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2,328,300
Multiple Sclerosis and the Choroid Plexus: Emerging Concepts of Disease Immunopathophysiology.
The coexistence of multiple sclerosis and intracranial neoplasms is very rare, and whether this occurrence can be explained by a causal relationship or by coincidence remains a matter of debate. Possible roles of the choroid plexus as a site of tumor cell invasion and lymphocyte infiltration into the central nervous system have been hypothesized in recent studies.</AbstractText>We describe a 13-year-old boy with concurrent multiple sclerosis and choroid plexus papilloma, then review the published literature with a focus on the pathophysiologic mechanisms of neuroinflammation in multiple sclerosis and the potential role of the choroid plexus in this process.</AbstractText>A growing body of evidence suggests that both physical and functional dysregulation of the choroid plexus may be a common mechanism underlying the pathophysiology of central nervous system inflammation.</AbstractText>In multiple sclerosis, the choroid plexus could act as a gateway for lymphocyte entry from the peripheral blood into the central nervous system at its earlier stages. However, future studies are needed to identify whether structural alterations of the choroid plexus play a role in the pathophysiology of multiple sclerosis and to provide suitable models to determine their consequences.</AbstractText>Copyright &#xa9; 2019 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,328,301
Fibrolipoma of the left ventricle: an uncommon incidental autopsy finding.
Fibrolipoma of the heart is an unusual benign tumorous entity encountered, if present, during an ordinary imaging workout or at autopsy. It is often clinically silent but it can also be symptomatic depending on the size and location of the tumor. We report a case of an 82-year-old man with a medical history of malignant pleural mesothelioma. The decedent was referred to our department to undergo a forensic autopsy after a fall. Postmortem examination revealed a large encapsulated gelatinous, yellowish cardiac mass with its pedicle on the subendocardial region of the left ventricular anterior wall and interventricular septum, protruding into the left ventricular cavity. Histological examination confirmed the diagnosis of cardiac fibro-lipoma, a rare histologic variant of lipoma, irrelevant to the cause of death in the present case. The rarity of the occurrence of fibro-lipomas provides clinical implications for the inclusion of the entity in the differential diagnosis of a cardiac mass.
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Simple Identification of Cerebrospinal Fluid Turbulent Motion Using a Dynamic Improved Motion-sensitized Driven-equilibrium Steady-state Free Precession Method Applied to Various Types of Cerebrospinal Fluid Motion Disturbance.
The motion of cerebrospinal fluid (CSF) within the subarachnoid space and ventricles is greatly modulated when propagating synchronously with the cardiac pulse and respiratory cycle and path through the nerves, blood vessels, and arachnoid trabeculae. Water molecule movement that propagates between two spaces via a stoma, foramen, or duct presents increased acceleration when passing through a narrow area and can exhibit "turbulence." Recently, neurosurgeons have started to perform fenestration procedures using neuroendoscopy to treat hydrocephalus and cystic lesions. As part of the postoperative evaluation, a noninvasive diagnostic technique to visualize the water molecules at the fenestrated site is necessary. Because turbulence is observed at this fenestrated site, an imaging technique appropriate for observing this turbulence is essential. We therefore investigated the usefulness of a dynamic improved motion-sensitized driven-equilibrium steady-state free precession (Dynamic iMSDE SSFP) sequence of magnetic resonance imaging that is superior for ascertaining turbulent motions in healthy volunteers and patients. Images of Dynamic iMSDE SSFP from volunteers revealed that CSF motion at the ventral surface of the brainstem and the third ventricle is augmented and turbulent. Moreover, our findings confirmed that this technique is useful for evaluating treatments that utilize neuroendoscopy. As a result, Dynamic iMSDE SSFP, a simple sequence for visualizing CSF motion, entails a short imaging time, can extensively visualize CSF motion, does not require additional processes such as labeling or trigger setting, and is anticipated to have wide-ranging clinical applications in the future.
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Pretreatment with KGA-2727, a selective SGLT1 inhibitor, is protective against myocardial infarction-induced ventricular remodeling and heart failure in mice.
Recent studies demonstrated that sodium-glucose co-transporter 1 (SGLT1) is associated with human ischemic cardiomyopathy. However, whether SGLT1 blockade is effective against ischemic cardiomyopathy is still uncertain. We examined the effects of KGA-2727, a selective SGLT1 inhibitor, on myocardial infarction (MI)-induced ischemic cardiomyopathy. To create MI, left anterior descending coronary artery (LAD) ligation with or without KGA-2727 administration was performed in C57BL/6J mice. Four weeks after the operation, all mice were investigated. Left ventricular fractional shortening (LVFS) was reduced and KGA-2727 significantly improved it in LAD-ligated MI mice. The cardiomyocyte diameter, and ANP, BNP, &#x3b2;-MHC, and IL-18 gene expressions significantly increased in LAD-ligated mouse left ventricles compared with those of sham-operated mouse left ventricles, and KGA-2727 inhibited increases in them. Myocardial fibrosis and upregulation of CTGF and MMP-3 gene expressions in the left ventricle were increased in LAD-ligated mice compared with sham-operated mice, and KGA-2727 decreased them in the LAD-ligated left ventricles. SGLT1 protein expression level was significantly higher in LAD-ligated compared with sham-operated mouse ventricles regardless of KGA-2727 treatment. These results suggest that KGA-2727 pretreatment protects against MI-induced left ventricular remodeling through SGLT1 blockade and that it may become a new pharmacological therapy for ischemia-induced cardiomyopathy.
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The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus.
Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer's disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediators, are known to have pro-inflammatory properties in the periphery; however, this has yet to be tested in the brain. Lowering the consumption of n-6 PUFA is associated with a decreased risk of depression and AD in human observational studies. The purpose of this study was to investigate the inflammation-modulating effects of lowering dietary n-6 PUFA in the mouse hippocampus.</AbstractText>C57BL/6 male mice were fed either an n-6 PUFA deprived (2% of total fatty acids) or an n-6 PUFA adequate (23% of total fatty acids) diet from weaning to 12&#x2009;weeks of age. Animals then underwent intracerebroventricular surgery, in which lipopolysaccharide (LPS) was injected into the left lateral ventricle of the brain. Hippocampi were collected at baseline and following LPS administration (1, 3, 7, and 14&#x2009;days). A microarray (n&#x2009;=&#x2009;3 per group) was used to identify candidate genes and results were validated by real-time PCR in a separate cohort of animals (n&#x2009;=&#x2009;5-8 per group).</AbstractText>Mice administered with LPS had significantly increased Gene Ontology categories associated with inflammation and immune responses. These effects were independent of changes in gene expression in any diet group. Results were validated for the effect of LPS treatment on astrocyte, cytokine, and chemokine markers, as well as some results of the diets on Ifrd2 and Mfsd2a expression.</AbstractText>LPS administration increases pro-inflammatory and lipid-metabolizing gene expression in the mouse hippocampus. An n-6 PUFA deprived diet modulated inflammatory gene expression by both increasing and decreasing inflammatory gene expression, without impairing the resolution of neuroinflammation following LPS administration.</AbstractText>
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Fluctuations in intracranial pressure can be estimated non-invasively using near-infrared spectroscopy in non-human primates.
Intracranial pressure (ICP) is typically measured invasively through a sensor placed inside the brain or a needle inserted into the spinal canal, limiting the patient population on which this assessment can be performed. Currently, non-invasive methods are limited due to lack of sensitivity and thus only apply to extreme cases of increased ICP, instead of use in general clinical practice. We demonstrate a novel application for near-infrared spectroscopy (NIRS) to accurately estimate ICP changes over time. Using a non-human primate (Rhesus Macaque) model, we collected optical data while we induced ICP oscillations at multiple ICP levels obtained by manipulating the height of a fluid column connected via a catheter to the lateral ventricle. Hemodynamic responses to ICP changes were measured at the occipital pole and compared to changes detected by a conventional intraparenchymal ICP probe. We demonstrate that hemoglobin concentrations are highly correlated with induced ICP oscillations and that this response is frequency dependent. We translated the NIRS data into non-invasive ICP measurements via a fitted non-parametric transfer function, demonstrating a match in both magnitude and time alignment with an invasively measured reference. Our results demonstrate that NIRS has the potential for non-invasive ICP monitoring.
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Co-infection of <i>Dirofilaria immitis</i> and Japanese encephalitis virus in a spotted seal (<i>Phoca largha</i>) in the Republic of Korea.
A 10-year-old male spotted seal presented with loss of appetite and decreased activity. Grossly, the internal organs revealed several filarial nematodes in the right ventricle of the heart and the pulmonary vessels. Histopathological examination of the brain revealed moderate nonsuppurative meningoencephalitis with glial nodules and neuronophagia. Japanese encephalitis virus (JEV) of genotype I was isolated from the brain. All nematodes were identified as <i>Dirofilaria immitis</i>. This is the first clinical case of co-infection with <i>D. immitis</i> and JEV in a seal, suggesting that the seal, may be a dead-end host, like the human and horse, for JEV.
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Endocardial irrigated catheter for volumetric optoacoustic mapping of radio-frequency ablation lesion progression.
Radiofrequency (RF) catheter ablation is widely employed for various minimally invasive procedures, including treatment of tumors, cardiac arrhythmias and varicose veins. Accurate real-time monitoring of the ablation treatments remains challenging with the existing clinical imaging modalities due to the lack of spatial or temporal resolution or insufficient tissue contrast for differentiating thermal lesions. Optoacoustic (OA) imaging has been recently suggested for monitoring temperature field and lesion progression during RF interventions. However, strong light absorption by standard metallic catheters hindered practical implementations of this approach. Herein, we introduce a new RF ablation catheter concept for combined RF ablation and OA lesion monitoring. The catheter tip encapsulates a multimode fiber bundle for OA excitation with near-infrared (NIR) light, whereas the electric current is conducted through the irrigation solution, thus avoiding direct exposure of the metallic parts to the excitation light. We optimized the catheter diameter and the saline flow rate in order to attain uniform and deep lesions. The newly introduced hybrid catheter design was successfully tested by real-time monitoring of the ablation process in smooth ventricle and rough atrium walls of a blood-filled ex vivo porcine heart, mimicking in vivo conditions in the clinical setting.
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Spinal cord injury alters purinergic neurotransmission to mesenteric arteries in rats.
Complications associated with spinal cord injury (SCI) result from unregulated reflexes below the lesion level. Understanding neurotransmission distal to the SCI could improve quality of life by mitigating complications. The long-term impact of SCI on neurovascular transmission is poorly understood, but reduced sympathetic activity below the site of SCI enhances arterial neurotransmission (1). We studied sympathetic neurovascular transmission using a rat model of long-term paraplegia (T2-3) and tetraplegia (C6-7). Sixteen weeks after SCI, T2-3 and C6-7 rats had lower blood pressure (BP) than sham rats (103&#x2009; &#xb1; &#x2009;2 and 97&#x2009; &#xb1;&#x2009; 4 vs. 117&#x2009; &#xb1; &#x2009;6 mmHg, <i>P</i> &lt; 0.05). T2-3 rats had tachycardia (410&#x2009; &#xb1; &#x2009;6 beats/min), and C6-7 rats had bradycardia (299&#x2009; &#xb1;&#x2009; 10 beats/min) compared with intact rats (321&#x2009; &#xb1;&#x2009; 4 beats/min, <i>P</i> &lt; 0.05). Purinergic excitatory junction potentials (EJPs) were measured in mesenteric arteries (MA) using microlectrodes, and norepinephrine (NE) release was measured using amperometry. NE release was similar in all groups, while EJP frequency-response curves from T2-3 and C6-7 rats were left-shifted vs. sham rats. EJPs in T2-3 and C6-7 rats showed facilitation followed by run-down during stimulation trains (10 Hz, 50 stimuli). MA reactivity to exogenous NE and ATP was similar in all rats. In T2-3 and C6-7 rats, NE content was increased in left cardiac ventricles compared with intact rats, but was not changed in MA, kidney, or spleen. Our data indicate that peripheral purinergic, but not adrenergic, neurotransmission increases following SCI via enhanced ATP release from periarterial nerves. Sympathetic BP support is reduced after SCI, but improving neurotransmitter release might maintain cardiovascular stability in individuals living with SCI.<b>NEW &amp; NOTEWORTHY</b> This study revealed increased purinergic, but not noradrenergic, neurotransmission to mesenteric arteries in rats with spinal cord injury (SCI). An increased releasable pool of ATP in periarterial sympathetic nerves may contribute to autonomic dysreflexia following SCI, suggesting that purinergic neurotransmission may be a therapeutic target for maintaining stable blood pressure in individuals living with SCI. The selective increase in ATP release suggests that ATP and norepinephrine may be stored in separate synaptic vesicles in periarterial sympathetic varicosities.
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MiR-135a inhibitor alleviates pulmonary arterial hypertension through &#x3b2;-Catenin/GSK-3&#x3b2; signaling pathway.
The aim of this study was to investigate the regulatory role of micro-ribonucleic acid (miR)-135a in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats, and to analyze the possible regulatory mechanism.</AbstractText>A total of 30 Sprague-Dawley rats were randomly divided into three groups, including the blank control group, model group and miR-135a inhibitor intervention group. The right ventricular systolic pressure (RVSP) and right ventricle hypertrophy index (RVHI) were measured in rats of each group. Hematoxylin and eosin (HE) staining was adopted to detect the pathological changes in lung tissues of rats. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of interleukin-6 (IL-6) and IL-1&#x3b2; in lung tissues. Meanwhile, the messenger RNA (mRNA) and protein levels of &#x3b2;-catenin and glycogen synthase kinase-3&#x3b2; (GSK-3&#x3b2;) in lung tissues of rats were determined via Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting assay, respectively.</AbstractText>Compared with the blank control group, RVSP and RVHI increased significantly in the model group. The pathological morphology of the lung tissues was poor, and the content of IL-6 and IL-1&#x3b2; was markedly up-regulated in the model group. Meanwhile, the mRNA and protein levels of &#x3b2;-catenin and GSK-3&#x3b2; were notably elevated in the model group than the blank control group. In the miR-135a inhibitor intervention group, RVSP and RVHI decreased significantly, and the pathological morphology of lung tissues was evidently improved when compared with the blank control group. Furthermore, the content of IL-6 and IL-1&#x3b2; was remarkably reduced, and the mRNA and protein levels of &#x3b2;-catenin and GSK-3&#x3b2; were significantly declined in the miR-135a inhibitor intervention group.</AbstractText>MiR-135a inhibitor significantly alleviates inflammatory response in the lung tissues and ameliorates damage to the pathological morphology. The possible underlying mechanism may be associated with the &#x3b2;-catenin/GSK-3&#x3b2; signaling pathway.</AbstractText>
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[Placement of ventricle peritoneal shunt in the adult patient. A new protocol].
Ventriculoperitoneal shunting is considered a relatively straightforward procedure, though it might ensure multiple complications. Our surgical team developed and implemented a new protocol since June 2016. The objective of this paper is to describe and illustrate the surgical technique step by step and to demonstrate that the use of the "new protocol" significantly reduces the complications associated with the procedure.</AbstractText>A retrospective descriptive study of 184 patients related with cerebrospinal fluid derivation systems from June 2014 to November 2017. One hundred and fourteen patients complied with the inclusion criteria. They were divided into two groups according to the protocol involved, previous (n</i> = 59) and new (n</i> = 55). The technique was described by photographic archive and surgical protocols.</AbstractText>The technique consisting in seven phases was described. With the used of the new protocol the complications decreased significantly. After the new protocol, no ventriculoperitoneal shunt associated infections were observed.</AbstractText>The technique for ventriculoperitoneal shunt consisting in seven phases was described thoroughly. This technique as well as a series of rules constitutes the new protocol. The implementation of the latter lessened the number of complications associated with the procedure. The "zero infection" rate is not a utopia.</AbstractText>Copyright: &#xa9; 2019 Surgical Neurology International.</CopyrightInformation>
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An Unusual Cause of Dyspnea and Thoracic Pressure.
There is a high prevalence of hepatic cysts in the general population. Simple cysts are most of the times asymptomatic and are usually detected incidentally on ultrasonography, computed tomography, or magnetic resonance imaging. Symptoms may range from abdominal discomfort and pain, early satiety, dyspepsia, nausea, and vomiting to jaundice and portal hypertension due to obstruction of adjacent structures. Complications include spontaneous hemorrhage, infection, thrombosis, and atrophy of surrounding hepatic tissue. We present a unique case of a middle-aged patient with acute onset of dyspnea and thoracic pressure due to compression of the right ventricle by a large hepatic cyst.
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Abundant Expression of OCT2, MATE1, OAT1, OAT3, PEPT2, BCRP, MDR1, and xCT Transporters in Blood-Arachnoid Barrier of Pig and Polarized Localizations at CSF- and Blood-Facing Plasma Membranes.
The physiologic and pharmacologic roles of the blood-arachnoid barrier (BAB) remain unclear. Therefore, the purpose of the present study was to comprehensively evaluate and compare the absolute protein expression levels of transporters in the leptomeninges and plexus per cerebrum, and to determine the localizations of transporters at the cerebrospinal fluid (CSF)-facing and blood (dura)-facing plasma membranes of the BAB in pig. Using multidrug resistance protein 1 (MDR1) and organic anion transporter (OAT) 1 as blood (dura)-facing and CSF-facing plasma membrane marker proteins, respectively, we established that breast cancer resistance protein (BCRP), multidrug resistance-associated protein (MRP) 4, organic anion-transporting polypeptide (OATP) 2B1, multidrug and toxin extrusion protein 1 (MATE1), and glucose transporter 1 (GLUT1) are localized at the blood-facing plasma membrane, and OAT3, peptide transporter (PEPT) 2, MRP3, organic cation transporter (OCT) 2, xCT, monocarboxylate transporter (MCT) 1, MCT4, and MCT8 are localized at the CSF-facing plasma membrane of the BAB. The absolute protein expression levels of OAT1, OAT3, MDR1, BCRP, PEPT2, xCT, MATE1, OCT2, and 4f2hc in the whole BAB surrounding the entire cerebrum were much larger than those in the total of the choroid plexuses forming the blood-cerebrospinal fluid barrier (BCSFB). Although MRP4, OATP2B1, MCT8, GLUT1, and MCT1 were also statistically significantly more abundant in the BAB than in the choroid plexuses per porcine cerebrum, these transporters were nevertheless almost equally distributed between the two barriers. In contrast, OATP1A2, MRP1, OATP3A1, and OCTN2 were specifically expressed in the choroid plexus. These results should be helpful in understanding the relative overall importance of transport at the BAB compared with that at the BCSFB, as well as the rank order of transport capacities among different transporters at the BAB, and the directions of transport mediated by individual transporters. SIGNIFICANCE STATEMENT: We found that BCRP, MRP4, OATP2B1, MATE1, and GLUT1 localize at the blood-facing plasma membrane of the blood-arachnoid barrier (BAB), while OAT3, PEPT2, MRP3, OCT2, xCT, MCT1, MCT4, and MCT8 localize at the CSF-facing plasma membrane. 4F2hc is expressed in both membranes. For OAT1, OAT3, MDR1, BCRP, PEPT2, xCT, MATE1, OCT2, and 4f2hc, the absolute protein expression levels in the whole BAB surrounding the entire cerebrum are much greater than the total amounts in the choroid plexuses.
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MicroRNA-495 serves as a diagnostic biomarker in patients with sepsis and regulates sepsis-induced inflammation and cardiac dysfunction.
Sepsis leads to severe inflammatory and cardiac dysfunction. This study aimed to explore the clinical value of miR-495 in sepsis, as well as its role in sepsis-induced inflammation and cardiac dysfunction.</AbstractText>105 sepsis patients were recruited; receiver operating characteristic (ROC) curve was plotted to assess the diagnostic value of miR-495 in sepsis. A model of sepsis in rats was created via performing cecal ligation and puncture (CLP). After modeling, the cardiac function, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (&#xb1;&#x2009;dp/dtmax</sub>), and serum cardiac troponin I (CTn-I), creative kinase isoenzyme MB (CK-MB) were detected. The blood cytokines levels including TNF-&#x3b1;, IL-6, IL-1&#x3b2; were also measured. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-495.</AbstractText>MiR-495 was significantly downregulated in sepsis patients, especially patients who suffered from septic shock (SS). MiR-495 expression was negatively associated with Scr, WBC, CRP, PCT, APACHE II score and SOFA score. MiR-495 could distinguish patients with SS from non-SS patients. MiR-495 and SOFA score were better indictors for the occurrence of cardiac dysfunction in sepsis patients. In CLP-induced sepsis model. CLP rats experienced deterioration of LVSP, LVEDP, &#xb1;&#x2009;dp/dtmax</sub>, and had a rise in serum CTn-I, CK-MB, TNF-&#x3b1;, IL-6 and IL-1&#x3b2;, which were improved by miR-495 agomir injection.</AbstractText>MiR-495 might be a potential diagnostic biomarker for sepsis patients, and overexpression of miR-495 alleviated sepsis-induced inflammation and cardiac dysfunction.</AbstractText>
2,328,314
The Many Faces of Cardiac Sarcoidosis.
