Unnamed: 0 int64 0 2.34M | titles stringlengths 5 21.5M | abst stringlengths 1 21.5M |
|---|---|---|
2,328,500 | Interaction of the Mechano-Electrical Feedback With Passive Mechanical Models on a 3D Rat Left Ventricle: A Computational Study. | In this paper, we are investigating the interaction between different passive material models and the mechano-electrical feedback (MEF) in cardiac modeling. Various types of passive mechanical laws (nearly incompressible/compressible, polynomial/exponential-type, transversally isotropic/orthotropic material models) are integrated in a fully coupled electromechanical model in order to study their specific influence on the overall MEF behavior. Our computational model is based on a three-dimensional (3D) geometry of a healthy rat left ventricle reconstructed from magnetic resonance imaging (MRI). The electromechanically coupled problem is solved using a fully implicit finite element-based approach. The effects of different passive material models on the MEF are studied with the help of numerical examples. It turns out that there is a significant difference between the behavior of the MEF for compressible and incompressible material models. Numerical results for the incompressible models exhibit that a change in the electrophysiology can be observed such that the transmembrane potential (TP) is unable to reach the resting state in the repolarization phase, and this leads to non-zero relaxation deformations. The most significant and strongest effects of the MEF on the rat cardiac muscle response are observed for the exponential passive material law. |
2,328,501 | A Multifocal Glioneuronal Tumor with RGNT-Like Morphology Occupying the Supratentorial Ventricular System and Infiltrating the Brain Parenchyma. | Rosette-forming glioneuronal tumors (RGNTs) with multifocal growth throughout the ventricular system are extremely rare, and only 1 case of RGNT with dissemination limited to supratentorial ventricles has previously been reported. Recent evidence based on molecular data suggest that low-grade glioneuronal tumors (GNT) involving the septum pellucidum and the lateral ventricles, with either dysembryoplastic neuroepithelial tumor-like or RGNT-like features, may belong to a neuropathologic entity distinct from cortical dysembryoplastic neuroepithelial tumor and "typical" fourth ventricle RGNT, respectively. Given their rarity, the classification of these neoplasms is still uncertain and their clinicopathological and radiological aspects are only partially known.</AbstractText>A 24-year-old male presented a GNT with RGNT-like morphological features centered in the septum pellucidum with multifocal masses occupying the lateral ventricles and the third ventricle with extraventricular infiltration of the frontal lobe. The patient underwent subtotal resection and 4 years follow-up. The clinicopathological and radiological features of the neoplasm are discussed.</AbstractText>Advanced magnetic resonance imaging (magnetic resonance spectroscopy and perfusion-weighted imaging) may provide valuable information in the differential diagnosis between rare GNTs and other more frequent intraventricular neoplasms. In the present case, the enhancing remnant portion of the tumor showed remarkable contrast enhancement variability during the follow-up with slow in situ progression. However, available data suggest that spontaneous contrast enhancement "fluctuations" over time in RGNT may not represent a reliable indicator of tumor behavior.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,502 | An age- and sex-dependent role of catecholaminergic neurons in the control of breathing and hypoxic chemoreflex during postnatal development. | The respiratory system undergoes significant development during the postnatal phase. Maturation of brainstem catecholaminergic (CA) neurons is important for the control and modulation of respiratory rhythmogenesis, as well as for chemoreception in early life. We demonstrated an inhibitory role for CA neurons in CO<sub>2</sub> chemosensitivity in neonatal and juvenile male and female rats, but information regarding their role in the hypoxic ventilatory response (HVR) is lacking. We evaluated the contribution of brainstem CA neurons in the HVR during postnatal (P) development (P7-8, P14-15 and P20-21) in male and female rats through chemical injury with conjugated saporin anti-dopamine beta-hydroxylase (DβH-SAP, 420 ng·μL<sup>-1</sup>) injected in the fourth ventricle. Ventilation (V̇<sub>E</sub>) and oxygen consumption were recorded one week after the lesion in unanesthetized rats during exposure to normoxia and hypoxia. Hypoxia reduced breathing variability in P7-8 control rats of both sexes. At P7-8, the HVR for lesioned males and females increased 27% and 24%, respectively. Additionally, the lesion reduced the normoxic breathing variability in both sexes at P7-8, but hypoxia partially reverted this effect. For P14-15, the increase in V̇<sub>E</sub> during hypoxia was 30% higher for male and 24% higher for female lesioned animals. A sex-specific difference was detected at P20-21, as lesioned males exhibited a 24% decrease in the HVR, while lesioned females experienced a 22% increase. Furthermore, the hypoxia-induced body temperature reduction was attenuated in P20-21 lesioned females. We conclude that brainstem CA neurons modulate the HRV during the postnatal phase, and possibly thermoregulation during hypoxia. |
2,328,503 | Effects of Interleukin 17A Inhibition on Myocardial Deformation and Vascular Function in Psoriasis. | Interleukin (IL)-17A activity is implicated in psoriasis. We investigated the effects of IL-17A inhibition on vascular and left ventricular (LV) function in patients with psoriasis.</AbstractText>A total of 150 patients with psoriasis received either an anti-IL-17A agent (secukinumab, n = 50), cyclosporine (n = 50), or methotrexate treatment (n = 50). At baseline and after 4 and 12 months of treatment, we measured (1) LV global longitudinal strain (GLS), GLS rate (GLSR), GLSR at early diastole, LV twisting, and untwisting; (2) coronary flow reserve (CFR); (3) pulse wave velocity (PWV); and (4) malondialdehyde and protein carbonyl as markers of oxidative stress.</AbstractText>Compared with cyclosporine and methotrexate, anti-IL-17A treatment resulted in a greater increase in GLS at 4 and 12 months after treatment (10% and 14% with anti-IL-17A vs 2% and 2% with cyclosporine vs 4% and 4% with methotrexate, respectively), GLSR, GLSR at early diastole (45% and 41% vs 5% and 4% vs 7% and 9%, respectively), and LV twisting (32% and 28% vs 6% and 8% vs 7% and 6%, respectively) (P < 0.05). Anti-IL-17A treatment resulted in greater improvement of CFR and PWV than cyclosporine or methotrexate (P < 0.05). PWV increased after cyclosporine treatment (+11% at 4 and +14% and 12 months) (P < 0.05). Markers of oxidative stress were reduced only after anti-IL-17A treatment (P < 0.05). Changes of myocardial deformation markers and CFR after anti-IL-17A treatment correlated with a concomitant reduction of oxidative stress.</AbstractText>In psoriasis, inhibition of IL-17A results in a greater improvement of vascular and myocardial function compared with cyclosporine or methotrexate treatment, indicating a beneficial effect on overall cardiovascular function.</AbstractText>Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,504 | Monitoring diffuse injury during disease progression in experimental autoimmune encephalomyelitis with on resonance variable delay multiple pulse (onVDMP) CEST MRI. | Multiple sclerosis (MS) is an autoimmune disorder that targets myelin proteins and results in extensive damage in the central nervous system in the form of focal lesions as well as diffuse molecular changes. Lesions are currently detected using T1-weighted, T2-weighted, and gadolinium-enhanced magnetic resonance imaging (MRI); however, monitoring such lesions has been shown to be a poor predictor of disease progression. Chemical exchange saturation transfer (CEST) MRI is sensitive to many of the biomolecules in the central nervous system altered in MS that cannot be detected using conventional MRI. We monitored disease progression in an experimental autoimmune encephalomyelitis (EAE) model of MS using on resonance variable delay multiple pulse (onVDMP) CEST MRI. Alterations in onVDMP signal were observed in regions responsible for hindlimb function throughout the central nervous system. Histological analysis revealed glial activation in areas highlighted in onVDMP CEST MRI. onVDMP signal changes in the 3rd ventricle preceded paralysis onset that could not be observed with conventional MRI techniques. Hence, the onVDMP CEST MRI signal has potential as a novel imaging biomarker and predictor of disease progression in MS. |
2,328,505 | An iterative multi-path fully convolutional neural network for automatic cardiac segmentation in cine MR images. | Segmentation of the left ventricle (LV), right ventricle (RV) cavities and the myocardium (MYO) from cine cardiac magnetic resonance (MR) images is an important step for diagnosis and monitoring cardiac diseases. Spatial context information may be highly beneficial for segmentation performance improvement. To this end, this paper proposes an iterative multi-path fully convolutional network (IMFCN) to effectively leverage spatial context for automatic cardiac segmentation in cine MR images.</AbstractText>To effectively leverage spatial context information, the proposed IMFCN explicitly models the interslice spatial correlations using a multi-path late fusion strategy. First, the contextual inputs including both the adjacent slices and the already predicted mask of the above adjacent slice are processed by independent feature-extraction paths. Then, an atrous spatial pyramid pooling (ASPP) module is employed at the feature fusion process to combine the extracted high-level contextual features in a more effective way. Finally, deep supervision (DS) and batch-wise class re-weighting mechanism are utilized to enhance the training of the proposed network.</AbstractText>The proposed IMFCN was evaluated and analyzed on the MICCAI 2017 automatic cardiac diagnosis challenge (ACDC) dataset. On the held-out training dataset reserved for testing, our method effectively improved its counterparts that without spatial context and that with spatial context but using an early fusion strategy. On the 50 subjects test dataset, our method achieved Dice similarity coefficient of 0.935, 0.920, and 0.905, and Hausdorff distance of 7.66, 12.10, and 8.80 mm for LV, RV, and MYO, respectively, which are comparable or even better than the state-of-the-art methods of ACDC Challenge. In addition, to explore the applicability to other datasets, the proposed IMFCN was retrained on the Sunnybrook dataset for LV segmentation and also produced comparable performance to the state-of-the-art methods.</AbstractText>We have presented an automatic end-to-end fully convolutional architecture for accurate cardiac segmentation. The proposed method provides an effective way to leverage spatial context in a two-dimensional manner and results in precise and consistent segmentation results.</AbstractText>© 2019 American Association of Physicists in Medicine.</CopyrightInformation> |
2,328,506 | Cavernous Malformations in and Around the Third Ventricle: Indications, Approaches, and Outcomes. | Cavernous malformations in structures in and around the third ventricle are a challenging conceptual and surgical problem. No consensus exists on the ideal approach to such lesions.</AbstractText>To perform a retrospective review of our institutional database to identify and evaluate approaches used to treat cavernous malformations located in and around the third ventricle.</AbstractText>Information was extracted regarding lesion size and location, extent of resection, time to last follow-up, surgical approach, presenting symptoms, preoperative and postoperative neurological status, and specific approach-related morbidity.</AbstractText>All 39 neurosurgical operations (in 36 patients) were either an anterior interhemispheric (AIH) (44%, 17/39) or a supracerebellar infratentorial (SCIT) (56%, 22/39) approach. Gross-total resection was achieved in 23 of 39 procedures (59%), a near-total resection in 1 (3%), and subtotal resection in 15 (38%). For the 31 patients with at least 3 mo of follow-up, the mean modified Rankin Scale (mRS) score was 1.5. Of the 31 patients, 25 (81%) had an mRS score of 0 to 2, 4 had a mRS score of 3 (13%), and 1 each had a mRS score of 4 (3%) or 5 (3%).</AbstractText>Most approaches to cavernous malformations in and around the third ventricle treated at our institution have been either an AIH or a SCIT approach. The AIH approach was used for lesions involving the lateral wall of the third ventricle or the midline third ventricular floor, whereas the SCIT approach was used for lesions extending from the third ventricle into the dorsolateral midbrain, with acceptable clinical results.</AbstractText>Copyright © 2019 by the Congress of Neurological Surgeons.</CopyrightInformation> |
2,328,507 | Adverse prognosis of glioblastoma contacting the subventricular zone: Biological correlates. | The subventricular zone (SVZ) in the brain is associated with gliomagenesis and resistance to treatment in glioblastoma. In this study, we investigate the prognostic role and biological characteristics of subventricular zone (SVZ) involvement in glioblastoma.</AbstractText>We analyzed T1-weighted, gadolinium-enhanced MR images of a retrospective cohort of 647 primary glioblastoma patients diagnosed between 2005-2013, and performed a multivariable Cox regression analysis to adjust the prognostic effect of SVZ involvement for clinical patient- and tumor-related factors. Protein expression patterns of a.o. markers of neural stem cellness (CD133 and GFAP-δ) and (epithelial-) mesenchymal transition (NF-κB, C/EBP-β and STAT3) were determined with immunohistochemistry on tissue microarrays containing 220 of the tumors. Molecular classification and mRNA expression-based gene set enrichment analyses, miRNA expression and SNP copy number analyses were performed on fresh frozen tissue obtained from 76 tumors. Confirmatory analyses were performed on glioblastoma TCGA/TCIA data.</AbstractText>Involvement of the SVZ was a significant adverse prognostic factor in glioblastoma, independent of age, KPS, surgery type and postoperative treatment. Tumor volume and postoperative complications did not explain this prognostic effect. SVZ contact was associated with increased nuclear expression of the (epithelial-) mesenchymal transition markers C/EBP-β and phospho-STAT3. SVZ contact was not associated with molecular subtype, distinct gene expression patterns, or markers of stem cellness. Our main findings were confirmed in a cohort of 229 TCGA/TCIA glioblastomas.</AbstractText>In conclusion, involvement of the SVZ is an independent prognostic factor in glioblastoma, and associates with increased expression of key markers of (epithelial-) mesenchymal transformation, but does not correlate with stem cellness, molecular subtype, or specific (mi)RNA expression patterns.</AbstractText> |
2,328,508 | Neurocysticercosis: A new concept and insight into basic and future pharmacotherapy. | Neurocysticercosis is a neurological infection caused by the larva of taenia solium. The larva infection may affect different parts of the human brain and spinal cord, leading to focal neurological deficit with/without inflammatory reactions. Neurocysticercosis is one of the major causes of epilepsy in the developing countries. It is of two types. One is extra-parenchymal neurocysticercosis in which cysticerci cysts at subarachinoid space and ventricles lead to obstructive hydrocephalus and increase in the intracranial pressure. The other type is intra-parenchymal neurocysticercosis in which the cysticerci cyst grows inside the brain parenchyma, causing the feature of space-occupying lesion. The common presentation of intra-parenchymal neurocysticercosis is secondary epilepsy which is due to focal lesion and/or local inflammatory reactions. Cysticidal therapy increases the risk of seizure due to the induction of host inflammatory reactions. Therefore, coadministration of corticosteroids reduces the risk of seizure through attenuation of inflammatory reactions and brain oedema. Praziquantel alone or in combination with albendazole is regarded as the basic cysticidal therapy against neurocysticercosis. Newer drugs and agents are recommended to overcome the partial failure of standard cysticidal therapy. |
