomy (retreatment rate 17%). The median discharge modified Rankin scale score was 4, including 3 patients who improved to functional independence at follow-up durations of 3 months. Two patients died from medical complications (mortality rate 33%).</AbstractText>MIS could represent a reasonable alternative to conventional surgery for the treatment of appropriately selected patients with cerebellar ICH. However, further studies are needed to clarify the perioperative and long-term risk to benefit profiles of this technique.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,162 | Prolonged post-differentiation culture influences the expression and biophysics of Na<sup>+</sup> and Ca<sup>2+</sup> channels in induced pluripotent stem cell-derived ventricular-like cardiomyocytes. | Several studies have been reported in various domains from induction methods to utilities of somatic cell pluripotent reprogramming. However, one of the major struggles facing the research field of induced pluripotent stem cell (iPSC)-derived target cells is the lack of consistency in observations. This could be due to variety of reasons including varied culture periods post-differentiation. The cardiomyocytes (CMs) derived from iPSCs are commonly studied and proposed to be utilized in the comprehensive in vitro proarrhythmia initiative for drug safety screening. As the influence of varied culture periods on the electrophysiological properties of iPSC-CMs is not clearly known, using whole-cell patch clamp technique, we compared two groups of differentiated ventricular-like iPSC-CMs that are cultured for 10 to 15 days (D10-15) and more than 30 days (≥ D30) both under current and voltage clamps. The prolonged culture imparts increased excitability with high-frequency spontaneous action potentials, robust increase in the magnitude of peak Na<sup>+</sup> current density, relatively shallow inactivation kinetics of Na<sup>+</sup> channels, faster recovery from inactivation, and augmented Ca<sup>2+</sup> current density. Quantitative real-time PCR studies of α-subunit transcripts showed enhanced mRNA expression of SCN1A, SCN5A Na<sup>+</sup> channel subtypes, and CACNA1C, CACNA1G, and CACNA1I Ca<sup>2+</sup> channel subtypes, in ≥ D30 group. Conclusively, the prolonged culture of differentiated iPSC-CMs affects the excitability, single-cell electrophysiological properties, and ion channel expressions. Therefore, following standard periods of culture across research studies while utilizing ventricular-like iPSC-CMs for in vitro health/disease modeling to study cellular functional mechanisms or test high-throughput drugs' efficacy and toxicity becomes crucial. |
2,329,163 | Altered brain diffusion tensor imaging indices in adolescents with the Fontan palliation. | Single ventricle heart disease (SVHD) patients show injury in brain sites that regulate autonomic, mood, and cognitive functions. However, the nature (acute or chronic changes) and extent of brain injury in SVHD are unclear. Our aim was to examine regional brain tissue damage in SVHD over controls using DTI-based mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) procedures.</AbstractText>We collected two DTI series (3.0-T MRI), mood and cognitive data, from 27 SVHD and 35 control adolescents. Whole-brain MD, AD, RD, and FA maps were calculated from each series, realigned and averaged, normalized to a common space, smoothed, and compared between groups using ANCOVA (covariates, age and sex; false discovery rate, p < 0.05). Region-of-interest analyses were performed to calculate MD, AD, RD, and FA values for magnitude assessment between groups.</AbstractText>SVHD patients showed impaired mood and cognitive functions over healthy adolescents. Multiple brain sites in SVHD showed increased MD values, including the insula, caudate, cingulate, hypothalamus, thalamus, medial prefrontal and frontal cortices, parahippocampal gyrus, hippocampus, precentral gyrus, amygdala, cerebellum, corpus callosum, basal forebrain, mammillary bodies, internal capsule, midbrain, fornix, and occipital, parietal, and temporal cortices, indicating chronic tissue changes. Similar areas showed either increased AD or RD values, with RD changes more enhanced over AD in SVHD compared to controls. Few brain regions emerged with increased or decreased FA values in SVHD patients over controls.</AbstractText>SVHD adolescents, more than a decade from their last surgical procedure, show widespread brain abnormalities in autonomic, mood, and cognitive regulatory areas. These findings indicate that brain injury is in a chronic stage in SVHD with predominantly myelin changes that may result from previous hypoxia/ischemia- or developmental-induced processes.</AbstractText> |
2,329,164 | Double outlet right ventricle and aortopulmonary window in a neonate with Bohring-Opitz (Oberklaid-Danks) syndrome: First case report. | Bohring-Opitz syndrome (BOS) is a rare, sporadic genetic disorder, characterized by feeding difficulties, developmental delay, flexion abnormalities, dysmorphic facial features and typical body posture (BOS posture). This syndrome is diagnosed on the basis of distinctive clinical features with or without confirmation by genetic studies. Cardiac abnormalities are seen in almost half of the patients, but are nonspecific. We present a case of a 3-week-old male baby with BOS who was referred to our hospital with congestive heart failure, seizures and failure to thrive. He was diagnosed to have double outlet right ventricle and aortopulmonary window (DORV and APW). To our knowledge, this is the first case of Bohring-Opitz Syndrome ever reported with such clinical presentation. |
2,329,165 | Intracranial Mature Teratoma in an Adult Patient: A Case Report. | <b>Introduction</b> : Primary intracranial teratoma is a subtype of germ cell tumors, classified into three subtypes. They occur very rarely, with only several reported individual cases in adults. <b>Case Description</b>  We present a patient with an intermittent headache in the right frontal region. Magnetic resonance imaging (MRI) revealed a right sided high frontal parasagittal mass that compressed the falx, the right lateral ventricle, as well as the brain parenchyma. Patient underwent surgical treatment. Histopathological analysis described mature teratoma. Four months after the surgical treatment there were no signs of residual intracranial mass or relapse. <b>Discussion</b>  Primary intracranial teratoma in adults has a nonspecific clinical presentation. MRI reveals a solitary irregular mass with multilocularity and mixed signals derived from different tissues. The patients age, biochemical markers, and patohistological analysis are necessary to confirm the diagnosis. <b>Conclusion</b>  Teratoma treatment strategy still remains controversial. It includes radical resection whenever possible. Since the residual portion of mature teratoma may contain part of immature or malignant tissue, tumor recurrence after surgical removal is possible. Also, new tumor mass could occur at other sites intracranial after the initial one was removed. Thus, although patients usually recover, they should be followed-up for a long period of time. |
2,329,166 | Nutrient Sensing by Hypothalamic Tanycytes. | Nutritional signals have long been implicated in the control of cellular processes that take place in the hypothalamus. This includes food intake regulation and energy balance, inflammation, and most recently, neurogenesis. One of the main glial cells residing in the hypothalamus are tanycytes, radial glial-like cells, whose bodies are located in the lining of the third ventricle, with processes extending to the parenchyma and reaching neuronal nuclei. Their unique anatomical location makes them directly exposed to nutrients in the cerebrospinal fluid. Several research groups have shown that tanycytes can respond to nutritional signals by different mechanisms, such as calcium signaling, metabolic shift, and changes in proliferation/differentiation potential. Despite cumulative evidence showing tanycytes have the molecular components to participate in nutrient detection and response, there are no enough functional studies connecting tanycyte nutrient sensing with hypothalamic functions, nor that highlight the relevance of this process in physiological and pathological context. This review will summarize recent evidence that supports a nutrient sensor role for tanycytes in the hypothalamus, highlighting the need for more detailed analysis on the actual implications of tanycyte-nutrient sensing and how this process can be modulated, which might allow the discovery of new metabolic and signaling pathways as therapeutic targets, for the treatment of hypothalamic related diseases. |