The objective of this study was to review and illustrate the sometimes diagnostically challenging features of cardiac sarcoidosis. We emphasize variable phenotypes presented at explant and biopsy evaluation and review literature regarding ancillary clinical and pathologic studies to enhance diagnostic accuracy.</AbstractText>A literature review was performed and two cardiac sarcoidosis cases were illustrated.</AbstractText>Our cases and literature review demonstrate the pathologic spectrum of cardiac sarcoidosis. Irregular left ventricular free wall involvement is most common, followed by the interventricular septum and right ventricle. Although granulomas are often composed of tight epithelioid macrophage aggregates, early granulomas comprise loosely associated macrophages with lymphocyte predominance. Chronic disease leads to fibrosis and end-stage heart failure. Sampling errors and variable histology cause low endomyocardial biopsy sensitivity.</AbstractText>Current guidelines use clinical, radiologic, and immunohistologic criteria for diagnosing cardiac sarcoidosis. Knowledge of these guidelines will assist pathologists in making accurate diagnosis of this disease.</AbstractText>&#xa9; American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</CopyrightInformation>
2,328,315
Intracranial pressure modulates aqueous humour dynamics of the eye.
An elevation in intracranial pressure (ICP) lowers conventional outflow facility (increases aqueous outflow resistance) of rat eyes. The reduction in outflow facility correlates with an increase in intraocular pressure (IOP). The effect of ICP elevation on outflow facility and IOP is blocked by TTX. The results indicate that aqueous humour dynamics is modulated by ICP-driven neural feedback from the brain. This feedback mechanism may act to stabilize translaminar pressure across the optic nerve head and may provide a new avenue for glaucoma therapy.</AbstractText>While intraocular pressure (IOP) is a well-known risk factor for glaucoma, intracranial pressure (ICP) is attracting heightened interest because of its influence on optic nerve head biomechanics. Studies have shown that ICP can have marked impacts on posterior eye health by modifying the translaminar pressure gradient across the optic nerve. There is also growing evidence that IOP and ICP may be interconnected, although the mechanism of their putative interaction is unknown. We sought to test the hypothesis that ICP modulates IOP by altering aqueous humour dynamics. The anterior chamber and lateral ventricle of anaesthetized Brown-Norway rats were cannulated with fine-gauge needles connected to a programmable pump and saline reservoir, respectively. ICP was manipulated by varying reservoir height, and eye outflow facility (C) was determined from the pump flow rate required to hold IOP at different levels. C was 22&#xa0;&#xb1;&#xa0;4&#xa0;nl/min/mmHg at resting ICP and 13&#xa0;&#xb1;&#xa0;3&#xa0;nl/min/mmHg when ICP was raised 15&#xa0;mmHg, a reduction of 41&#xa0;&#xb1;&#xa0;13% (n&#xa0;=&#xa0;18). The decrease in outflow facility was independent of blood pressure, reversible, scaled with ICP elevation and correlated with increases in resting IOP. It was physiological in origin because C returned to baseline values after the rats were killed and corneal application of TTX though ICP remained elevated. These results indicate that a neural feedback mechanism driven by ICP regulates conventional outflow facility in rats. The mechanism may protect the eye from translaminar pressure swings and may offer a new target for glaucoma treatment.</AbstractText>&#xa9; 2019 The Authors. The Journal of Physiology &#xa9; 2019 The Physiological Society.</CopyrightInformation>
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Modulating Pro-inflammatory Cytokines, Tissue Damage Magnitude, and Motor Deficit in Spinal Cord Injury with Subventricular Zone-Derived Extracellular Vesicles.
The upregulation of TNF-&#x3b1;, IL-1&#x3b2;, IL-18, and IL-6 exacerbates the spinal cord injury by amplifying the neuroinflammation. Impeding the release and activation of these cytokines can stop the progression of lesion and promote healing. Modulating the inflammatory response with subventricular zone-derived extracellular vesicles (SVZ-EVs) is one highly promising approach.</AbstractText>SVZ tissue was cultured and EVs were prepared, isolated, and injected intrathecal, in spinal cord-injured (SCI) rats. BBB locomotor scoring, qRT-PCR, Western Blot, H&amp;E, and Nissl staining techniques were applied to record the outcomes.</AbstractText>The intracisternally injected SVZ-EVs significantly decreased the gene and protein expression of TNF-&#x3b1;, IL-1&#x3b2;, IL-18, and IL-6, prevented extensive tissue damage, allowed healing, and improved the hind limb motor function in SCI models.</AbstractText>The results of the present study showed that SVZ-EVs therapy ameliorate inflammation, tissue damage, and motor deficit in traumatic spinal cord injury.</AbstractText>
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Patient-Specific Monitoring and Trend Analysis of Model-Based Markers of Fluid Responsiveness in Sepsis: A Proof-of-Concept Animal Study.
Total stressed blood volume ([Formula: see text]) and arterial elastance ([Formula: see text]) are two potentially important, clinically applicable metrics for guiding treatment in patients with altered hemodynamic states. Defined as the total pressure generating blood in the circulation, [Formula: see text] is a potential direct measurement of tissue perfusion, a critical component in treatment of sepsis. [Formula: see text] is closely related to arterial tone thus provides insight into cardiac efficiency. However, it is not clinically feasible or ethical to measure [Formula: see text] in patients, so a three chambered cardiovascular system model using measured left ventricle pressure and volume, aortic pressure and central venous pressure is implemented to identify [Formula: see text] and [Formula: see text] from clinical data. [Formula: see text] and [Formula: see text] are identified from clinical data from six (6) pigs, who have undergone clinical procedures aimed at simulating septic shock and subsequent treatment, to identify clinically relevant changes. A novel, validated trend analysis method is used to adjudge clinically significant changes in state in the real-time [Formula: see text] and [Formula: see text] traces. Results matched hypothesised increases in [Formula: see text] during fluid therapy, with a mean change of +&#xa0;21% during initial therapy, and hypothesised decreases during endotoxin induced sepsis, with a mean change of -&#xa0;29%. [Formula: see text] displayed the hypothesised reciprocal behaviour with a mean changes of -&#xa0;12 and +&#xa0;30% during initial therapy and endotoxin induced sepsis, respectively. The overall results validate the efficacy of [Formula: see text] in tracking changes in hemodynamic state in septic shock and fluid therapy.
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Converting Pediatric Patients and Young Adults From a Shunt to a Third Ventriculostomy: A Multicenter Evaluation.
Endoscopic third ventriculostomy (ETV) is an effective primary treatment for certain forms of hydrocephalus. However, its use in children with an existing shunt is less well known.</AbstractText>To report a multicenter experience in attempting to convert patients from shunt dependence to a third ventriculostomy and to determine predictors of success.</AbstractText>Three participating centers provided retrospectively collected information on patients with an attempted conversion from a shunt to an ETV between December 1, 2008, and April 1, 2018. Demographic, clinical, and radiological data were recorded. Success was defined as shunt independence at the last follow-up.</AbstractText>Eighty patients with an existing ventricular shunt underwent an ETV. The median age at the time of the index ETV was 9.9 yr, and 44 (55%) patients were male. The overall success rate was 64% (51/80), with a median duration of follow-up of 2.0 yr (range, 0.1-9.4&#xa0;yr). Four patients required a successful repeat ETV at a median of 1.7 yr (range, 0.1-5.7&#xa0;yr) following the index ETV. Only age was predictive of ETV failure on multivariate analysis (odds ratio 0.86 [95% CI 0.78-0.94], P&#xa0;=&#xa0;.005). No patient less than 6 mo of age underwent an ETV, and of the 5 patients between 6 and 12 mo of age, 4 failed.</AbstractText>Although not every shunted patient will be a candidate for an ETV, nor will they be successfully converted, an ETV should at least be considered in every child who presents with a shunt malfunction or who has an externalized shunt.</AbstractText>Copyright &#xa9; 2019 by the Congress of Neurological Surgeons.</CopyrightInformation>
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Olfactory identification associates with cognitive function and the third ventricle width in patients with relapsing-remitting multiple sclerosis.
Olfactory dysfunction is a known clinical feature of multiple sclerosis (MS). Some studies have shown that odor identification impairment is an essential feature associated with cognitive function in MS. This study investigates the relationship between olfactory identification and the disease state, including cognitive function and central brain volume, to evaluate the utility of olfactory identification in the clinical assessment of relapsing-remitting (RR) MS.</AbstractText>Forty patients with RRMS and 40 healthy controls (HCs) were included. Their olfactory identification was measured using the Odor Stick Identification Test for the Japanese (OSIT-J). Cognitive function was evaluated by the Japanese version of the Wechsler Adult Intelligence Scale, 3rd edition (WAIS-III), and depressive mood was evaluated by the Center for Epidemiologic Studies Depression Scale. Magnetic resonance imaging was used to measure the third ventricle width (3rd VW) as a marker of central brain atrophy.</AbstractText>RRMS patients had a significantly lower OSIT-J score than HCs. The OSIT-J score was significantly lower in RRMS patients with low processing speed (PS) and working memory (WM) scores than RRMS patients with normal PS or WM scores. The OSIT-J score was significantly related to the PS, WM, and the 3rd VW. The OSIT-J score also showed a mild correlation with the expanded disability status scale and disease duration, but not with the number of clinical attacks or patient's age.</AbstractText>Our results suggest that olfactory identification impairment occurs in association with cognitive dysfunction and central brain atrophy. Thus, olfactory identification is a possible disease marker of RRMS as with cognitive impairment, especially PS, reflecting the diffuse neurodegeneration in RRMS.</AbstractText>Copyright &#xa9; 2019 Elsevier B.V. All rights reserved.</CopyrightInformation>
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K-Net: Integrate Left Ventricle Segmentation and Direct Quantification of Paired Echo Sequence.
The integration of segmentation and direct quantification on the left ventricle (LV) from the paired apical views(i.e., apical 4-chamber and 2-chamber together) echo sequence clinically achieves the comprehensive cardiac assessment: multiview segmentation for anatomical morphology, and multidimensional quantification for contractile function. Direct quantification of LV, i.e., to automatically quantify multiple LV indices directly from the image via task-aware feature representation and regression, avoids accumulative error from the inter-step target. This integration sequentially makes a stereoscopical reflection of cardiac activity jointly from the paired orthogonal cross views sequences, overcoming limited observation with a single plane. We propose a K-shaped Unified Network (K-Net), the first end-to-end framework to simultaneously segment LV from apical 4-chamber and 2-chamber views, and directly quantify LV from major- and minor-axis dimensions (1D), area (2D), and volume (3D), in sequence. It works via four components: 1) the K-Net architecture with the Attention Junction enables heterogeneous tasks learning of segmentation task of pixel-wise classification, and direct quantification task of image-wise regression, by interactively introducing the information from segmentation to jointly promote spatial attention map to guide quantification focusing on LV-related region, and transferring quantification feedback to make global constraint on segmentation; 2) the Bi-ResLSTMs distributed in K-Net layer-by-layer hierarchically extract spatial-temporal information in echo sequence, with bidirectional recurrent and short-cut connection to model spatial-temporal information among all frames; 3) the Information Valve tailing the Bi-ResLSTMs selectively exchanges information among multiple views, by stimulating complementary information and suppressing redundant information to make the efficient cross-flow for each view; 4) the Evolution Loss comprehensively guides sequential data learning, with static constraint for frame values, and dynamic constraint for inter-frame value changes. The experiments show that our K-Net gains high performance with a Dice coefficient up to 91.44% and a mean absolute error of the major-axis dimension down to 2.74mm, which reveal its clinical potential.
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Trend in ventricle size during pregnancy and its use for prediction of ventriculoperitoneal shunt in fetal open neural tube defect.
Fetal surgery for repair of open neural tube defect (ONTD) typically results in decreased need for a ventriculoperitoneal shunt (VPS). Our objectives were to determine the trend in ventricle size (VS) during pregnancy and whether VS and change in VS, as assessed by ultrasound, were predictive of the need for VPS in pregnancy with ONTD.</AbstractText>This was a retrospective analysis of prospectively collected data of consecutive pregnancies with ONTD, evaluated in a single center from January 2012 to May 2018. Two groups were identified: the first consisted of pregnancies that underwent in-utero repair (IUR) and the second those that had postnatal repair (PNR). Penalized B splines were used to determine the trend in VS, across 2-week gestational-age (GA) epochs, between 24 and 36&#x2009;weeks of gestation. VS at each GA epoch and the change in VS between each GA epoch were compared between the IUR and PNR groups. To determine whether VS at any GA was predictive of VPS, receiver-operating-characteristics (ROC) curves were used and the optimal cut-off at each GA epoch was identified. Univariate analysis and multiple logistic regression were used for further analysis.</AbstractText>ONTD was diagnosed in 110 fetuses, of whom 69 underwent IUR and 41 had PNR. Fetuses in the IUR group were more likely to have Chiari II malformation (100.0% vs 82.9%; P&#x2009;&lt;&#x2009;0.01), lower GA at delivery (34.9&#x2009;&#xb1;&#x2009;3.2 vs 37.1&#x2009;&#xb1;&#x2009;2.1&#x2009;weeks; P&#x2009;&lt;&#x2009;0.01) and lower rates of VPS within the first year postpartum (36.2% vs 61.0%; P&#x2009;=&#x2009;0.02) compared with the PNR group. In both groups, VS increased steadily with GA from the initial evaluation to delivery. In the IUR group, there was a significant change in VS between the 24&#x2009;+&#x2009;0 to 25&#x2009;+&#x2009;6-week and the 26&#x2009;+&#x2009;0 to 27&#x2009;+&#x2009;6-week epochs (2.3 (95%&#x2009;CI, 0.4-4.1) mm; P&#x2009;=&#x2009;0.02). There was a positive trend in the change in VS at later GAs, but this was not significant. Although there was no significant change in VS in the PNR group before 30&#x2009;weeks, there was a positive trend after that time. On multivariate analysis, each week of advancing GA was associated with a mean increase of 0.74&#x2009;mm in VS (P&#x2009;&lt;&#x2009;0.0001) in both groups. VS was not associated with the level or type of lesion, but presence of Chiari II malformation was associated with a mean increase of 5.88&#x2009;mm (P&#x2009;&lt;&#x2009;0.0001) in VS in both the IUR and PNR groups. VS was modestly predictive of need for VPS in both groups, with area under ROC curves between 0.68 and 0.76 at the different GA epochs. Change in VS between the first and last measurements was also modestly predictive of the need for VPS, with better performance in the PNR group.</AbstractText>VS increased with advancing GA in all fetuses with ONTD, although in the IUR group this increase occurred immediately after fetal surgery and in the PNR group it occurred after 30&#x2009;weeks of gestation. In-utero surgery was associated with a decreased rate of VPS and was more predictive of need for VPS than was VS. Postnatal factors resulting in increased need for VPS in the PNR group need to be assessed further. Copyright &#xa9; 2019 ISUOG. Published by John Wiley &amp; Sons Ltd.</AbstractText>Copyright &#xa9; 2019 ISUOG. Published by John Wiley &amp; Sons Ltd.</CopyrightInformation>
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Colpocephaly Diagnosed in a Neurologically Normal Adult in the Emergency Department.
Colpocephaly is a form of congenital ventriculomegaly characterized by enlarged occipital horns of the lateral ventricles with associated neurologic abnormalities. The diagnosis of colpocephaly is typically made in infancy. Its diagnosis in adulthood without associated clinical symptoms is exceptionally rare. We report a case of colpocephaly diagnosed incidentally in an adult without neurologic abnormalities in the emergency department. To our knowledge, this is only the ninth reported case in an asymptomatic adult and the first to be described in the emergency medicine literature.
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Cardioprotective effects of curcumin and carvacrol in doxorubicin-treated rats: Stereological study.
Doxorubicin (DOX) is a cardiotoxic drug. To reduce the harmful effects of DOX, two plant-derived components, including curcumin (CUR) and carvacrol (CAR), were considered. This study aimed to assess the protective effects of CUR and CAR on DOX-induced cardiotoxicity using physiological and stereological evaluations. Male rats were randomly allocated to six groups. Group's I-VI received phosphate-buffered saline (PBS), CUR (100&#xa0;mg&#xa0;kg<sup>-1</sup>&#xa0;day<sup>-1</sup>), CAR (50&#xa0;mg&#xa0;kg<sup>-1</sup>&#xa0;day<sup>-1</sup>), DOX (4&#xa0;mg&#xa0;kg<sup>-1</sup>&#xa0;week<sup>-1</sup>), DOX-CUR, and DOX-CAR, respectively. On day 24, plasma troponin I and ECG were analyzed and the left ventricle underwent stereological assessment. The results showed a fivefold increase in troponin I in the DOX-treated animals compared to the PBS ones. Additionally, heart rate and QRS amplitude, respectively, reduced by 18% and 31% and QT interval and QRS duration, respectively, increased by 41% and 24% in the DOX group in comparison with the PBS rats (<i>p</i>&#xa0;&lt;&#xa0;.05). The total volume of the myocardium and vessels and the number of cardiomyocyte nuclei also, respectively, decreased by 30%, 45%, and 43% in the DOX group compared to the PBS animals (atrophy of the ventricular tissues, <i>p</i>&#xa0;&lt;&#xa0;.01). Besides, the mean volumes of the connective tissue and cardiomyocytes, respectively, increased by 46% and 52% in the DOX group (<i>p</i>&#xa0;&lt;&#xa0;.01). In the DOX-CUR and DOX-CAR groups, the changes were prevented extensively in comparison with the DOX group (<i>p</i>&#xa0;&lt;&#xa0;.01). Co-administration of CUR or CAR and doxorubicin for 24&#xa0;days could improve the heart function and structural changes.
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Fast parameter inference in a biomechanical model of the left ventricle by using statistical emulation.
A central problem in biomechanical studies of personalized human left ventricular modelling is estimating the material properties and biophysical parameters from <i>in vivo</i> clinical measurements in a timeframe that is suitable for use within a clinic. Understanding these properties can provide insight into heart function or dysfunction and help to inform personalized medicine. However, finding a solution to the differential equations which mathematically describe the kinematics and dynamics of the myocardium through numerical integration can be computationally expensive. To circumvent this issue, we use the concept of emulation to infer the myocardial properties of a healthy volunteer in a viable clinical timeframe by using <i>in vivo</i> magnetic resonance image data. Emulation methods avoid computationally expensive simulations from the left ventricular model by replacing the biomechanical model, which is defined in terms of explicit partial differential equations, with a surrogate model inferred from simulations generated before the arrival of a patient, vastly improving computational efficiency at the clinic. We compare and contrast two emulation strategies: emulation of the computational model outputs and emulation of the loss between the observed patient data and the computational model outputs. These strategies are tested with two interpolation methods, as well as two loss functions. The best combination of methods is found by comparing the accuracy of parameter inference on simulated data for each combination. This combination, using the output emulation method, with local Gaussian process interpolation and the Euclidean loss function, provides accurate parameter inference in both simulated and clinical data, with a reduction in the computational cost of about three orders of magnitude compared with numerical integration of the differential equations by using finite element discretization techniques.
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sEVD-smartphone-navigated placement of external ventricular drains.
Currently, the trajectory for insertion of an external ventricular drain (EVD) is mainly determined using anatomical landmarks. However, non-assisted implantations frequently require multiple attempts and are associated with EVD malpositioning and complications. The authors evaluated the feasibility and accuracy of a novel smartphone-guided, angle-adjusted technique for assisted implantations of an EVD (sEVD) in both a human artificial head model and a cadaveric head.</AbstractText>After computed tomography (CT), optimal insertion angles and lengths of intracranial trajectories of the EVDs were determined. A smartphone was calibrated to the mid-cranial sagittal line. Twenty EVDs were placed using both the premeasured data and smartphone-adjusted insertion angles, targeting the center of the ipsilateral ventricular frontal horn. The EVD positions were verified with post-interventional CT.</AbstractText>All 20 sEVDs (head model, 8/20; cadaveric head, 12/20) showed accurate placement in the ipsilateral ventricle. The sEVD tip locations showed a mean target deviation of 1.73&#xb0; corresponding to 12 mm in the plastic head model, and 3.45&#xb0; corresponding to 33 mm in the cadaveric head. The mean duration of preoperative measurements on CT data was 3 min, whereas sterile packing, smartphone calibration, drilling, and implantation required 9 min on average.</AbstractText>By implementation of an innovative navigation technique, a conventional smartphone was used as a protractor for the insertion of EVDs. Our ex vivo data suggest that smartphone-guided EVD placement offers a precise, rapidly applicable, and patient-individualized freehand technique based on a standard procedure with a simple, cheap, and widely available multifunctional device.</AbstractText>
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Under pressure: Cerebrospinal fluid contribution to the physiological homeostasis of the eye.
The cerebrospinal fluid (CSF) is a waterly, colorless fluid contained within the brain ventricles and the cranial and spinal subarachnoid spaces. CSF physiological functions range from hydromechanical protection of the central nervous system (CNS) to CNS modulation of developmental processes and regulation of interstitial fluid homeostasis. Optic nerve (ON) is surrounded by CSF circulating in the subarachnoid spaces and is exposed to both CSF (CSFP) and intra ocular (IOP) pressures, which converge at the lamina cribrosa (LC) as two opposite forces. The trans-lamina cribrosa pressure gradient (TLPG) is defined as IOP - CSFP and its alterations (due either to an elevation in IOP or a reduction in ICP) could result in structural damaging of the ON, including glaucomatous changes. The purpose of this review is to update the readers on the CSF contribution in controlling the functions/dysfunctions of ON by regulating homeostasis at LC. We also highlight emerging parallelisms regarding the expression of cilia-related genes in the regulation of common functions of body fluids in both brain and eye structures.