2,328,509 | Choroid Plexus Enlargement and Allostatic Load in Schizophrenia. | Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) were significantly larger, whereas amygdala volume (P = .001) was significantly smaller in patients. The choroid plexus alone was significantly correlated with higher allostatic load after age, sex, education level, and the total intracranial volume were taken into account (t = 3.60, P < .001). Allostatic load was also significantly correlated with PANSS positive (r = 0.28, P = .016) and negative (r = -0.31, P = .008) symptoms, but in opposite directions. The peripheral multisystemic and central nervous system abnormalities in schizophrenia may interact through the choroid plexus during the early stage of the illness. The choroid plexus might provide a sensitive structural biomarker to study the treatment and prevention of brain-periphery interaction abnormalities in schizophrenia. |
2,328,510 | Neonatal frontal lobe: sonographic reference values and suggested clinical use. | Intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHHC) remain major problems among premature infants. The need, timing and type of ventricular drainage are based on sonographic ventricular measures, without assessment of the dimensions of the frontal lobe. The aim of our study was to establish new reference values for sonographic frontal lobe cortico-ventricular thickness (FL-CVT) in a large cohort of infants.</AbstractText>All normal head ultrasound scans that were performed in our center during the first 4 days of life between January 2014 and December 2016 were retrospectively evaluated.</AbstractText>Scans were evaluated and plotted to create a reference range for the thickness of the frontal lobe in normal infants of 24-40 weeks' gestation. The FL-CVT increased significantly during gestation. Calculating the area under the curve of the FL-CVT in 9 infants with post-hemorrhagic-hydrocephalus (PHHC) reveals a 20% mean loss of FL-CVT. The impact of increasing ventricular dilatation and of the various ventricular drainage procedures on the frontal lobe growth were described in two infants demonstrating the potential clinical value of this tool.</AbstractText>Head ultrasound provides a simple, non-invasive method for measuring the thickness of the frontal lobe, which grows significantly between 24 and 40 weeks' gestation. In premature infants with PHHC, we suggest the use of the FL-CVT measure, in addition to ventricular size measures, as a direct assessment of the impact of the enlarged ventricles on the surrounding brain parenchyma. This could assist in the management of PHHC and determine the need and optimal timing for intervention.</AbstractText> |
2,328,511 | Relationships between Head Circumference Percentile, Lumbar Puncture Pressure, and Cerebrospinal Fluid Space in Young Children: Increased Cerebrospinal Space and Pressure May Result in Compensatory Enlargement of Head Circumference Only in the Infant Period. | The aim of this study was to retrospectively evaluate and analyze the relationships between head circumference percentile (HCP), lumbar puncture pressure (LPP), and cerebrospinal fluid (CSF) space.</AbstractText>The 88 patients were divided into 3 age groups (group 1, up to 12 months; group 2, 12-36 months; group 3, 36-72 months).</AbstractText>In group 1 (n = 40), there was a significant positive correlation of the HCP with the LPP (r =0.414, p =0.008), Evans ratio (r =0.365, p =0.021), and thickness of subdural hygroma (SDHG; r =0.403, p =0.010). Group 2 (n = 29) revealed a significant positive correlation between the LPP and the thickness of SDHG (r =0.459, p =0.012). Group 3 (n = 19) showed no significant correlation among these factors. Overall, age was related with SDHG thickness both in infants and toddlers, while HCP was related with LPP, Evans ratio, and SDHG thickness only in infants, and LPP was related with SDHG thickness only in toddlers.</AbstractText>We suggest that increased cerebrospinal space and pressure may result in compensatory enlargement of head circumference only in the infant period, and the SDHG thickness decreases with age during the infant and toddler phases.</AbstractText>© 2019 S. Karger AG, Basel.</CopyrightInformation> |
2,328,512 | Cardiac remodeling in response to embryonic crude oil exposure involves unconventional NKX family members and innate immunity genes. | Cardiac remodeling results from both physiological and pathological stimuli. Compared with mammalian hearts, fish hearts show a broader array of remodeling changes in response to environmental influences, providing exceptional models for dissecting the molecular and cellular bases of cardiac remodeling. We recently characterized a form of pathological remodeling in juvenile pink salmon (<i>Oncorhynchus gorbuscha</i>) in response to crude oil exposure during embryonic cardiogenesis. In the absence of overt pathology (cardiomyocyte death or inflammatory infiltrate), cardiac ventricles in exposed fish showed altered shape, reduced thickness of compact myocardium and hypertrophic changes in spongy, trabeculated myocardium. Here, we used RNA sequencing to characterize molecular pathways underlying these defects. In juvenile ventricular cardiomyocytes, antecedent embryonic oil exposure led to dose-dependent upregulation of genes involved in innate immunity and two NKX homeobox transcription factors not previously associated with cardiomyocytes, <i>nkx2.3</i> and <i>nkx3.3</i> Absent from mammalian genomes, the latter is largely uncharacterized. In zebrafish embryos, <i>nkx3.3</i> demonstrated a potent effect on cardiac morphogenesis, equivalent to that of <i>nkx2.5</i>, the primary transcription factor associated with ventricular cardiomyocyte identity. The role of <i>nkx3.3</i> in heart growth is potentially linked to the unique regenerative capacity of fish and amphibians. Moreover, these findings support a cardiomyocyte-intrinsic role for innate immune response genes in pathological hypertrophy. This study demonstrates how an expanding mechanistic understanding of environmental pollution impacts - i.e. the chemical perturbation of biological systems - can ultimately yield new insights into fundamental biological processes. |
2,328,513 | Treatment with the Neurotrophic Protein S100B Increases Synaptogenesis after Traumatic Brain Injury. | Release of neurotrophic and growth factors such as S100 calcium-binding protein B (S100B) yields an endogenous repair mechanism following traumatic brain injury (TBI). Although nanomolar S100B concentrations enhance hippocampal progenitor cell proliferation, neuronal differentiation, and cognitive recovery, micromolar concentrations may foster inflammatory effects counteracting neuroplasticity. The purpose of the present study was to investigate the effect of S100B on synaptogenesis and microglial activation following experimental TBI. Male Sprague-Dawley rats (n = 40) were subjected to lateral fluid percussion or sham injury, and S100B (50 ng/h) or phosphate buffered saline (PBS) was infused into the lateral ventricle for 7 days using osmotic micropumps. The animals were euthanized on day 5 or, 5 weeks post-injury, and 5 μm sections, 100 μm apart (bregma -3.3 to -5.6mm) were analyzed histologically. Cell proliferation was assessed injecting the mitotic marker Bromodeoxyuridine (BrdU) on day 2. S100B enhanced significantly the synaptophysin (SYN) expression and microglial activation (ectodysplasin [ED1]) in the hippocampus in TBI and uninjured sham animals. The glial activation (glial fibrillary acidic protein [GFAP], S100B immunoreactive cells), axonal injury (APP) and cell death (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) were not altered. Triple-labelling with BrdU, NeuN, and SYN confirmed a significant participation of S100B in hippocampal synaptogenesis in TBI and uninjured sham animals. Our results demonstrate that S100B augments hippocampal neuro- and synaptogenesis in TBI and uninjured sham animals, thereby improving cognitive function as demonstrated earlier. The S100B-induced microglial activation does not counteract this effect within the first 5weeks. Further studies are required to elucidate respective cellular signaling mechanisms and possible long-term effects. |
2,328,514 | Unusual Form of Obstructive Hydrocephalus in Association with 6q Terminal Deletion Syndrome: A Case Report and Literature Review. | Terminal deletion of chromosome 6q is a rare chromosomal abnormality associated with intellectual disabilities and various structural brain abnormalities. We present a case of 6q terminal deletion syndrome with unusual magnetic resonance imaging (MRI) findings in a neonate.</AbstractText>The neonate, who was prenatally diagnosed with dilation of both lateral ventricles, was born at 38 weeks of gestation. MRI demonstrated abnormal membranous structure continuing to the hypertrophic massa intermedia in the third ventricle that had obscured the cerebrospinal fluid pathway, causing hydrocephalus. G-band analysis revealed a terminal deletion of 6q with the karyotype 46, XY, add(6)(q25.3) or del(6)(q26). He underwent ventriculoperitoneal shunt successfully, and his head circumference has been stable.</AbstractText><AbstractText Label="DISCUSSION/CONCLUSION" NlmCategory="CONCLUSIONS">6q terminal deletion impacts the molecular pathway, which is an essential intracellular signaling cascade inducing neurological proliferation, migration, and differentiation during neuronal development. In patients with hydrocephalus in association with hypertrophy of the massa intermedia, this chromosomal abnormality should be taken into consideration. This case may offer an insight into the pathogenesis of hydrocephalus in this rare chromosomal abnormality.</AbstractText>© 2019 S. Karger AG, Basel.</CopyrightInformation> |
2,328,515 | Reversible Progressive Multiple Cranial Nerve Paresis in the Isolated Fourth Ventricle following Placement of Fourth Ventricle Shunt: Case Report and Review of the Literature. | <AbstractText Label="BACKGROUND/AIMS" NlmCategory="OBJECTIVE">Multiple lower cranial nerve paresis occurring after placement of a fourth ventricle shunt for an isolated fourth ventricle is an uncommon complication in the postoperative period. Of the various etiologies, direct brain stem injury by the catheter and rapid decompression of the fourth ventricle by the shunt causing traction on the cranial nerves have been reported in the literature.</AbstractText>We report the case of a 9-year-old girl with an isolated fourth ventricle who developed bilateral facial and multiple lower cranial nerve paresis with bilateral internuclear ophthalmoplegia a month after placement of a ventriculoperitoneal shunt. The postprocedure MRI showed a well-decompressed fourth ventricle with catheter tip located along the long axis of the fourth ventricle.</AbstractText>She was managed non-operatively. She improved gradually in her cranial nerve paresis over the next 3 months and completely recovered at 9 months.</AbstractText>We believe the reversible multiple cranial nerve neuropathies resulted from acute decompression of the fourth ventricle following the shunt insertion. A gradual decompression of the dilated fourth ventricle by an aqueductal stent or a high-pressure shunting system could prevent this potential complication.</AbstractText>© 2019 S. Karger AG, Basel.</CopyrightInformation> |
2,328,516 | Modeling Physiological Flow in Fontan Models With Four-Dimensional Flow Magnetic Resonance Imaging, Particle Image Velocimetry, and Arterial Spin Labeling. | The Fontan procedure is a successful palliation for single ventricle defect. Yet, a number of complications still occur in Fontan patients due to abnormal blood flow dynamics, necessitating improved flow analysis and treatment methods. Phase-contrast magnetic resonance imaging (MRI) has emerged as a suitable method for such flow analysis. However, limitations on altering physiological blood flow conditions in the patient while in the MRI bore inhibit experimental investigation of a variety of factors that contribute to impaired cardiovascular health in these patients. Furthermore, resolution and flow regime limitations in phase contrast (PC) MRI pose a challenge for accurate and consistent flow characterization. In this study, patient-specific physical models were created based on nine Fontan geometries and MRI experiments mimicking low- and high-flow conditions, as well as steady and pulsatile flow, were conducted. Additionally, a particle image velocimetry (PIV)-compatible Fontan model was created and flow was analyzed with PIV, arterial spin labeling (ASL), and four-dimensional (4D) flow MRI. Differences, though nonstatistically significant, were observed between flow conditions and between patient-specific models. Large between-model variation supported the need for further improvement for patient-specific modeling on each unique Fontan anatomical configuration. Furthermore, high-resolution PIV and flow-tracking ASL data provided flow information that was not obtainable with 4D flow MRI alone. |
2,328,517 | Left Ventricular Pseudoaneurysm Complicated With Very Late Rupture 5 Years After Myocardial Infarction. | This is a case of a chronic left ventricular pseudoaneurysm after inferior myocardial infarction that remained clinically silent for 5 years before presenting with sudden rupture, leading to hemopericardium and cardiac tamponade. We discuss the importance of surveillance for left ventricular pseudoaneurysms, the limitations of echocardiography, and the critical role of computed tomography angiography imaging to establish the diagnosis and guide therapy. (<b>Level of Difficulty: Beginner.</b>). |
2,328,518 | Characterization of Alzheimer's Disease Using Ultra-high b-values Apparent Diffusion Coefficient and Diffusion Kurtosis Imaging. | The aim of the study is to investigate the diffusion characteristics of Alzheimer's disease (AD) patients using an ultra-high b-values apparent diffusion coefficient (ADC_uh) and diffusion kurtosis imaging (DKI). A total of 31 AD patients and 20 healthy controls (HC) who underwent both MRI examination and clinical assessment were included in this study. Diffusion weighted imaging (DWI) was acquired with 14 b-values in the range of 0 and 5000 s/mm<sup>2</sup>. Diffusivity was analyzed in selected regions, including the amygdala (AMY), hippocampus (HIP), thalamus (THA), caudate (CAU), globus pallidus (GPA), lateral ventricles (LVe), white matter (WM) of the frontal lobe (FL), WM of the temporal lobe (TL), WM of the parietal lobe (PL) and centrum semiovale (CS). The mean, median, skewness and kurtosis of the conventional apparent diffusion coefficient (ADC), DKI (including two variables, D<sub>app</sub> and K<sub>app</sub>) and ADC_uh values were calculated for these selected regions. Compared to the HC group, the ADC values of AD group were significantly higher in the right HIP and right PL (WM), while the ADC_uh values of the AD group increased significantly in the WM of the bilateral TL and right CS. In the AD group, the K<sub>app</sub> values in the bilateral LVe, bilateral PL/left TL (WM) and right CS were lower than those in the HC group, while the D<sub>app</sub> value of the right PL (WM) increased. The ADC_uh value of the right TL was negatively correlated with MMSE (mean, r=-0.420, p=0.019). The ADC value and D<sub>app</sub> value have the same regions correlated with MMSE. Compared with the ADC_uh, combining ADC_uh and ADC parameters will result in a higher AUC (0.894, 95%CI=0.803-0.984, p=0.022). Comparing to ADC or DKI, ADC_uh has no significant difference in the detectability of AD, but ADC_uh can better reflect characteristic alternation in unconventional brain regions of AD patients. |