2,329,167 | Enhanced in vitro model of the CSF dynamics. | Fluid dynamics of the craniospinal system are complex and still not completely understood. In vivo flow and pressure measurements of the cerebrospinal fluid (CSF) are limited. Whereas in silico modeling can be an adequate pathway for parameter studies, in vitro modeling of the craniospinal system is essential for testing and evaluation of therapeutic measures associated with innovative implants relating to, for example, normal pressure hydrocephalus and other fluid disorders. Previously-reported in vitro models focused on the investigation of only one hypothesis of the fluid dynamics rather than developing a modular set-up to allow changes in focus of the investigation. The aim of this study is to present an enhanced and validated in vitro model of the CSF system which enables the future embedding of implants, the validation of in silico models or phase-contrast magnetic resonance imaging (PC-MRI) measurements and a variety of sensitivity analyses regarding pathological behavior, such as reduced CSF compliances, higher resistances or altered blood dynamics.</AbstractText>The in vitro model consists of a ventricular system which is connected via the aqueduct to the cranial and spinal subarachnoid spaces. Two compliance chambers are integrated to cushion the arteriovenous blood flow generated by a cam plate unit enabling the modeling of patient specific flow dynamics. The CSF dynamics are monitored using three cranial pressure sensors and a spinal ultrasound flow meter. Measurements of the in vitro spinal flow were compared to cervical flow data recorded with PC-MRI from nine healthy young volunteers, and pressure measurements were compared to the literature values reported for intracranial pressure (ICP) to validate the newly developed in vitro model.</AbstractText>The maximum spinal CSF flow recorded in the in vitro simulation was 133.60 ml/min in the caudal direction and 68.01 ml/min in the cranial direction, whereas the PC-MRI flow data of the subjects showed 122.82 ml/min in the caudal and 77.86 ml/min in the cranial direction. In addition, the mean ICP (in vitro) was 12.68 mmHg and the pressure wave amplitude, 4.86 mmHg, which is in the physiological range.</AbstractText>The in vitro pressure values were in the physiological range. The amplitudes of the flow results were in good agreement with PC-MRI data of young and healthy volunteers. However, the maximum cranial flow in the in vitro model occurred earlier than in the PC-MRI data, which might be due to a lack of an in vitro dynamic compliance. Implementing dynamic compliances and related sensitivity analyses are major aspects of our ongoing research.</AbstractText> |
2,329,168 | Myocardial mechano-energetic efficiency and insulin resistance in non-diabetic members of the Strong Heart Study cohort. | Myocardial energetic efficiency (MEE), is a strong predictor of CV events in hypertensive patient and is reduced in patients with diabetes and metabolic syndrome. We hypothesized that severity of insulin resistance (by HOMA-IR) negatively influences MEE in participants from the Strong Heart Study (SHS).</AbstractText>We selected non-diabetic participants (n = 3128, 47 ± 17 years, 1807 women, 1447 obese, 870 hypertensive) free of cardiovascular (CV) disease, by merging two cohorts (Strong Heart Study and Strong Heart Family Study, age range 18-93). MEE was estimated as stroke work (SW = systolic blood pressure [SBP] × stroke volume [SV])/"double product" of SBP × heart rate (HR), as an estimate of O2</sub> consumption, which can be simplified as SV/HR ratio and expressed in ml/sec. Due to the strong correlation, MEE was normalized by left ventricular (LV) mass (MEEi).</AbstractText>Linear trend analyses showed that with increasing quartiles of HOMA-IR patients were older, more likely to be women, obese and hypertensive, with a trend toward a worse lipid profile (all p for trend < 0.001), progressive increase in LV mass index, stroke index and cardiac index and decline of wall mechanics (all p < 0.0001). In multivariable regression, after adjusting for confounders, and including a kinship coefficient to correct for relatedness, MEEi was negatively associated with HOMA-IR, independently of significant associations with age, sex, blood pressure, lipid profile and central obesity (all p < 0.0001).</AbstractText>Severity of insulin resistance has significant and independent negative impact on myocardial mechano-energetic efficiency in nondiabetic individual from a population study of American Indians. Trial registration number NCT00005134, Name of registry: Strong Heart Study, URL of registry: https://clinicaltrials.gov/ct2/show/NCT00005134 , Date of registration: May 25, 2000, Date of enrolment of the first participant to the trial: September 1988.</AbstractText> |
2,329,169 | PI3Kα Pathway Inhibition With Doxorubicin Treatment Results in Distinct Biventricular Atrophy and Remodeling With Right Ventricular Dysfunction. | Background Cancer therapies inhibiting PI 3Kα (phosphoinositide 3-kinase-α)-dependent growth factor signaling, including trastuzumab inhibition of HER 2 (Human Epidermal Growth Factor Receptor 2), can cause adverse effects on the heart. Direct inhibition of PI 3Kα is now in clinical trials, but the effects of PI 3Kα pathway inhibition on heart atrophy, remodeling, and function in the context of cancer therapy are not well understood. Method and Results Pharmacological PI 3Kα inhibition and heart-specific genetic deletion of p110α, the catalytic subunit of PI 3Kα, was characterized in conjunction with anthracycline (doxorubicin) treatment in female murine models. Biventricular changes in heart morphological characteristics and function were analyzed, with molecular characterization of signaling pathways. Both PI 3Kα inhibition and anthracycline therapy promoted heart atrophy and a combined effect of distinct right ventricular dilation, dysfunction, and cardiomyocyte remodeling in the absence of pulmonary arterial hypertension. Congruent findings of right ventricular dilation and dysfunction were seen with pharmacological and genetic suppression of PI 3Kα signaling when combined with doxorubicin treatment. Increased p38 mitogen-activated protein kinase activation was mechanistically linked to heart atrophy and correlated with right ventricular dysfunction in explanted failing human hearts. Conclusions PI 3Kα pathway inhibition promotes heart atrophy in mice. The right ventricle is specifically at risk for dilation and dysfunction in the setting of PI 3K inhibition in conjunction with chemotherapy. Inhibition of p38 mitogen-activated protein kinase is a proposed therapeutic target to minimize this mode of cardiotoxicity. |
2,329,170 | Prospective detection and differential diagnosis of cystic posterior fossa anomalies by assessing posterior brain at 11-14 weeks. | The role of the first-trimester scan has expanded from aneuploidy screening to the diagnosis of fetal malformations. Abnormal appearance of the posterior brain at 11-14 weeks gestation is a marker of cerebral anomalies; in fact an increased amount of fluid, particularly when the choroid plexus of the fourth ventricle is not visible and only 2 brain spaces instead of 3 are seen, may indicate the presence of cystic or cyst-like posterior fossa anomalies, such as Blake's pouch cyst or Dandy-Walker malformation.</AbstractText>The purpose of this study was to assess the role of ultrasound scanning in the identification of cystic posterior fossa anomalies at 11-14 weeks gestation.</AbstractText>A prospective cohort study of fetuses with cystic appearance of the posterior fossa at 11-14 weeks gestation was performed. In all cases and in a control group of 40 normal fetuses, the brainstem-tentorium angle was also measured. The presence or absence of cystic posterior anomalies was determined at birth or at postmortem evaluation.</AbstractText>In the period 2014-2018, 32 fetuses with an increased brainstem-occipital bone distance and/or failure to visualize the choroid plexus of fourth ventricle (2 brain spaces) were seen. Of these, 18 fetuses were terminated in the first trimester because of associated anomalies and were excluded from the study because of unavailable autoptic findings. The remaining 14 fetuses eventually were found to have a Dandy-Walker malformation in 4 cases, a Blake's pouch cyst in 8 cases, and normal brain anatomy in 2 cases. Two brain spaces were seen in all cases with Dandy-Walker malformation and in 2 of 8 cases with Blake's pouch cyst. Both brainstem-occipital bone measurement and brainstem-tentorium angle were significantly different in fetuses with Dandy-Walker malformation, Blake's pouch cyst, and control subjects (P<.0001). The brainstem-occipital bone z-scores of fetuses with Dandy-Walker malformation and Blake's pouch cyst were always +3 or more and +1.7 or more, respectively. The brainstem-tentorium angle z-scores were always -5 or less and -0.1 or less, respectively.