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Intracerebroventricular Delivery of Human Umbilical Cord Mesenchymal Stem Cells as a Promising Therapy for Repairing the Spinal Cord Injury Induced by Kainic Acid.
Spinal cord injury (SCI) is a common pathological condition that leads to permanent or temporal loss of motor and autonomic functions. Kainic acid (KA), an agonist of kainate receptors, a type of ionotropic glutamate receptor, is widely used to induce experimental neurodegeneration models of CNS. Mesenchymal Stem Cells (MSC) therapy applied at the injured nervous tissue have emerged as a promising therapeutic treatment. Here we used a validated SCI experimental model in which an intraparenchymal injection of KA into the C5 segment of rat spinal cord induced an excitotoxic lesion. Three days later, experimental animals were treated with an intracerebroventricular injection of human umbilical cord (hUC) MSC whereas control group only received saline solution. Sensory and motor skills as well as neuronal and glial reaction of both groups were recorded. Differences in motor behavior, neuronal counting and glial responses were observed between hUC-MSC-treated and untreated rats. According to the obtained results, we suggest that hUC-MSC therapy delivered into the fourth ventricle using the intracerebroventricular via can exert a neuroprotective or neurorestorative effect on KA-injected animals.
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Magnetic resonance imaging in boxers with repeated traumatic brain injury.
Currently, neuroimaging changes in boxers who have suffered repeated traumatic brain injury (TBI) have not been sufficiently studied and analyzed. To detect such changes, magnetic resonance imaging (MRI) is the most informative.</AbstractText>The aim of study was to investigate the features of MRI changes in boxers with repeated TBI.</AbstractText>An MRI scan of the brain was carried out on 174 amateur boxers aged 16 to 42 years who had a history of repeated TBI. In the control group, 30 practically healthy people of similar age were examined. Patients were analyzed by gender, age, weight category, number of fights conducted.</AbstractText>A significant increase in the width of the lateral ventricles (LV) on both sides, 3rd ventricle and cavum septum pellucidum (CSP) was noted in boxers, among whom men dominated. There was an increase in the width of the LV on both sides, 3rd ventricle and CSP with increasing age, weight category, number of fights. A normal MRI scan of the brain was more common in the younger age group female boxers. There has been an increase in the frequency of expansion of the CSP with increasing age, the number of fights held. There was an increase in the frequency of foci of the modified MRI signal (subcortical, periventricular) with increasing age. Frequency of arachnoid cysts increased with an increase in weight category, and the frequency of diffuse expansion of subarachnoid spaces increased with an increase in the number of fights conducted.</AbstractText>In boxers who had a history of repeated TBI, there are changes according to MRI of the brain from both the cerebrospinal fluid pathways and the brain matter. Studying the features of MRI scans of the boxers will make it possible to predict their competitive activity, timely diagnose brain disorders, carry out the necessary treatment and take preventive measures in order to prevent possible long-term effects of trauma.</AbstractText>&#xa9; 2019 MEDPRESS.</CopyrightInformation>
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Cavum velum interpositum cysts in normal and anomalous fetuses in second trimester of pregnancy: Comparison of its size and prevalence.
Cavum veli interpositi (CVI) is a potential space below the splenium of corpus callosum and sometimes presents as a cyst.</AbstractText>In this prospective cross-sectional study, 360 fetuses with normal second trimester scan and 152&#xa0;s trimester fetuses with structural abnormalities were included.</AbstractText>The CVI cysts were more common in fetuses with brain anomaly compared to normal fetuses and fetuses with extra-central nervous system (CNS) anomalies (23% vs 18.3% and 18% respectively; p value&#xa0;&lt;&#xa0;0.01). The mean size of cysts in normal fetuses, fetuses with extra-CNS anomalies and fetuses with brain abnormalities was 4.6&#xa0;mm, 5.8&#xa0;mm and 9.2&#xa0;mm respectively. There was a significant difference between cysts size in normal fetuses and fetuses with brain anomalies (p value&#xa0;&lt;&#xa0;0.01) and the cut-point was 7.1&#xa0;mm.</AbstractText>The prevalence of CVI cysts is more in fetuses with brain anomaly. Fetuses with a cyst size &gt;7.1&#xa0;mm need a more detailed brain examination.</AbstractText>Copyright &#xa9; 2019. Published by Elsevier B.V.</CopyrightInformation>
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Oral repeated-dose toxicity studies of BIA 10-2474 in Wistar rat.
BIA 10-2474 is a novel fatty acid amide hydrolase (FAAH) inhibitor developed for the treatment of medical conditions which would benefit from enhanced levels of endogenous anandamide (AEA) such as pain disorders. During a Phase I clinical trial one subject died after receiving BIA 10-2474 and four other subjects displayed neurological signs. As part of series of papers presenting all the toxicology data available prior to the clinical trial, we report here the preclinical toxicology studies examining once-a-day oral administration of BIA 10-2474 to male and female Wistar rats. These included a 14-day dose range finding (150, 200 and 250&#xa0;mg/kg/day), a 4-week study (30, 90 and 150&#xa0;mg/kg/day) and 13- and 26-week studies (both at 10, 30 and 90&#xa0;mg/kg/day). The 13- and 26-week studies also included a 4-week recovery arm and a toxicokinetic arm for the parent compound, BIA 10-2474, and the two major metabolites (BIA 10-2445 and BIA 10-2583) were also measured in the 26-week study. At 150&#xa0;mg/kg and below, all animals survived the scheduled treatment periods although neurological side-effects (abnormal or stiff gait, dragging of fore- or hind-limbs) were seen at 150&#xa0;mg/kg in both the dose-range finding and 4-week studies. At 90&#xa0;mg/kg/day, even up to 26-weeks treatment, no clinical signs were seen apart from some decreases in body weight gain. A number of consistent hematological and biochemical changes were noted which were considered related to treatment with BIA 10-2474. Morphologically, in the 4-week study, except for a slight gliosis in the hippocampus of one female at 150&#xa0;mg/kg, no CNS histopathology was observed; hippocampus gliosis was not observed in subsequent studies. In the 13-week study axonal swelling was present in the medulla oblongata in about half the animals at 90&#xa0;mg/kg/day and this increased to nearly all the rats at 90&#xa0;mg/kg/day in the 26-week study. Additional signs seen only in the 26-week study at 90&#xa0;mg/kg/day included axonal swelling of the fasiculus gracilis and vacuolar changes in the medulla oblongata and ventral commissure of the 3rd ventricle. Other findings included vacuolar degeneration in the ganglia of the GI tract, salivary glands, prostate gland, uterus, and parathyroid glands. The pituitary gland showed edema and mitotic figures in the pars nervosa. These observations outside the CNS were seen in most rats at 90 and 150&#xa0;mg/kg/day independent of study duration. At 30&#xa0;mg/kg/day, most of these observations were only seen in isolated cases except for the vacuolar degeneration in GI tract ganglia, which was absent at this dose after 4 weeks treatment but was present in almost all rats at 13 and 26 weeks. Hepatocellular hypertrophy and nephropathy were seen across all studies and the extent of these changes was similar in the 13- and 26-week studies. Most findings resolved after the 4-week recovery periods except for the axonal swelling seen in the medulla oblongata and spinal cord. BIA 10-2474 exposure was markedly higher than the exposure to either metabolite, BIA 10-2445 (19- to 192-fold) and BIA 10-2583 (63- to 526-fold). Exposure to metabolites differed between sexes with higher concentrations of BIA 10-2445 in females compared to males, but the inverse for BIA 10-2583. Although a No Observed Adverse Effect Level (NOAEL) of 30&#xa0;mg/kg/day was concluded following the 4-week study, the histopathological findings at that dose in the 13- and 26-week studies resulted in the NOAEL being determined to be 10&#xa0;mg/kg/day.
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Mesial temporal lobe epilepsy: A West Indian Neurosurgical Experience.
We sought to highlight a case of refractory mesial temporal lobe epilepsy managed via an anterior temporal lobectomy. To our knowledge, this is the first of its kind to be performed and published in the English-speaking Caribbean.</AbstractText>A 44-year-old female, known seizure disorder for 25 years was referred to the outpatient clinic. Several trials of varying anti-epileptic drugs failed to provide remittance of her frequent partial seizures over the last two decades. Magnetic resonance imaging displayed asymmetry of the hippocampus, with a prominent right temporal horn of lateral ventricle, in keeping with right anteromesial temporal lobe sclerosis. She underwent a right anterior temporal lobectomy after exhaustive counselling; with the guidance of a multidisciplinary team. The post-operative period was uneventful and currently, the patient has been seizure-free since operation.</AbstractText>Drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used anti-epileptic drug schedules to attain sustained seizure freedom. Medical management of mesial temporal lobe epilepsy has a relatively poor long-term outcome, with 30&#x202f;% of patients falling into the category of pharmaco-resistant.</AbstractText>Surgical management of these cases have been proven to be a safe and effective alternative but is currently greatly underutilized. In our literature review, we present the first published case of epilepsy surgery in the English-speaking Caribbean for temporal lobe epilepsy.</AbstractText>Copyright &#xa9; 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation>
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A new frameshift mutation in L1CAM producing X-linked hydrocephalus.
X-linked hydrocephalus (XLH), characterized by mental retardation and bilateral adducted thumbs, often come out to be a genetic disorder of L1CAM. It codes the protein L1 cell adhesion molecule (L1CAM), playing a crucial role in the development of the nervous system. The objective of the study was to report a new disease-causing mutation site of L1CAM, and gain further insight into the pathophysiology of hydrocephalus.</AbstractText>We collect the samples of a couple and their second hydrocephalic fetus. Then, the whole-exome sequencing and in-depth mutation analysis were performed.</AbstractText>The variant c.2491delG (p.V831fs), located in the exon 19 of L1CAM (chrX:153131214), could damage the L1CAM function by producing a frameshift in the translation of fibronectin type-III of L1CAM.</AbstractText>We identified a novel disease-causing mutation in L1CAM for the first time, which further confirmed L1CAM as a gene underlying XLH cases.</AbstractText>&#xa9; 2019 Sichuan Provincial Hospital for Women and Children. Molecular Genetics &amp; Genomic Medicine published by Wiley Periodicals, Inc.</CopyrightInformation>
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Myocardial deformation and acute cellular rejection after heart transplantation: Impact of inter-vendor variability in diagnostic effectiveness.
Our objective was to investigate the impact of inter-vendor variability in the ability of myocardial strain analysis to detect acute cellular rejection (ACR) in heart transplant recipients.</AbstractText>We performed serial echocardiographic examinations in 18 consecutive adult heart transplanted patients, in their first year post-transplantation, within 3&#xa0;hours of the routine surveillance endomyocardial biopsies (EMB) in a single center. Myocardial strain was analyzed using two software in two different institutions, and inter-vendor variability of strain values and its association with ACR (any grade or grade &#x2265;2R) was investigated. The parameter of comparison was the peak value of the average curve of strain during the entire cardiac cycle.</AbstractText>A total of 147 pairs of EMB-echocardiogram were performed, 65 with no ACR, 63 with ACR grade 1R, and 19 with ACR grade &#x2265;2R. Intra-class correlation coefficients for left ventricle longitudinal, radial, and circumferential strain were 0.38, 0.39, and 0.77, respectively, and 0.32 for right ventricular longitudinal strain. Neither software found significant association of left ventricular longitudinal strain with rejection. Grade &#x2265;2R ACR was associated with left ventricular circumferential strain measured with the first software and with left ventricular radial strain with the other; and ACR of any grade was only significantly associated with right ventricle longitudinal strain measured with the first software.</AbstractText>Inter-vendor reproducibility of strain values was low in this study. Some strain parameters were associated to ACR, although these results were inconsistent between two commercially available software. Specific validation of each software is warranted for this clinical indication.</AbstractText>&#xa9; 2019 Wiley Periodicals, Inc.</CopyrightInformation>
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Correlation of OCTA and Volumetric MRI in Mild Cognitive Impairment and Alzheimer's Disease.
To evaluate the relationship between retinal microvascular parameters on optical coherence tomography angiography (OCTA) and neurodegenerative changes assessed by measurement of brain volume on volumetric magnetic resonance imaging (MRI) in Alzheimer's disease (AD) and mild cognitive impairment (MCI).</AbstractText>Sixteen subjects with AD and MCI underwent OCTA imaging (3 mm &#xd7; 3 mm and 6 mm &#xd7; 6 mm scans) and volumetric brain MRI imaging with automated volumetric segmentation and quantification. Spearman's correlation (&#x3c1;) was performed between forebrain parenchyma, cortical gray matter, inferolateral ventricle (ILV), lateral ventricle (LV), and hippocampus (HP) MRI volumes and vessel density (VD), along with perfusion density (PD) for the 6-mm circle, 6-mm ring, 3-mm circle, and 3-mm ring Early Treatment Diabetic Retinopathy Study regions of the superficial capillary plexus.</AbstractText>Thirty eyes of 16 patients (seven MCI and nine AD) with good-quality OCTA images were analyzed. ILV volume inversely correlated with the VD in the 6-mm circle (&#x3c1; = -0 .565, P = .028) and 3-mm ring (&#x3c1; = -0.569, P = .027) and PD in the 3-mm ring (&#x3c1; = -0.605, P = .0169). Forebrain, cortical gray matter, LV, and HP volumes did not significantly correlate with either VD or PD (P &gt; .05).</AbstractText>In this pilot investigation, the authors found a significant correlation between reduction in the superficial capillary plexus VD and PD on OCTA and expansion of the ILV in MCI and AD. This relationship between the retinal microvasculature and cerebral volumetric changes deserves further investigation. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:709-718.].</AbstractText>Copyright 2019, SLACK Incorporated.</CopyrightInformation>
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Immunoreactivities for hepcidin, ferroportin, and hephaestin in astrocytes and choroid plexus epithelium of human brains.
Iron plays essential roles in the central nervous system. However, how the iron level is regulated in brain cells including glia and neurons remains to be fully clarified. In this study, the localizations of hepcidin, ferroportin, and hephaestin, which are known to be involved in iron efflux, were immunohistochemically examined in autopsied human brains. Immunoreactivities for hepcidin and ferroportin were observed in granular structures within the cytoplasm of reactive astrocytes and epithelial cells of the choroid plexus. Granular structures showing immunoreactivities for hepcidin and ferroportin were also stained with antibodies for early endosome antigen 1 (EEA1). In addition, immunoreactivity for hephaestin was observed in the cytoplasm of epithelial cells of the choroid plexus as well as reactive astrocytes. Immunoreactivity for hephaestin in the cytoplasm of reactive astrocytes was occasionally colocalized with immunoreactivity for EEA1, while that of hephaestin was frequently observed in the cytoplasm showing no immunoreactivity for EEA1. These findings suggest that immunoreactivities for hepcidin and ferroportin are localized in close proximity to granular structures showing immunoreactivity for EEA1 in the cytoplasm of human brain astrocytes. They also suggest that immunoreactivity of hephaestin is localized in the cytoplasm of the choroid plexus epithelium as well as reactive astrocytes of human brains.
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Ependymal fluorescence in fluorescence-guided resection of malignant glioma: a systematic review.
Fluorescence in the ventricular wall or the ependyma during fluorescence-guided resection (FGR) of malignant glioma is commonly observed when malignant gliomas infiltrate the ventricles. However, the underlying pathophysiology and clinical importance are largely unknown but may play a role in deciding whether to continue resection into the ventricles or not. Here, we systematically review available data regarding ependymal fluorescence in FGR using five aminolevulinic acid (5-ALA) and sodium fluorescein (SF).</AbstractText>A literature search on MEDLINE, EMBASE, and WEB OF SCIENCE was performed using the following headings and search operators: ependy* fluorescence AND (5-ALA OR five aminolevulinic acid), ventric* wall fluorescence AND (5-ALA OR five aminolevulinic acid), ependy* fluorescence AND fluorescein, and ventric* wall fluorescence AND fluorescein. Both authors analyzed abstracts independently. Included articles were further reviewed for prevalence of ependymal fluorescence, patterns of fluorescence, and histopathological characteristics of sampled tissues as well as radiological signs of ependymal fluorescence. Results are reported according to the PRISMA statement.</AbstractText>Of 202 records identified, 6 studies were included compiling a total number of 198 patients treated with FGR using 5-ALA. No study on ependymal fluorescence after administration of SF was found. Overall prevalence of ependymal fluorescence was 61.4%. A total of 54.5% of cases were found to be positive for tumor cells. A total of 25.5% of patients with ependymal fluorescence were related to contrast enhancement in ventricular walls.</AbstractText>The phenomenon of ventricular wall fluorescence in 5-ALA-derived fluorescence-guided resection of malignant glioma is poorly understood and not always may fluorescence represent tumor infiltration. A larger scale prospective sampling study with molecular analyses is currently ongoing and will hopefully provide further insight into pathophysiology and clinical implications of ependymal fluorescence.</AbstractText>
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Longitudinal morphological changes during recovery from brain deformation due to idiopathic normal pressure hydrocephalus after ventriculoperitoneal shunt surgery.
The present study aimed to examine time-dependent change in cerebrospinal fluid distribution and various radiological indices for evaluating shunt effectiveness in patients with idiopathic normal pressure hydrocephalus (iNPH). This study included 54 patients with iNPH who underwent MRI before and after ventriculoperitoneal shunt surgery. The volume of the total ventricles and subarachnoid spaces decreased within 1 month after shunting. However, more than 1 year after shunting, the volume of the total ventricles decreased, whereas that of the total subarachnoid spaces increased. Although cerebrospinal fluid distribution changed considerably throughout the follow-up period, the brain parenchyma expanded only 2% from the baseline brain volume within 1 month after shunting and remained unchanged thereafter. The volume of the convexity subarachnoid space markedly increased. The changing rate of convexity subarachnoid space per ventricle ratio (CVR) was greater than that of any two-dimensional index. The brain per ventricle ratio (BVR), callosal angle and z-Evans index continued gradually changing, whereas Evans index did not change throughout the follow-up period. Both decreased ventricular volume and increased convexity subarachnoid space volume were important for evaluating shunt effectiveness. Therefore, we recommend CVR and BVR as useful indices for the diagnosis and evaluation of treatment response in patients with iNPH.
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Endoscopic surgery for thalamic hemorrhage breaking into ventricles: Comparison of endoscopic surgery, minimally invasive hematoma puncture, and&#xa0;external ventricular drainage.
Thalamic hemorrhage breaking into ventricles (THBIV) is a devastating disease with high morbidity and mortality rates. Endoscopic surgery (ES) may improve outcomes, although there is no consensus on its superiority. We investigated the efficacy and safety of ES and compared the outcomes of different management strategies by ES, hematoma puncture and drainage (HPD), and external ventricular drainage (EVD) in patients with THBIV.</AbstractText>We retrospectively analyzed patients with THBIV treated by ES, HPD, or EVD at our hospital from June 2015 to June 2018. Patients were categorized into anteromedial and posterolateral groups based on THBIV location, and then the two groups were further divided into ES, HPD, and EVD subgroups. Individualized surgical approach was adopted according to the location of the hematoma in the ES subgroups. Patient characteristics and surgical outcomes were investigated.</AbstractText>We analyzed 211 consecutive patients. There were no significant differences in clinical characteristics or incidence of perioperative procedure-related complications (postoperative rebleeding and intracranial infection) in either anteromedial or posterolateral groups. Compared with other therapeutic methods, the ES subgroups had the highest hematoma evacuation rate, shortest drainage time, and lowest incidence of chronic ventricular dilatation (all p&#xa0;&lt;&#xa0;0.05). Among the three anteromedial subgroups, ES subgroup had the best clinical outcomes which was assessed by the modified Rankin Scale, followed by HPD and EVD subgroups (p&#xa0;&lt;&#xa0;0.01); while in the posterolateral subgroups, clinical outcomes in the ES and HPD subgroups were similar and better than that in the EVD subgroup (p = 0.037).</AbstractText>Individualized surgical ES approach for removal of thalamic and ventricular hematomas is a minimally invasive, safe, and effective strategy for the treatment of THBIV with a thalamic hematoma volume of 10-30&#xa0;mL.</AbstractText>Copyright &#xa9; 2019 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.</CopyrightInformation>
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Distinct migratory pattern of naive and effector T cells through the blood-CSF barrier following Echovirus 30 infection.
Echovirus 30 (E-30) is one of the most frequently isolated pathogens in aseptic meningitis worldwide. To gain access to the central nervous system (CNS), E-30 and immune cells have to cross one of the two main barriers of the CNS, the epithelial blood-cerebrospinal fluid barrier (BCSFB) or the endothelial blood-brain barrier (BBB). In an in vitro model of the BCSFB, it has been shown that E-30 can infect human immortalized brain choroid plexus papilloma (HIBCPP) cells.</AbstractText>In this study we investigated the migration of different T cell subpopulations, naive and effector T cells, through HIBCPP cells during E-30 infection. Effects of E-30 infection and the migration process were evaluated via immunofluorescence and flow cytometry analysis, as well as transepithelial resistance and dextran flux measurement.</AbstractText>Th1 effector cells and enterovirus-specific effector T cells migrated through HIBCPP cells more efficiently than naive CD4+</sup> T cells following E-30 infection of HIBCPP cells. Among the different naive T cell populations, CD8+</sup> T cells crossed the E-30-infected HIBCPP cell layer in a significantly higher number than CD4+</sup> T cells. A large amount of effector T cells also remained attached to the basolateral side of the HIBCPP cells compared with naive T cells. Analysis of HIBCPP barrier function showed significant alteration after E-30 infection and trans- as well as paracellular migration of T cells independent of the respective subpopulation. Morphologic analysis of migrating T cells revealed that a polarized phenotype was induced by the chemokine CXCL12, but reversed to a round phenotype after E-30 infection. Further characterization of migrating Th1 effector cells revealed a downregulation of surface adhesion proteins such as LFA-1 PSGL-1, CD44, and CD49d.</AbstractText>Taken together these results suggest that naive CD8+</sup> and Th1 effector cells are highly efficient to migrate through the BCSFB in an inflammatory environment. The T cell phenotype is modified during the migration process through HIBCPP cells.</AbstractText>
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Left ventricular mass normalization for body size in children based on an allometrically adjusted ratio is as accurate as normalization based on the centile curves method.