2,328,519 | Basal Sodium-Dependent Vitamin C Transporter 2 polarization in choroid plexus explant cells in normal or scorbutic conditions. | Vitamin C is incorporated into the cerebrospinal fluid (CSF) through choroid plexus cells. While the transfer of vitamin C from the blood to the brain has been studied functionally, the vitamin C transporter, SVCT2, has not been detected in the basolateral membrane of choroid plexus cells. Furthermore, it is unknown how its expression is induced in the developing brain and modulated in scurvy conditions. We concluded that SVCT2 is intensely expressed in the second half of embryonic brain development and postnatal stages. In postnatal and adult brain, SVCT2 is highly expressed in all choroidal plexus epithelial cells, shown by colocalization with GLUT1 in the basolateral membranes and without MCT1 colocalization, which is expressed in the apical membrane. We confirmed that choroid plexus explant cells (in vitro) form a sealed epithelial structure, which polarized basolaterally, endogenous or overexpressed SVCT2. These results are reproduced in vivo by injecting hSVCT2wt-EYFP lentivirus into the CSF. Overexpressed SVCT2 incorporates AA (intraperitoneally injected) from the blood to the CSF. Finally, we observed in Guinea pig brain under scorbutic condition, that normal distribution of SVCT2 in choroid plexus may be regulated by peripheral concentrations of vitamin C. Additionally, we observed that SVCT2 polarization also depends on the metabolic stage of the choroid plexus cells. |
2,328,520 | Cavum Septum Pellucidum Causing Obstructive Hydrocephalus in a Toddler. | Cavum septi pellucidi (CSP) are benign developmental cystic midline cavities that are located between the lateral ventricles through the foramina of Monro. CSP are usually asymptomatic and have no cerebrospinal fluid (CSF) flow. Although their incidence is increased in association with head trauma, as well as psychiatric and behavioural disorders, this increase seldom causes disease. Herein, we discuss the case of a toddler who presented with episodic headaches for 6 weeks with associated vomiting triggered by strenuous activity. His neurological examination was normal. His MRI brain scan revealed large cavum septum pellucidum with obstructive hydrocephalus. He underwent endoscopic fenestration of the cyst with resolution of both hydrocephalus and the symptoms. Although CSP are generally asymptomatic, in rare situations, as in our illustrative case, they may cause obstructive hydrocephalus that requires urgent attention. CSF flow studies are helpful in confirming the diagnosis. |
2,328,521 | [Extremely preterm birth in Sweden - clear progress but remaining challenges]. | The recently documented high survival of extremely preterm infants in Sweden is related to a high degree of centralization of pre- and postnatal care and to recently issued national consensus guidelines providing recommendations for perinatal care at 22-24 gestational weeks. The prevalence of major neonatal morbidity remains high and exceeded 60 % in a recent study of extremely preterm infants born at < 27 gestational weeks delivered in Sweden in 2014-2016 and surviving to 1 year of age. Damage to immature organ systems inflicted during the neonatal period causes varying degrees of functional impairment with lasting effects in the growing child. There is an urgent need for evidence-based novel interventions aiming to prevent neonatal morbidity with a subsequent improvement of long-term outcome. |
2,328,522 | Parathyroid hormone-related protein promotes bone loss in T-cell leukemia as well as in solid tumors. | Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein-1α (MIP-1α) are important factors that increase bone resorption and hypercalcemia in adult T-cell leukemia (ATL). We investigated the role of PTHrP and MIP-1α in the development of local osteolytic lesions in T-cell leukemia through overexpression in Jurkat T-cells. Injections of Jurkat-PTHrP and Jurkat-MIP-1α into the tibia and the left ventricle of NSG mice were performed to evaluate tumor growth and metastasis <i>in vivo</i>. Jurkat-pcDNA tibial neoplasms grew at a significantly greater rate and total tibial tumor burden was significantly greater than Jurkat-PTHrP neoplasms. Despite the lower tibial tumor burden, Jurkat-PTHrP bone neoplasms had significantly greater osteolysis than Jurkat-pcDNA and Jurkat-MIP-1α neoplasms. Jurkat-PTHrP and Jurkat-pcDNA cells preferentially metastasized to bone following intracardiac injection, though the overall metastatic burden was lower in Jurkat-PTHrP mice. These findings demonstrate that PTHrP induced pathologic osteolysis in T-cell leukemia but did not increase the incidence of skeletal metastasis. |
2,328,523 | JAK2/STAT3 Pathway is Required for α7nAChR-Dependent Expression of POMC and AGRP Neuropeptides in Male Mice. | <AbstractText Label="BACKGROUND/AIMS" NlmCategory="OBJECTIVE">Cholinergic signalling mediated by the activation of muscarinic and nicotinic receptors has been described in the literature as a classic and important signalling pathway in the regulation of the inflammatory response. Recent research has investigated the role of acetylcholine, the physiological agonist of these receptors, in the control of energy homeostasis at the central level. Studies have shown that mice that do not express acetylcholine in brain regions regulating energy homeostasis present with excessive weight gain and hyperphagia. However, it has not yet been well-described in the literature which cholinergic receptor subunits are involved in this response; moreover, the signalling pathways responsible for the observed effects are not fully delineated. The hypothalamus is the regulating centre of energy homeostasis, and the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) is highly expressed in this region. When active, α7nAChR recruits proteins such as JAK2/STAT3 to mediate its signalling; the same intracellular components are required by leptin, an anorexigenic hormone. The aim of the present study was to evaluate the role of the hypothalamic α7nAChR in the control of energy homeostasis.</AbstractText>The work was performed on Swiss male mice. Initially, using immunofluorescent staining on brain sections, the presence of α7nAChR in hypothalamic cells regulating energy homeostasis was evaluated. Animals were submitted to stereotaxis in the lateral ventricle and intracerebroventricular stimulation (ICV) was used for the administration of an agonist (PNU) or antagonist (α-bungarotoxin) of α7nAChR. Metabolic parameters were evaluated and the expression of neuropeptides was evaluated in the hypothalamus by real-time PCR and western blot. The expression of hypothalamic neuropeptides was evaluated in mice treated with siRNA or inhibitors of JAK2/STAT3 (AG490 and STATTIC) proteins. We also evaluated food intake in α7nAChR knockout animals (α7KO). Additionally, in mouse hypothalamic cell culture (the mypHoA-POMC/GFP lineage), we evaluated the expression of neuropeptides and pSTAT3 after stimulation with PNU.</AbstractText>Our results indicate co-localisation of α7nAChR with α-MSH, AgRP and NPY in hypothalamic cells. Pharmacological activation of α7nAChR reduced food intake and increased hypothalamic POMC expression and decreased NPY and AgRP mRNA levels and the protein content of pAMPK. Inhibition of α7nAChR with an antagonist increased the mRNA content of NPY and AgRP. Inhibition of α7nAChR with siRNA led to the suppression of POMC expression and an increase in AgRP mRNA levels. α7KO mice showed no changes in food intake. Inhibition of proteins involved in the JAK2/STAT3 signalling pathway reversed the effects observed after PNU stimulation. POMC-GFP cells, when treated with PNU, showed increased POMC expression and nuclear translocation of pSTAT3.</AbstractText>Thus, selective activation of α7nAChR is able to modulate important markers of the response to food intake, suggesting that α7nAChR activation can suppress the expression of orexigenic markers and favour the expression of anorexics using the intracellular JAK2/STAT3 machinery.</AbstractText>© Copyright by the Author(s). Published by Cell Physiol Biochem Press.</CopyrightInformation> |
2,328,524 | Diagnosis of a Rare Intraventricular Schwannoma. | Intraventricular schwannoma is extremely rare, with only 35 cases reported to date in the literature. Consequently, its etiology and pathogenesis are still unclear, and therefore require further investigations. Here, we report on and discuss a rare case of intraventricular schwannoma to elucidate on this matter.</AbstractText>A 26-year-old man was admitted to our institution with a 1-month history of headaches and left hemianopsia. At diagnosis, magnetic resonance imaging of the brain revealed a well-demarcated mass with surrounding edema in the right lateral ventricle. Total resection of the tumor was performed by a transsulcal approach through the right parietal lobe. In surgery, it was observed that the tumor was attached to the choroid plexus without invading the wall of the right lateral ventricle. The respective histologic examination confirmed the diagnosis of intraventricular schwannoma. Six months after the surgery, there was no recurrence. Additionally, during this follow-up period, the patient did not develop any neurologic deficit, including visual field narrowing or parietal symptoms, such as acalculia and right-left, finger, and space agnosias.</AbstractText>Although intraventricular schwannomas are rare, 35 cases have already been reported to date. We emphasize the importance of diagnosing such cases correctly to increase knowledge on the origin and pathogenesis of intraventricular tumors, which would facilitate disease management.</AbstractText>Copyright © 2019. Published by Elsevier Inc.</CopyrightInformation> |
2,328,525 | Intraventricular atypical teratoid rhabdoid tumour in an adult: a case report and literature review. | We report a case of atypical teratoid/rhabdoid tumour (AT/RT) in an adult patient in the deep grey matter with extension into the lateral ventricle. To our knowledge, this is the first example of AT/RT involving the lateral ventricle in an adult. The patient presented with headache and confusion, and subsequently required emergent surgery. His postoperative course was complicated by hemorrhage into the surgical site. The location and vascularity of the tumour affected the extent of resection achieved and likely contributed to postoperative complications. We discuss radiological features of AT/RT in adults and implications for investigations and management. |
2,328,526 | The Maximum Diameter of the Left Ventricle May Not Be the Optimum Target for Chest Compression During Cardiopulmonary Resuscitation: A Preliminary, Observational Study Challenging the Traditional Assumption. | Researchers have assumed that compressing the point beneath which the left ventricle (LV) diameter is maximum (P_max.LV) would improve cardiopulmonary resuscitation outcomes. Defining the midsternum, the currently recommended location for chest compression, as the reference (x = 0), the lateral deviation (x_max.LV) of personalized P_max.LV has become estimable using posteroanterior chest radiography. The authors investigated whether out-of-hospital cardiac arrest (OHCA) patients, whose x_max.LV was closer to the midsternum and thus had their P_max.LV compressed closer during cardiopulmonary resuscitation, showed better chances of return of spontaneous circulation (ROSC) and survival to discharge.</AbstractText>Retrospective, cross-sectional study.</AbstractText>A university hospital.</AbstractText>Adult OHCA patients with available previous posteroanterior chest radiography.</AbstractText>None.</AbstractText>For each clinical outcome, multivariable logistic regression was performed, grouping x_max.LV into tertiles and adjusting the variables selected among the core elements of the Utstein template showing possible differences (p > 0.10) in univariate analysis. Odds ratios were presented as OR (95% confidence interval). Among 268 cases (age 64.4 ± 15.8 y, female 89 [33.2%]), 123 (45.9%) achieved ROSC and 40 (14.9%) survival to discharge. Compared with the third tertile of x_max.LV (59 to ∼101 mm), the first (31 to ∼48 mm) and second (48 to ∼59 mm) tertiles, which had a P_max.LV closer to the midsternum, were negatively associated with ROSC (OR 0.502 [0.262-0.960]; p = 0.037 and OR 0.442 [0.233-0.837]; p = 0.012, respectively) and survival to discharge (OR 0.286 [0.080-1.03]; p = 0.055 and OR 0.046 [0.007-0.308]; p = 0.002, respectively).</AbstractText>OHCA patients with a P_max.LV located closer to the midsternum showed worse chances of ROSC and survival to discharge, which challenges the traditional assumption of identifying P_max.LV as the optimum compression point.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,527 | A comparison between unfocused and focused transmit strategies in cardiac strain imaging. | Unfocused ultrasound imaging, particularly coherent compounding with diverging waves, is a commonly employed high-frame rate transmit strategy in cardiac strain imaging. However, the accuracy and precision of diverging wave imaging compared to focused-beam transmit approaches in human subjects is unknown. Three transmit strategies-coherent compounding imaging, composite focused imaging with ECG gating and narrow-beams, and focused imaging with wide-beams-were compared in simulation and in transthoracic imaging of healthy human subjects (n  =  7). The focused narrow-beam sequence estimated radial end-systolic cumulative strains of a simulated left ventricular deformation with 26%  ±  1.5% and 34%  ±  1.5% greater accuracy compared with compounding and wide-beam imaging, respectively. Strain estimation precision in transthoracic imaging was then assessed with the Strain Filter on cumulative end-systolic radial strains. Within the strain values where statistically significant differences in precision (E(SNR<sub>e</sub>|ε)) were found between transmit strategies, the narrow-beam sequence estimated radial strain 13%  ±  0.71% and 34%  ±  8.9% more precisely on average compared to compounding or wide-beam imaging, respectively. |
2,328,528 | Acute restraint stress increases blood pressure and oxidative stress in the cardiorenal system of rats: a role for AT<sub>1</sub> receptors. | We evaluate whether acute restraint stress may affect the oxidative state of the cardiorenal system and the possible contribution of angiotensin II/AT<sub>1</sub> receptors in such response. Male Wistar rats were restrained for 60 min within wire mesh chambers. Some rats were treated with losartan (selective AT<sub>1</sub> receptor antagonist, 10 mg/kg, p.o., gavage) 30 min before being stressed. Biochemical analyses were conducted after the 60-min period of restraint. Treatment with losartan prevented the increase in mean arterial pressure (MAP), but not heart rate (HR) induced by acute stress. Phenylephrine-induced contraction of endothelium-intact aortas was not affected by acute stress. Losartan prevented the increase in both superoxide anion (O<sub>2</sub><sup>•-</sup>) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) levels induced by acute stress in the aorta and renal cortex. Similarly, the augmented activity of superoxide dismutase (SOD) induced by acute stress in the aorta and renal cortex was prevented by losartan. Enhanced levels of O<sub>2</sub><sup>•-</sup> and thiobarbituric acid reactive species (TBARS) were detected in the left ventricle (LV) of stressed rats, but losartan did not prevent these responses. Similarly, losartan did not inhibited stress-induced decrease in the concentration of nitrate/nitrite (NO<i>x</i>) and H<sub>2</sub>O<sub>2</sub> in the left ventricle. Stress increased ROS generation and affected the enzymatic antioxidant system in the cardiorenal system. In addition to its well-known cardiovascular changes during acute stress, angiotensin II also induces ROS generation in the cardiorenal system in a tissue-specific manner. The increase in oxidative stress mediated by angiotensin II/AT<sub>1</sub> receptors could be one mechanism by which acute stress predisposes to cardiorenal dysfunctions. |