</AbstractText>Our study confirms that sonography of the posterior brain at 11-14 weeks gestation allows the identification of cystic posterior fossa anomalies. A large brainstem-occipital bone predicts Dandy-Walker malformation or Blake's pouch cyst. The presence of 2 brain spaces and a small brainstem-tentorium angle are correlated significantly with the presence of Dandy-Walker malformation.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,171 | AQP1 Overexpression in the CSF of Obstructive Hydrocephalus and Inversion of Its Polarity in the Choroid Plexus of a Chiari Malformation Type II Case. | The choroid plexus (ChP) is involved in the production of cerebrospinal fluid (CSF) and is intimately related to CSF physiopathology. Aquaporin-1 (AQP1) is the water channel directly implicated in CSF production and a potential therapeutic target in the management of CSF circulation disorders. Pathologies that present ventriculomegaly are associated with defective CSF turnover and AQPs are involved in both the production and reabsorption of CSF. This work examines the levels of AQP1 and its dynamics in ventriculomegaly conditions such as congenital hydrocephalus (communicating and obstructive) or type II lissencephaly versus control. We specifically address the expression of AQP1 in the CSF of 16 term-pregnancy infants where it was found to be significantly increased in obstructive cases when compared with communicating hydrocephalus or control patients. We also defined histologically the expression of AQP1 in the ChP from 6 nonsurvival preterm-pregnancy infants ranging ages between 20 and 25 gestational weeks in which AQP1 was mainly expressed at the apical pole of the ChP epithelium (ChPE) in control and lissencephalic patients. AQP1 expression from the Chiari malformation case showed an inverted polarity being expressed in the basal pole of the ChPE colocalizing with the glucose transporter 1 where this transporter is naturally located. |
2,329,172 | Neuroprotective effects of lipopolysaccharide and naltrexone co‑preconditioning in the photothrombotic model of unilateral selective hippocampal ischemia in rat. | Preconditioning with lipopolysaccharide (LPS) or opioid antagonists has a neuroprotective effect in ischemic insults. However, the co‑preconditioning effect of toll‑like receptor ligands and opioid antagonists has not been investigated. In this study we examined the neuroprotective effect of LPS and naltrexone (NTX) preconditioning and co‑preconditioning in unilateral selective hippocampal ischemia in rats to assess for possible synergistic protective effects. LPS and NTX were injected unilaterally into the left cerebral ventricle of male rats. Forty‑eight hours after LPS and twenty‑four hours after NTX injection, ipsilateral selective hippocampal ischemia was induced using a modified version of the photothrombotic method. Protective effects for LPS and NTX were assessed by evaluating infarct volume (using 2,3,5‑triphenyltetrazolium chloride staining), and cognitive function (using radial arm water maze and passive avoidance tests). Animals in the ischemic group had an infarct lesion and considerable cognitive impairment, compared with the sham group. LPS or NTX preconditioning significantly reduced the infarct size and improved cognitive function. Moreover, co‑preconditioning with LPS and NTX increased the protective effect compared with preconditioning with LPS or NTX alone. Our data showed that LPS and NTX preconditioning resulted in a neuroprotective effect in hippocampal ischemia. Furthermore, co‑preconditioning with LPS and NTX resulted in a synergistic protective effect. |
2,329,173 | Deep Learning for Diagnosis of Chronic Myocardial Infarction on Nonenhanced Cardiac Cine MRI. | Background Renal impairment is common in patients with coronary artery disease and, if severe, late gadolinium enhancement (LGE) imaging for myocardial infarction (MI) evaluation cannot be performed. Purpose To develop a fully automatic framework for chronic MI delineation via deep learning on non-contrast material-enhanced cardiac cine MRI. Materials and Methods In this retrospective single-center study, a deep learning model was developed to extract motion features from the left ventricle and delineate MI regions on nonenhanced cardiac cine MRI collected between October 2015 and March 2017. Patients with chronic MI, as well as healthy control patients, had both nonenhanced cardiac cine (25 phases per cardiac cycle) and LGE MRI examinations. Eighty percent of MRI examinations were used for the training data set and 20% for the independent testing data set. Chronic MI regions on LGE MRI were defined as ground truth. Diagnostic performance was assessed by analysis of the area under the receiver operating characteristic curve (AUC). MI area and MI area percentage from nonenhanced cardiac cine and LGE MRI were compared by using the Pearson correlation, paired <i>t</i> test, and Bland-Altman analysis. Results Study participants included 212 patients with chronic MI (men, 171; age, 57.2 years ± 12.5) and 87 healthy control patients (men, 42; age, 43.3 years ± 15.5). Using the full cardiac cine MRI, the per-segment sensitivity and specificity for detecting chronic MI in the independent test set was 89.8% and 99.1%, respectively, with an AUC of 0.94. There were no differences between nonenhanced cardiac cine and LGE MRI analyses in number of MI segments (114 vs 127, respectively; <i>P</i> = .38), per-patient MI area (6.2 cm<sup>2</sup> ± 2.8 vs 5.5 cm<sup>2</sup> ± 2.3, respectively; <i>P</i> = .27; correlation coefficient, <i>r</i> = 0.88), and MI area percentage (21.5% ± 17.3 vs 18.5% ± 15.4; <i>P</i> = .17; correlation coefficient, <i>r</i> = 0.89). Conclusion The proposed deep learning framework on nonenhanced cardiac cine MRI enables the confirmation (presence), detection (position), and delineation (transmurality and size) of chronic myocardial infarction. However, future larger-scale multicenter studies are required for a full validation. Published under a CC BY 4.0 license. <i>Online supplemental material is available for this article.</i> See also the editorial by Leiner in this issue. |
2,329,174 | [Effects of Electroacupuncture and Intracerebral Injection of VEGF on Caspase12, Caspase3, and <i>GRP78</i> Genes in Rats with Cerebral Ischemia-Reperfusion Injury]. | To determine the effects of electroacupuncture (EA) and intracerebral injection of vascular endothelial growth factor (VEGF) on caspase12, caspase3, and glucose regulated protein 78 kD (GRP78) genes of rats with cerebral ischemia reperfusion injury.</AbstractText>60 SD rats were randomly divided into sham-operation group, model group, EA group and EA+VEGF group with 15 rats in each group. Middle cerebral artery occlusion (MCAO) method was used to establish the model of cerebral ischemia reperfusion injury. Electro-acupuncture intervention was introduced 1 day after the injury in the EA group and EA+VEGF group: 30 minutes each session and once a day for a total of 14 d [acupoint selection: Baihui (GV 20), Quchi(Li 11), Zusanli (ST36)]. The rats in the EA+VEGF group were also injected with 10 μL of VEGF165 (0.025 μg/μL) into the lateral ventricle after the first session of EA. Five rats in each group were sacrificed after obtaining a neurological function score (mNSS) at day 0 (1 d after modeling, before EA intervention), day 7 and day 14, respectively. Nissl staining was used to observe the histomorphology of cerebral infarction areas. Immunohistochemistry was used to CM(155mm]detect GRP78 activity in the ischemic brain tissues. Real-time fluorescence quantitative PCR (real-time PCR) was used to detect the expressions of caspase12, caspase3 and GRP78</i> mRNA in the ischemic brain tissues.</AbstractText>Compared with the sham-operation group, rats in the model group had higher mNSS scores ( P</i><0.05), showed signs of cerebral infarction (with reduced numbers of and disordered Nissl bodies and unclear structure), increased GRP78 immunopositive cells, increased expression of GRP78</i> mRNA ( P</i><0.05), and increased expressions of caspase12 and caspase3 mRNA ( P</i><0.05). Compared with the model group, EA and EA+VEGF decreased mNSS scores at day 7 and 14 ( P</i><0.05), showing alleviated signs of cerebral infarction, increased GRP78 immunopositive cells ( P</i><0.05), increased GRP78</i> mRNA expression ( P</i><0.05), and decreased caspase12 and caspase3 mRNA expressions ( P</i><0.05). The most obvious changes were found in the EA+VEGF group ( P</i><0.05). No significant changes were observed in the sham-operation group over time ( P</i><0.05). In comparison, mNSS scores, the signs of cerebral infarction, and the expressions of caspase12 and caspase3 decreased over time in the other groups ( P</i><0.05), accompanied with increased GRP78 immunopositive cells and the expression of GRP78</i> gene ( P</i><0.05).</AbstractText>Electroacupuncture and intracerebral injection of VEGF promote tissue repair of rats with cerebral ischemic injury, possibly through down-regulating the expressions of caspase12 and caspase3 genes and up-regulating the expression of GRP78</i> gene. The effect of electroacupuncture in combination with intracerebral injection of VEGF is superior to that of the single use of electroacupuncture.</AbstractText>Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).</CopyrightInformation> |