Normalization for body size is required for reliable left ventricular mass (LVM) evaluation, especially in children due to the large variability of body size. In clinical practice, the allometrically adjusted ratio of LVM to height raised to the power of 2.7 is often used. However, studies presenting normative LVM data for children recommend centile curves as optimal for the development of normative data. This study aimed to assess whether the allometrically adjusted LVM-to-height ratio can reliably reproduce the results of LVM normalization for height based on the centile curves method.</AbstractText>Left ventricular mass was computed for 464 boys and 327 girls, 5-18 years old, based on echocardiographic examination. Normalized data representing LVM for height were developed using the centile curves construction method and two variants of the allometrically adjusted ratio method: one variant with the allometric exponents specific to the study groups, and one variant with the universal exponent of 2.7. The agreement between the allometric methods and the centile curves method was analyzed using the concordance correlation coefficient, sensitivity, and specificity.</AbstractText>For both the specific allometric variant and the universal variant, the analysis of concordance has indicated high reproducibility compared to the centile curves method. The respective coefficient values were 0.9917 and 0.9916 for girls, and 0.9886 and 0.9869 for boys. The sensitivity and specificity test has also shown high agreement. However, for girls, the sensitivity was higher for the specific variant (100% vs. 90.9%).</AbstractText>The results of the study show that allometric scaling of LVM for height can very reliably reproduce the results of LVM normalization for height based on the centile curves method. However, the analysis of sensitivity and specificity indicates greater agreement for the allometric normalization with the group-specific allometric exponents.</AbstractText>
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Cambridge Cognitive Examination and Hachinski Ischemic Score as predictors of MRI confirmed pathology in dementia: A cross-sectional study.
Dementia is diagnosed through a combination of clinical assessment, cognitive assessment tools and neuroimaging. The aim of this retrospective, naturalistic study was to explore the association between the clinical assessment tools used in a memory clinic and the findings of Magnetic Resonance Imaging (MRI) scans in patients with dementia.</AbstractText>Data were collected through routine clinical practice for all patients assessed at a memory assessment clinic in East Sussex, UK. Included patients had an MRI scan and received a formal diagnosis of dementia. Multinomial logistic regression was used to investigate the associations between atrophy on MRI with age, gender, Cambridge Cognitive Examination (CAMCOG) and Hachinski Ischemic Score (HIS). Ordinal logistic regression was used to study the associations between vascular findings on MRI with age, gender, CAMCOG and HIS. Because of the distribution of HIS scores a cut-off of 1 or greater was used in the regression analysis.</AbstractText>Male gender was associated with an increased likelihood of moderate atrophy (relative risk ratio (RRR)&#xa0;=&#xa0;1.99, 95% confidence interval (CI)&#xa0;=&#xa0;1.04-3.82), severe atrophy (RRR&#xa0;=&#xa0;3.04, 95%&#xa0;CI&#xa0;=&#xa0;1.38-6.68) and regional atrophy (RRR&#xa0;=&#xa0;2.25, 95%&#xa0;CI&#xa0;=&#xa0;1.26-4.00) on MRI. An increase of one point on the CAMCOG was associated with a decreased risk of regional atrophy (RRR&#xa0;=&#xa0;0.98, 95%&#xa0;CI&#xa0;=&#xa0;0.96-1.00) on MRI. There were no significant associations between age, or HIS, and atrophy on MRI. An increase in age of one year was associated with an increase in severity of vascular pathology reported on MRI (OR&#xa0;=&#xa0;1.08, 95%&#xa0;CI&#xa0;=&#xa0;1.05-1.12). Male gender was associated with reduced severity of vascular pathology reported on MRI (OR&#xa0;=&#xa0;0.53, 95%&#xa0;CI&#xa0;=&#xa0;0.36-0.78). There were no associations between CAMCOG, or HIS, and vascular pathology on MRI.</AbstractText>Our data show that CAMCOG was associated with MRI findings of regional atrophy and vascular pathology was greater in older patients. We highlight the importance of using a multi-modal approach to dementia diagnosis.</AbstractText>&#xa9; 2019 John Wiley &amp; Sons Ltd.</CopyrightInformation>
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Sex-related Left Ventricle Rotational and Torsional Mechanics by Block Matching Algorithm.
The aim of the present study was to evaluate how left ventricular twist and torsion are associated with sex between sex groups of the same age.</AbstractText>In this analytical study, twenty one healthy subjects were scanned in left ventricle basal and apical short axis views to run the block matching algorithm; instantaneous changes in the base and apex rotation angels were estimated by this algorithm and then instantaneous changes of the twist and torsion were calculated over the cardiac cycle.</AbstractText>The rotation amount between the consecutive frames in basal and apical levels was extracted from short axis views by tracking the speckle pattern of images. The maximum basal rotation angle for men and women were -6.94&#xb0;&#xb1;1.84 and 9.85&#xb0;&#xb1;2.36 degrees (p-value = 0.054), respectively. Apex maximum rotation for men was -8.89&#xb0;&#xb1;2.04 and for women was 12.18&#xb0;&#xb1;2.33 (p-value &lt; 0.05). The peak of twist angle for men and women was 16.78 &#xb1; 1.83 and 20.95&#xb1; 2.09 degrees (p-value &lt; 0.05), respectively. In men and women groups, the peak of calculated torsion angle was 5.49&#xb0;&#xb1;1.04 and 7.12&#xb1; 1.38 degrees (p-value &lt; 0.05), respectively.</AbstractText>The conclusion is that although torsion is an efficient parameter for left ventricle function assessment, because it can take in account the heart diameter and length, statistic evaluation of the results shows that among men and women LV mechanical parameters are significantly different. This study was mainly ascribed to the dependency of the torsion and twist on patient sex.</AbstractText>Copyright: &#xa9; Shiraz University of Medical Sciences.</CopyrightInformation>
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Detailed insight in intraoperative eABR measurements to assist auditory brainstem implantation in a patient with neurofibromatosis type 2.
Auditory brainstem implant (ABI) is used to provide auditory sensations in patients with neurofibromatosis type 2 who lost their hearing due to a surgical removal of the tumor. ABI surgery, implant activation and follow-up sessions present unique challenges including the exact placement of the electrode pad in the lateral recess of the IVth ventricle, identification of electrodes that trigger non-auditory sensation and their deactivation which lowers the number of electrodes responsible for hearing, changes of T- and C-levels across follow-up sessions. We present a complete procedure using an example case starting from the surgical part with the detailed description of intraoperative eABR measurement as a guidance for pad placement to the ABI activation and first fitting sessions with auditory sensation assessment. Since the first ABI electrode pad position presented non-satisfactory intraoperative eABR results it was decided to move the pad slightly which resulted in better eABR (more electrodes with auditory responses). The discussed patient demonstrated great auditory and speech perception results after the first ABI fitting (which included three sessions over 2 consecutive days). Repositioning of the ABI electrode pad during the surgery was carried out taking into account the intraoperative eABR results and this led to an overall positive outcome for the patient. The placement of ABI electrode pad is crucial for later auditory results. This study provides detailed insight in this very specialized procedure that is not performed in every clinic and adds to the knowledge of intraoperative navigation using eABR measurements during ABI surgery.
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Right ventricular 2D speckle-tracking echocardiography in children with osteosarcoma under chemotherapy.
Cardiotoxicity from anthracyclin chemotherapy is a leading cause of death in patients with cancer. Therefore, left ventricular (LV) function is routinely assessed during protocol to detect cardiotoxicity; however, animal studies suggest that right ventricular (RV) function may be also impaired. So, our objective was to investigate the incidence of RV dysfunction in children with osteosarcoma receiving anthracyclines and to highlight the role of 2D STE in early detection of RV dysfunction.</AbstractText>RV function was affected by anthacyclines through direct cardiotoxic effect on RV myocardium without simultaneous derangement of LV function. Furthermore, there is a direct proportion between the incidence of RV dysfunction and the cumulative dose of anthracyclines. At the first echo follow-up at 10th week, 7 patients had impaired RV GLS in comparison to baseline study. At 20th week, the number of patients with impaired RV strain increased to 10. At 29th week, it reaches 12 patients. This effect was early detected by RV 2DSTE before adversely affecting TAPSE and FAC. The incidence of RV dysfunction from anthracyclines was around 12%, and the recovery rate was around 8% in 3&#xa0;months after completion of chemotherapy.</AbstractText>RV 2DSTE is the best modality to detect early affection of RV function in comparison with other modalities. RV function decreases early even before derangement of LV function. Accordingly, it should be assessed separately in all patients who received anthracyclines even without evident LV affection.</AbstractText>
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Linear vs volume measures of ventricle size: Relation to present and future gait and cognition.
To compare the clinical utility of volume-based ratios with the standard linear ratio of Evans index (EI) by examining their associations with gait, cognition, and other patient and imaging variables.</AbstractText>From MRI scans of 1,774 participants in the Mayo Clinic Study of Aging, we calculated 3 ventricle size measures: Evan index (frontal horn width divided by widest width of skull inner table), total ventricular volume, and frontal horn volume as ratios of total intracranial volume. Gait was measured by a timed 25-foot walk and cognition by a composite of psychometric tests. We also evaluated variables associated with the measures of ventricular size. Further, we evaluated gait and cognition associations with MRI of extraventricular findings seen in normal-pressure hydrocephalus: disproportionate enlargement of subarachnoid space (DESH) and focal sulcal dilations (FSD).</AbstractText>Ventricular volume measures had stronger association with gait and cognition measures than EI. In decreasing order of strength of association with ventricle size were DESH, FSD, white matter hyperintensity volume ratio, age, male sex, cortical thickness, and education. Modest evidence was observed that FSD was associated with future decline in gait and cognition.</AbstractText>Ventricular volume measures are clinically more useful than EI in indicating current and future gait and cognition. Multiple factors are associated with ventricle volume size, including FSD and DESH, suggesting that changes in CSF dynamics may go beyond simple ventriculomegaly.</AbstractText>&#xa9; 2019 American Academy of Neurology.</CopyrightInformation>
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The anatomy and metabolome of the lymphatic system in the brain in health and disease.
Recent studies have demonstrated that the brain is equipped with a lymphatic drainage system that is actively involved in parenchymal waste clearance, brain homeostasis and immune regulation. However, the exact anatomic drainage routes of brain lymph fluid (BLF) remain elusive, hampering the physiological study and clinical application of this system. In this study, we systematically dissected the anatomy of the BLF pathways in a rat model. Moreover, we developed a protocol to collect BLF from the afferent lymphatic vessels of deep cervical lymph nodes (dcLNs) and cerebrospinal fluid (CSF) from the fourth ventricle. Nuclear magnetic resonance spectroscopy showed that BLF contains more metabolites than CSF, suggesting that BLF might be a more sensitive indicator of brain dynamics under physiological and pathological conditions. Finally, we identified several metabolites as potential diagnostic biomarkers for glioma, Parkinson's disease and CNS infectious diseases. Together, these data may provide insight into the physiology of the lymphatic system in the brain and into the clinical diagnosis of CNS disorders.
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Simultaneous multislice imaging of the heart using multiband balanced SSFP with blipped-CAIPI.
In this work, we explore the use of multiband (MB) balanced steady-state free precession (bSSFP) with blipped-controlled aliasing in parallel imaging (CAIPI), which avoids the issues of altered frequency response associated with RF&#xa0;phase cycling, and show its application to accelerating cardiac cine imaging.</AbstractText>Blipped and RF-cycled CAIPI were implemented into a retrospective-gated segmented cine multiband bSSFP sequence. The 2 methods were compared at 3T using MB2 to demonstrate the effect on frequency response. Further data (4 subjects) were acquired at both 1.5T and 3T collecting 12-slice short axis stacks using blipped-CAIPI with MB acceleration factors of 1-4. The impact on SNR and contrast was evaluated along with g-factors at different accelerations.</AbstractText>Data acquired with blipped-CAIPI multiband bSSFP up to factor 4 yielded functional cine data with good SNR and contrast, while reliably keeping dark-band artefacts clear of the heart at 1.5T. SAR limits the maximum MB acceleration, particularly at 3T, where minimum TR increase is problematic and leakage artefacts are more prevalent. Mean g-factors across the heart were measured at 1.00, 1.06, and 1.12 for MB2-MB4, whereas blood-pool SNR measures (end-diastole) decreased by 11.8, 21.5, and 36.9%; ultimately LV-myocardium CNR remained sufficient at 1.5T with values ranging: 15.6, 13.4, 11.9, and 9.6 (MB1-MB4).</AbstractText>Blipped-CAIPI multiband bSSFP can be used in cardiovascular applications without affecting the frequency response because of controlled aliasing and can be readily incorporated into segmented cine acquisitions without adding any additional constraints because of phase cycling requirements. The method was used to collect full ventricular coverage within a single breath-hold.</AbstractText>&#xa9; 2019 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.</CopyrightInformation>
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Ventricular Distribution Pattern of the Novel Sympathetic Nerve PET Radiotracer <sup>18</sup>F-LMI1195 in Rabbit Hearts.
We aimed to determine a detailed regional ventricular distribution pattern of the novel cardiac nerve PET radiotracer <sup>18</sup>F-LMI1195 in healthy rabbits. Ex-vivo high resolution autoradiographic imaging was conducted to identify accurate ventricular distribution of <sup>18</sup>F-LMI1195. In healthy rabbits, <sup>18</sup>F-LMI1195 was administered followed by the reference perfusion marker <sup>201</sup>Tl for a dual-radiotracer analysis. After 20&#x2009;min of <sup>18</sup>F-LMI1195 distribution time, the rabbits were euthanized, the hearts were extracted, frozen, and cut into 20-&#x3bc;m short axis slices. Subsequently, the short axis sections were exposed to a phosphor imaging plate to determine <sup>18</sup>F-LMI1195 distribution (exposure for 3&#x2009;h). After complete <sup>18</sup>F decay, sections were re-exposed to determine <sup>201</sup>Tl distribution (exposure for 7 days). For quantitative analysis, segmental regions of Interest (ROIs) were divided into four left ventricular (LV) and a right ventricular (RV) segment on mid-ventricular short axis sections. Subendocardial, mid-portion, and subepicardial ROIs were placed on the LV lateral wall. <sup>18</sup>F-LMI1195 distribution was almost homogeneous throughout the LV wall without any significant differences in all four LV ROIs (anterior, posterior, septal and lateral wall, 99&#x2009;&#xb1;&#x2009;2, 94&#x2009;&#xb1;&#x2009;5, 94&#x2009;&#xb1;&#x2009;4 and 97&#x2009;&#xb1;&#x2009;3%LV, respectively, n.s.). Subepicardial <sup>201</sup>Tl uptake was significantly lower compared to the subendocardial portion (subendocardial, mid-portion, and subepicardial activity: 90&#x2009;&#xb1;&#x2009;3, 96&#x2009;&#xb1;&#x2009;2 and *80&#x2009;&#xb1;&#x2009;5%LV, respectively, *p&#x2009;&lt;&#x2009;0.01 vs. mid-portion). This was in contradistinction to the transmural wall profile of <sup>18</sup>F-LMI1195 (90&#x2009;&#xb1;&#x2009;4, 96&#x2009;&#xb1;&#x2009;5 and 84&#x2009;&#xb1;&#x2009;4%LV, n.s.). A slight but significant discrepant transmural radiotracer distribution pattern of <sup>201</sup>Tl in comparison to <sup>18</sup>F-LMI1195 may be a reflection of physiological sympathetic innervation and perfusion in rabbit hearts.
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Heartech: Another parachute looking for a landing zone in interventions for heart failure.
Maladaptive left ventricular remodeling after acute myocardial infarction is defined by increased left ventricular dimensions and is associated with poor clinical outcomes. Left ventricular partitioning devices mechanically reduce left ventricular dimensions and are postulated to improve symptomatic heart failure. In this first in human study, deployment of the Heartech LVPD was shown to be feasible without a prohibitive safety signal precluding future pivotal trials.
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Emerging clinical applications of strain imaging and three-dimensional echocardiography for the assessment of ventricular function in adult congenital heart disease.
Management of congenital heart disease (CHD) in adults (ACHD) remains an ongoing challenge due to the presence of residual hemodynamic lesions and development of ventricular dysfunction in a large number of patients. Echocardiographic imaging plays a central role in clinical decision-making and selection of patients who will benefit most from catheter interventions or cardiac surgery.. Recent advances in both strain imaging and three-dimensional (3D)-echocardiography have significantly contributed to a greater understanding of the complex pathophysiological mechanisms involved in CHD. The aim of this paper is to provide an overview of emerging clinical applications of speckle-tracking imaging and 3D-echocardiography in ACHD with focus on functional assessment, ventriculo-ventricular interdependency, mechanisms of electromechanical delay, and twist abnormalities in adults with tetralogy of Fallot (TOF), a systemic RV after atrial switch repair or in double discordance ventricles, and in those with a Fontan circulation.
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Meningeal Foam Cells and Ependymal Cells in Axolotl Spinal Cord Regeneration.
A previously unreported population of foam cells (foamy macrophages) accumulates in the invasive fibrotic meninges during gap regeneration of transected adult Axolotl spinal cord (salamander <i>Ambystoma mexicanum</i>) and may act beneficially. Multinucleated giant cells (MNGCs) also occurred in the fibrotic meninges. Actin-label localization and transmission electron microscopy showed characteristic foam cell and MNGC podosome and ruffled border-containing sealing ring structures involved in substratum attachment, with characteristic intermediate filament accumulations surrounding nuclei. These cells co-localized with regenerating cord ependymal cell (ependymoglial) outgrowth. Phase contrast-bright droplets labeled with Oil Red O, DiI, and DyRect polar lipid live cell label showed accumulated foamy macrophages to be heavily lipid-laden, while reactive ependymoglia contained smaller lipid droplets. Both cell types contained both neutral and polar lipids in lipid droplets. Foamy macrophages and ependymoglia expressed the lipid scavenger receptor CD36 (fatty acid translocase) and the co-transporter toll-like receptor-4 (TLR4). Competitive inhibitor treatment using the modified fatty acid Sulfo-N-succinimidyl Oleate verified the role of the lipid scavenger receptor CD36 in lipid uptake studies <i>in vitro</i>. Fluoromyelin staining showed both cell types took up myelin fragments <i>in situ</i> during the regeneration process. Foam cells took up DiI-Ox-LDL and DiI-myelin fragments <i>in vitro</i> while ependymoglia took up only DiI-myelin <i>in vitro</i>. Both cell types expressed the cysteine proteinase cathepsin K, with foam cells sequestering cathepsin K within the sealing ring adjacent to the culture substratum. The two cell types act as sinks for Ox-LDL and myelin fragments within the lesion site, with foamy macrophages showing more Ox-LDL uptake activity. Cathepsin K activity and cellular localization suggested that foamy macrophages digest ECM within reactive meninges, while ependymal cells act from within the spinal cord tissue during outgrowth into the lesion site, acting in complementary fashion. Small MNGCs also expressed lipid transporters and showed cathepsin K activity. Comparison of <sup>3</sup>H-glucosamine uptake in ependymal cells and foam cells showed that only ependymal cells produce glycosaminoglycan and proteoglycan-containing ECM, while the cathepsin studies showed both cell types remove ECM. Interaction of foam cells and ependymoglia <i>in vitro</i> supported the dispersion of ependymal outgrowth associated with tissue reconstruction in Axolotl spinal cord regeneration.
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A solitary fibrous tumor/hemangiopericytoma of the fourth ventricle: case report and literature review.
Solitary fibrous tumors/hemangiopericytomas (SFTs/HPCs) are rare in the central nervous system and intraventricular SFTs/HPCs are even rarer. We present a clinical case of SFT/HPC that was located in the fourth ventricle and performed a literature review of radiological findings of SFT/HPC. The patient was a 52-year-old man who presented to our hospital with dizziness and progressive weakness in his left extremities. Computed tomography and magnetic resonance imaging showed an irregular-shaped mass in the fourth ventricle. The upper anterior and lower posterior parts of the mass showed different densities and signal intensities, which formed a black and white sign. The upper anterior and lower posterior parts of the mass were enhanced to different degrees, and showed heterogeneous reversed enhancement. The patient underwent surgical resection and the mass was histologically confirmed to be an SFT/HPC. SFTs/HPCs of the fourth ventricle are rare, but show characteristic radiological presentations. In the present case, we observed a solid mass with flow voids, black and white sign, and heterogeneously reversed enhancement in the fourth ventricle. Collectively, these radiological features suggested the diagnosis of SFT/HPC.
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The Effective Contact Force to Minimize Edema Relative to Chronic Lesion Formation During Radiofrequency Ablation in Ventricular Wall.