2,328,529 | Xanthogranulomatous colloid cyst: Radiologic- pathologic correlation and diagnostic difficulties. | Despite colloid cyst in the third ventricle is a very usual cause of hydrocephalus, its xanthogranulomatous variant is rare. The most important differential diagnosis is the third ventricular craniopharyngioma. To the best of the authors' knowledge, there have been few cases of xanthogranulomatous variant colloid cysts reported in the English literature.</AbstractText>A 77-year-old white woman presented with headaches, memory loss, and abnormal gait for the past 4 months. Magnetic resonance imaging revealed a solid cystic lesion measuring 3.0 cm×2.8 cm×2.9 cm located inside the anterior portion of the third ventricle causing obstructive hydrocephalus. The posterior portion of the lesion was predominantly solid and hypointense on T2 and T1, with areas of post- contrast enhancement, and the anterior portion was predominantly cystic with both hyper- and hypointense areas on T1 and T2, with no suppression on fluid-attenuated inversion recovery and no restriction to diffusion. The patient underwent a left frontal craniotomy with pterional approach, and the lesion was removed microsurgically.</AbstractText>Xanthogranulomatous reaction is rarely described in colloid cysts, which happens as a response to desquamation of epithelial lining, subsequent lipid accumulation, and as tissue inflammatory response to intracystic hemorrhage. Microsurgical resection is the treatment of choice. As compared to the plain colloid cyst, these lesions are difficult to fully excise as the inflammatory reaction to the xanthomatous material leads to adhesions to adjacent structures; therefore, the aspiration of cystic contents without spillage is advisable to achieve maximal resection of cyst walls.</AbstractText>Copyright: © 2019 Surgical Neurology International.</CopyrightInformation> |
2,328,530 | [Median Sternotomy( Re-do and Closure)]. | Median sternotomy is a basic procedure in the cardiovascular surgery. Minimally invasive surgery (MICS) develops and becomes able to accomplish various operation on the cardiovascular surgery, but it cannot carry out all maneuvers. Medline incision is inferior at beauty and infection control than MICS. But medianstenotomy is still used widely. It's provided good field of vision and the incision method that evade the complexity of the operation. It is vital to carry it out surely and carefully so that there are not later complications by mediansternotomy. It is necessary to be careful about the right ventricle injury the case of the redo-sternotomy. |
2,328,531 | Neuroendoscopic Evacuation for Spontaneous Cerebellar Hemorrhage Is a Safe and Secure Approach and May Become a Mainstream Technique. | Patients with spontaneous cerebellar hemorrhage present with rapidly deteriorating neurological symptoms due to a hematoma-induced mass effect in the brainstem. We compared the standard surgical approach of a suboccipital craniectomy with neuroendoscopic surgery for treating spontaneous cerebellar hemorrhage. We performed a retrospective analysis of 41 patients indicated for surgery to treat spontaneous cerebellar hemorrhage. At our hospital, craniectomy was performed until 2010, and neuroendoscopic surgery was performed thereafter when a qualified surgeon was available. Duration of surgery and intraoperative blood loss were lower in the neuroendoscopic surgery group. The extent of hematoma removal and the percentage of patients requiring shunting were similar between groups. The mass effect was resolved in all patients in both groups, and no substantial re-bleeding was observed in either group. The outcomes at discharge were comparable between the two groups. Our surgeons used the supine lateral position, which involves fewer burdens to the patient than the prone position. Selection of the site of the burr hole is important to avoid the midline and to avoid the area exactly above the transverse and sigmoid sinus. Our results suggest that minimally invasive neuroendoscopic surgery is safe and superior to craniectomy due to shortened duration of surgery and decreased intraoperative bleeding. |
2,328,532 | Synthesis and Biological Activity of a Bis-steroid-Methanocyclobutanaphthalene- dione Derivative against Ischemia/Reperfusion Injury via Calcium Channel Activation. | There is some experimental data on the effect exerted by some steroid derivatives against ischemia/reperfusion injury; however, the molecular mechanism is very confusing, perhaps this phenomenon could be due to the protocols used and/or differences in the chemical structure of each one of the steroid derivatives.</AbstractText>The aim of this study was to synthesize a new bis-steroid-methanocyclobutanaphthalene- dione derivative using some tools chemical.</AbstractText>The biological activity exerted by the bis-steroid-methanocyclobutanaphthalene- dione derivative against ischemia/reperfusion injury was evaluated in an isolated heart model using noradrenaline, milrinone, dobutamine, levosimendan, and Bay-K- 8644 as controls. In addition, other alternative experiments were carried out to evaluate the biological activity induced by the bis-steroid-methanocyclobuta-naphthalene-dione derivative against left ventricular pressure in the absence or presence of nifedipine.</AbstractText>The results showed that 1) the bis-steroid-methanocyclobuta-naphthalene-dione derivative significantly decreases the ischemia-reperfusion injury translated as a decrease in the the infarct area in a similar manner to levosimendan drug; 2) both bis-steroidmethanocyclobuta- naphthalene-dione and Bay-K-8644 increase the left ventricular pressure and 3) the biological activity exerted by bis-steroid-methanocyclobuta-naphthalenedione derivative against left ventricular pressure is inhibited by nifedipine.</AbstractText>In conclusion, the bis-steroid-methanocyclobuta-naphthalene-dione derivative decreases the area of infarction and increases left ventricle pressure via calcium channels activation; this phenomenon could constitute a new therapy for ischemia/reperfusion injury.</AbstractText>Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.</CopyrightInformation> |
2,328,533 | The effect of intra-cerebroventricular injection of insulin on the levels of monoamines on the raphe magnus nucleus of non-diabetic and short-term diabetic rats in the formalin test. | Systemic and intracerebroventricular (ICV) injection of insulin possess analgesic effects. The raphe magnus nucleus (RMN) is part of the endogenous analgesia system. The objective of the present study was to evaluate the effects of ICV injection of insulin on the levels of monoamines and their related metabolites in the RMN during the formalin test in non-diabetic and short-term diabetic rats.</AbstractText>Sixty four adult male rats were used. Diabetes was induced by Streptozotocin (STZ) (60 mg/kg, IP); insulin (5 mU/animal, 5 μl) was injected into the left ventricle. Microdialysis was performed in each rat. Samples were collected at 15 min intervals. After taking the base sample of microdialysis, 50 μl of 2.5% formalin was injected into the plantar surface of the hind paw, and the level of nociception was recorded every 15 sec for 1 hr. Monoamines and their metabolites concentrations were measured using the HPLC-ECD method.</AbstractText>Findings showed that ICV injection of insulin in non-diabetic rats increased the concentration of monoamines and their related metabolites in the RMN. In diabetic rats, injection of insulin decreased the concentrations of monoamines and their related metabolites in the RMN (P</i><0.05). Our results determined that, at least in part, insulin is associated with antinociceptive effect in non-diabetic rats.</AbstractText>Based on the results, it seems that ICV injection of insulin in non-diabetic rats increased the activity of the central pain control pathways leading to antinociceptive response, but this condition was not seen in diabetic rats.</AbstractText> |
2,328,534 | Opportunistic Disease or Metastatic Lesions: A Rare Finding in a Patient with Bladder Cancer. | A 66-year-old male with a history of human immunodeficiency virus infection and metastatic bladder cancer presented to our hospital for a further workup of a focal seizure involving the patients left upper extremity. The patient was undergoing active chemotherapy at the time of admission and had a CD4 count of 111. Magnetic resonance imaging of the brain revealed multiple ring-enhancing lesions in the right frontal lobe associated with vasogenic edema, and mass effect at the right frontal horn of the lateral ventricles. As the imaging was not consistent with typical metastatic disease of the bladder, further testing was performed. A lumbar puncture was performed to assist in differentiating between malignant and infectious causes in the setting of a low CD4 count. The cerebral spinal fluid was sterile and no malignant cells were identified. Protein and glucose levels of the cerebral spinal fluid were within normal range. To confirm the presence of metastatic disease, a brain biopsy was performed and found to be consistent with metastatic carcinoma with a bladder primary. The patient subsequently underwent radiation therapy to the site of the brain metastasis. |
2,328,535 | Inhibition of Hypothalamic MCT4 and MCT1-MCT4 Expressions Affects Food Intake and Alters Orexigenic and Anorexigenic Neuropeptide Expressions. | Feeding behavior regulation is a complex process, which depends on the central integration of different signals, such as glucose, leptin, and ghrelin. Recent studies have shown that glial cells known as tanycytes that border the basal third ventricle (3V) detect glucose and then use glucose-derived signaling to inform energy status to arcuate nucleus (ARC) neurons to regulate feeding behavior. Monocarboxylate transporters (MCT) 1 and MCT4 are localized in the cellular processes of tanycytes, which could facilitate monocarboxylate release to orexigenic and anorexigenic neurons. We hypothesize that MCT1 and MCT4 inhibitions could alter the metabolic communication between tanycytes and ARC neurons, affecting feeding behavior. We have previously shown that MCT1 knockdown rats eat more and exhibit altered satiety parameters. Here, we generate MCT4 knockdown rats and MCT1-MCT4 double knockdown rats using adenovirus-mediated transduction of a shRNA into the 3V. Feeding behavior was evaluated in MCT4 and double knockdown animals, and neuropeptide expression in response to intracerebroventricular glucose administration was measured. MCT4 inhibition produced a decrease in food intake, contrary to double knockdown. MCT4 inhibition was accompanied by a decrease in eating rate and mean meal size and an increase in mean meal duration, parameters that are not changed in the double knockdown animals with exception of eating rate. Finally, we observed a loss in glucose regulation of orexigenic neuropeptides and abnormal expression of anorexigenic neuropeptides in response to fasting when these transporters are inhibited. Taken together, these results indicate that MCT1 and MCT4 expressions in tanycytes play a role in feeding behavior regulation. |
2,328,536 | Ventricular volume expansion in presymptomatic genetic frontotemporal dementia.<Pagination><StartPage>e1699</StartPage><EndPage>e1706</EndPage><MedlinePgn>e1699-e1706</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1212/WNL.0000000000008386</ELocationID><Abstract><AbstractText Label="OBJECTIVE">To characterize the time course of ventricular volume expansion in genetic frontotemporal dementia (FTD) and identify the onset time and rates of ventricular expansion in presymptomatic FTD mutation carriers.</AbstractText><AbstractText Label="METHODS">Participants included patients with a mutation in <i>MAPT</i>, <i>PGRN</i>, or <i>C9orf72</i>, or first-degree relatives of mutation carriers from the GENFI study with MRI scans at study baseline and at 1 year follow-up. Ventricular volumes were obtained from MRI scans using FreeSurfer, with manual editing of segmentation and comparison to fully automated segmentation to establish reliability. Linear mixed models were used to identify differences in ventricular volume and in expansion rates as a function of time to expected disease onset between presymptomatic carriers and noncarriers.</AbstractText><AbstractText Label="RESULTS">A total of 123 participants met the inclusion criteria and were included in the analysis (18 symptomatic carriers, 46 presymptomatic mutation carriers, and 56 noncarriers). Ventricular volume differences were observed 4 years prior to symptom disease onset for presymptomatic carriers compared to noncarriers. Annualized rates of ventricular volume expansion were greater in presymptomatic carriers relative to noncarriers. Importantly, time-intensive manually edited and fully automated ventricular volume resulted in similar findings.</AbstractText><AbstractText Label="CONCLUSIONS">Ventricular volume differences are detectable in presymptomatic genetic FTD. Concordance of results from time-intensive manual editing and fully automatic segmentation approaches support its value as a measure of disease onset and progression in future studies in both presymptomatic and symptomatic genetic FTD.</AbstractText><CopyrightInformation>Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tavares</LastName><ForeName>Tamara P</ForeName><Initials>TP</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mitchell</LastName><ForeName>Derek G V</ForeName><Initials>DGV</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coleman</LastName><ForeName>Kristy</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shoesmith</LastName><ForeName>Christen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bartha</LastName><ForeName>Robert</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cash</LastName><ForeName>David M</ForeName><Initials>DM</Initials><Identifier Source="ORCID">0000-0001-7833-616X</Identifier><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moore</LastName><ForeName>Katrina M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Swieten</LastName><ForeName>John</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Borroni</LastName><ForeName>Barbara</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Galimberti</LastName><ForeName>Daniela</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tartaglia</LastName><ForeName>Maria Carmela</ForeName><Initials>MC</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rowe</LastName><ForeName>James</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Graff</LastName><ForeName>Caroline</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tagliavini</LastName><ForeName>Fabrizio</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Frisoni</LastName><ForeName>Giovanni</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cappa</LastName><ForeName>Stefano</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Laforce</LastName><ForeName>Robert</ForeName><Initials>R</Initials><Suffix>Jr</Suffix><Identifier Source="ORCID">0000-0002-2031-490X</Identifier><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Mendonça</LastName><ForeName>Alexandre</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sorbi</LastName><ForeName>Sandro</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wallstrom</LastName><ForeName>Garrick</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Masellis</LastName><ForeName>Mario</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rohrer</LastName><ForeName>Jonathan D</ForeName><Initials>JD</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Finger</LastName><ForeName>Elizabeth C</ForeName><Initials>EC</Initials><AffiliationInfo><Affiliation>From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada. elizabeth.finger@lhsc.on.ca.