2,329,175 | Hemangioblastoma of the Central Nervous System: A Case Series of Patients Surgically Treated at Shohada-e-Tajrish Hospital, Tehran, Iran during 2004-2014. | Hemangioblastoma refers to a benign vascular neoplasm that comprises stromal and capillary cells. Based on the classification of nervous system tumors proposed by WHO, hemangioblastomas are classified as Grade I meningeal tumors of uncertain origin. These tumors are found almost exclusively in the central nervous system (CNS) and account for 0.9% to 2.1% of all primary CNS tumors.</AbstractText><AbstractText Label="MATERIALS & METHODS" NlmCategory="METHODS">In this descriptive retrospective study, the archives of pathology reports were reviewed in the Department of Pathology of Shohada-e-Tajrish Hospital, Tehran, Iran and patients with definite diagnosis of hemangioblastoma made through histopathological examinations during 2004-2014 were identified. Age, gender and the location of tumor were extracted from the medical records and entered into SPSS statistical software v.22 for analysis.</AbstractText>Thirty patients including 16 males (53.3%) and 14 females (46.7%) were identified. The mean age of the patients was calculated to be 41.2±13.47 yr, ranging from 19 to 62 yr old. The majority of lesions had been found in the cerebellum of the patients (93.3%); only one had occurred in the cerebrum (3.3%) and another in the fourth ventricle (3.3%).</AbstractText>Cerebellum is the most commonly affected location in patients with CNS hemangioblastomas, and a male preponderance is observed in these cases.</AbstractText> |
2,329,176 | Reduced Estimated GFR and Cardiac Remodeling: A Population-Based Autopsy Study. | <AbstractText Label="RATIONALE & OBJECTIVE">Evidence suggests that cardiac remodeling, including left ventricular hypertrophy and myocardial fibrosis, develops with progression of kidney disease. Few studies have examined cardiac pathology across a range of estimated glomerular filtration rates (eGFRs), which was the objective of this investigation.</AbstractText>Population-based cross-sectional study of deceased patients undergoing autopsy.</AbstractText><AbstractText Label="SETTING & PARTICIPANTS">334 of 694 consecutive deceased patients undergoing autopsy with available cardiac tissue, with a prior health examination within 6 years and without a prior diagnosis of heart disease.</AbstractText>eGFR.</AbstractText>The thickness of the left ventricular wall, sizes of cardiac cells, and percentages of fibrosis, estimated from pathology examination of autopsy samples.</AbstractText>Generalized estimating equations.</AbstractText>Lower eGFRs were associated with greater left ventricular wall thickness. Deceased patients with eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2</sup> had left ventricular wall thicknesses of 9.1, 9.5, 9.8, and 10.3mm, respectively (P for trend<0.05). Lower eGFRs were also significantly associated with greater mean values of cardiac cell size in the left ventricular wall after adjusting for confounders: 15.3, 16.1, 16.4, and 17.4μm for eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2</sup> (P for trend<0.01). Patients with lower eGFRs had significantly higher multivariable-adjusted geometric mean values for fibrosis percentage in the left ventricular wall: 3.22%, 4.33%, 3.83%, and 6.14% for eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2</sup> (P for trend<0.001). The negative association of eGFR with multivariable-adjusted mean values of cardiac cell width was stronger among patients with than those without anemia.</AbstractText>Cross-sectional study with a high proportion of elderly patients, no available information for severity or duration of hypertension and other cardiovascular risk factors, no information for medication use.</AbstractText>These findings suggest that reduced eGFR is associated with cardiac hypertrophy and fibrosis of the left ventricle, cardiac cell enlargement, and cardiac fibrosis.</AbstractText>Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,177 | Ventricular volumetry and free-water corrected diffusion tensor imaging of the anterior thalamic radiation in idiopathic normal pressure hydrocephalus. | The pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) has not been completely clarified. We investigated the brain structure in iNPH using automatic ventricular volumetry, single-tensor diffusion tensor imaging (DTI) and bi-tensor free-water (FW) imaging analyses while focusing on cognitive impairments before and after lumboperitoneal shunt surgery.</AbstractText>This retrospective study included 12 iNPH patients with structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) on a 3T-MRI scanner who underwent neuropsychological assessments before and after shunting and 8 healthy controls. Ventricular volumetry was conducted on structural MRI datasets using FreeSurfer. Ventricular volume was compared pre- and postoperatively. Correlation analyses were performed between ventricular volume or volume change and neuropsychological scores or score change. Tract-based spatial statistics were performed using dMRI datasets for group analyses between iNPH and controls and between pre- and post-surgery iNPH patients and for correlation analyses using neuropsychological scores. Tract-specific analyses were performed in the anterior thalamic radiation (ATR), followed by comparison and correlation analyses.</AbstractText>The third ventricular volume was significantly decreased after shunting; its volume reduction negatively correlated with a neuropsychological improvement. Compared with controls, iNPH patients had lower fractional anisotropy and higher axial, radial, and mean diffusivities, and FW in the periventricular white matter including ATR, resulting in no difference in FW-corrected indices. Single-tensor DTI indices partially correlated with neuropsychological improvements, while FW-corrected indices had no correlations.</AbstractText>Third ventricle enlargement is possibly linked to cognitive impairment and FW imaging possibly provides better white matter characterization in iNPH.</AbstractText>Copyright © 2019 Elsevier Masson SAS. All rights reserved.</CopyrightInformation> |
2,329,178 | AIN-93 Diet as an Alternative Model to Lieber-DeCarli Diet for Alcoholic Cardiomyopathy. | The Lieber-DeCarli alcoholic liquid diet is a classical method for establishing animal models of alcoholic cardiomyopathy (ACM). No study has reported whether the AIN-93 diet, which is widely used as a standard diet for both long-term and short-term studies with laboratory animals, could be used to construct the ACM animal model. The present study intended to investigate whether the AIN-93 diet could be used to establish a mouse ACM model.</AbstractText>Twenty-four C57BL/6 male mice were randomly divided into 4 equally sized groups. In ethanol (EtOH)-fed groups, mice were fed a 4%-EtOH (w/v, 28% of total calories) alcoholic liquid diet of Lieber-DeCarli or the AIN-93 diet for chronic alcohol exposure for 180 days. In control-fed groups, mice were fed with non-EtOH liquid diets with the same calories as EtOH-fed groups. Morphological observations of the hearts and molecular investigation of the brain natriuretic peptide (BNP) were carried out by echocardiography, hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining, real-time quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay.</AbstractText>Echocardiography showed that mice fed with either the 4%-EtOH Lieber-DeCarli diet or the 4%-EtOH AIN-93 diet had dilated ventricles and poor cardiac function. IHC staining of BNP, qPCR of BNP mRNA, and plasma concentration of BNP showed an up-regulated expression in mice fed with both the 4%-EtOH Lieber-DeCarli and 4%-EtOH AIN-93 diets. Less fatty liver was also observed in mice fed the AIN-93 alcoholic diet than those fed the Lieber-DeCarli alcoholic diet.</AbstractText>The AIN-93 alcoholic liquid diet can be used to establish ACM animal models, as with the conventional Lieber-DeCarli alcoholic liquid diet.</AbstractText>© 2019 by the Research Society on Alcoholism.</CopyrightInformation> |