Radiofrequency (RF) ablation results in creation of acute edema which can lead to temporary disruption of electrical propagation.The goal of this study was to find the effective contact force (CF) to minimize edema formation in comparison to the lesion size.Ventricular RF lesions (n = 49) were created by a CF-sensing catheter in a canine model (n = 10) with varying force for 30 seconds. Animals underwent T2-weighted (T2w) and late gadolinium enhancement MRI (LGE-MRI) immediately after ablation and at 12 weeks. Acute LGE lesion volume, acute edema, and chronic LGE lesion volume were measured. Acute edema/acute LGE lesion volume ratio was used to divide the lesions into two groups.Mean edema/lesion volume ratio was 5.0 &#xb1; 2.8. The lesions were divided into greater edema group (n = 8) and smaller edema group (n = 41) based on a cutoff edema/lesion volume ratio. When comparing the two groups, the CF and force time integral (FTI) were significantly lower in the greater edema group. There was no difference in catheter power setting, tip temperature change, impedance drop, and bipolar electrogram voltage change. Acute LGE volume and chronic lesion depth were significantly smaller in the greater edema group. Moreover, receiver-operator characteristic curve for the smaller edema lesion group showed that the most discriminant cutoff values for CF and FTI were 12.4 g and 584 gs, respectively.To minimize edema size while still forming permanent lesions, ablation should be performed with FTI &gt; 584 gs or CF &gt; 12.4 g.
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Neuroinflammation induced by lipopolysaccharide leads to memory impairment and alterations in hippocampal leptin signaling.
Peripheral inflammation promotes immune-to-brain communication, mediated by cytokines that affect brain activity. Lipopolysaccharide (LPS) has been widely used to mimic systemic inflammation, and the adipokine leptin, released in this condition, modulates hypothalamic leptin receptors (ObR), contributing to sickness behavior. In this study, we used the intracerebroventricular (ICV) route for LPS administration in an attempt to evaluate an acute and direct of this pathogen-associated molecular pattern on leptin-mediated signaling in the hippocampus, where ObR has been implicated in modulating cognitive response. We used bilateral ICV injection of LPS (25&#x202f;&#x3bc;g/ventricle) in 60-day-old male Wistar rats and the analysis were performed 48&#x202f;h after surgery. Neuroinflammation was characterized in the LPS group by an increase in concentration of IL-1&#x3b2;, COX-2 and TLR4 in the hippocampus as well as glial fibrillary acidic protein (GFAP), indicating an astrocyte commitment. Cognitive damage was observed in the animals of the LPS group by an inability to increase the recognition index during the object recognition test. We observed an increase in the concentration of leptin receptors in the hippocampus, which was unaccompanied by changes in the proteins involved in leptin intracellular signaling (p-STAT3 and SOCS3). Moreover, we found a decrease in leptin concentration in the serum of the animals in the LPS group accompanied by an increase in TNF-&#x3b1; levels. Our results showed that neuroinflammation, even in an acute state, can lead to cognitive impairment and may be associated with leptin signaling disturbances in the hippocampus.
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Interaction between ventricular expansion and structural changes in the corpus callosum and putamen in males with FMR1 normal and premutation alleles.
Ventricular enlargement (VE) is commonly observed in aging and fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. VE may generate a mechanical force causing structural deformation. In this longitudinal study, we examined the relationships between VE and structural changes in the corpus callosum (CC) and putamen. MRI scans (2-7/person over 0.2-7.5&#xa0;years) were acquired from 22 healthy controls, 26 unaffected premutation carriers (PFX-), and 39 carriers affected with FXTAS (PFX+). Compared with controls, PFX- demonstrated enlarged fourth ventricles, whereas PFX+ displayed enlargement in both third and fourth ventricles, CC thinning, putamen atrophy/deformation (thinning and increased distance), and accelerated expansions in lateral ventricles. Common for all groups, baseline VE predicted accelerated CC thinning and putamen atrophy/deformation and conversely, baseline CC and putamen atrophy/deformation and enlarged third and fourth ventricles predicted accelerated lateral ventricular expansion. The results suggest a progressive VE within the 4 ventricles as FXTAS develops and a deleterious cycle between VE and brain deformation that may commonly occur during aging and FXTAS progression but become accelerated in FXTAS.
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Subventricular zone volumetric and dosimetric changes during postoperative brain tumor irradiation and its impact on overall survival.
The aim of this retrospective study was to investigate the relationship between the dose to the subventricular zone (SVZ) and overall survival (OS) of 41 patients with glioblastoma multiforme (GBM), who were treated with an adaptive approach involving repeated topometric CT and replanning at two-thirds (40&#x202f;Gy) of their course of postoperative radiotherapy for planning of a 20&#x202f;Gy boost.</AbstractText>We examined changes in the ipsilateral lateral ventricle (LV) and SVZ (iLV and iSVZ), as well as in the contralateral LV and SVZ (cLV and cSVZ). We evaluated the volumetric changes on both planning CT scans (primary CT1 and secondary CT2). The survival of the GBM patients was analyzed using the Kaplan-Meier method; the multivariate Cox regression was also performed.</AbstractText>Median follow-up and OS were 34.5&#x202f;months and 17.6&#x202f;months, respectively. LV and SVZ structures exhibited significant volumetric changes on CT2, resulting in an increase of dose coverage. At a cut-off point of 58&#x202f;Gy, a significant correlation was detected between the iSVZ2 mean dose and OS (27.8 vs 15.6&#x202f;months, p&#x202f;=&#x202f;0.048). In a multivariate analysis, GBM patients with a shorter time to postoperative chemoradiotherapy (&lt;3.8&#x202f;weeks), with good performance status (&#x2265;70%) and higher mean dose (&#x2265;58&#x202f;Gy) to the iSVZ2 had significantly better OS.</AbstractText>Significant anatomical and dose distribution changes to the brain structures were observed, which have a relevant impact on the dose-effect relationship for GBM; therefore, involving the iSVZ in the target volume should be considered and adapted to the changes.</AbstractText>Copyright &#xa9; 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
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Physical exercise mitigates behavioral impairments in a rat model of sporadic Alzheimer's disease.
Physical exercise has proven to be beneficial to mitigate several deleterious effects associated with neurodegenerative diseases, including Alzheimer's Disease (AD). Here, we investigated the role of long-term exercise as a preventive and therapeutic tool against AD cognitive and behavioral impairments using a sporadic AD-like rat model, established through the administration of streptozotocin (STZ) inside both cerebral ventricles (icv). Six-weeks-old Wistar male rats (56) were divided into groups (either saline or STZ): sedentary (Sed), voluntary physical activity (VPA), VPA&#x202f;+&#x202f;endurance treadmill training (VPA&#x202f;+&#x202f;ET) and VPA&#x202f;+&#x202f;ET only after the injection (VPA&#x202f;+&#x202f;ET-post). Surgeries occurred at 16wks and the animals were sacrificed at 28 wks. VPA, VPA&#x202f;+&#x202f;ET, and VPA&#x202f;+&#x202f;ET-post had continuous access to the running wheels during the entire experimental protocol. VPA&#x202f;+&#x202f;ET (entire protocol) and VPA&#x202f;+&#x202f;ET-post (only after surgical procedure) ran 60&#x202f;min/d, 25&#x202f;m/min, 5d/wk in a treadmill. Both ET regimens led to significant improvements in the compromised spatial learning and long-term memory of STZ-infused animals that were not observed neither in the saline Sed nor in VPA STZ groups. General activity patterns and exploration habits were also ameliorated with chronic-exercise in STZ treated animals, while freezing patterns were decreased in these groups. these results were further. Positive alterations were seen in mitochondrial oxygen consumption endpoints (synaptosomal and non-synaptosomal brain mitochondria) that might underlie the neurobehavioral improvements observed. Data suggest that VPA alone was not able to counteract the AD-related deleterious consequences, although when accompanied by endurance training (either lifelong or later-life) may be able to prevent and reverse cognitive and phenotypic impairments associated with AD.
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Neonatal care bundles are associated with a reduction in the incidence of intraventricular haemorrhage in preterm infants: a multicentre cohort study.
To investigate the effect of a nursing intervention bundle, applied during the first 72&#x2009;hours of life, on the incidence of germinal matrix-intraventricular haemorrhage (GMH-IVH) in very preterm infants.</AbstractText>Multicentre cohort study.</AbstractText>Two Dutch tertiary neonatal intensive care units.</AbstractText>The intervention group consisted of 281 neonates, whereas 280 infants served as historical controls (gestational age for both groups &lt;30 weeks).</AbstractText>After a training period, the nursing intervention bundle was implemented and applied during the first 72&#x2009;hours after birth. The bundle consisted of maintaining the head in the midline, tilting the head of the incubator and avoidance of flushing/rapid withdrawal of blood and sudden elevation of the legs.</AbstractText>The incidence of GMH-IVH occurring and/or increasing after the first ultrasound (but within 72&#x2009;hours), cystic periventricular leukomalacia and/or in-hospital death was the primary composite outcome measure. Logistic regression analysis was used to explore differences between groups.</AbstractText>The nursing intervention bundle was associated with a lower risk of developing a GMH-IVH (any degree), cystic periventricular leukomalacia and/or mortality (adjusted OR 0.42, 95%&#x2009;CI 0.27 to 0.65). In the group receiving the bundle, also severe GMH-IVH, cystic periventricular leukomalacia and/or death were less often observed (adjusted OR 0.54, 95%&#x2009;CI 0.33 to 0.91).</AbstractText>The application of a bundle of nursing interventions is associated with reduced risk of developing a new/progressive (severe) GMH-IVH, cystic periventricular leukomalacia and/or mortality in very preterm infants when applied during the first 72&#x2009;hours postnatally.</AbstractText>&#xa9; Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation>
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Ligusticum chuanxiong exerts neuroprotection by promoting adult neurogenesis and inhibiting inflammation in the hippocampus of ME cerebral ischemia rats.
Cerebral ischemia, also known as stroke, can stimulate the proliferation and migration of endogenous neural stem cells (NSCS</sub>) in subventricular zone of the lateral ventricle and subgranularzone of the dentate gyrus in the adult hippocampus as a defense response to damage. However, the proliferation of endogenous NSCS</sub> is insufficient for central nervous system repair. Neurogenesis and anti-neuroinflammation are two important aspects for neuroprotection. Rhizome Ligusticum chuanxiong (LC), the dried rhizomes of Ligusticum striatum DC., has been widely used to treat stroke for over hundreds of years in Traditional Chinese Medicine.</AbstractText>of the study: Previous reports on pharmacological mechanism of LC mainly focus on the cerebral blood flow and thrombolysis. We aim to explore whether LC provides neuroprotective effect by increasing neurogenesis and inhibiting the IL-1&#x3b2;, TNF-&#x3b1; and expressions of glial fibrillary acidic protein.</AbstractText>LC extract was delivered to microsphere-embolized (ME) cerebral ischemia Wister rats to examine its neuroprotection. Body weight, neurological scores, hematoxylin-eosin staining (HE), TUNEL assay were conducted for neurological damage. Neurogenesis was evaluated by assessing the expression of Doublecortin (DCX) and neurogenic differentiation1 (NeuroD1) through immunofluorescence staining. Western blot performed to measure the protein levels of growth associated protein-43(GAP-43), glial fibrillary acidic protein (GFAP). IL-1&#x3b2; and TNF-&#x3b1; was detected by Elisa.</AbstractText>LC alleviated pathomorphological change and apoptosis of neurons in the hippocampus caused by ME surgery. Furthermore, LC significantly increased the DCX in the DG of adult rat hippocampus at 14 days after surgery. A significant upregulation of GAP-43 compared to the ME after LC was administered. Besides, LC decreased pro-inflammatory cytokine (IL-1&#x3b2;, TNF-&#x3b1;) and protein level of GFAP.</AbstractText>The finding suggested that LC had the ability to protect neurons by promoting the endogenous proliferation of neuroblast and production of neural differentiation factor in rats after ischemia injury. Meanwhile, LC can anti-neuroinflammation, which is important for the treatment of neuron injury. Accordingly, LC perhaps a promising medicine for neuron damage therapy after cerebral ischemia.</AbstractText>Copyright &#xa9; 2019 Elsevier B.V. All rights reserved.</CopyrightInformation>
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Variants in nuclear factor I genes influence growth and development.
The nuclear factor one (NFI) site-specific DNA-binding proteins represent a family of transcription factors that are important for the development of multiple organ systems, including the brain. During brain development in mice, the expression patterns of Nfia, Nfib, and Nfix overlap, and knockout mice for each of these exhibit overlapping brain defects, including megalencephaly, dysgenesis of the corpus callosum, and enlarged ventricles, which implies a common but not redundant function in brain development. In line with these models, human phenotypes caused by haploinsufficiency of NFIA, NFIB, and NFIX display significant overlap, sharing neurodevelopmental deficits, macrocephaly, brain anomalies, and variable somatic overgrowth. Other anomalies may be present depending on the NFI gene involved. The possibility of variants in NFI genes should therefore be considered in individuals with intellectual disability and brain overgrowth, with individual NFI-related conditions being differentiated from one another by additional signs and symptoms. The exception is provided by specific NFIX variants that act in a dominant negative manner, as these cause a recognizable entity with more severe cognitive impairment and marked bone dysplasia, Marshall-Smith syndrome. NFIX duplications are associated with a phenotype opposite to that of haploinsufficiency, characterized by short stature, small head circumference, and delayed bone age. The spectrum of NFI-related disorders will likely be further expanded, as larger cohorts are assessed.
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Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension.
This study investigated the impact of experimental pulmonary arterial hypertension (PAH) progression by evaluating morphometric and functional parameters, oxidative stress, autonomic nervous system (ANS) activation, and inflammation in the right (RV) and left (LV) ventricles. Male rats were first divided into two groups: monocrotaline (MCT) and control. The MCT group received a single MCT injection (60&#xa0;mg/kg, intraperitoneal), while control received saline. The MCT and control groups were further divided into four cohorts based on how long they were observed: 1, 2, 3, and 4&#xa0;weeks. Animals were submitted to echocardiographic and hemodynamic analysis. RV and LV were used for morphometric, biochemical, and histological measurements. Autonomic modulation was evaluated by cardiac spectral analysis, considering two components: low frequency (LF) and high frequency (HF). Lung and liver weight was used for morphometric analysis. MCT induced 100% mortality at 4&#xa0;weeks. In the RV, disease progression led to mild inflammation and enhanced reactive oxygen species (ROS) in week 1, followed by moderate inflammation, ROS production, and hypertrophy in week 2. By week 3, there was moderate inflammation, oxidative stress, and ANS imbalance, with development of right heart dysfunction. LV biochemical changes and inflammation were observed at week 3. The initial changes appeared to be related to inflammation and ROS, and the later ones to inflammation, oxidative stress, and ANS imbalance in MCT animals. This study reinforces the severity of the disease in the RV, the late effects in the LV, and the role of ANS imbalance in the development of heart dysfunction.
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Midline Craniotomy for Resection of Cavernous Malformation: 2-Dimensional Operative Video.
This patient presented with a cavernous malformation in the inferior posterior third ventricle extending into the aqueduct. The patient was positioned supine on the operating room table with the head rotated into the horizontal plane. The choroidal fissure is opened lateral to the choroid plexus. This technique allows for the choroid plexus to serve as protection against forniceal manipulation. Rigid retraction was applied to the cerebral falx and corpus callosum to permit aqueductal visualization. The lighted instruments are paramount for adequate visualization of the third ventricle and during dissection of the lesion. Intraoperative visualization and postoperative imaging confirm gross total resection of the lesion. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute.
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Anterior Interhemispheric Transcallosal Approach for Thalamic Cavernous Malformation: 2-Dimensional Operative Video.
This patient had a large left ventral thalamic cavernous malformation abutting the third ventricle with evidence of recent hemorrhage. The patient was placed supine with the head in the horizontal position with the dependent hemisphere down to permit use of the anterior interhemispheric transcallosal approach. The lateral ventricle is entered, and the septum pellucidum is opened to prevent it from obstructing the surgical field. The deep cavernous malformation is located with stereotactic neuronavigation and removed piecemeal with the aid of lighted suckers and bipolars. Surgical visualization and postoperative imaging demonstrate a complete resection of the lesion, and the patient remained neurologically stable postoperatively. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
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Biomechanical assessment of remote and postinfarction scar remodeling following myocardial infarction.
The importance of collagen remodeling following myocardial infarction (MI) is extensively investigated, but little is known on the biomechanical impact of fibrillar collagen on left ventricle post-MI. We aim to identify the significant effects of the biomechanics of types I, III, and V collagen on physio-pathological changes of murine hearts leading to heart failure. Immediately post-MI, heart reduces its function (EF&#x2009;=&#x2009;40.94&#x2009;&#xb1;&#x2009;2.12%) while sarcomeres' dimensions are unchanged. Strikingly, as determined by immunohistochemistry staining, type V collagen fraction significantly grows in remote and scar for sustaining de novo-types I and III collagen fibers' assembly while hindering their enzymatic degradation. Thereafter, the compensatory heart function (EF&#x2009;=&#x2009;63.04&#x2009;&#xb1;&#x2009;3.16%) associates with steady development of types I and III collagen in a stiff remote (12.79&#x2009;&#xb1;&#x2009;1.09&#x2009;MPa) and scar (22.40&#x2009;&#xb1;&#x2009;1.08&#x2009;MPa). In remote, the soft de novo-type III collagen uncoils preventing further expansion of elongated sarcomeres (2.7&#x2009;&#xb1;&#x2009;0.3&#x2009;mm). Once the compensatory mechanisms are surpassed, the increased turnover of stiff type I collagen (&gt;50%) lead to a pseudo-stable biomechanical regime of the heart (&#x2245;9&#x2009;MPa) with reduced EF (50.55&#x2009;&#xb1;&#x2009;3.25%). These end-characteristics represent the common scenario evidenced in patients suffering from heart failure after MI. Our pre-clinical data advances the understanding of the cause of heart failure induced in patients with extended MI.
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Correlation of lateral ventricular size and deep gray matter volume in MRI at term equivalent age with neurodevelopmental outcome at a corrected age of 24 months and with handedness in preterm infants.
The aim of this study was to correlate ventricular size and volumes of deep gray matter (DGM) in MRI at term equivalent age (TEA) with outcome at a corrected age of 24 months in preterm infants and with handedness. Seventy-three infants born before 32 weeks of gestation or with birth weight &lt; 1500 g &#xa0;were included in this retrospective analysis and measurement of lateral ventricles, and DGM was performed on MRI scans. The left lateral ventricle was significantly larger than the right lateral ventricle (p = 0.001). There was no correlation between volumes of the right and left ventricles and the DGM volume (p = 0.207 and p = 0.597, respectively), nor with the head circumference at TEA (p = 0.177 and p = 0.976, respectively). The total volume of both lateral ventricles did not correlate with Mental Develomental Index&#xa0;(MDI, p = 0.336) or Psychomotor Developmental Index&#xa0;(PDI, p = 0.650) score (Bayley Scales of Infant Development,&#xa0;BSID II). However, a correlation of total DGM volume with birth weight (p = 0.0001; r = 0.437), head circumference at TEA (p &lt; 0.0001; r = 0.640), MDI (p = 0.029; r = 0.310), and PDI (p = 0.002; r = 0.456) was observed. No significant difference between right- and left-handed infants was seen in relation to volumes of both lateral ventricles and of DGM.Conclusion: DGM volume at TEA was significantly associated with the&#xa0;outcome at a corrected age of&#xa0;24 months. Handedness did not correlate with DGM or lateral ventricle size.What is Known:&#x2022; White matter injury as well as altered development of deep gray matter is associated with neurodevelopmental disability in preterm infants.&#x2022; No study analyzed the association between deep gray matter volume or volumes of lateral ventricle and handedness in former preterm infants so far.What is New:&#x2022; Volume of deep gray matter, but not lateral ventricular size was significantly associated with outcome at a corrected age of 24 months in preterm infants.&#x2022; There was no correlation of handedness with volumes of lateral ventricular size or with deep gray matter volumes.
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Red cell transfusion practices after stage 1 palliation: a survey of practitioners from the Pediatric Cardiac Intensive Care Society.
Neonates may require increased red cell mass to optimise oxygen content after stage 1 palliation; however, data informing transfusion practices are limited. We hypothesise there is a patient-, provider-, and institution-based heterogeneity in red cell transfusion decision-making after stage 1 palliation.</AbstractText>We conducted an online survey of Pediatric Cardiac Intensive Care Society practitioners in 2016. Respondents answered scenario-based questions that defined transfusion indications and identified haematocrit transfusion thresholds. Respondents were divided into restrictive and liberal groups based on a haematocrit score. Fisher's exact test was used to determine the associations between transfusion likelihood and patient, provider, and institutional characteristics. Bonferroni correction was applied to adjust the p-value to 0.004 for multiple comparisons.</AbstractText>There was a 21% response rate (116 responses). Most were male (58.6%), attending physicians (85.3%) with &gt;5 year of intensive care experience (88.7%) and subspeciality training in critical care medicine (47.4%). The majority of institutions were academic (96.6%), with a separate cardiac ICU (86.2%), and performed &gt;10 stage 1 palliation cases annually (68.1%). After Bonferroni correction, there were no significant patient, respondent, or institutional differences between the restrictive and liberal groups. No respondent or institutional characteristics influenced transfusion decision-making after stage 1 palliation.</AbstractText>Decision-making around red cell transfusion after stage 1 palliation is heterogeneous. We found no clear relationships between patient, respondent, or institutional characteristics and transfusion decision-making among surveyed respondents. Given the lack of existing data informing red cell transfusion after stage 1 palliation, further studies are necessary to inform evidence-based guidelines.</AbstractText>
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Acute Effects of Hypoxic Gas Admixtures on Pulmonary Blood Flow and Regional Oxygenation in Children Awaiting Norwood Palliation.