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>Genetic FTD Initiative, GENFI</CollectiveName></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Acronym>WT_</Acronym><Agency>Wellcome Trust</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MOP 327387</GrantID><Agency>CIHR</Agency><Country>Canada</Country></Grant><Grant><GrantID>MR/J009482/1</GrantID><Acronym>MRC_</Acronym><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MR/M023664/1</GrantID><Acronym>MRC_</Acronym><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MR/M008525/1</GrantID><Acronym>MRC_</Acronym><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>10</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Neurology</MedlineTA><NlmUniqueID>0401060</NlmUniqueID><ISSNLinking>0028-3878</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000073885">C9orf72 Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C568651">C9orf72 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C492314">GRN protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C054369">MAPT protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000077153">Progranulins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016875">tau Proteins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000073885" MajorTopicYN="N">C9orf72 Protein</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002552" MajorTopicYN="N">Cerebral Ventricles</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="Y">diagnostic imaging</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057180" MajorTopicYN="N">Frontotemporal Dementia</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="Y">diagnostic imaging</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006579" MajorTopicYN="N">Heterozygote</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008279" MajorTopicYN="N">Magnetic Resonance Imaging</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009929" MajorTopicYN="N">Organ Size</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D062706" MajorTopicYN="Y">Prodromal Symptoms</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000077153" MajorTopicYN="N">Progranulins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016875" MajorTopicYN="N">tau Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList><InvestigatorList><Investigator ValidYN="Y"><LastName>Andersson</LastName><ForeName>Christin</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Archetti</LastName><ForeName>Silvana</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Arighi</LastName><ForeName>Andrea</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Benussi</LastName><ForeName>Luisa</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Black</LastName><ForeName>Sandra</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bocchetta</LastName><ForeName>Martina</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cosseddu</LastName><ForeName>Maura</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fallström</LastName><ForeName>Marie</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ferreira</LastName><ForeName>Carlos</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ferreira</LastName><ForeName>Catarina B</ForeName><Initials>CB</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fenoglio</LastName><ForeName>Chiara</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fox</LastName><ForeName>Nick C</ForeName><Initials>NC</Initials></Investigator><Investigator ValidYN="Y"><LastName>Freedman</LastName><ForeName>Morris</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fumagalli</LastName><ForeName>Giorgio</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Gazzina</LastName><ForeName>Stefano</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ghidoni</LastName><ForeName>Roberta</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Grisoli</LastName><ForeName>Marina</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jelic</LastName><ForeName>Vesna</ForeName><Initials>V</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jiskoot</LastName><ForeName>Lize</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Keren</LastName><ForeName>R</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lombardi</LastName><ForeName>Gemma</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Maruta</LastName><ForeName>Carolina</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Meeter</LastName><ForeName>Lieke</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>van Minkelen</LastName><ForeName>Rick</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Miltenberger</LastName><ForeName>Gabriel</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Nacmias</LastName><ForeName>Benedetta</ForeName><Initials>B</Initials></Investigator><Investigator ValidYN="Y"><LastName>Öijerstedt</LastName><ForeName>Linn</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ourselin</LastName><ForeName>Sebastien</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Padovani</LastName><ForeName>Alessandro</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Panman</LastName><ForeName>Jessica</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Pievani</LastName><ForeName>Michela</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Polito</LastName><ForeName>Cristina</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Premi</LastName><ForeName>Enrico</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Prioni</LastName><ForeName>Sara</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Rademakers</LastName><ForeName>Rosa</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Redaelli</LastName><ForeName>Veronica</ForeName><Initials>V</Initials></Investigator><Investigator ValidYN="Y"><LastName>Rogaeva</LastName><ForeName>Ekaterina</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Rossi</LastName><ForeName>Giacomina</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Rossor</LastName><ForeName>Martin N</ForeName><Initials>MN</Initials></Investigator><Investigator ValidYN="Y"><LastName>Scarpini</LastName><ForeName>Elio</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Tang-Wai</LastName><ForeName>David</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Tartaglia</LastName><ForeName>Carmela</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Thomas</LastName><ForeName>David</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Thonberg</LastName><ForeName>Hakan</ForeName><Initials>H</Initials></Investigator><Investigator ValidYN="Y"><LastName>Tiraboschi</LastName><ForeName>Pietro</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Verdelho</LastName><ForeName>Ana</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Warren</LastName><ForeName>Jason D</ForeName><Initials>JD</Initials></Investigator></InvestigatorList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>12</Month><Day>19</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>5</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>10</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>10</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31578297</ArticleId><ArticleId IdType="pmc">PMC6946476</ArticleId><ArticleId IdType="doi">10.1212/WNL.0000000000008386</ArticleId><ArticleId IdType="pii">WNL.0000000000008386</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Rademakers R, Neumann M, Mackenzie IR. Advances in understanding the molecular basis of frontotemporal dementia. Nat Rev Neurol 2012;8:423–434.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3629543</ArticleId><ArticleId IdType="pubmed">22732773</ArticleId></ArticleIdList></Reference><Reference><Citation>Tsai RM, Boxer AL. Therapy and clinical trials in frontotemporal dementia: past, present, and future. J Neurochem 2016;138(suppl 1):211–221.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5217534</ArticleId><ArticleId IdType="pubmed">27306957</ArticleId></ArticleIdList></Reference><Reference><Citation>Rohrer JD, Nicholas JM, Cash DM, et al. . Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal Dementia Initiative (GENFI) study: a cross-sectional analysis. Lancet Neurol 2015;14:253–262.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6742501</ArticleId><ArticleId IdType="pubmed">25662776</ArticleId></ArticleIdList></Reference><Reference><Citation>Rohrer JD. Structural brain imaging in frontotemporal dementia. Biochim Biophys Acta 2012;1822:325–332.</Citation><ArticleIdList><ArticleId IdType="pubmed">21839829</ArticleId></ArticleIdList></Reference><Reference><Citation>Whitwell JL, Xu J, Mandrekar J, et al. . Frontal asymmetry in behavioral variant frontotemporal dementia: clinicoimaging and pathogenetic correlates. Neurobiol Aging 2013;34:636–639.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3404265</ArticleId><ArticleId IdType="pubmed">22502999</ArticleId></ArticleIdList></Reference><Reference><Citation>Whitwell JL, Jack CR Jr, Pankratz VS, et al. . Rates of brain atrophy over time in autopsy-proven frontotemporal dementia and Alzheimer disease. Neuroimage 2008;39:1034–1040.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2268641</ArticleId><ArticleId IdType="pubmed">17988893</ArticleId></ArticleIdList></Reference><Reference><Citation>Nestor SM, Rupsingh R, Borrie M, et al. . Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's Disease Neuroimaging Initiative database. Brain 2008;131:2443–2454.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2724905</ArticleId><ArticleId IdType="pubmed">18669512</ArticleId></ArticleIdList></Reference><Reference><Citation>Reuter M, Schmansky NJ, Rosas HD, Fischl B. Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage 2012;61:1402–1418.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3389460</ArticleId><ArticleId IdType="pubmed">22430496</ArticleId></ArticleIdList></Reference><Reference><Citation>Reuter M, Rosas HD, Fischl B. Highly accurate inverse consistent registration: a robust approach. Neuroimage 2010;53:1181–1196.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2946852</ArticleId><ArticleId IdType="pubmed">20637289</ArticleId></ArticleIdList></Reference><Reference><Citation>Whitwell JL, Weigand SD, Boeve BF, et al. . Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain 2012;135:794–806.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3286334</ArticleId><ArticleId IdType="pubmed">22366795</ArticleId></ArticleIdList></Reference><Reference><Citation>Rohrer JD, Ridgway GR, Modat M, et al. . Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by progranulin and tau mutations. Neuroimage 2010;53:1070–1076.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2941039</ArticleId><ArticleId IdType="pubmed">20045477</ArticleId></ArticleIdList></Reference><Reference><Citation>Irwin DJ, McMillan CT, Xie SX, et al. . Asymmetry of post-mortem neuropathology in behavioural-variant frontotemporal dementia. Brain 2018;141:288–301.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5837322</ArticleId><ArticleId IdType="pubmed">29228211</ArticleId></ArticleIdList></Reference><Reference><Citation>Knopman DS, Jack CR Jr, Kramer JH, et al. . Brain and ventricular volumetric changes in frontotemporal lobar degeneration over 1 year. Neurology 2009;72:1843–1849.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2690986</ArticleId><ArticleId IdType="pubmed">19470967</ArticleId></ArticleIdList></Reference><Reference><Citation>Mahoney CJ, Downey LE, Ridgway GR, et al. . Longitudinal neuroimaging and neuropsychological profiles of frontotemporal dementia with C9ORF72 expansions. Alzheimers Res Ther 2012;4:41.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3580398</ArticleId><ArticleId IdType="pubmed">23006986</ArticleId></ArticleIdList></Reference><Reference><Citation>Whitwell JL, Boeve BF, Weigand SD, et al. . Brain atrophy over time in genetic and sporadic frontotemporal dementia: a study of 198 serial magnetic resonance images. Eur J Neurol 2015;22:745–752.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4390434</ArticleId><ArticleId IdType="pubmed">25683866</ArticleId></ArticleIdList></Reference><Reference><Citation>Jones DT, Weig S, Przybelski S, et al. . Longitudinal changes in brain MRI and neuropsychological measures in asymptomatic and symptomatic familial frontotemporal lobar degeneration with mutations in MAPT. Alzheimers Dis Demen 2014;10(suppl):P6.</Citation></Reference><Reference><Citation>Floeter MK, Bageac D, Danielian LE, Braun LE, Traynor BJ, Kwan JY. Longitudinal imaging in C9orf72 mutation carriers: relationship to phenotype. Neuroimage Clin 2016;12:1035–1043.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5153604</ArticleId><ArticleId IdType="pubmed">27995069</ArticleId></ArticleIdList></Reference><Reference><Citation>Avants BB, Epstein CL, Grossman M, Gee JC. Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal 2008;12:26–41.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2276735</ArticleId><ArticleId IdType="pubmed">17659998</ArticleId></ArticleIdList></Reference><Reference><Citation>Whitwell JL. Biomarkers in randomized clinical trials: magnetic resonance imaging. Front Neurol Neurosci 2016;39:101–108.</Citation><ArticleIdList><ArticleId IdType="pubmed">27463684</ArticleId></ArticleIdList></Reference><Reference><Citation>McMillan CT. Neurodegenerative disease: MRI biomarkers: a precision medicine tool in neurology? Nat Rev Neurol 2016;12:323–324.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5512159</ArticleId><ArticleId IdType="pubmed">27080517</ArticleId></ArticleIdList></Reference><Reference><Citation>Boeve BF, Tremont-Lukats IW, Waclawik AJ, et al. . Longitudinal characterization of two siblings with frontotemporal dementia and parkinsonism linked to chromosome 17 associated with the S305N tau mutation. Brain 2005;128:752–772.</Citation><ArticleIdList><ArticleId IdType="pubmed">15615814</ArticleId></ArticleIdList></Reference><Reference><Citation>Cash DM, Bocchetta M, Thomas DL, et al. . Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study. Neurobiol Aging 2018;62:191–196.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5759893</ArticleId><ArticleId IdType="pubmed">29172163</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">31580634</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK547304</ArticleId></ArticleIdList><Book><Publisher><PublisherName>University of Washington, Seattle</PublisherName><PublisherLocation>Seattle (WA)</PublisherLocation></Publisher><BookTitle book="gene">GeneReviews<sup>®</sup></BookTitle><PubDate><Year>1993</Year></PubDate><BeginningDate><Year>1993</Year></BeginningDate><EndingDate><Year>2023</Year></EndingDate><AuthorList Type="editors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Adam</LastName><ForeName>Margaret P</ForeName><Initials>MP</Initials></Author><Author ValidYN="Y"><LastName>Mirzaa</LastName><ForeName>Ghayda M</ForeName><Initials>GM</Initials></Author><Author ValidYN="Y"><LastName>Pagon</LastName><ForeName>Roberta A</ForeName><Initials>RA</Initials></Author><Author ValidYN="Y"><LastName>Wallace</LastName><ForeName>Stephanie E</ForeName><Initials>SE</Initials></Author><Author ValidYN="Y"><LastName>Bean</LastName><ForeName>Lora JH</ForeName><Initials>LJH</Initials></Author><Author ValidYN="Y"><LastName>Gripp</LastName><ForeName>Karen W</ForeName><Initials>KW</Initials></Author><Author ValidYN="Y"><LastName>Amemiya</LastName><ForeName>Anne</ForeName><Initials>A</Initials></Author></AuthorList><Medium>Internet</Medium></Book><ArticleTitle book="gene" part="isca1-mmds"><i>ISCA1</i>-Related Multiple Mitochondrial Dysfunctions Syndrome | To characterize the time course of ventricular volume expansion in genetic frontotemporal dementia (FTD) and identify the onset time and rates of ventricular expansion in presymptomatic FTD mutation carriers.</AbstractText>Participants included patients with a mutation in MAPT</i>, PGRN</i>, or C9orf72</i>, or first-degree relatives of mutation carriers from the GENFI study with MRI scans at study baseline and at 1 year follow-up. Ventricular volumes were obtained from MRI scans using FreeSurfer, with manual editing of segmentation and comparison to fully automated segmentation to establish reliability. Linear mixed models were used to identify differences in ventricular volume and in expansion rates as a function of time to expected disease onset between presymptomatic carriers and noncarriers.</AbstractText>A total of 123 participants met the inclusion criteria and were included in the analysis (18 symptomatic carriers, 46 presymptomatic mutation carriers, and 56 noncarriers). Ventricular volume differences were observed 4 years prior to symptom disease onset for presymptomatic carriers compared to noncarriers. Annualized rates of ventricular volume expansion were greater in presymptomatic carriers relative to noncarriers. Importantly, time-intensive manually edited and fully automated ventricular volume resulted in similar findings.</AbstractText>Ventricular volume differences are detectable in presymptomatic genetic FTD. Concordance of results from time-intensive manual editing and fully automatic segmentation approaches support its value as a measure of disease onset and progression in future studies in both presymptomatic and symptomatic genetic FTD.</AbstractText>Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.</CopyrightInformation> |