2,329,179 | miRNAs, target genes expression and morphological analysis on the heart in gestational protein-restricted offspring. | Gestational protein restriction was associated with low birth weight, hypertension and higher prevalence of cardiac disorders in adults. Several mechanisms, including epigenetics, could be related with the cardiovascular phenotype on protein-restricted offspring. Thus, we investigated the morphological cardiac effects of gestational protein restriction and left ventricle miRNAs and target genes expression pattern in both 12-day and 16-week old gestational protein-restricted male offspring. Pregnant Wistar rats were allocated into two groups, according to protein supply during pregnancy: NP (normal protein diet- 17%) or LP (low protein diet-6%). Dams on the gestational protein-restricted diet had lower body weight gain and higher food intake. Gestational protein-restricted offspring had low birth weight, followed by rapidly body weight recovery, hypertension, and increased myocytes cross-sectional area and collagen fraction at 16-week old age. At 12-days old, miR-184, miR-192, miR-376c, miR-380-3p, miR-380-5p, miR-451, and miR-582-3p had increased expression, and miR-547 and miR-743a had decreased expression in the gestational protein-restricted left ventricle. At 16-week old, let-7b, miR-125a-3p, miR-142-3p, miR-182 and miR-188-5p had increased expression and let-7g, miR-107, miR-127, miR-181a, miR-181c, miR-184, miR-324-5p, miR-383, miR-423-5p and miR-484 had decreased expression in gestational protein-restricted left ventricle. Target predicted gene expression analysis showed higher expression of Dnmt3a, Oxct1, Rictor and Trps1 and lower expression of Bbs1 and Calml3 in 12-day old protein-restricted offspring. 16-week old protein-restricted offspring had higher expression of Adrbk1, Bbs1, Dnmt3a, Gpr22, Inppl1, and Oxct1 genes. In conclusion, gestational protein restriction was related to offspring low birth weight, increased systolic blood pressure and morphological heart alterations that could be related to early heart miRNA expression changes that perpetuate into adulthood and which are associated with the regulation of essential genes involved in cardiovascular development, heart morphology, function, and metabolism. |
2,329,180 | Chemotherapy-induced loss of bone and muscle mass in a mouse model of breast cancer bone metastases and cachexia. | Chemotherapy used to treat malignancy can lead to loss of skeletal muscle mass and reduced force production, and can reduce bone volume in mice. We have shown that bone-muscle crosstalk is a key nexus in skeletal muscle function and bone homeostasis in osteolytic breast cancer bone metastases. Because chemotherapy has significant negative side effects on bone mass, and because bone loss can drive skeletal muscle weakness, we have examined the effects of chemotherapy on the musculoskeletal system in mice with breast cancer bone metastases.</AbstractText>Six-week-old Female athymic nude mice were inoculated with 105</sup> MDA-MB231 human breast cancer cells into the left ventricle and bone metastases were confirmed by X-ray. Mice were injected with carboplatin at a dose of 60mg/kg once per week starting 4 days after tumor inoculation. Skeletal muscle was collected for biochemical analysis and extensor digitorum longus (EDL) whole muscle contractility was measured. The femur and tibia bone parameters were assessed by microCT and tumor burden in bone was determined by histology. Healthy mice treated with carboplatin lose whole body weight and have reduced individual muscle weights (gastrocnemius, tibialis anterior (TA), and EDL), reduced trabecular bone volume (BV/TV), and reduced EDL function. Mice with MDA-MB-231 bone metastases treated with carboplatin lose body weight, and have reduced EDL function as healthy mice treated with carboplatin. Mice with MDA-MB-231 bone metastases plus carboplatin do have reduced proximal tibia BV/TV compared to carboplatin alone, but carboplatin does reduce tumor burden in bone.</AbstractText>Our data shows that carboplatin treatment, aimed at reducing tumor burden, contributes to cachexia and trabecular bone loss. The muscle atrophy and weakness may occur through bone-muscle crosstalk and would lead to a feed-forward cycle of musculoskeletal degradation. Despite anti-tumor effects of chemotherapy, musculoskeletal impairment is still significant in mice with bone metastases.</AbstractText> |
2,329,181 | Evaluating the effect of Avastin on breast cancer angiogenesis using synchrotron radiation. | The visualization of microvasculature is an essential step in understanding the mechanisms underlying early vessel disorders involved in breast cancer and for developing effective therapeutic strategies. However, generating detailed and reproducible data using immunohistochemistry analysis of breast cancer angiogenesis has been difficult.</AbstractText>To analyze the diversification of angiogenesis in the development of tumor growth and evaluate the anti-vascular effects of Avastin (bevacizumab), we used new X-ray microangiography and third-generation synchrotron radiation-based micro-computed tomography (SR micro-CT) technology. With these techniques, we were able to investigate the structures and density of microvessels in xenograft mouse models (n=24). Barium sulfate nanoparticles were injected into the left cardiac ventricle of the mice to allow the visualization of blood vessels.</AbstractText>Three-dimensional structures of microvessels were displayed with a high spatial image resolution of 20-30 µm. The density of angiogenesis and the incidence of lung metastasis were significantly reduced in xenograft mouse models of breast cancer treated with Avastin compared with control groups. Also, the density of smaller vessels (diameter <50 µm) was significantly decreased in the Avastin-treated mice, while the density of larger vessels (diameter >100 µm) was not significantly changed.</AbstractText>Avastin inhibited tumor growth and lung metastasis by reducing microvessels. Additionally, synchrotron radiation (SR) techniques are useful as an additional tool for more precise quantification of angiogenesis.</AbstractText> |
2,329,182 | Bone Marrow Stromal Cells With Exercise and Thyroid Hormone Effect on Post-Stroke Injuries in Middle-aged Mice. | Based on our previous findings, the treatment of stem cells alone or in combination with thyroid hormone (T3</sub>) and mild exercise could effectively reduce the risk of stroke damage in young mice. However, it is unclear whether this treatment is effective in aged or middle-aged mice. Therefore, this study designed to assess whether combination of Bone Marrow Stromal Cells (BMSCs) with T3</sub> and mild treadmill exercise can decrease stroke complications in middle-aged mice.</AbstractText>Under laser Doppler flowmetry monitoring, transient focal cerebral ischemia was produced by right Middle Cerebral Artery Occlusion (MCAO) for 45 min followed by 7 days of reperfusion in middle-aged mice. BMSCs (1×105</sup>) were injected into the right cerebral ventricle 24 h after MCAO, followed by daily injection of triiodothyronine (T3</sub>) (20 μg/100 g/d SC) and 6 days of running on a treadmill. Infarct size, neurological function, apoptotic cells and expression levels of Glial Fibrillary Acidic Protein (GFAP) were evaluated 1 week after stroke.</AbstractText>Post-ischemic treatment with BMSCs or with T3</sub> and or mild treadmill exercise alone or in combination did not significantly change neurological function, infarct size, and apoptotic cells 7 days after ischemia in middle-aged mice (P>0.05). However, the expression of GFAP significantly reduced after treatment with BMSCs and or T3</sub> (P<0.01).</AbstractText>Our findings indicate that post-stroke treatment BMSCs with exercise and thyroid hormone cannot reverse neuronal damage 7 days after ischemia in middle-aged mice. These findings further support that age is an important variable in stroke treatment.</AbstractText> |