Introduction Oxygen delivery in patients with functionally univentricular hearts awaiting Norwood palliation depends on a balance between systemic blood flow (Qs) and pulmonary blood flow (Qp). Modulations of pulmonary vascular resistance and systemic vascular resistance are utilized to maintain balanced Qp:Qs in a circulation prone to pulmonary overcirculation at the expense of systemic perfusion. This study aimed to characterize changes in Qp:Qs and regional (cerebral and renal) oxygen delivery in patients awaiting Norwood palliation receiving hypoxic gas admixture therapy. Methods Patients who received care prior to Norwood palliation were identified from 2014 to 2018. Of these patients, those with cerebral and renal near-infrared spectroscopy were identified (NIRS). Arterial oxygen saturation by pulse oximetry, renal NIRS, and cerebral NIRS prior to hypoxic gas admixture initiation were compared to values six hours, 12 hours, and 24 hours after initiation. Results A total of 28 patients were eligible for inclusion in the study. Arterial saturation by pulse oximetry was 91% prior to initiation and decreased to 86% 24 hours after initiation (p&lt;0.001). Cerebral NIRS were a mean of 60 prior to initiation compared to 58 at 24 hours (p=0.187). Renal NIRS were a mean of 60 prior to initiation compared to 57 at 24 hours (p=0.120). Calculated Qp:Qs was 9.6 at baseline compared to 2.5 at 24 hours (p=0.006). Arteriovenous difference and lactate did not significantly change with hypoxic gas admixture administration. Conclusion Administration of hypoxic gas admixture to patients with functionally univentricular hearts awaiting Norwood palliation decreases the ratio of Qp and Qs but does not improve regional oxygenation delivery.
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Trans-labyrinthine Infra-trigeminal Approach for Recurrent Pontomedullary Cavernoma: A Step-wise Technical Note.
Recurrent brainstem cavernoma is a challenging lesion due to the neurological risks associated with different surgical approaches. In this technical report, we present a 35-year-old female with a history of multiple brain cavernomas. She underwent&#xa0;midline suboccipital craniotomy and trans-fourth ventricle approach for resection of the brain stem cavernoma following two major bleeding episodes, one year prior to the presentation. Following the trans-labyrinthine infra-trigeminal approach, the patient recovered well&#xa0;postoperatively with a baseline neuro exam and was discharged to acute rehab on postoperative day 5 (POD5). The translabyrinthine approach is a safe and effective corridor for pontine or pontomedullary lesions in carefully selected patients. Appropriate selection of surgical approach (based on location), meticulous surgical technique, and intraoperative neuromonitoring help in maximizing surgical resection while minimizing neurological deficits.
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Optimal concentration of necrostatin-1 for protecting against hippocampal neuronal damage in mice with status epilepticus.
Hippocampal neurons undergo various forms of cell death after status epilepticus. Necrostatin-1 specifically inhibits necroptosis mediated by receptor interacting protein kinase 1 (RIP1) and RIP3 receptors. However, there are no reports of necroptosis in mouse models of status epilepticus. Therefore, in this study, we investigated the effects of necrostatin-1 on hippocampal neurons in mice with status epilepticus, and, furthermore, we tested different amounts of the compound to identify the optimal concentration for inhibiting necroptosis and apoptosis. A mouse model of status epilepticus was produced by intraperitoneal injection of kainic acid, 12 mg/kg. Different concentrations of necrostatin-1 (10, 20, 40, and 80 &#x3bc;M) were administered into the lateral ventricle 15 minutes before kainic acid injection. Hippocampal damage was assessed by hematoxylin-eosin staining 24 hours after the model was successfully produced. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, western blot assay and immunohistochemistry were used to evaluate the expression of apoptosis-related and necroptosis-related proteins. Necrostatin-1 alleviated damage to hippocampal tissue in the mouse model of epilepsy. The 40 &#x3bc;M concentration of necrostatin-1 significantly decreased the number of apoptotic cells in the hippocampal CA1 region. Furthermore, necrostatin-1 significantly downregulated necroptosis-related proteins (MLKL, RIP1, and RIP3) and apoptosis-related proteins (cleaved-Caspase-3, Bax), and it upregulated the expression of anti-apoptotic protein Bcl-2. Taken together, our findings show that necrostatin-1 effectively inhibits necroptosis and apoptosis in mice with status epilepticus, with the 40 &#x3bc;M concentration of the compound having an optimal effect. The experiments were approved by the Animal Ethics Committee of Fujian Medical University, China (approval No. 2016-032) on November 9, 2016.
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Intra-tracheal administration of a naked plasmid expressing stromal derived factor-1 improves lung structure in rodents with experimental bronchopulmonary dysplasia.
Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification and disordered angiogenesis. Stromal derived factor-1 (SDF-1) is a chemokine which modulates cell migration, proliferation, and angiogenesis. Here we tested the hypothesis that intra-tracheal (IT) administration of a naked plasmid DNA expressing SDF-1 would attenuate neonatal hyperoxia-induced lung injury in an experimental model of BPD, by promoting angiogenesis.</AbstractText><AbstractText Label="DESIGN/METHODS" NlmCategory="METHODS">Newborn Sprague-Dawley rat pups (n&#x2009;=&#x2009;18-20/group) exposed to room air (RA) or hyperoxia (85% O2) from postnatal day (P) 1 to 14 were randomly assigned to receive IT a naked plasmid expressing SDF-1, JVS-100 (Juventas Therapeutics, Cleveland, Ohio) or placebo (PL) on P3. Lung alveolarization, angiogenesis, inflammation, vascular remodeling and pulmonary hypertension (PH) were assessed on P14. PH was determined by measuring right ventricular systolic pressure (RVSP) and the weight ratio of the right to left ventricle + septum (RV/LV&#x2009;+&#x2009;S). Capillary tube formation in SDF-1 treated hyperoxia-exposed human pulmonary microvascular endothelial cells (HPMEC) was determined by matrigel assay. Data is expressed as mean&#x2009;&#xb1;&#x2009;SD and analyzed by two-way ANOVA.</AbstractText>Exposure of neonatal pups to 14&#x2009;days of hyperoxia decreased lung SDF-1 gene expression. Moreover, whilst hyperoxia exposure inhibited capillary tube formation in HPMEC, SDF-1 treatment increased tube length and branching in HPMEC. PL-treated hyperoxia-exposed pups had decreased alveolarization and lung vascular density. This was accompanied by an increase in RVSP, RV/LV&#x2009;+&#x2009;S, pulmonary vascular remodeling and inflammation. In contrast, IT JVS-100 improved lung structure, reduced inflammation, PH and vascular remodeling.</AbstractText>Intratracheal administration of a naked plasmid expressing SDF-1 improves alveolar and vascular structure in an experimental model of BPD. These findings suggest that therapies which modulate lung SDF-1 expression may have beneficial effects in preterm infants with BPD.</AbstractText>
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Cranial irradiation in juvenile mice leads to early and sustained defects in the stem and progenitor cell pools and late cognitive impairments.
Cranial irradiation is used in combination with other therapies as a treatment for brain tumours and is thought to contribute to long-term cognitive deficits. Several rodent models have demonstrated that these cognitive deficits may be correlated with damage to neural progenitor cells in the subventricular zone (SVZ) and dentate gyrus (DG), the two neurogenic niches of the brain. Studies in rodent models typically assess the proliferating progenitor population, but rarely investigate the effect of cranial irradiation on the neural stem cell pool. Further, few studies evaluate the effects in juveniles, an age when children typically receive this treatment. Herein, we examine the cellular and behavioural effects of juvenile cranial irradiation on stem and progenitor populations in the two neurogenic regions of the brain and assess cognitive outcomes. We found regionally distinct effects of cranial irradiation in the juvenile brain. In the SVZ, we observed a defect in the stem cell pool and a concomitant decrease in proliferating cells that were maintained for at least one week. In the DG, a similar defect in the stem cell pool and proliferating cells was observed and persisted in the stem cell population. Finally, we demonstrated that cranial irradiation resulted in late cognitive deficits. This study demonstrates that juvenile cranial irradiation leads to regionally distinct defects in the stem and progenitor populations, and late cognitive deficits, which may be important factors in determining therapeutic targets and timing of interventions following cranial irradiation.
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Effects of 6-mercaptopurine in pressure overload induced right heart failure.
Several antineoplastic drugs have been proposed as new compounds for pulmonary arterial hypertension treatment but many have cardiotoxic side effects. The chemotherapeutic agent 6-mercaptopurine may have an effect in treatment of pulmonary arterial hypertension but at the same time, its effects on the afterload adaption of the right ventricle is unpredictable due to interaction with multiple downstream signalling pathways in the cardiomyocytes. We investigated the direct cardiac effects of 6-mercaptopurine in rats with isolated right heart failure caused by pulmonary trunk banding (PTB).</AbstractText>Male Wistar rat weanlings (112&#xb1;2 g) were randomized to sham operation (sham, n = 10) or PTB. The PTB animals were randomized to placebo (PTB-control, n = 10) and 6-mercaptopurine (7.5 mg/kg/day) groups with treatment start before the PTB procedure (PTB-prevention, n = 10) or two weeks after (PTB-reversal, n = 10). Right ventricular effects were evaluated by echocardiography, cardiac MRI, invasive pressure-volume measurements, and histological and molecular analyses.</AbstractText>PTB increased right ventricular afterload and caused right ventricular hypertrophy and failure. 6-mercaptopurine did not improve right ventricular function nor reduce right ventricular remodelling in both prevention and reversal studies compared with placebo-treated rats.</AbstractText>Treatment with 6-mercaptopurine did not have any beneficial or detrimental effects on right ventricular function or remodelling. Our data suggest that treatment of pulmonary arterial hypertension with 6-mercaptopurine is not harmful to the failing right ventricle.</AbstractText>
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[Clinical features and efficacy of microsurgery for treatment of cerebral cysticercosis of the fourth ventricle: a report of 24 patients].
<b>&#xff3b;&#x6458;&#x8981;&#xff3d;</b> <b>&#x76ee;&#x7684;</b> &#x5206;&#x6790;24&#x4f8b;&#x7b2c;&#x56db;&#x8111;&#x5ba4;&#x56ca;&#x5c3e;&#x86b4;&#x75c5;&#x60a3;&#x8005;&#x4e34;&#x5e8a;&#x7279;&#x5f81;, &#x8bc4;&#x4f30;&#x663e;&#x5fae;&#x624b;&#x672f;&#x6cbb;&#x7597;&#x6548;&#x679c;&#x3002;<b>&#x65b9;&#x6cd5;</b> &#x6536;&#x96c6; 2000 &#x5e74;1&#x6708;&#x81f3;2018&#x5e74; 12&#x6708;&#x9752;&#x6d77;&#x5927;&#x5b66;&#x9644;&#x5c5e;&#x533b;&#x9662;&#x795e;&#x7ecf;&#x5916;&#x79d1;&#x6536;&#x6cbb;&#x7684;24&#x4f8b;&#x7b2c;&#x56db;&#x8111;&#x5ba4;&#x56ca;&#x5c3e;&#x86b4;&#x75c5;&#x60a3;&#x8005;&#x4e34;&#x5e8a;&#x8d44;&#x6599;, &#x5bf9;&#x5176;&#x4e34;&#x5e8a;&#x7279;&#x5f81;&#x3001;&#x5f71;&#x50cf;&#x5b66;&#x8868;&#x73b0;&#x3001;&#x624b;&#x672f;&#x5165;&#x8def;&#x65b9; &#x5f0f;&#x53ca;&#x6548;&#x679c;&#x3001;&#x672f;&#x540e;&#x5e76;&#x53d1;&#x75c7;&#x7b49;&#x8fdb;&#x884c;&#x5206;&#x6790;&#x3002;<b>&#x7ed3;&#x679c;</b> 24 &#x4f8b;&#x7b2c;&#x56db;&#x8111;&#x5ba4;&#x56ca;&#x5c3e;&#x86b4;&#x75c5;&#x60a3;&#x8005;&#x4e2d;, &#x7537;&#x6027;15&#x4f8b;, &#x5973;&#x6027;9&#x4f8b;; &#x5e74;&#x9f84;16&#xff5e;68&#x5c81;, &#x5e73;&#x5747; 43.5&#x5c81;&#x3002;&#x672f;&#x524d;CT&#x53ca;MRI&#x68c0;&#x67e5;&#x793a;&#x60a3;&#x8005;&#x53cc;&#x4fa7;&#x4fa7;&#x8111;&#x5ba4;&#x3001;&#x4e09;&#x8111;&#x5ba4;&#x3001;&#x4e2d;&#x8111;&#x5bfc;&#x6c34;&#x7ba1;&#x660e;&#x663e;&#x6269;&#x5f20;, &#x7b2c;&#x56db;&#x8111;&#x5ba4;&#x7403;&#x5f62;&#x6216;&#x56ca;&#x5f62;&#x6269;&#x5f20;&#x3002;18&#x4f8b;&#x60a3;&#x8005;&#x6297; &#x56ca;&#x5c3e;&#x86b4;&#x6297;&#x4f53;&#x9633;&#x6027;; 21&#x4f8b;&#x884c;&#x7caa;&#x4fbf;&#x68c0;&#x67e5;, &#x5176;&#x4e2d;3&#x4f8b;&#x68c0;&#x51fa;&#x866b;&#x5375;&#x3002;24&#x4f8b;&#x75c5;&#x4f8b;&#x5747;&#x884c;&#x663e;&#x5fae;&#x624b;&#x672f;&#x6cbb;&#x7597;, &#x5176;&#x4e2d;8&#x4f8b;&#x91c7;&#x7528;&#x6b63;&#x4e2d;&#x5b54;&#x5165;&#x8def;&#x3001;7&#x4f8b;&#x91c7; &#x7528;&#x6b63;&#x4e2d;&#x5b54;-&#x5c0f;&#x8111;&#x8693;&#x90e8;&#x5165;&#x8def;&#x3001;9&#x4f8b;&#x7ecf;&#x5c0f;&#x8111;&#x5ef6;&#x9ad3;&#x88c2;&#x5165;&#x8def;; &#x56ca;&#x6ce1;&#x5b8c;&#x6574;&#x5a29;&#x51fa;17&#x4f8b;, &#x7834;&#x88c2;5&#x4f8b;, &#x7a7f;&#x523a;&#x62bd;&#x53d6;&#x56ca;&#x6db2;&#x540e;&#x518d;&#x5206;&#x79bb;&#x5207;&#x9664;&#x56ca;&#x58c1;2&#x4f8b;&#x3002; &#x672f;&#x540e;&#x60a3;&#x8005;&#x8111;&#x5ba4;&#x7cfb;&#x7edf;&#x5747;&#x660e;&#x663e;&#x56de;&#x7f29;&#x3001;&#x9885;&#x5185;&#x9ad8;&#x538b;&#x75c7;&#x72b6;&#x6d88;&#x5931;; 19 &#x4f8b; (79.17%) &#x6062;&#x590d;&#x826f;&#x597d;, &#x5c0f;&#x8111;&#x51fa;&#x73b0;&#x5171;&#x6d4e;&#x5931;&#x8c03;&#x6216;&#x75c7;&#x72b6;&#x52a0;&#x91cd;5 &#x4f8b; (20.83%), &#x524d;&#x8005;&#x7ecf;&#x6cbb;&#x7597;1&#xff5e;2&#x5468;&#x6062;&#x590d;&#x3002;<b>&#x7ed3;&#x8bba;</b> &#x7ecf;&#x5c0f;&#x8111;&#x5ef6;&#x9ad3;&#x88c2;&#x5165;&#x8def;&#x5b89;&#x5168;&#x3001;&#x635f;&#x4f24;&#x5c0f;, &#x662f;&#x76ee;&#x524d;&#x6cbb;&#x7597;&#x7b2c;&#x56db;&#x8111;&#x5ba4;&#x56ca;&#x5c3e;&#x86b4;&#x75c5;&#x8f83;&#x597d;&#x7684;&#x624b;&#x672f; &#x5165;&#x8def;&#x3002;.
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Fusion of 3D real-time echocardiography and cine MRI using a saliency analysis.
This paper presents a novel 3D multimodal registration strategy to fuse 3D real-time echocardiography images with cardiac cine MRI images. This alignment is performed in a saliency space, which is designed to maximize similarity between the two imaging modalities. This fusion improves the quality of the available information.</AbstractText>The method performs in two steps: temporal and spatial registrations. A temporal alignment is firstly achieved by nonlinearly matching pairs of correspondences between the two modalities using a dynamic time warping. A temporal registration is then carried out by applying nonrigid transformations in a common saliency space where normalized cross correlation between temporal pairs of salient volumes is maximized.</AbstractText>The alignment performance was evaluated with a set of 18 subjects, 3 with cardiomyopathies and 15 healthy, by computing the Dice score and Hausdorff distance with respect to manual delineations of the left ventricle cavity in both modalities. A Dice score and Hausdorff distance of [Formula: see text] and [Formula: see text], respectively, were obtained. In addition, the deformation field was estimated by quantifying its foldings, obtaining a 98% of regularity in the deformation field.</AbstractText>The 3D multimodal registration strategy presented is performed in a saliency space. Unlike state-of-the-art methods, the presented one takes advantage of the temporal information of the heart to construct this common space, ending up with two well-aligned modalities and regular deformation fields. This preliminary study was evaluated on heterogeneous data composed of two different datasets, healthy and pathological cases, showing similar performances in both cases. Future work will focus on testing the presented strategy in a larger dataset with a balanced number of classes.</AbstractText>
2,328,375
Adamts18 deficiency in zebrafish embryo causes defective trunk angiogenesis and caudal vein plexus formation.
ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin type I motifs) enzymes play an important role in various morphogenesis processes. To determine the functions of Adamts18 in the early stages of organogenesis, we created Adamts18 deficient zebrafish using morpholino antisense oligonucleotides (MO) to generate exon 3 skipped adamts18 mRNA transcripts. Results showed that Adamts18 deficiency in zebrafish embryos caused developmental defects, including expanded brain ventricle and hindbrain edema, eye defects, and accumulation of blood in the caudal vein. Adamts18 deficiency also led to impaired trunk angiogenesis and formation of the caudal vein plexus (CVP). Consequently, Adamts18 deficient zebrafish embryos exhibited incomplete formation of intersegment vessels (ISVs), disruption of the honeycomb structure of CVP, and reduced CVP area and loop number. Furthermore, Adamts18 deficiency resulted in impaired blood circulation in major trunk, caudal vein (CV), and common cardinal vein (CCV). These aberrant vascular phenotypes in mutant zebrafish embryos were shown to be associated with a decreased expression of multiple angiogenesis-related signaling genes, including slit/robo, dll4/Notch, cox2, and fgfr. These findings indicate the critical role of Adamts18 in the early stages of vascular network development.
2,328,376
Genome-wide association study identifies <i>SIAH3</i> locus influencing the rate of ventricular enlargement in non-demented elders.
Ventricular enlargement occurs in several neurodegenerative and psychiatric diseases. A large genome-wide association study (GWAS) has identified seven loci associated with ventricular volume. The rate of ventricular enlargement increased in the progression of disease from normal cognition to dementia. Here, we aimed to use the rate of ventricular enlargement as an endophenotype for the development and progression of neurodegenerative diseases to discover more common genetic variants. We performed a GWAS of the rate of ventricular enlargement using 507 nondemented non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Linear regression model was used to identify the association of the rate of ventricular enlargement with single nucleotide polymorphisms (SNPs) in PLINK software. The associations of genome-wide significant SNPs with other four phenotypes were further discussed. Two SNPs (rs11620312, P = 4.04&#xd7;10<sup>-8</sup>; rs79174114, P = 4.28&#xd7;10<sup>-8</sup>) within <i>SIAH3</i> gene in linkage disequilibrium (LD) reached genome-wide significance for association with increased rate of ventricular enlargement. Some intergenic SNPs and SNPs within <i>NKAIN2, TBC1D2, GALNT18, ABCC1</i> and <i>SRCIN1</i> genes were identified as potential candidates. <i>SIAH3</i> rs11620312-C carriers were associated with poor cognition and brain hypometabolism longitudinally. Our findings indicated that <i>SIAH3</i> gene may have potential influence on the pathogenesis of neurodegenerative diseases.
2,328,377
EML1-associated brain overgrowth syndrome with ribbon-like heterotopia.
EML1 encodes the protein Echinoderm microtubule-associated protein-like 1 or EMAP-1 that binds to the microtubule complex. Mutations in this gene resulting in complex brain malformations have only recently been published with limited clinical descriptions. We provide further clinical and imaging details on three previously published families, and describe two novel unrelated individuals with a homozygous partial EML1 deletion and a homozygous missense variant c.760G&gt;A, p.(Val254Met), respectively. From review of the clinical and imaging data of eight individuals from five families with biallelic EML1 variants, a very consistent imaging phenotype emerges. The clinical syndrome is characterized by mainly neurological features including severe developmental delay, drug-resistant seizures and visual impairment. On brain imaging there is megalencephaly with a characteristic ribbon-like subcortical heterotopia combined with partial or complete callosal agenesis and an overlying polymicrogyria-like cortical malformation. Several of its features can be recognized on prenatal imaging especially the abnormaly formed lateral ventricles, hydrocephalus (in half of the cases) and suspicion of a neuronal migration disorder. In conclusion, biallelic EML1 disease-causing variants cause a highly specific pattern of congenital brain malformations, severe developmental delay, seizures and visual impairment.