2,328,537 | Phytochemical study, molecular docking, genotoxicity and therapeutic efficacy of the aqueous extract of the stem bark of Ximenia americana L. in the treatment of experimental COPD in rats. | Ximenia americana L. is popularly known as yellow plum, brave plum or tallow wood. All the parts of this plant are used in popular medicine. Its reddish and smooth bark are used to treat skin infections, inflammation of the mucous membranes and in the wound healing process.</AbstractText>Verification of phytochemical profile, the molecular interaction between flavonoid, (-) epi-catechin and 5-LOX enzyme, by means of in silico study, the genotoxic effect and to investigate the pharmacological action of the aqueous extract of the stem bark of X. americana in pulmonary alterations caused by experimental COPD in Rattus norvegicus.</AbstractText>The identification of secondary metabolites was carried out by TLC and HPLC chromatographic methods, molecular anchoring tests were applied to analyze the interaction of flavonoid present in the extract with the enzyme involved in pulmonary inflammation process and the genotoxic effect was assessed by comet assay and micronucleus test. For induction of COPD, male rats were distributed in seven groups. The control group was exposed only to ambient air and six were subjected to passive smoke inhalations for 20 min/day for 60 days. One of the groups exposed to cigarette smoke did not receive treatment. The others were treated by inhalation with beclomethasone dipropionate (400 mcg/kg) and aqueous and lyophilized extracts of X. americana (500 mg/kg) separately or in combination for a period of 15 days. The structural and inflammatory pulmonary alterations were evaluated by histological examination. Additional morphometric analyses were performed, including the alveolar diameter and the thickness of the right ventricle wall.</AbstractText>The results showed that the aqueous extract of the bark of X. americana possesses (-) epi -catechin, in silico studies with 5-LOX indicate that the EpiC ligand showed better affinity parameters than the AracA ligand, which is in accordance with the results obtained in vivo studies. Genotoxity was not observed at the dose tested and the extract was able to stagnate the alveolar enlargement caused by the destruction of the interalveolar septa, attenuation of mucus production and decrease the presence of collagen fibers in the bronchi of animals submitted to cigarette smoke.</AbstractText>Altogether, the results proved that the aqueous extract of X. americana presents itself as a new option of therapeutic approach in the treatment of COPD.</AbstractText>Copyright © 2019 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,328,538 | Targeting Extracellular Heat Shock Protein 70 Ameliorates Doxorubicin-Induced Heart Failure Through Resolution of Toll-Like Receptor 2-Mediated Myocardial Inflammation. | Background Heart failure (HF) is one of the most significant causes of morbidity and mortality for the cardiovascular risk population. We found previously that extracellular HSP70 (heat shock protein) is an important trigger in cardiac hypertrophy and fibrosis, which are associated with the development of heart dysfunction. However, the potential role of HSP70 in response to HF and whether it could be a target for the therapy of HF remain unknown. Methods and Results An HF mouse model was generated by a single IP injection of doxorubicin at a dose of 15 mg/kg. Ten days later, these mice were treated with an HSP70 neutralizing antibody for 5 times. We observed that doxorubicin treatment increased circulating HSP70 and expression of HSP70 in myocardium and promoted its extracellular release in the heart. Blocking extracellular HSP70 activity by its antibody significantly ameliorated doxorubicin-induced left ventricular dilation and dysfunction, which was accompanied by a significant inhibition of cardiac fibrosis. The cardioprotective effect of the anti-HSP70 antibody was largely attributed to its ability to promote the resolution of myocardial inflammation, as evidenced by its suppression of the toll-like receptor 2-associated signaling cascade and modulation of the intracellular distribution of the p50 and p65 subunits of nuclear factor-κB. Conclusions Extracellular HSP70 serves as a noninfectious inflammatory factor in the development of HF, and blocking extracellular HSP70 activity may provide potential therapeutic benefits for the treatment of HF. |
2,328,539 | Association between bone mineral density and brain parenchymal atrophy and ventricular enlargement in healthy individuals. | Bone, vascular smooth muscle, and arachnoid trabeculae are composed of the same type of collagen. However, no studies have investigated the relationship between bone mineral density deterioration and cerebral atrophy, both of which occur in normal, healthy aging. Accordingly, we evaluated whether bone mineral density was associated with brain parenchymal atrophy and ventricular enlargement in healthy individuals. Intracranial cavity, brain parenchyma, and lateral ventricles volumes were measured using brain magnetic resonance imaging (MRI) with a semiautomated tool. We included 267 individuals with no history of dementia or other neurological diseases, who underwent one or more dual-energy X-ray absorptiometry scans and brain MRIs simultaneously (within 3 years of each other) at our hospital over an 11-year period. We found that progression of brain parenchymal atrophy was positively associated with bone mineral density after full adjustment (B, 0.94; P < 0.001). In addition, individuals with osteoporosis showed more parenchymal atrophy among those younger than 80 years. In addition, we observed greater ventricular enlargement in individuals with osteoporosis among those older than 80 years. We believe that osteoporosis may play a role in the acceleration of parenchymal atrophy during the early-stages, and ventricular enlargement in the late-stages, of normal aging-related cerebral atrophy. |
2,328,540 | Intracardiac Echocardiography-Guided Biopsy of a Left Ventricular Mass. | Intracardiac echocardiography (ICE) has been used to guide percutaneous biopsies of atrial masses. However, the use of ICE to direct left ventricular mass sampling has not been described. This clinical vignette illustrates the role of ICE-guided left ventricular biopsy in establishing a definitive diagnosis after a failed computed tomography-guided lung mass biopsy. (<b>Level of Difficulty: Intermediate.</b>). |
2,328,541 | Myelomeningocele-associated hydrocephalus: nationwide analysis and systematic review. | Myelomeningocele (MMC), the most severe form of spina bifida, is characterized by protrusion of the meninges and spinal cord through a defect in the vertebral arches. The management and prevention of MMC-associated hydrocephalus has evolved since its initial introduction with regard to treatment of MMC defect, MMC-associated hydrocephalus treatment modality, and timing of hydrocephalus treatment.</AbstractText>The Nationwide Inpatient Sample (NIS) database from the years 1998-2014 was reviewed and neonates with spina bifida and hydrocephalus status were identified. Timing of hydrocephalus treatment, delayed treatment (DT) versus simultaneous MMC repair with hydrocephalus treatment (ST), and treatment modality (ETV vs ventriculoperitoneal shunt [VPS]) were analyzed. Yearly trends were assessed with univariable logarithmic regression. Multivariable logistic regression identified correlates of inpatient shunt failure. A PRISMA systematic literature review was conducted that analyzed data from studies that investigated 1) MMC closure technique and hydrocephalus rate, 2) hydrocephalus treatment modality, and 3) timing of hydrocephalus treatment.</AbstractText>A weighted total of 10,627 inpatient MMC repairs were documented in the NIS, 8233 (77.5%) of which had documented hydrocephalus: 5876 (71.4%) were treated with VPS, 331 (4.0%) were treated with ETV, and 2026 (24.6%) remained untreated on initial inpatient stay. Treatment modality rates were stable over time; however, hydrocephalic patients in later years were less likely to receive hydrocephalus treatment during initial inpatient stay (odds ratio [OR] 0.974, p = 0.0331). The inpatient hydrocephalus treatment failure rate was higher for patients who received ETV treatment (17.5% ETV failure rate vs 7.9% VPS failure rate; p = 0.0028). Delayed hydrocephalus treatment was more prevalent in the later time period (77.9% vs 69.5%, p = 0.0287). Predictors of inpatient shunt failure included length of stay, shunt infection, jaundice, and delayed treatment. A longer time between operations increased the likelihood of inpatient shunt failure (OR 1.10, p < 0.0001). However, a meta-analysis of hydrocephalus timing studies revealed no difference between ST and DT with respect to shunt failure or infection rates.</AbstractText>From 1998 to 2014, hydrocephalus treatment has become more delayed and the number of hydrocephalic MMC patients not treated on initial inpatient stay has increased. Meta-analysis demonstrated that shunt malfunction and infection rates do not differ between delayed and simultaneous hydrocephalus treatment.</AbstractText> |
2,328,542 | Progressive hydrocephalus despite early complete reversal of hindbrain herniation after prenatal open myelomeningocele repair. | Open prenatal myelomeningocele (MMC) repair is typically associated with reversal of in utero hindbrain herniation (HBH) and has been posited to be associated with a reduction in both postoperative prenatal and immediate postnatal hydrocephalus (HCP) risks. However, the long-term postnatal risk of HCP following HBH reversal in these cases has not been well defined. The authors describe the results of a long-term HCP surveillance in a cohort of patients who underwent prenatal MMC repair at their institution.</AbstractText>A retrospective review of all prenatal MMC repair operations performed at the Mayo Clinic between 2012 and 2017 was conducted. Pertinent data regarding the clinical courses of these patients before and after MMC repair were summarized. Outcomes of interest were occurrences of HBH and HCP and the need for intervention.</AbstractText>A total of 9 prenatal MMC repair cases were identified. There were 7 cases in which MRI clearly demonstrated prenatal HBH, and of these 86% (6/7) had evidence of HBH reversal after repair and prior to delivery. After a mean postnatal follow-up of 20 months, there were 3 cases of postnatal HCP requiring intervention. One case that failed to show complete HBH reversal after MMC repair required early ventriculoperitoneal shunting. The other 2 cases were of progressive, gradual-onset HCP despite complete prenatal HBH reversal, requiring endoscopic third ventriculostomy with choroid plexus cauterization at ages 5 and 7 months.</AbstractText>Although prenatal MMC repair can achieve HBH reversal in a majority of well-selected cases, the prevention of postnatal HCP requiring intervention appears not to be predicated on this outcome alone. In fact, it appears that in a subset of cases in which HBH reversal is achieved, patients can experience a progressive, gradual-onset HCP within the 1st year of life. These findings support continued rigorous postnatal surveillance of all prenatal MMC repair patients, irrespective of postoperative HBH outcome.</AbstractText> |
2,328,543 | Navigable Channel-Based Trans-Sulcal Resection of Third Ventricular Colloid Cysts: A Multicenter Retrospective Case Series and Review of the Literature. | Developments in frameless neuronavigation and tubular retractors hold the potential for minimizing iatrogenic injury to the overlying cortex and subcortical tracts, with improved access to the ventricular system. The objective of the present study was to evaluate the surgical outcomes after resection of third ventricular colloid cysts using an integrated neuronavigation and channel-based approach.</AbstractText>We performed a multicenter retrospective analysis of surgical Outcomes after surgical resection of third ventricular colloid cysts via a transtubular trans-sulcal approach.</AbstractText>A total of 16 patients were included, with a mean age of 42 years (range, 23-62 years). The mean maximum diameter of cysts was 14 mm (range, 7-28 mm), and preoperative hydrocephalous was present in 12 patients (75%). Gross total resection was achieved in all 16 cases. Of the 12 patients, 4 (25%) had undergone septum pellucidotomy, in addition to cyst resection. No case had required conversion to open craniotomy. No perioperative mortalities occurred. Three patients (18.8%) had developed transient memory deficits, 1 of whom had also developed a pulmonary thromboembolism. The median length of hospital stay was 4 days (range, 2-18 days). All the patients reported resolution of preoperative symptoms at the 1-month follow-up examination. Only 1 patient (6.25%) had required insertion of a ventriculoperitoneal shunt. The median follow-up duration was 6.5 months (range, 3-24 months), and no recurrences were observed.</AbstractText>Use of a channel-based navigable retractor provided a minimal trans-sulcal approach to third ventricular colloid cysts with the benefit of bimanual surgical control in an air medium for definitive resection of third ventricular colloid cysts.</AbstractText>Copyright © 2019. Published by Elsevier Inc.</CopyrightInformation> |
2,328,544 | Suprasellar Cyst Presenting With Bobble-Head Doll Syndrome. | Bobble-head doll syndrome is a rare neurological syndrome presenting with repetitive anteroposterior head movements. It is usually associated with expansile cystic lesions in the third ventricular region.</AbstractText>An 8-year-old boy presented with involuntary bobbling head movements. Magnetic resonance imaging of the brain revealed an extensive suprasellar cyst resulting in obstructive hydrocephalus. Endoscopic ventriculo-cysto-cisternostomy resulted in improved clinical outcome.</AbstractText>Endoscopic ventriculo-cysto-cisternostomy is an effective, less-invasive technique in the treatment of suprasellar cysts that results in resolution of the bobbling head movements.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,545 | Simulation of Brain Response to Noncontact Impacts Using Coupled Eulerian-Lagrangian Method. | Finite element (FE) method has been widely used for gaining insights into the mechanical response of brain tissue during impacts. In this study, a coupled Eulerian-Lagrangian (CEL) formulation is implemented in impact simulations of a head system to overcome the mesh distortion difficulties due to large deformation in the cerebrospinal fluid (CSF) region and provide a biofidelic model of the interaction between the brain and skull. The head system used in our FE model is constructed from the transverse section of the human brain, with CSF modeled by Eulerian elements. Spring connectors are applied to represent the pia-arachnoid connection between the brain and skull. Validations of the CEL formulation and the FE model are performed using the experimental results. The dynamic response of brain tissue under noncontact impacts and the brain regions susceptible to injury are evaluated based on the intracranial pressure (ICP), maximum principal strain (MPS), and von Mises stress. While tracking the critical MPS location on the brain, higher likelihood of contrecoup injury than coup injury is found when sudden brain-skull motion takes place. The accumulation effect of CSF in the ventricle system, under large relative brain-skull motion, is also identified. The FE results show that adding relative angular velocities, to the translational impact model, not only causes a diffuse high strain area, but also cause the temporal lobes to be susceptible to cerebral contusions since the protecting CSF is prone to be squeezed away at the temporal sites due to the head rotations. |