2,329,183 | [Analysis of L1CAM gene mutation in pedigrees with X-linked genetic hydrocephalus]. | To analyze L1CAM gene mutation in a family featuring X-linked recurrent fetal hydrocephalus.</AbstractText>The family had three pregnancies where a male fetus was detected at 22 weeks with hydrocephalus by ultrasonography. DNA was extracted from peripheral blood samples from the parents as well as fetal tissue from the third abortion. The fetal DNA was subjected to testing of folic acid metabolism ability gene and chromosomal microarray analysis (CMA). Next-generation sequencing (NGS) was employed to detect potential mutation of related genes. Suspected mutation was verified by Sanger sequencing.</AbstractText>Testing of folic acid metabolism ability gene (MTHFR C677T) and CMA were both normal. A c.512G>A (p.Trp171Ter) hemizygous mutation of the L1CAM gene was detected in the fetal tissue, which was inherited from the phenotypically normal mother. The novel mutation was predicted to be pathogenic.</AbstractText>The c.512G>A (p.Trp171Ter) mutation of the L1CAM gene probably underlies the X-linked hydrocephalus in this family. Screening of L1CAM gene variations should be carried out for couples experiencing recurrent fetal hydrocephalus affecting the male gender.</AbstractText> |
2,329,184 | The Purely Endoscopic Supracerebellar Infratentorial Approach for Resecting Pineal Region Tumors with Preservation of Cerebellomesencephalic Vein: Technical Note and Preliminary Clinical Outcomes. | The cerebellomesencephalic vein (CMV) was frequently sacrificed in surgery approached via the supracerebellar infratentorial (SCIT) route for resecting pineal region tumors, which resulted in potential risk of neurologic deficit. Preserving the CMV in the SCIT approach could enhance the safety and effectiveness of this natural corridor surgery. The aim of this article was to identify the probability and safety of preserving the CMV through the application of neuroendoscopy in the SCIT approach.</AbstractText>Clinical data of patients who underwent pineal region tumor resection through a purely endoscopic SCIT approach were retrospectively analyzed, focusing on surgical techniques and clinical outcomes.</AbstractText>The study included 8 patients with pineal region tumors. The CMV was preserved intact in all patients. Total tumor removal was achieved in 7 of 8 patients. In 1 patient with 2 tumors in the pineal region and roof of the third ventricle, the tumor in the pineal region was resected completely, followed by subsequent chemotherapy combined with radiotherapy, after which the other tumor disappeared totally. All patients recovered normally with uneventful postoperative outcomes.</AbstractText>The advantage of close observation and panoramic view provided by neuroendoscopy combined with meticulous manipulation improved the ability to preserve the CMV in resecting pineal region tumors via the SCIT approach. The neuroendoscopic technique enhances the safety and efficacy of the SCIT approach.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,329,185 | Dilated cavum septi pellucidi as sole prenatal ultrasound defect: Case-base analysis of fetal outcomes. | This retrospective study was undertaken to examine fetuses with dilated cavum septi pellucidi (CSP) as an isolated finding and to identify factors impacting postnatal outcomes.</AbstractText>Fully documented cases of dilated CSP as a sole prenatal defect were selected for study. Recorded data included serial sonographic examinations, fetal MRI studies, chromosomal testing, screening for infection, and postnatal follow-up. Fetal subjects were further stratified by gender, gestational age at diagnosis (<28 w or ≥28 w), CSP width at diagnosis (<10 mm or ≥10 mm), evolution at term (persistent vs non-persistent CSP), and postnatal MRI diagnosis (presence/absence of CSP cyst). Chi-square or Fisher's exact test (as appropriate) was used to compare categorical variables and patient groups.</AbstractText>A total of 48 fetuses met our inclusion criteria, none exhibiting chromosomal abnormalities. Six (12.5%) of these 48 were subsequently diagnosed with neurodevelopmental delays. However, such delays were unrelated to any categorical variable listed above (p > 0.05).</AbstractText>Dilated CSP as an isolated prenatal finding by ultrasound or MRI carries a low risk of chromosomal abnormalities but a high risk of neurodevelopmental delay. These perils should be adequately conveyed to the parents of such infants.</AbstractText>Copyright © 2019 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,329,186 | Neurodegenerative Changes in Rat Brain in Streptozotocin Model of Alzheimer's Disease. | One of the most common models of sporadic form of Alzheimer's disease is injection of streptozotocin into the lateral ventricles of rat brain. In 3 months after this injection, an increase in the expression of astroglia in the corpus callosum and a decrease in the thickness of the corpus callosum and intensity of its staining with luxol fast blue were observed. This can reflect a decrease in the content of myelinated fibers. In layer V of the sensorimotor cortex, intensive degeneration of neurons was revealed. The lateral ventricles were significantly enlarged and the expression of PSA-NCAM protein, a marker of immature neurons, was reduced in subventricular zone, which can be associated with disturbed neurogenesi. |
2,329,187 | Distillation of Posterior Fossa Demyelination in Acute Vestibular Syndrome: the Eyes Have It. | Separating the etiologies of an acute vestibular syndrome (AVS) of central origin is a clinical challenge; the common causes include (1) stroke of the brainstem/cerebellum and (2) demyelinating disorders such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Overshadowed by the vascular etiologies, the literature describing AVS due to demyelinating disorders has been growing through the last decade. The discovery of IgG-NMO, a specific pathogenic antibody directed against the astrocytic water channel aquaporin-4 (AQP4), has improved the differential diagnoses between MS and NMOSD. AQP4 is particularly expressed in ependymal/subependymal astrocytes and glia limitans astrocyte processes, including around the fourth ventricle. Adding a clinical biomarker to distinguish MS and NMOSD in AVS patients, as reported in this issue, will be of great clinical value. |
2,329,188 | Biodegradable polymeric nanoparticles administered in the cerebrospinal fluid: Brain biodistribution, preferential internalization in microglia and implications for cell-selective drug release. | Cell-selective drug release in the central nervous system (CNS) holds great promise for the treatment of many CNS disorders but it is still challenging. We previously demonstrated that polymeric nanoparticles (NPs) injected intra-parenchyma in the CNS can be internalized specifically in microglia/macrophages surrounding the injection site. Here, we explored NPs administration in the cerebrospinal fluid (CSF) to achieve a wider spreading and increased cell targeting throughout the CNS; we generated new NPs variants and studied the effect of modifying size and surface charge on NPs biodistribution and cellular uptake. Intra-cerebroventricular administration resulted in prevalent localization of the NPs in proximity to stem-cell niches, such as around the lateral ventricles, the subventricular zone and the rostral migratory stream. NPs internalization occurred preferentially in brain myeloid cells/microglia. We demonstrated that brain biodistribution and extent of internalization in microglia are influenced by NPs dimensions and can be improved by applying a transient disruption of the blood-brain barrier with mannitol, leading to NPs internalization in up to 25% of brain myeloid/microglia cells. A fraction of the targeted cells was positive for markers of proliferation or stained positive for stemness/progenitor-cell markers such as Nestin, c-kit, or NG2. Interestingly, through these newly formulated NPs we obtained controlled and selective release of drugs otherwise difficult to formulate (such as busulfan and etoposide) to the target cells, preventing unwanted side effects and the toxicity obtained by direct brain delivery of the not encapsulated drugs. Overall, these data provide proof of concept of the applicability of these novel NP-based drug formulations for achieving internalization not only in mature microglia but also possibly in more immature myeloid cells in the brain and pave the way for brain-restricted microglia-targeted drug delivery regimens. |