2,328,378
Deep-Learning-Based Preprocessing for Quantitative Myocardial Perfusion MRI.
Quantitative myocardial perfusion cardiac MRI can provide a fast and robust assessment of myocardial perfusion status for the noninvasive diagnosis of myocardial ischemia while being more objective than visual assessment. However, it currently has limited use in clinical practice due to the challenging postprocessing required, particularly the segmentation.</AbstractText>To evaluate the efficacy of an automated deep learning (DL) pipeline for image processing prior to quantitative analysis.</AbstractText>Retrospective.</AbstractText>In all, 175 (350 MRI scans; 1050 image series) clinical patients under both rest and stress conditions (135/10/30 training/validation/test).</AbstractText><AbstractText Label="FIELD STRENGTH/SEQUENCE">3.0T/2D multislice saturation recovery T1</sub> -weighted gradient echo sequence.</AbstractText>Accuracy was assessed, as compared to the manual operator, through the mean square error of the distance between landmarks and the Dice similarity coefficient of the segmentation and bounding box detection. Quantitative perfusion maps obtained using the automated DL-based processing were compared to the results obtained with the manually processed images.</AbstractText>Bland-Altman plots and intraclass correlation coefficient (ICC) were used to assess the myocardial blood flow (MBF) obtained using the automated DL pipeline, as compared to values obtained by a manual operator.</AbstractText>The mean (SD) error in the detection of the time of peak signal enhancement in the left ventricle was 1.49 (1.4) timeframes. The mean (SD) Dice similarity coefficients for the bounding box and myocardial segmentation were 0.93 (0.03) and 0.80 (0.06), respectively. The mean (SD) error in the RV insertion point was 2.8 (1.8) mm. The Bland-Altman plots showed a bias of 2.6% of the mean MBF between the automated and manually processed MBF values on a per-myocardial segment basis. The ICC was 0.89, 95% confidence interval = [0.87, 0.90].</AbstractText>We showed high accuracy, compared to manual processing, for the DL-based processing of myocardial perfusion data leading to quantitative values that are similar to those achieved with manual processing.</AbstractText>3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1689-1696.</AbstractText>&#xa9; 2019 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.</CopyrightInformation>
2,328,379
Analysis of 270 fetuses with non-visualization of cavum septi pellucidi and vergae on in-utero magnetic resonance imaging.
To analyze a large retrospective cohort of fetuses in which the cavum septi pellucidi and vergae (CSPV) was not present or was not in its expected position on in-utero magnetic resonance imaging (iuMRI), in order to describe the possible causes of that finding and provide a diagnostic approach to assess such cases in clinical practice using iuMRI.</AbstractText>This was a retrospective study of fetuses that underwent iuMRI at a single institution, over an 18-year period (2000-2017 inclusive), in which the CSPV was not visualized or was abnormal. All iuMRI studies were reviewed and classified as CSPV being not present, disrupted (visualization of remnants of an otherwise normally placed CSPV) or malpositioned (CSPV was present, but not in its expected position). We describe the neuropathology present in each of the groups.</AbstractText>Of the 270 fetuses that met the inclusion criteria, the CSPV was described as malpositioned in 150 (56%), disrupted in 71 (26%) and not present in 49 (18%). Malpositioned CSPV was present only in cases with agenesis of the corpus callosum and three specific patterns of malpositioning are described, depending on the location of the leaflets of the CSPV and fornix. Disrupted CSPV was present in fetuses with hydrocephalus or pathologies causing extensive brain parenchymal injury. Not present CSPV was found in cases with holoprosencephaly or when absence of the CSPV appeared to be an isolated finding.</AbstractText>We have described a large cohort of fetuses with non-visualization of a normal CSPV on iuMRI and present a categorical classification system based on the CSPV being not present, disrupted or malpositioned. This approach should help in the diagnosis of the underlying cause of a CSPV abnormality. &#xa9; 2019 The Authors. Ultrasound in Obstetrics &amp; Gynecology published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.</AbstractText>&#xa9; 2019 The Authors. Ultrasound in Obstetrics &amp; Gynecology published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.</CopyrightInformation>
2,328,380
Microglial Morphometric Parameters Correlate With the Expression Level of IL-1&#x3b2;, and Allow Identifying Different Activated Morphotypes.
Microglia are the resident macrophages in the brain. Traditionally, two forms of microglia have been described: one considered as a resting/surveillant state in which cells have a highly branched morphology, and another considered as an activated state in which they acquire a de-ramified or amoeboid form. However, many studies describe intermediate microglial morphologies which emerge during pathological processes. Since microglial form and function are closely related, it is of interest to correlate microglial morphology with the extent of its activation. To address this issue, we used a rat model of neuroinflammation consisting in a single injection of the enzyme neuraminidase (NA) within the lateral ventricle. Sections from NA-injected animals were co-immunolabeled with the microglial marker IBA1 and the cytokine IL-1&#x3b2;, which highlight features of the cell's shape and inflammatory activation, respectively. Activated (IL-1&#x3b2; positive) microglial cells were sampled from the dorsal hypothalamus nearby the third ventricle. Images of single microglial cells were processed in two different ways to obtain (1) an accurate measure of the level of expression of IL-1&#x3b2; (indicating the degree of activation), and (2) a set of 15 morphological parameters to quantitatively and objectively describe the cell's shape. A simple regression analysis revealed a dependence of most of the morphometric parameters on IL-1&#x3b2; expression, demonstrating that the morphology of microglial cells changes progressively with the degree of activation. Moreover, a hierarchical cluster analysis pointed out four different morphotypes of activated microglia, which are characterized not only by morphological parameters values, but also by specific IL-1&#x3b2; expression levels. Thus, these results demonstrate in an objective manner that the activation of microglial cells is a gradual process, and correlates with their morphological change. Even so, it is still possible to categorize activated cells according to their morphometric parameters, each category presenting a different activation degree. The physiological relevance of those activated morphotypes is an issue worth to be assessed in the future.
2,328,381
Pharmacokinetics and distribution of 2-hydroxypropyl-&#x3b2;-cyclodextrin following a single intrathecal dose to cats.
2-Hydroxypropyl-&#x3b2;-cyclodextrin (HP-&#x3b2;-CD) is an experimental therapy for Niemann-Pick disease type C (NPC) that reduced neuronal cholesterol and ganglioside storage, reduced Purkinje cell death, and increased lifespan in npc1-/- mice and NPC1 cats. In this study, tissue distribution was investigated in normal cats that received a single 120-mg dose of [<sup>14</sup> C]-HP-&#x3b2;-CD (approximately 200&#x2009;&#x3bc;Ci/cat) via the cerebellomedullary cistern (CBMC) and lumbar cistern. One cat was euthanized at each of various time points up to 24&#x2009;hours postdose for subsequent processing and quantitative whole-body autoradiographic analysis. HP-&#x3b2;-CD-derived radioactivity absorbed from the CBMC was widely distributed to cat tissues; most tissues were observed to have reached their highest concentration at 1&#x2009;hour postdose. HP-&#x3b2;-CD-derived radioactivity penetrated into the deeper parts of the central nervous system with the highest concentration at 4 hours (403&#x2009;&#x3bc;g&#x2009;Eq/g or 0.28&#x2009;mM) and remained high (49.7 &#x3bc;g&#x2009;Eq/g or 0.03&#x2009;mM) at 24&#x2009;hours. The relatively long half-life (11-30&#x2009;hours) in cerebral ventricles and the subarachnoid space surrounding the brain and spinal cord might contribute to the efficacy of HP-&#x3b2;-CD in NPC1 cats. Other tissues with high concentrations of radioactivity were nasal turbinates, pituitary gland, and urinary bladder, while relatively low concentrations were observed in blood and bile.
2,328,382
Hemodynamic effects of support modes of LVADs on the aortic valve.<Pagination><StartPage>2657</StartPage><EndPage>2671</EndPage><MedlinePgn>2657-2671</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s11517-019-02058-y</ELocationID><Abstract><AbstractText>As the alternative treatment for heart failure, left ventricular assist devices (LVADs) have been widely applied to clinical practice. However, the effects of the support modes of LVADs on the biomechanical states of the aortic valve are still poorly understood. Hence, the present study investigates such effects and proposes a novel fluid-structure interaction (FSI) approach that combines the lattice Boltzmann method (LBM) and finite element (FE) method. Two support modes of LVADs, namely constant speed mode and constant flow mode, which have been widely applied to clinical practice, are also designed. Results demonstrate that the support modes of LVADs could significantly affect the biomechanical states of the aortic valve and the blood flow pattern of the ascending aorta. Compared with those in the constant flow mode, the leaflets in the constant speed mode could achieve better dynamic performance and lower stress during the systolic phase. The max radial displacement of the leaflets in the constant speed mode is at 8 mm, whereas that in the constant flow mode is at 0.8 mm. Furthermore, the outflow of LVADs directly impacts the aortic surfaces of the leaflets during the diastolic phase by increasing the level of wall shear stress of the leaflets. The leaflets in the constant speed mode receive less impact than those in the constant flow mode. The condition with such minimal impact is conducive to maintaining the normal structure of leaflets and benefits the reduction of the risk of valvular diseases. In sum, the support modes of LVADs exert a crucial effect on the biomechanical environment of the aortic valve. The constant speed mode is better than the constant flow mode in terms of providing a good hemodynamic environment for the aortic valve.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Bin</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0002-5297-9199</Identifier><AffiliationInfo><Affiliation>School of Life Science and BioEngineering, Beijing University of Technology, Beijing, 100124, People's Republic of China. tiancaigao7@163.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Qi</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>School of Life Science and BioEngineering, Beijing University of Technology, Beijing, 100124, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Yu</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>School of Life Science and BioEngineering, Beijing University of Technology, Beijing, 100124, People's Republic of China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>11602007</GrantID><Agency>Young Scientists Fund</Agency><Country/></Grant><Grant><GrantID>11572014</GrantID><Agency>Major Research Plan</Agency><Country/></Grant><Grant><GrantID>11832003</GrantID><Agency>Key Programme</Agency><Country/></Grant><Grant><GrantID>2016YFC0103201</GrantID><Agency>Key Technologies Research and Development Program</Agency><Country/></Grant><Grant><GrantID>2017YFC0111104</GrantID><Agency>Key Technologies Research and Development Program</Agency><Country/></Grant><Grant><GrantID>015000514118002</GrantID><Agency>New Talent</Agency><Country/></Grant><Grant><GrantID>61931013</GrantID><Agency>National Natural Science Foundation of China</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>11</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Med Biol Eng Comput</MedlineTA><NlmUniqueID>7704869</NlmUniqueID><ISSNLinking>0140-0118</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001011" MajorTopicYN="N">Aorta</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001021" MajorTopicYN="N">Aortic Valve</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006333" MajorTopicYN="N">Heart Failure</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006349" MajorTopicYN="N">Heart Valve Diseases</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006353" MajorTopicYN="N">Heart-Assist Devices</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006439" MajorTopicYN="N">Hemodynamics</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008955" MajorTopicYN="N">Models, Cardiovascular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011673" MajorTopicYN="N">Pulsatile Flow</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012756" MajorTopicYN="N">Sheep</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Aortic valve</Keyword><Keyword MajorTopicYN="N">Fluid-structure interaction</Keyword><Keyword MajorTopicYN="N">LVAD</Keyword><Keyword MajorTopicYN="N">Lattice Boltzmann method</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>4</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>11</Month><Day>2</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>5</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31707689</ArticleId><ArticleId IdType="doi">10.1007/s11517-019-02058-y</ArticleId><ArticleId IdType="pii">10.1007/s11517-019-02058-y</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31707601</PMID><DateRevised><Year>2019</Year><Month>11</Month><Day>26</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1556-2891</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Nov</Month><Day>09</Day></PubDate></JournalIssue><Title>Forensic science, medicine, and pathology</Title><ISOAbbreviation>Forensic Sci Med Pathol</ISOAbbreviation></Journal>Sudden death in a case of recurrent Takotsubo syndrome.
As the alternative treatment for heart failure, left ventricular assist devices (LVADs) have been widely applied to clinical practice. However, the effects of the support modes of LVADs on the biomechanical states of the aortic valve are still poorly understood. Hence, the present study investigates such effects and proposes a novel fluid-structure interaction (FSI) approach that combines the lattice Boltzmann method (LBM) and finite element (FE) method. Two support modes of LVADs, namely constant speed mode and constant flow mode, which have been widely applied to clinical practice, are also designed. Results demonstrate that the support modes of LVADs could significantly affect the biomechanical states of the aortic valve and the blood flow pattern of the ascending aorta. Compared with those in the constant flow mode, the leaflets in the constant speed mode could achieve better dynamic performance and lower stress during the systolic phase. The max radial displacement of the leaflets in the constant speed mode is at 8 mm, whereas that in the constant flow mode is at 0.8 mm. Furthermore, the outflow of LVADs directly impacts the aortic surfaces of the leaflets during the diastolic phase by increasing the level of wall shear stress of the leaflets. The leaflets in the constant speed mode receive less impact than those in the constant flow mode. The condition with such minimal impact is conducive to maintaining the normal structure of leaflets and benefits the reduction of the risk of valvular diseases. In sum, the support modes of LVADs exert a crucial effect on the biomechanical environment of the aortic valve. The constant speed mode is better than the constant flow mode in terms of providing a good hemodynamic environment for the aortic valve.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Bin</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0002-5297-9199</Identifier><AffiliationInfo><Affiliation>School of Life Science and BioEngineering, Beijing University of Technology, Beijing, 100124, People's Republic of China. tiancaigao7@163.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Qi</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>School of Life Science and BioEngineering, Beijing University of Technology, Beijing, 100124, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Yu</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>School of Life Science and BioEngineering, Beijing University of Technology, Beijing, 100124, People's Republic of China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>11602007</GrantID><Agency>Young Scientists Fund</Agency><Country/></Grant><Grant><GrantID>11572014</GrantID><Agency>Major Research Plan</Agency><Country/></Grant><Grant><GrantID>11832003</GrantID><Agency>Key Programme</Agency><Country/></Grant><Grant><GrantID>2016YFC0103201</GrantID><Agency>Key Technologies Research and Development Program</Agency><Country/></Grant><Grant><GrantID>2017YFC0111104</GrantID><Agency>Key Technologies Research and Development Program</Agency><Country/></Grant><Grant><GrantID>015000514118002</GrantID><Agency>New Talent</Agency><Country/></Grant><Grant><GrantID>61931013</GrantID><Agency>National Natural Science Foundation of China</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>11</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Med Biol Eng Comput</MedlineTA><NlmUniqueID>7704869</NlmUniqueID><ISSNLinking>0140-0118</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001011" MajorTopicYN="N">Aorta</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001021" MajorTopicYN="N">Aortic Valve</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006333" MajorTopicYN="N">Heart Failure</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006349" MajorTopicYN="N">Heart Valve Diseases</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006353" MajorTopicYN="N">Heart-Assist Devices</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006439" MajorTopicYN="N">Hemodynamics</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008955" MajorTopicYN="N">Models, Cardiovascular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011673" MajorTopicYN="N">Pulsatile Flow</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012756" MajorTopicYN="N">Sheep</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Aortic valve</Keyword><Keyword MajorTopicYN="N">Fluid-structure interaction</Keyword><Keyword MajorTopicYN="N">LVAD</Keyword><Keyword MajorTopicYN="N">Lattice Boltzmann method</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>4</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>11</Month><Day>2</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>5</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31707689</ArticleId><ArticleId IdType="doi">10.1007/s11517-019-02058-y</ArticleId><ArticleId IdType="pii">10.1007/s11517-019-02058-y</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31707601</PMID><DateRevised><Year>2019</Year><Month>11</Month><Day>26</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1556-2891</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Nov</Month><Day>09</Day></PubDate></JournalIssue><Title>Forensic science, medicine, and pathology</Title><ISOAbbreviation>Forensic Sci Med Pathol</ISOAbbreviation></Journal><ArticleTitle>Sudden death in a case of recurrent Takotsubo syndrome.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1007/s12024-019-00163-w</ELocationID><Abstract>Herein we report an unusual case of sudden death occurring in a 65 year old woman during a minor oral surgery. The subject, who had a medically treated anxiety, had a history of two reversible left ventricle dysfunction episodes consistent with recurrent Takotsubo Syndrome that had occurred seven and six years before, respectively. She also suffered from moderate, well treated post-menopausal systemic hypertension. Post-mortem examination showed apical biventricular ballooning of the heart with no cardiac rupture, coronary artery lesion or other cardiac/extra-cardiac disease. Toxicological tests and forensic investigations excluded unnatural causes of death, including pharmacological or iatrogenic causes related to medical malpractice. Only non-specific contraction bands and mild hypertrophy were observed by histology in the left ventricle myocytes. Takotsubo syndrome is usually an acute and reversible heart failure syndrome with acute left ventricle apex ballooning, no coronary artery disease or other macroscopic or microscopic cardiac changes; physical or emotional stress are well known triggering factors. Nevertheless, recurrent forms, major cardiac adverse events and even sudden death may occur in a minority of cases, meaning that a diagnosis of Takotsubo syndrome must be considered in cases of sudden death and in forensic investigations.
2,328,383
Cardioprotective effect of hyperkalemic cardioplegia in an aquaporin 7-deficient murine heart.
Hyperkalemic cardioplegia using St. Thomas' Hospital solution No. 2 (STH2) is commonly used to protect the myocardium during surgery. Mice deficient in the myocyte channel aquaporin 7 (AQP7) show significantly reduced glycerol and ATP contents and develop obesity; however, the influence of AQP7 on cardioplegia effectiveness remains unclear.</AbstractText>After determining the influence of ischemic duration on cardiac function, isolated hearts of male wild-type (WT) and AQP7-knockout (KO) mice (&gt;&#x2009;13&#xa0;weeks old) were aerobically Langendorff-perfused with bicarbonate buffer, and randomly allocated to the control group (25&#xa0;min of global ischemia) and STH2 group (5&#xa0;min of STH2 infusion before 20&#xa0;min of global ischemia, followed by 60&#xa0;min of reperfusion).</AbstractText>Final recovery of left ventricular developed pressure (LVDP) of WT and AQP7-KO hearts in the control group was 24.5&#x2009;&#xb1;&#x2009;12.4% and 20.6&#x2009;&#xb1;&#x2009;8.4%, respectively, which were significantly lower than those of the STH2 group (96.4&#x2009;&#xb1;&#x2009;12.7% and 92.9&#x2009;&#xb1;&#x2009;27.6%). Troponin T levels of WT and AQP-KO hearts significantly decreased in the STH2 groups (142.9&#x2009;&#xb1;&#x2009;27.2 and 219.9&#x2009;&#xb1;&#x2009;197.3) compared to those of the control (1725.0&#x2009;&#xb1;&#x2009;768.6 and 1710&#x2009;&#xb1;&#x2009;819.9).</AbstractText>AQP7 was not involved in the protective efficacy of STH2 in this mouse model, suggesting its clinical utility even in complications of metabolic disease.</AbstractText>
2,328,384
Independent Validation of the Colloid Cyst Risk Score to Predict Symptoms and Hydrocephalus in Patients with Colloid Cysts of the Third Ventricle.
The Colloid Cyst Risk Score (CCRS) was devised to identify patients with symptomatic colloid cyst and stratify risk of hydrocephalus. The CCRS considers patient age, presence of headache, colloid cyst diameter, fluid-attenuated inversion recovery hyperintensity, and location within the third ventricle.</AbstractText>The purpose of this study was to independently evaluate the validity of the CCRS.</AbstractText>Patients with a colloid cyst of the third ventricle were identified retrospectively from institutional billing records and radiology report archives. Patients without a confirmed diagnosis of colloid cyst of the third ventricle or magnetic resonance imaging of the brain were excluded. Data were collected via retrospective chart review.</AbstractText>One hundred and fifty-six patients met inclusion and exclusion criteria. In our cohort, the CCRS stratified symptomatic patients and patients with hydrocephalus across all scores (P &lt; 0.001). From CCRS 2 to 5, the percentage of symptomatic patients increased from 13% to 100%, whereas the percentage of patients with hydrocephalus increased from 8% to 83%. Simple logistic regression showed that total CCRS, headache, axial diameter, fluid-attenuated inversion recovery hyperintensity, and risk zone were all highly predictive of symptomatic status and hydrocephalus (P &lt; 0.001). Logistic regression with receiver operating curves for the CCRS showed an area under the curve of 0.914 for symptomatic colloid cysts and an area under the curve of 0.892 for colloid cysts with hydrocephalus.</AbstractText>Our data analysis validates the predictive value of the CCRS for both symptomatic status and hydrocephalus and supports the use of the CCRS in risk stratification and clinical decision making.</AbstractText>Copyright &#xa9; 2019 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,328,385
Origin and development of circumventricular organs in living vertebrate.