2,328,546 | An Unbiased Proteomics Method to Assess the Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes. | Human pluripotent stem cell (hPSC)-derived cardiomyocytes exhibit the properties of fetal cardiomyocytes, which limits their applications. Various methods have been used to promote maturation of hPSC-cardiomyocytes; however, there is a lack of an unbiased and comprehensive method for accurate assessment of the maturity of hPSC-cardiomyocytes.</AbstractText>We aim to develop an unbiased proteomics strategy integrating high-throughput top-down targeted proteomics and bottom-up global proteomics for the accurate and comprehensive assessment of hPSC-cardiomyocyte maturation.</AbstractText>Utilizing hPSC-cardiomyocytes from early- and late-stage 2-dimensional monolayer culture and 3-dimensional engineered cardiac tissue, we demonstrated the high reproducibility and reliability of a top-down proteomics method, which enabled simultaneous quantification of contractile protein isoform expression and associated post-translational modifications. This method allowed for the detection of known maturation-associated contractile protein alterations and, for the first time, identified contractile protein post-translational modifications as promising new markers of hPSC-cardiomyocytes maturation. Most notably, decreased phosphorylation of α-tropomyosin was found to be associated with hPSC-cardiomyocyte maturation. By employing a bottom-up global proteomics strategy, we identified candidate maturation-associated markers important for sarcomere organization, cardiac excitability, and Ca2+</sup> homeostasis. In particular, upregulation of myomesin 1 and transmembrane 65 was associated with hPSC-cardiomyocyte maturation and validated in cardiac development, making these promising markers for assessing maturity of hPSC-cardiomyocytes. We have further validated α-actinin isoforms, phospholamban, dystrophin, αB-crystallin, and calsequestrin 2 as novel maturation-associated markers, in the developing mouse cardiac ventricles.</AbstractText>We established an unbiased proteomics method that can provide accurate and specific assessment of the maturity of hPSC-cardiomyocytes and identified new markers of maturation. Furthermore, this integrated proteomics strategy laid a strong foundation for uncovering the molecular pathways involved in cardiac development and disease using hPSC-cardiomyocytes.</AbstractText> |
2,328,547 | Anesthetic management of stab wound in right ventricle of heart. | Stab wound in right ventricle of heart requires a prompt and focused surgical intervention. Cardiac tamponade is a common finding when dealing with stabbed hearts, which must be diagnosed and treated in a timely fashion. We report a case of 28-year-old man who presented in emergency department following accidental stab trauma during a religious ceremony. The challenges faced in the perioperative period were the management of impending cardiac tamponade and hemodynamic stability. |
2,328,548 | Comparative Volumetric Analysis of the Brain and Cerebrospinal Fluid in Chiari Type I Malformation Patients: A Morphological Study. | Chiari Type I malformation (CM-I) is defined as the migration of cerebellar tonsils from the foramen magnum in the caudal direction and is characterized by the disproportion of the neural structures. The aim of this study was to investigate the brain volume differences between CM-I patients and normal population using a comparative volumetric analysis.</AbstractText>140 patients with CM-I and 140 age- and sex-matched healthy controls were included in this study. The magnetic resonance imaging (MRI) data of both groups were analyzed with an automated MRI brain morphometry system. Total intracranial, cerebrum, cerebellum, brainstem, cerebrospinal fluid (CSF), and lateral ventricle volumes as well as cerebrum and cerebellum gray/white matter (GM/WM) volumes were measured. Statistical analysis was performed.</AbstractText>Both total CSF and lateral ventricle volumes and volume percentages (Pct) were found significantly higher in CM-I patients compared to the control group. However, there were significant decreases in cerebrum and cerebellum volume Pct in CM-I patients. Although there were no significant differences in cerebrum WM volumes and volume Pct, cerebrum GM volume Pct were found to be significantly lower in CM-I patients.</AbstractText>Revealing the increased CSF and lateral ventricle volume, and volume Pct supported concomitant ventricular enlargement and hydrocephalus in some CM-I patients. Decreased cerebrum GM volume Pct compared to the control group might be the underlying factor of some cortical dysfunctions in CM-I patients.</AbstractText> |
2,328,549 | Telovelar approach for microsurgical resection of fourth ventricular subependymoma arising from rhomboid fossa: operative video and technical nuances. | Fourth ventricular tumors have traditionally been removed via transvermian approaches, which can result in potential dysequilibrium and mutism. The telovelar approach is an excellent alternative to widely expose fourth ventricular tumors without transgressing the cerebellar vermis. This is achieved by opening the cerebellomedullary fissure and incising the tela choroidea and inferior medullary velum, which form the lower half of the roof of the fourth ventricle. In this operative video manuscript, the authors demonstrate microsurgical resection of a fourth ventricular subependymoma arising from the rhomboid fossa via the telovelar approach. The key technical nuance in this video is to demonstrate a gentle and safe technique to identify a dissectable plane to peel the tumor off of the rhomboid fossa using a microspreading technique with fine micro-bayonetted forceps. A gross-total resection was achieved, and the patient was neurologically intact. The video can be found here: https://youtu.be/ZEHHbUGb9zk. |
2,328,550 | Posterior transcallosal intervenous-interforniceal approach to a periaqueductal tumor. | Described by Dandy in 1921, the posterior interhemispheric transcallosal approach provides an operative corridor to the pineal region, posterior third ventricle, and upper midbrain. Intervenous-interforniceal and paravenous-interforniceal variants have been utilized for midline and paramidline pathology, respectively. The intervenous-interforniceal variant capitalizes on the natural separation of the internal cerebral veins, which are found medial to the forniceal crura at this level, to provide a safe corridor to the tumor while minimizing the risk of injury to the fornices. Here, the authors describe a posterior interhemispheric transcallosal approach using the intervenous-interforniceal variant for resection of a periaqueductal pilocytic astrocytoma. The video can be found here: https://youtu.be/mtQKEXEveTg. |
2,328,551 | Cisterna magna reconstruction with arachnoid suturing in brainstem surgery. | We present an effective and easily applied technique for cisterna magna reconstruction with arachnoid suturing in brainstem surgery. Suturing with 10-0 monofilament was done in a patient with a medulla oblongata hemangioblastoma (diagnosed von Hippel-Lindau disease). Seven years later, follow-up imaging revealed a new lesion close to the previous one and the patient underwent reoperation. The craniotomy and dural incision were repeated, and the intact arachnoid was visualized with no meningocerebral adhesions. This technique preserves normal anatomic landmarks and facilitates and shortens dissection in reoperations, almost like a virgin case. We propose this technique for every lower brainstem and fourth ventricle procedure. The video can be found here: https://youtu.be/RKMcSoK6ycY. |
2,328,552 | Endoscopic endonasal approach for brainstem cavernous malformation. | This 25-year-old woman presented after a second hemorrhage from a mesencephalic cavernous malformation. High-definition fiber tracking demonstrated lateral displacement of the corticospinal tracts, making a midline approach ideal. The lesion appeared to present to the third ventricle, but a transcallosal approach was abandoned due to the posterior third ventricular location and after FIESTA imaging revealed a superior and medial rim of normal parenchyma that would have to be transgressed to access the malformation. An endoscopic endonasal approach with interdural pituitary hemitransposition was performed. The interpeduncular cistern was accessed and the thalamoperforating arteries dissected to access the cavernous malformation that was completely removed in a piecemeal fashion. The patient's preexisting internuclear ocular palsies and hemiparesis were slightly worsened after surgery as predicted by a drop in anterior tibialis motor evoked potentials. Postoperative MRI showed no infarct, and the hemiparesis was back to baseline at 1-month follow-up. The video can be found here: https://youtu.be/e6203R9HHmk. |
2,328,553 | A review of exercise pulmonary hypertension in systemic sclerosis. | In general, pulmonary vascular disease has important negative prognostic implications, regardless of the associated condition or underlying mechanism. In this regard, systemic sclerosis is of particular interest as it is the most common connective tissue disease associated with pulmonary hypertension, and a well-recognized at-risk population. In the setting of systemic sclerosis and unexplained dyspnea, the concept of using exercise to probe for underlying pulmonary vascular disease has acquired significant interest. In theory, a diagnosis of systemic sclerosis-associated exercise pulmonary hypertension may allow for earlier therapeutic intervention and a favorable alteration in the natural history of the pulmonary vascular disease. In the context of underlying systemic sclerosis, the purpose of this article is to provide a comprehensive review of the evolving definition of exercise pulmonary hypertension, the current role and methodologies for non-invasive and invasive exercise testing, and the importance of the right ventricle. |
2,328,554 | Adult neurogenesis in the mammalian dentate gyrus. | Earlier observations in neuroscience suggested that no new neurons form in the mature central nervous system. Evidence now indicates that new neurons do form in the adult mammalian brain. Two regions of the mature mammalian brain generate new neurons: (a) the border of the lateral ventricles of the brain (subventricular zone) and (b) the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. This review focuses only on new neuron formation in the dentate gyrus of the hippocampus. During normal prenatal and early postnatal development, neural stem cells (NSCs) give rise to differentiated neurons. NSCs persist in the dentate gyrus SGZ, undergoing cell division, with some daughter cells differentiating into functional neurons that participate in learning and memory and general cognition through integration into pre-existing neural networks. Axons, which emanate from neurons in the entorhinal cortex, synapse with dendrites of the granule cells (small neurons) of the dentate gyrus. Axons from granule cells synapse with pyramidal cells in the hippocampal CA3 region, which send axons to synapse with CA1 hippocampal pyramidal cells that send their axons out of the hippocampus proper. Adult neurogenesis includes proliferation, differentiation, migration, the death of some newly formed cells and final integration of surviving cells into neural networks. We summarise these processes in adult mammalian hippocampal neurogenesis and discuss the roles of major signalling molecules that influence neurogenesis, including neurotransmitters and some hormones. The recent controversy raised concerning whether or not adult neurogenesis occurs in humans also is discussed. |
2,328,555 | Comparative Early Hemodynamic Profiles in Patients Presenting to the Emergency Department with Septic and Nonseptic Acute Circulatory Failure Using Focused Echocardiography. | We evaluated the early hemodynamic profile of patients presenting with acute circulatory failure to the Emergency Department (ED) using focused echocardiography performed by emergency physicians after a dedicated training program.</AbstractText>Patients presenting to the ED with an acute circulatory failure of any origin were successively examined by a recently trained emergency physician and by an expert in critical care echocardiography. Operators independently performed and interpreted online echocardiographic examinations to determine the leading mechanism of acute circulatory failure.</AbstractText>Focused echocardiography could be performed in 100 of 114 screened patients (55 with sepsis/septic shock and 45 with shock of other origin) after a median fluid loading of 500 mL (interquartile range: 187-1,500 mL). A hypovolemic profile was predominantly observed whether the acute circulatory failure was of septic origin or not (33/55 [60%] vs. 23/45 [51%]: P = 0.37). Although a vasoplegic profile associated with a hyperkinetic left ventricle was most frequently identified in septic patients when compared with their counterparts (17/55 [31%] vs. 5/45 [11%]: P = 0.02), early left or right ventricular failure was observed in 31% of them. Hemodynamic profiles were adequately appraised by recently trained emergency physicians, as reflected by a good-to-excellent agreement with the expert's assessment (Κ: 0.61-0.85).</AbstractText>Hypovolemia was predominantly identified in patients presenting to the ED with acute circulatory failure. Although vasoplegia was more frequently associated with sepsis, early ventricular dysfunction was also depicted in septic patients. Focused echocardiography seemed reliable when performed by recently trained emergency physicians without previous experience in ultrasound.</AbstractText> |
2,328,556 | Brain lesion distribution criteria distinguish demyelinating diseases in China. | To verify the utility of brain lesion distribution criteria in distinguishing multiple sclerosis (MS) from aquaporin-4 (AQP4)-immunoglobulin G (IgG)-positive/-negative neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated encephalomyelitis (MOG-EM) in the Chinese population.</AbstractText>A total of 253 patients with MS (80), NMOSD (129 AQP4-IgG positive, 34 AQP4-IgG negative), and MOG-EM (10) were enrolled. Anonymized magnetic resonance imaging results were scored on the previous reported criteria of "at least one lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion; or a Dawson's finger-type lesion." Chi-squared test (or Fisher's exact test) was used to analyze the data.</AbstractText>The distribution criteria were able to distinguish MS with a same sensitivity of 93.8% from all type of NMOSD and MOG-EM, with a specificity of 89.7% from the whole NMOSD cohort, 89.1% from AQP4-IgG-positive NMOSD 91.2% from AQP4-IgG-negative NMOSD, and 70.0% from MOG-EM. Dawson's finger-type lesion was the most sensitive and specific feature, whereas the U-fiber lesion was the least.</AbstractText>The brain lesion distribution criteria were helpful in distinguishing MS from NMOSD and MOG-EM in the Chinese population. Dawson's finger-type lesion was highly suggestive of MS.</AbstractText>© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.</CopyrightInformation> |
2,328,557 | Does Compression of the Fourth Ventricle Cause Preterm Labor? Analysis of Data From the PROMOTE Study. | The technique for the compression of the fourth ventricle (CV4) in the brain has been described as a method of reaching the physiologic centers that reside in its floor and of restoring optimal flow of the cerebrospinal fluid. However, a study published as an abstract in 1992 questioned whether CV4, when applied to pregnant women, could induce uterine contractions and possibly labor.</AbstractText>To further examine whether CV4 could induce uterine contractions and labor as part of the osteopathic manipulative treatment (OMT) protocol used in the Pregnancy Research in Osteopathic Manipulation Optimizing Treatment Effects (PROMOTE) study.</AbstractText>Labor and delivery data collected during the PROMOTE study from 2007-2011 were analyzed. The PROMOTE study was funded by the National Institutes of Health and was a randomized controlled clinical trial that measured the primary outcomes of back-specific functioning and pain in pregnant women aged 18 to 34 years. Participants were randomly divided into 3 groups-usual obstetric care only, placebo ultrasound treatment plus usual obstetric care, and OMT plus usual obstetric care. Study participants were scheduled for 7 treatment visits. Presented data were gathered from labor and delivery records.</AbstractText>Four hundred participants were included. No significant differences were identified between treatment groups for the development of high-risk status (P=.293) or preterm delivery (P=.673). Evaluation of high-risk status by preterm delivery for the groups also showed no significant differences between groups (P=.455).</AbstractText>The application of CV4 as part of an OMT protocol during the third trimester caused neither a higher incidence of preterm labor nor the development of high-risk status.</AbstractText> |