2,329,189 | Preconditioning with toll-like receptor agonists attenuates seizure activity and neuronal hyperexcitability in the pilocarpine rat model of epilepsy. | Neuroinflammation plays an important role in epileptic disorders. Toll-like receptors (TLRs) are the key signal transduction tools by which neuroinflammation may promote epileptogenesis. Depending on the stimulus nature, TLRs may engage a distinct signaling pathway. We examined the impact of early minor activation of TLR4 and TLR2 on the severity of seizure in the pilocarpine rat model of temporal lobe epilepsy (TLE). One μg of Lipopolysaccharides (LPS), Monophosphoryl lipid A (MPL), Pam3Cysor or vehicles were microinjected into the right lateral ventricle of the male Wistar rats. 24 h later, seizures were induced by intraperitoneal injection of pilocarpine, and seizure-related behaviors were monitored. 24 h after seizure induction, the hippocampal level of pro/anti-inflammatory mediators and electrophysiological properties of the dentate gyrus (DG) granular cells were investigated by western blot and whole cell patch clamp techniques, respectively. Pretreatment with TLR ligands resulted in decreased seizure severity, lower hippocampal pro-inflammatory (IL-1β and IL-6) cytokines and higher anti-inflammatory (IL-10 and TGF- β) mediators in the pilocarpine-treated rats. Pilocarpine induced profound hyperexcitability in the DG granule cells accompanied by potentiated excitatory postsynaptic currents (EPSCs) and dampened inhibitory postsynaptic currents (IPSCs), in contrast to the control group. However, pretreatment with TLR ligands preserved almost normal excitability and synaptic transmission against the pilocarpine. In conclusion, early activation of TLR4 and TLR2, probably through preserving normal hippocampal cytokine profile and neuronal function attenuates seizure severity in the rat model of TLE. |
2,329,190 | JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy. | JC virus (JCV) can cause a lytic infection of oligodendrocytes and astrocytes in the central nervous system (CNS) leading to progressive multifocal leukoencephalopathy (PML). JCV can also infect meningeal and choroid plexus cells causing JCV meningitis (JCVM). Whether JCV also infects meningeal and choroid plexus cells in PML patients and other immunosuppressed individuals with no overt symptoms of meningitis remains unknown. We therefore analyzed archival formalin-fixed, paraffin-embedded brain samples from PML patients, and HIV-seropositive and seronegative control subjects by immunohistochemistry for the presence of JCV early regulatory T Ag and JCV VP1 late capsid protein. In meninges, we detected JCV T Ag in 11/48 (22.9%) and JCV VP1 protein in 8/48 (16.7%) PML patients. In choroid plexi, we detected JCV T Ag in 1/7 (14.2%) and JCV VP1 protein in 1/8 (12.5%) PML patients. Neither JCV T Ag nor VP1 protein could be detected in meninges or choroid plexus of HIV-seropositive and HIV-seronegative control subjects without PML. In addition, examination of underlying cerebellar cortex of PML patients revealed JCV-infected cells in the molecular layer, including GAD 67+ interneurons, but not in HIV-seropositive and HIV-seronegative control subjects without PML. Our findings suggest that productive JCV infection of meningeal cells and choroid plexus cells also occurs in PML patients without signs or symptoms of meningitis. The phenotypic characterization of JCV-infected neurons in the molecular layer deserves further study. This data provides new insight into JCV pathogenesis in the CNS. |
2,329,191 | Effects of left ventricle wall thickness uncertainties on cardiac mechanics. | Computational models of the heart have reached a level of maturity that enables sophisticated patient-specific simulations and hold potential for important applications in diagnosis and therapy planning. However, such clinical use puts strict demands on the reliability and accuracy of the models and requires the sensitivity of the model predictions due to errors and uncertainty in the model inputs to be quantified. The models typically contain a large number of parameters, which are difficult to measure and therefore associated with considerable uncertainty. Additionally, patient-specific geometries are usually constructed by semi-manual processing of medical images and must be assumed to be a potential source of model uncertainty. In this paper, we assess the model accuracy by considering the impact of geometrical uncertainties, which typically occur in image-based computational geometries. An approach based on 17 AHA segments diagram is used to consider uncertainties in wall thickness and also in the material properties and fiber orientation, and we perform a comprehensive uncertainty quantification and sensitivity analysis based on polynomial chaos expansions. The quantities considered include stress, strain and global deformation parameters of the left ventricle. The results indicate that important quantities of interest may be more affected by wall thickness, and highlight the need for accurate geometry reconstructions in patient-specific cardiac mechanics models. |
2,329,192 | Surgical case of subacute headache in a young Latin American woman. | Neurocysticercosis (NCC) is the most common helmintic disease affecting the central nervous system and a major cause of adult-onset epilepsy in the developing world. <sup>1</sup> We describe a case of intraventricular NCC associated with hydrocephalus in a 28-year-old woman, Peruvian native, admitted to the emergency department for subacute headache and nausea. The cranial CT scan done showed asymmetric enlargement of the lateral ventricles which on cranial MRI was revealed to be due to an intraventricular cyst. An intraventricular endoscope was used to remove the cyst at the foramina of Monro, and therefore treat the obstructive hydrocephalus. NCC-a known cause of hydrocephalus in many Latin American countries-should be among the differential diagnosis in a patient with history of travel or residency in these countries. Treatment of choice for obstructive hydrocephalus caused by NCC is cyst removal with neuroendoscopy. |
2,329,193 | Silibinin efficacy in a rat model of pulmonary arterial hypertension using monocrotaline and chronic hypoxia. | C-X-C chemokine receptor type 4 (CXCR4) may be involved in the development of pulmonary arterial hypertension (PAH). CXCR4 inhibitor AMD3100 was described to have a positive effect on the prevention of pulmonary arterial muscularization in PAH models. Silibinin is a traditional medicine that has an antagonistic effect on CXCR4. We investigated the effect of silibinin using rat models of PAH.</AbstractText>PAH was induced by a single subcutaneous injection of monocrotaline. The rats were maintained in a chronic hypoxic condition (10% O2</sub>) with or without silibinin. To evaluate the efficacy of silibinin on PAH, right ventricular systolic pressure (RVSP), Fulton index (weight ratio of right ventricle to the left ventricle and septum), percent medial wall thickness (% MT), and vascular occlusion score (VOS) were measured and calculated. Immunohistochemical analysis was performed targeting CXCR4 and c-Kit. Reverse transcription-quantitative polymerase chain reaction was performed for the stem cell markers CXCR4, stromal cell derived factor-1 (SDF-1), c-Kit, and stem cell factor (SCF), and the inflammatory markers monocyte chemoattractant protein 1 (MCP1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα). Statistical analyses were performed using t-test and one-way analysis of variance with Bonferroni's post hoc test.</AbstractText>Silibinin treatment for 1 week reduced RVSP and Fulton index. Treatment for 2 weeks reduced RVSP, Fulton index, % MT, and VOS, as well as downregulating the expression of CXCR4, SDF-1, and TNFα in pulmonary arteries. In contrast, treatment for 3 weeks failed to ameliorate PAH. The time-course study demonstrated that RVSP, Fulton index, % MT, and VOS gradually increased over time, with a decrease in the expression of CXCR4 and TNFα occurring after 2 weeks of PAH development. After 3 weeks, SDF-1, c-Kit, and SCF began to decrease and, after 5 weeks, MCP1 and IL-6 gradually accumulated.</AbstractText>The CXCR4 inhibitor silibinin can ameliorate PAH, possibly through the suppression of the CXCR4/SDF-1 axis, until the point where PAH becomes a severe and irreversible condition. Silibinin results in reduced pulmonary arterial pressure and delays pulmonary arteriolar occlusion and pulmonary vascular remodeling.</AbstractText> |