The circumventricular organs (CVOs) function by mediating chemical communication between blood and brain across the blood-brain barrier. Their origin and developmental mechanisms involved are not understood in enough detail due to a lack of molecular markers common for CVOs. These rather small and inconspicuous organs are found in close vicinity to the third and fourth brain ventricles suggestive of ancient evolutionary origin. Recently, an integrated approach based on analysis of CVOs development in the enhancer-trap transgenic zebrafish led to an idea that almost all of CVOs could be highlighted by GFP expression in this transgenic line. This in turn suggested that an enhancer along with a set of genes it regulates may illustrate the first common element of developmental regulation of CVOs. It seems to be related to a mechanism of suppression of the canonical Wnt/ &#x3b2;-catenin signaling that functions in development of fenestrated capillaries typical for CVOs. Based on that observation the common molecular elements of the putative developmental mechanism of CVOs will be discussed in this review.
2,328,386
Periventricular Hemorrhagic Infarction in Very Preterm Infants: Characteristic Sonographic Findings and Association with Neurodevelopmental Outcome at Age 2&#xa0;Years.
To describe the sonographic characteristics of periventricular hemorrhagic infarction (PVHI) and their association with mortality and neurodevelopmental disability in very preterm infants born in 2008-2013.</AbstractText>Retrospective multicenter observational cohort study. Diagonal PVHI size was measured and severity score assessed. PVHI characteristics were scored and temporal trends were assessed. Neurodevelopmental outcome at 2&#xa0;years of corrected age was assessed using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales. Multigroup analyses were applied as appropriate.</AbstractText>We enrolled 160 infants with median gestational age of 26.6&#xa0;weeks. PVHI was mostly unilateral (90%), associated with an ipsilateral grade III intraventricular hemorrhage (84%), and located in the parietal lobe (51%). Sixty-four (40%) infants with PVHI died in the neonatal period. Of the survivors assessed at 2&#xa0;years of corrected age, 65% had normal cognitive and 69% had normal motor outcomes. The cerebral palsy rate was 42%. The composite outcome of death or severe neurodevelopmental disability was observed in 58%, with no trends over the study period (P&#xa0;=&#xa0;.6). Increasing PVHI severity score was associated with death (P&#xa0;&lt;&#xa0;.001). Increasing PVHI size and severity score were negatively associated with gross motor scores (P&#xa0;=&#xa0;.01 and .03, respectively). Trigone involvement was associated with cerebral palsy (41% vs 14%; P&#xa0;=&#xa0;.004). Associated posthemorrhagic ventricular dilation (36%) was an independent risk factor for poorer cognitive and motor outcomes (P &lt; .001 for both).</AbstractText>Increasing PVHI size and severity score were predictive of less optimal gross motor outcome and death in very preterm infants.</AbstractText>Copyright &#xa9; 2019 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,328,387
MicroRNA-429 inhibits bone metastasis in breast cancer by regulating CrkL and MMP-9.
Bone metastasis is common in late-stage breast cancer patients and leads to skeletal-related events that affect the quality of life and decrease survival. Numerous miRNAs have been confirmed to be involved in metastatic breast cancer, such as the miR200 family. Our previous study identified microRNA-429 (miR-429) as a regulatory molecule in breast cancer bone metastasis. However, the effects of miR-429 and its regulatory axis in the metastatic breast cancer bone microenvironment have not been thoroughly investigated. We observed a positive correlation between miR-429 expression in clinical tissues and the bone metastasis-free interval and a negative correlation between miR-429 expression and the degree of bone metastasis. We cultured bone metastatic MDA-MB-231 cells and used conditioned medium (CM) to detect the effect of miR-429 on osteoblast and osteoclast cells in vitro. We constructed an orthotopic bone destruction model and a left ventricle implantation model to examine the effect of miR-429 on the metastatic bone environment in vivo. The transfection experiments showed that the expression levels of V-crk sarcoma virus CT10 oncogene homolog-like (CrkL) and MMP-9 were negatively regulated by miR-429. The in vitro coculture experiments showed that miR-429 promoted osteoblast differentiation and that CrkL promoted osteoclast differentiation. The two animal models showed that miR-429 diminished local bone destruction and distant bone metastasis but CrkL enhanced these effects. Furthermore, CrkL and MMP-9 expression decreased simultaneously in response to increased miR-429 expression. These findings further reveal the possible mechanism and effect of the miR-429/CrkL/MMP-9 regulatory axis in the bone microenvironment in breast cancer bone metastasis.
2,328,388
Influence of wide opening of the lateral ventricle on survival for supratentorial glioblastoma patients with radiotherapy and concomitant temozolomide-based chemotherapy.
The prognosis for glioblastoma (GBM) varies among patients. Ventricular opening during surgery has been reported as a prognostic factor for GBM patients, but the influence of ventricular opening itself on patient prognosis remains controversial. We presumed that the degree of ventricular opening would correlate with the degree of subventricular zone (SVZ) resection and with prognosis in GBM patients. This study therefore investigated whether the degree of ventricular opening correlates with prognosis in GBM patients treated with the standard protocol of chemo-radiotherapy. Participants comprised 111 patients with newly diagnosed GBM who underwent surgery and received postoperative radiotherapy and temozolomide-based chemotherapy from 2005 to 2018. We classified 111 patients into "No ventricular opening (NVO)", "Ventricular opening, small (VOS; distance &lt;&#x2009;23.2&#xa0;mm)", and "Ventricular opening, wide (VOW; distance &#x2265;&#x2009;23.2&#xa0;mm)" groups. We evaluated the relationship between degree of ventricular opening and prognosis using survival analyses that included other clinicopathological factors. Log-rank testing revealed age, Karnofsky performance status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) status, isocitrate dehydrogenase (IDH)1 mutation, and degree of ventricular opening correlated significantly with overall survival. Multivariate analysis identified the degree of ventricular opening (small vs. wide) as the most significant prognostic factor (hazard ratio =&#x2009;3.674; p&#x2009;&lt;&#x2009;0.0001). We demonstrated that wide opening of the lateral ventricle (LV) contributes to longer survival compared with small opening among GBM patients. Our results indicate that wide opening of the LV may correlate with the removal of a larger proportion of tumor stem cells from the SVZ.
2,328,389
Diffused light attenuation at 664 nm for PDT in salted cadaver brain.
We investigated light attenuation at 664&#x2009;nm, which is the excitation wavelength of photodynamic therapy (PDT) using talaporfin sodium, in a salted cadaver brain. Estimation of therapeutic lesions is important to ensure the effectiveness and safety of brain tumor PDT. Previously reported optical properties of the human brain vary widely. In this study, we measured the light attenuation in brain tissue using a practical method. We employed a salted cadaver brain, in which the mechanical and optical properties can be maintained as close as possible to those under operative conditions.</AbstractText>A neuroendoscope was inserted into the brain until the cerebral ventricle was reached. A thin cylindrical diffuser probe was advanced 10&#x2009;mm from the endoscope tip. By another path from the brain surface, an optical fiber for measurement was inserted into a puncture needle, and a pair of needles was used to puncture the tissue and reach the same cerebral ventricle in which the endoscope tip was positioned. The attenuation of light intensities in the frontal lobe and cerebellum was measured by varying the bundle tip position. The starting positions of the bundle were confirmed by the endoscopic view. The measured light intensity attenuations were fitted with an exponential curve.</AbstractText>The following attenuation coefficients were obtained: 0.20&#x2009;&#xb1;&#x2009;0.05&#x2009;mm-1</sup> in the cerebrum and 0.27&#x2009;&#xb1;&#x2009;0.05&#x2009;mm-1</sup> in the cerebellum.</AbstractText>As conventional spectroscopic measurement may overestimate attenuation in the whole tissue, in situ measurement using the withdrawal technique might be appropriate for measurement of inhomogeneous biological tissues.</AbstractText>Copyright &#xa9; 2019 Elsevier B.V. All rights reserved.</CopyrightInformation>
2,328,390
Left Radiofrequency Thalamotomy for Drug-Refractory Essential Tremor.
Essential tremor is an idiopathic movement disorder characterized by bilateral action tremor of the upper limbs with or without other neurologic symptoms.<sup>1</sup> Pharmacologic management is the first-line treatment for this condition. Surgical treatment includes deep brain stimulation and thalamotomy procedures.<sup>2</sup> Furthermore, thalamotomy can be achieved by magnetic resonance imaging-guided focused ultrasound, stereotactic radiosurgery, or radiofrequency.<sup>3</sup> Advantages of modulation therapies include bilateral implementation, adjustability, and reversibility of the effect.<sup>2</sup> Disadvantages include delayed response, increased infection risk, and cost. Within ablation therapies, focused ultrasound is costly and not available widely, while stereotactic radiosurgery has a delayed symptomatic relief. Radiofrequency represents a cost-effective, widely available option with immediate results.<sup>3</sup> We present the case of a 91-year-old right-handed man with essential tremor refractory to medical management (Video 1). He was offered all available treatment modalities and opted for a radiofrequency thalamotomy. Preoperative planning included stereotactic head frame placement and computed tomography scan. A left thalamic target with coordinates 11.5 mm lateral to the wall of the third ventricle, 8 mm anterior to the posterior commissure, and at the rostrocaudal level of the anterior commissure-posterior commissure plane was chosen. A 1.1-mm diameter, 10-mm tip RF electrode was advanced to the target. A lateral radiograph was taken to verify the position of the electrode. After trial stimulation, 2 RF lesions were performed. No intraoperative complications occurred. Immediate postoperative MRI showed an enhancing focus in the left thalamic lobe corresponding to the left thalamotomy lesion. The patient had excellent relief of tremor during his last follow-up, 5 months postoperatively.
2,328,391
Charles H. Frazier's craniopharyngioma treatment: the pivotal role of the transfrontal approach.
Charles H. Frazier (1870-1936), one of the pioneers of neurosurgery in the US, is known worldwide for devising surgical procedures to relieve trigeminal neuralgia and intractable pain. Less well-known are his substantial contributions to understanding and treating pituitary and parahypophyseal lesions. Along with Bernard Alpers, he defined Rathke's cleft tumors as a different pathological entity from adenomas and hypophyseal stalk tumors (craniopharyngiomas [CPs]). The surgical challenge posed by CPs piqued Frazier's interest in these lesions, although he never published a complete account of his CP series. An examination of the Charles Frazier papers at the College of Physicians of Philadelphia allowed the authors to identify 54 CPs that he had treated during his career. In the early 1910s, Frazier developed the subfrontal approach, which would become the primary surgical route to access these lesions, providing better control of the adjacent vital neurovascular structures than the transsphenoidal route hitherto used. Nevertheless, strong adhesions between CPs and the third ventricle floor, the major reason underlying Frazier's disappointing results, moved him to advocate incomplete tumor removal followed by radiotherapy to reduce both the risk of hypothalamic injury and CP recurrence. This conservative strategy remains a judicious treatment for CPs to this day.
2,328,392
Biomechanics of Periventricular Injury.
Periventricular injury is frequently noted as one aspect of severe traumatic brain injury (TBI) and the presence of the ventricles has been hypothesized to be a primary pathogenesis associated with the prevalence of periventricular injury in patients with TBI. Although substantial endeavors have been made to elucidate the potential mechanism, a thorough explanation for this hypothesis appears lacking. In this study, a three-dimensional (3D) finite element (FE) model of the human head with an accurate representation of the cerebral ventricles is developed accounting for the fluid properties of the intraventricular cerebrospinal fluid (CSF) as well as its interaction with the brain. An additional model is developed by replacing the intraventricular CSF with a substitute with brain material. Both models are subjected to rotational accelerations with magnitudes suspected to induce severe diffuse axonal injury. The results reveal that the presence of the ventricles leads to increased strain in the periventricular region, providing a plausible explanation for the vulnerability of the periventricular region. In addition, the strain-exacerbation effect associated with the presence of the ventricles is also noted in the paraventricular region, although less pronounced than that in the periventricular region. The current study advances the understanding of the periventricular injury mechanism as well as the detrimental effects that the ventricles exert on the periventricular and paraventricular brain tissue.
2,328,393
Glucagon-Like Peptide-1 Receptor Agonist Differentially Affects Brain Activation in Response to Visual Food Cues in Lean and Obese Individuals with Type 2 Diabetes Mellitus.
To investigate the effects of a glucagon-like peptide-1 receptor agonist on functional brain activation in lean and obese individuals with type 2 diabetes mellitus (T2DM) in response to visual food cues.</AbstractText>In a randomized, single-blinded, crossover study, 15 lean and 14 obese individuals with T2DM were administered lixisenatide or normal saline subcutaneously with a 1-week washout period. We evaluated brain activation in response to pictures of high-calorie food, low-calorie food, and nonfood using functional magnetic resonance imaging and measured appetite and caloric intake in participants who were given access to an ad libitum</i> buffet.</AbstractText>Obese individuals with T2DM showed significantly greater activation of the hypothalamus, pineal gland, parietal cortex (high-calorie food vs. low-calorie food, P</i>&lt;0.05), orbitofrontal cortex (high-calorie food vs. nonfood, P</i>&lt;0.05), and visual cortex (food vs. nonfood, P</i>&lt;0.05) than lean individuals with T2DM. Lixisenatide injection significantly reduced the functional activation of the fusiform gyrus and lateral ventricle in obese individuals with T2DM compared with that in lean individuals with T2DM (nonfood vs. high-calorie food, P</i>&lt;0.05). In addition, in individuals who decreased their caloric intake after lixisenatide injection, there were significant interaction effects between group and treatment in the posterior cingulate, medial frontal cortex (high-calorie food vs. low-calorie food, P</i>&lt;0.05), hypothalamus, orbitofrontal cortex, and temporal lobe (food vs. nonfood, P</i>&lt;0.05).</AbstractText>Brain responses to visual food cues were different in lean and obese individuals with T2DM. In addition, acute administration of lixisenatide differentially affected functional brain activation in these individuals, especially in those who decreased their caloric intake after lixisenatide injection.</AbstractText>Copyright &#xa9; 2020 Korean Diabetes Association.</CopyrightInformation>
2,328,394
Left ventricular clefts - incidental finding or pathologic sign of Wilson's disease?
Wilson's disease is an inherited autosomal recessive multi-systemic disorder characterized by reduced excretion and consequently excessive accumulation of copper in different organs, such as the heart.</AbstractText>In a prospective controlled trial, which is the largest to date, we evaluated 61 patients with Wilson's disease, age- and sex-matched to 61 healthy patients, for cardiac manifestation using cardiac magnetic resonance imaging. Patients were under stable disease and had no signs of heart failure at the time of examination. We detected a left ventricular cleft, an invagination penetrating more than 50% wall thickness of the adjoining compact myocardium in diastole, in 20% of the patients (12 out of 61) compared to 5% among control patients (3 out of 61, p&#xa0;=&#x2009;0.013). No correlation between the incidence of cleft and a certain genotype of Wilson's disease was found. All described cases were incidental findings and none of the patients showed other signs of cardiac involvement.</AbstractText>To conclude, the results of this study suggests that the increased occurrence of left ventricular clefts is due to Wilson's disease. Large studies with a long observation period are needed for further evaluation.</AbstractText>
2,328,395
Flaxseed and evening primrose oil slightly affect systolic and diastolic function of isolated heart in male but not in female rats.
<b/>Considering that sex related differences in cardiac response to flaxseed (FSO) and evening primrose oil (EPO) are insufficiently known present investigation assessed the effect of these two oils, on the cardiac function of isolated rat hearts and the possible role of sex in this. The present study was carried out on 60 adult male Wistar albino rats randomly divided into 6 groups: male rats treated with EPO, dose of 10&#xa0;mg/kg/day; female rats treated with EPO, dose of 10&#xa0;mg/kg/day; male rats treated with FSO, dose of 300&#xa0;mg/kg/day; female rats treated with FSO, dose of 300&#xa0;mg/kg/day; control group of female rats treated with regular laboratory diet for animals; control group of male rats treated with regular laboratory diet for animals. Using the Langendorff technique, markers of the heart function were evaluated: the maximum and minimum rates of pressure development in the left ventricle (LV; dP/dtmax, dP/dtmin), systolic and diastolic left ventricular pressure (SLVP, DLVP, respectively), heart rate (HR) and coronary flow (CF). Male rats treated with EPO had significantly higher (p&#xa0;=&#xa0;0.016) mean values of dP/dtmax, dP/dtmin, SLVP and DLVP (average increase for all CPPs 20%, 25%, 30% and 110%, respectively), compared to the group of male rats treated with FSO (p&#xa0;=&#xa0;0.914). Our study results indicate that both types of PUFA oils only slightly changed the function of the isolated rat heart in male but not in female rats. Nevertheless, the difference between oil treatments was found in male rats who had stronger cardiac response after supplementation with EPO.
2,328,396
Splicing in the pathogenesis, diagnosis and treatment of ciliopathies.
Primary cilia are essential signalling organelles found on the apical surface of epithelial cells, where they coordinate chemosensation, mechanosensation and light sensation. Motile cilia play a central role in establishing fluid flow in the respiratory tract, reproductive tract, brain ventricles and ear. Genetic defects affecting the structure or function of cilia can lead to a broad range of developmental and degenerative diseases known as ciliopathies. Splicing contributes to the pathogenesis, diagnosis and treatment of ciliopathies. Tissue-specific alternative splicing contributes to the tissue-specific manifestation of ciliopathy phenotypes, for example the retinal-specific effects of some genetic defects, due to specific transcript expression in the highly specialised ciliated cells of the retina, the photoreceptor cells. Ciliopathies can arise both as a result of genetic variants in spliceosomal proteins, or as a result of variants affecting splicing of specific cilia genes. Here we discuss the opportunities and challenges in diagnosing ciliopathies using RNA sequence analysis and the potential for treating ciliopathies in a relatively mutation-neutral way by targeting splicing. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.
2,328,397
Default Mode Network structural alterations in Kocher-Monro trajectory white matter transection: A 3 and 7 tesla simulation modeling approach.
The Kocher-Monro trajectory to the cerebral ventricular system represents one of the most common surgical procedures in the field of neurosurgery. Several studies have analyzed the specific white matter disruption produced during this intervention, which has no reported adverse neurological outcomes. In this study, a graph-theoretical approach was applied to quantify the structural alterations in whole-brain level connectivity. To this end, 132 subjects were randomly selected from the Human Connectome Project dataset and used to create 3 independent 44 subjects groups. Two of the groups underwent a simulated left/right Kocher-Monro trajectory and the third was kept as a control group. For the right Kocher-Monro approach, the nodal analysis revealed decreased strength in the anterior cingulate gyrus of the transected hemisphere. The network-based statistic analysis revealed a set of right lateralized subnetworks with decreased connectivity strength that is consistent with a subset of the Default Mode Network, Salience Network, and Cingulo-Opercular Network. These findings could allow for a better understanding of structural alterations caused by Kocher-Monro approaches that could reveal previously undetected clinical alterations and inform the process of designing safer and less invasive cerebral ventricular approaches.
2,328,398
Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig Model.
Iron-mediated toxicity is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study was performed to investigate the noninvasive neuroimaging method for quantifying brain iron content using a minipig ICH model and assess the effects of minocycline treatment on ICH-induced iron overload and brain injury. The minipig ICH model was established by injecting 2&#xa0;ml of autologous blood into the right basal ganglia, which were then subjected to the treatments of minocycline and vehicle. Furthermore, the quantitative susceptibility mapping (QSM) was used to quantify iron content, and diffusion tensor imaging (DTI) was performed to evaluate white matter tract. Additionally, we also performed immunohistochemistry, Western blot, iron assay, Perl's staining, brain water content, and neurological score to evaluate the iron overload and brain injury. Interestingly, we found that the ICH-induced iron overload could be accurately quantified by the QSM. Moreover, the minocycline was quite beneficial for protecting brain injury by reducing the lesion volume and brain edema, preventing brain iron accumulation, downsizing ventricle enlargement, and alleviating white matter injury and neurological deficits. In summary, we suggest that the QSM be an accurate and noninvasive method for quantifying brain iron level, and the minocycline may be a promising therapeutic agent for patients with ICH.
2,328,399
Long-Term Follow-Up of Significant Improvement After CAPTEM Treatment for Rare Adrenocorticotropin-Producing Cardiac Neuroendocrine Tumor.
Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a rare cause of Cushing syndrome. If routine imaging examinations cannot identify the source of ACTH production, long-term follow-up observation is necessary to determine the etiology. We present the case of a middle-aged male with gradual weight gain and a Cushingoid appearance over 4 years; he provided written informed consent. Laboratory and endocrine tests strongly suggested EAS, although the origin was not detected by multiple imaging methods. Bilateral adrenalectomy was performed to prevent severe complications in the patient. Two and a half years later, a cardiac mass 18 &#xd7; 23 &#xd7; 27 mm in size at the junction between the anterior wall of the left ventricle and the middle septum was found together with multiple bone metastases by <sup>18</sup>F-FDG PET/CT, while the <sup>68</sup>Ga-DOTATE PET/CT findings were negative. Biopsy of the lumbar vertebrae revealed a neuroendocrine tumor (NET) with positive ACTH staining. The patient underwent chemotherapy by CAPTEM, resulting in shrinkage of the cardiac mass and a significant decrease in the ACTH level. In the case of EAS with an unusual cause, long-term follow-up observation is necessary to determine the source of ACTH production. Cardiac NETs are quite rare in EAS, so treatment selection was also challenging. CAPTEM chemotherapy proved effective in controlling the progression of tumor growth and decreasing the ACTH level in this patient.