2,329,194 | Effects of regular exercise plus food restriction on left ventricular pathological remodeling in heart failure‑induced rats. | Cardiac remodeling is the main pathophysiological process leading to heart failure. Exercise and food restriction have been shown to exert some profound physiological benefits.</AbstractText>This study investigated the effects of exercise plus food restriction (FR) on rat left ventricular remodeling.</AbstractText>Fifty male rats were randomly divided into 5 groups. 1) Sham (saline injection), 2) ISO (isoproterenol injection), 3) FR+ ISO (8 weeks with 60 % food restriction and then isoproterenol injection), 4) E+ISO (run-in period of 4 weeks on treadmill and then isoproterenol injection), and 5) FR+E+ISO. Serum levels of creatine kinase, nitric oxide, gene expression of microtubule-associated protein 1 light chain 3-I and II, Beclin-1, Bax and Bcl2 and TUNEL staining were investigated.</AbstractText>ISO increased the plasma CK-MB level, gene expression of Bax and TUNEL‑positive cells in left ventricle and at the same time, decreased the serum level of NO. Regular exercise plus food restriction enhanced the expression of LC3B-II, Beclin-1, Bcl2 genes and elevated LC3B-II / LC3B-Ι, while decreasing the gene expression of Bax and TUNEL‑positive cells in the left ventricle.</AbstractText>Our results propose that exercise plus food restriction is more effective than either therapy alone for possibly preserving cardiac internal defenses against heart failure consequences and remodeling (Tab. 2, Fig. 3, Ref. 20).</AbstractText> |
2,329,195 | WIPI1 is a conserved mediator of right ventricular failure. | Right ventricular dysfunction is highly prevalent across cardiopulmonary diseases and independently predicts death in both heart failure (HF) and pulmonary hypertension (PH). Progression towards right ventricular failure (RVF) can occur in spite of optimal medical treatment of HF or PH, highlighting current insufficient understanding of RVF molecular pathophysiology. To identify molecular mechanisms that may distinctly underlie RVF, we investigated the cardiac ventricular transcriptome of advanced HF patients, with and without RVF. Using an integrated systems genomic and functional biology approach, we identified an RVF-specific gene module, for which WIPI1 served as a hub and HSPB6 and MAP4 as drivers, and confirmed the ventricular specificity of Wipi1, Hspb6, and Map4 transcriptional changes in adult murine models of pressure overload induced RV- versus LV- failure. We uncovered a shift towards non-canonical autophagy in the failing RV that correlated with RV-specific Wipi1 upregulation. In vitro siRNA silencing of Wipi1 in neonatal rat ventricular myocytes limited non-canonical autophagy and blunted aldosterone-induced mitochondrial superoxide levels. Our findings suggest that Wipi1 regulates mitochondrial oxidative signaling and non-canonical autophagy in cardiac myocytes. Together with our human transcriptomic analysis and corroborating studies in an RVF mouse model, these data render Wipi1 a potential target for RV-directed HF therapy. |
2,329,196 | Prominent right ventricular mass in a young patient with a history of classic testicular seminoma: a case report. | The incidence of intracardiac masses is generally low. In most cases, the formation of a thrombus represents the principal diagnosis in clinical practice. The differential diagnosis mainly includes primary tumours of the heart as well as intracardiac metastases. Testicular cancer is a rare malignancy, accounting for approximately 1% of all male tumours. Cardiac metastasis of a seminoma is extremely rare.</AbstractText>A 30-year-old man with a history of a classic seminoma of the right testis was referred to our university hospital from an outside clinic. Transthoracic echocardiography showed a large space-occupying mass in the right ventricle (4.0 cm × 4.5 cm × 5.5 cm) attached to the apex and septum. Cardiac magnetic resonance imaging confirmed the finding of a 5.5 cm × 3.5 cm lesion without freely movable appendage or obstruction of the right ventricular outflow tract. Tissue characterization by T1- and T2-weighted black blood imaging revealed a signal behaviour comparable to pulmonary metastases. Additionally, positron emission tomography (PET) with 250 MBq induced 18-fluorodeoxyglucose (18</sup>F-FDG) as part of a re-staging showed significant FDG-uptake. Thus, the final diagnosis of an intracardiac metastasis of the testicular seminoma was made, and the patient was treated with cisplatin, etoposide, and bleomycin chemotherapy according to the current guidelines. A repeat trans-thoracic echocardiogram (TTE) performed 2 weeks later already demonstrated a significant reduction of the metastasis with a diameter of 3.3 cm × 3.0 cm.</AbstractText>In the past few years, multimodality imaging has become essential in the diagnostic evaluation of cardiac disease. In order to improve the diagnostic accuracy, a modern approach should preferably contain the integration of different imaging modalities. Cardiac magnetic resonance imaging as well as 18</sup>F-FDG-PET/computed tomography helped us reach the aetiological diagnosis of an intracardiac metastasis and to initiate prompt treatment.</AbstractText> |
2,329,197 | Case report: Unusual presentation of haemopericardium with haemodynamic instability secondary to a coronary graft pseudoaneurysm treated by an endovascular approach. | We report the successful endovascular treatment of a coronary graft pseudoaneurysm using a technique often seen in intracranial aneurysm coiling.</AbstractText>We present an unusual case of a patient who presents with haemopericardium and haemodynamic instability after saphenous vein bypass grafting. A pseudoaneurysm rapidly expanded from 5 cm to 7 cm over the follow-up period producing compressive mass effect on the lateral right ventricle with transient haemodynamic instability. The patient's declining clinical condition did not warrant a redo thoracotomy and sternotomy, so an endovascular approach was deemed to be the best treatment option.</AbstractText>The use of endovascular embolization techniques is indeed a technically viable alternative with positive outcomes without the need for thoracotomy and sternotomy.</AbstractText> |
2,329,198 | Large Right Ventricle Thrombus in Uhl's Anomaly: A Rare Presentation of Extremely Rare Disease. | Uhl's anomaly is an extremely rare congenital cardiac malformation and is characterized by the partial or complete absence of right ventricular myocardium. The absence of myocardium may be the result of primary non-development of myocytes or a form of selective apoptosis. It is mainly sporadic although some familial occurrences have been reported. Congestive cardiac failure is the most common mode of presentation. Associated congenital cardiac malformations are also reported. We report a case of a 17-year-old male who presented with symptoms and signs of right heart failure, during evaluation found to have large right ventricle free wall thrombus. |
2,329,199 | Relationship between stroke severity, extensity of leukoaraiosis, and brain atrophy in patients with ischaemic stroke. | Leukoaraiosis (LA), according to the latest classification, is white matter hyperintensity - morphological findings of small blood vessel disease of the brain. This radiological detection of small vessels disease is important because there are no technical possibilities to assess small vessels of the brain using computed tomography (CT) or magnetic resonance imaging (MRI) angiography. Our aim was to analysis the relationship between the extension of leukoaraiosis and severity of ischaemic stroke and brain atrophy.</AbstractText>We retrospectively analysed 77 head CT scans of patients admitted from the emergency room (ER) to the Radiology Department due to suspected stroke. We assessed the severity of leukoaraiosis using the van Swieten scale and brain atrophy by numerous linear measurements.</AbstractText>Statistical analysis failed to demonstrate differences between LA1 and LA2 groups with regard to stroke severity in National Institutes of Health Stroke Scale (NIHSS) (p</i> = 0.2159). There were no differences with regard to clinical severity of stroke between the study groups divided depending on the extent of brain atrophy. There were statistically significant differences with regard to the anterior horn width of the right and left lateral ventricle, posterior horn width of the right and left lateral ventricle, distance between occipital horn of the left lateral ventricle and internal surface of the cranium and third ventricle width depending on the severity of leukoaraiosis.</AbstractText>The results of our studies present an association between the degree leukoaraiosis extension and brain atrophy, but no association between central nervous system tissue atrophy of extent of leukoaraiosis and ischaemic stroke severity.</AbstractText> |
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