2,328,558 | Deterioration of biventricular strain is an early marker of cardiac involvement in confirmed sarcoidosis. | Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients.</AbstractText>LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: -18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001).</AbstractText>Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.</AbstractText>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.</CopyrightInformation> |
2,328,559 | Plasmatic NT-proBNP could help to select cases for screening echocardiography in healthy infants with Respiratory Syncytial Virus infection. | In Respiratory Syncytial Virus infection, the early identification of infants at risk for severe disease in order to potentially decrease morbidity could be considered a major goal. Current guidelines recommend only clinical observation for this purpose in infants without known comorbidities. However, recent evidence shows that the presence of pulmonary hypertension in this population is a relevant risk factor for the development of a severe illness, even in healthy infants. The determination of plasmatic NT-proBNP levels could help to identify those cases that benefit of echocardiographic screening to detect pulmonary hypertension in this population during hospitalization. |
2,328,560 | Predicting endoscopic third ventriculostomy success in adult hydrocephalus: preliminary assessment of a modified ETV success score for adults (ETVSS-A) in a series of 47 patients. | Endoscopic third ventriculostomy is an established treatment for non-communicating hydrocephalus. In carefully selected patients, it can be adopted for the management of communicating variant; however controversy exists in regards to the definition of the appropriate candidates. Predictive score of Endoscopic Third Ventriculostomy Success (ETVSS) has been reported for pediatric and mixed populations only. Our purpose was to define an ETV success score for adult population (ETVSS-A), measuring the strength of correlation between preoperative score retrospectively evaluated and the success rates achieved in a class of adult patients.</AbstractText>A retrospective analysis of 47 cases which received ETV procedure at our Institution between 2015 and 2018 was run. Demographic data,clinical history,preoperative and postoperative signs were reviewed and ETVSS-A was calculated.Thereafter ETVSS-A results were compared with the actual success rates.</AbstractText>Twenty-nine patients (61.7%) presented unchanged or improved clinical status with a mean ETVSS-A of 54.5%; 18 patients (38.3%) worsened with mean ETVSS-A of 37.7%. We found that age, type of hydrocephalus and symptoms of admission are each apart important factors in predicting ETV success: older patients and those with non-obstructive hydrocephalus had the lowest predicted ETV success. In patients in whom ETV was actually successful, the preoperative ETVSS-A was significantly higher as compared to those patients in whom we observed a poor surgical outcome.</AbstractText>From the results of this series, though small and retrospectively analyzed, it seems that ETVSS-A can be considered as a useful instrument to help neurosurgeon in predicting the ETV success and though define a more accurate surgical strategy in cases of hydrocephalus. Wider series and prospective studies are attended to validate these preliminary results.</AbstractText> |
2,328,561 | Contrast Echocardiography in two-dimensional left ventricular measurements: comparison with 256-row multi-detector computed tomography as a reference standard in Beagles. | Unenhanced echocardiography (UE), commonly used in veterinary practice, is limited by left ventricular (LV) foreshortening and observer dependency. Contrast echocardiography (CE) was used to compare two-dimensional (2D) LV measurements made using UE and 256-row multi-detector computed tomography (MDCT) as a reference standard. Seven healthy beagle dogs were evaluated in this study. Measurements obtained using CE, including LV wall thickness, internal diameter, and longitudinal and transverse length, were significantly greater than those obtained using UE. Measurements of LV internal dimension in diastole (LVIDd) and systole (LVIDs) were significantly larger with CE compared UE. Regardless of the cardiac cycle, LV longitudinal (LVLd and LVLs) and transverse diameter (LVTDd and LVTDs) measurements were significantly different with CE and approximated values from MDCT. Among automatically calculated parameters, LV end-systolic volume and the relative wall thickness were significantly different between UE and CE. In CE, the correlation coefficients of 4 major parameters (<i>r</i> = 0.87 in LVIDd; 0.91 in LVIDs; 0.87 in LVLd; and 0.81 in LVLs) showed higher values compared to the UE (<i>r</i> = 0.68 in LVIDd, 0.71 in LVIDs, 0.69 in LVLd, and 0.35 in LVLs). Inter-observer agreement was highest for MDCT and higher for CE than UE. In conclusion, CE is more accurate and reproducible than UE in assessing 2D LV measurements and can overcome the limitations of UE including LV foreshortening and high observer dependency. |
2,328,562 | Primary neuroendocrine tumour of the left ventricle. | Neuroendocrine tumours are rare neoplasms typically arising in the gastrointestinal tract that may result in carcinoid syndrome and/or acquired valvular dysfunction. Herein, we present a unique case of a 68-year-old asymptomatic woman with a primary left ventricular neuroendocrine tumour. |
2,328,563 | Spatio-Temporal Convolutional LSTMs for Tumor Growth Prediction by Learning 4D Longitudinal Patient Data. | Prognostic tumor growth modeling via volumetric medical imaging observations can potentially lead to better outcomes of tumor treatment management and surgical planning. Recent advances of convolutional networks (ConvNets) have demonstrated higher accuracy than traditional mathematical models can be achieved in predicting future tumor volumes. This indicates that deep learning based data-driven techniques may have great potentials on addressing such problem. However, current 2D image patch based modeling approaches can not make full use of the spatio-temporal imaging context of the tumor's longitudinal 4D (3D + time) patient data. Moreover, they are incapable to predict clinically-relevant tumor properties, other than the tumor volumes. In this paper, we exploit to formulate the tumor growth process through convolutional Long Short-Term Memory (ConvLSTM) that extract tumor's static imaging appearances and simultaneously capture its temporal dynamic changes within a single network. We extend ConvLSTM into the spatio-temporal domain (ST-ConvLSTM) by jointly learning the inter-slice 3D contexts and the longitudinal or temporal dynamics from multiple patient studies. Our approach can incorporate other non-imaging patient information in an end-to-end trainable manner. Experiments are conducted on the largest 4D longitudinal tumor dataset of 33 patients to date. Results validate that the proposed ST-ConvLSTM model produces a Dice score of 83.2%±5.1% and a RVD of 11.2%±10.8%, both statistically significantly outperforming (p < 0.05) other compared methods of traditional linear model, ConvLSTM, and generative adversarial network (GAN) under the metric of predicting future tumor volumes. Additionally, our new method enables the prediction of both cell density and CT intensity numbers. Last, we demonstrate the generalizability of ST-ConvLSTM by employing it in 4D medical image segmentation task, which achieves an averaged Dice score of 86.3%±1.2% for left-ventricle segmentation in 4D ultrasound with 3 seconds per patient case. |
2,328,564 | Brain Changes Induced by Electroconvulsive Therapy Are Broadly Distributed.<Pagination><StartPage>451</StartPage><EndPage>461</EndPage><MedlinePgn>451-461</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.biopsych.2019.07.010</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0006-3223(19)31543-4</ELocationID><Abstract><AbstractText Label="BACKGROUND">Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response.</AbstractText><AbstractText Label="METHODS">Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites.</AbstractText><AbstractText Label="RESULTS">Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean ± SD of 1.04 ± 1.03% (Cohen's d = 1.01, p < .001) and the subcortical gray matter volume increased by 1.47 ± 1.05% (d = 1.40, p < .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation ρ = -.44, p < .001), while total white matter volume remained unchanged (d = -0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome.</AbstractText><AbstractText Label="CONCLUSIONS">The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.</AbstractText><CopyrightInformation>Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ousdal</LastName><ForeName>Olga Therese</ForeName><Initials>OT</Initials><AffiliationInfo><Affiliation>Department of Radiology, Haukeland University Hospital, Bergen, Norway. Electronic address: olgatherese.ousdal@gmail.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Argyelan</LastName><ForeName>Miklos</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Center for Psychiatric Neuroscience at the Feinstein Institute for Medical Research, New York, New York.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Narr</LastName><ForeName>Katherine L</ForeName><Initials>KL</Initials><AffiliationInfo><Affiliation>Departments of Neurology, Psychiatry, and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abbott</LastName><ForeName>Christopher</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, New Mexico.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wade</LastName><ForeName>Benjamin</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Departments of Neurology, Psychiatry, and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vandenbulcke</LastName><ForeName>Mathieu</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Geriatric Psychiatry, University Psychiatric Center Katholieke Universiteit Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Urretavizcaya</LastName><ForeName>Mikel</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Psychiatry, Bellvitge University Hospital-Bellvitge Biomedical Research Institute; Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tendolkar</LastName><ForeName>Indira</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain Cognition and Behavior, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands; Faculty of Medicine and Landschaftsverband Rheinland Clinic for Psychiatry and Psychotherapy, University of Duisburg-Essen, Duisburg-Essen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Takamiya</LastName><ForeName>Akihiro</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Center for Psychiatry and Behavioral Science, Komagino Hospital, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stek</LastName><ForeName>Max L</ForeName><Initials>ML</Initials><AffiliationInfo><Affiliation>Geestelijke GezondheidsZorg inGeest Specialized Mental Health Care, Amsterdam, The Netherlands; Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Soriano-Mas</LastName><ForeName>Carles</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Psychiatry, Bellvitge University Hospital-Bellvitge Biomedical Research Institute; Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Redlich</LastName><ForeName>Ronny</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paulson</LastName><ForeName>Olaf B</ForeName><Initials>OB</Initials><AffiliationInfo><Affiliation>Neurobiology Research Unit, Department of Neurology, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oudega</LastName><ForeName>Mardien L</ForeName><Initials>ML</Initials><AffiliationInfo><Affiliation>Geestelijke GezondheidsZorg inGeest Specialized Mental Health Care, Amsterdam, The Netherlands; Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Opel</LastName><ForeName>Nils</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany; Interdisciplinary Centre for Clinical Research (IZKF), University of Muenster, Muenster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nordanskog</LastName><ForeName>Pia</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kishimoto</LastName><ForeName>Taishiro</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kampe</LastName><ForeName>Robin</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jorgensen</LastName><ForeName>Anders</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Psychiatric Center Copenhagen (Rigshospitalet), Mental Health Services of the Capital Region of Denmark, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hanson</LastName><ForeName>Lars G</ForeName><Initials>LG</Initials><AffiliationInfo><Affiliation>Center for Magnetic Resonance, Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark; Danish Research Centre for Magnetic Resonance, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hamilton</LastName><ForeName>J Paul</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Espinoza</LastName><ForeName>Randall</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Departments of Neurology, Psychiatry, and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Emsell</LastName><ForeName>Louise</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Geriatric Psychiatry, University Psychiatric Center Katholieke Universiteit Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Eijndhoven</LastName><ForeName>Philip</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain Cognition and Behavior, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dols</LastName><ForeName>Annemieke</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Geestelijke GezondheidsZorg inGeest Specialized Mental Health Care, Amsterdam, The Netherlands; Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dannlowski</LastName><ForeName>Udo</ForeName><Initials>U</Initials><AffiliationInfo><Affiliation>Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cardoner</LastName><ForeName>Narcis</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain; Department of Mental Health, University Hospital Parc Taulí-I3PT, Sabadell, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bouckaert</LastName><ForeName>Filip</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Geriatric Psychiatry, University Psychiatric Center Katholieke Universiteit Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anand</LastName><ForeName>Amit</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Cleveland Clinic, Center for Behavioral Health, Cleveland, Ohio.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bartsch</LastName><ForeName>Hauke</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kessler</LastName><ForeName>Ute</ForeName><Initials>U</Initials><AffiliationInfo><Affiliation>Norwegian Centre for Mental Disorders Research, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oedegaard</LastName><ForeName>Ketil J</ForeName><Initials>KJ</Initials><AffiliationInfo><Affiliation>Norwegian Centre for Mental Disorders Research, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dale</LastName><ForeName>Anders M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California; Department of Neurosciences, University of California, San Diego, La Jolla, California.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oltedal</LastName><ForeName>Leif</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>GEMRIC</CollectiveName></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 MH111359</GrantID><Acronym>MH</Acronym><Agency>NIMH NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U24 DA041123</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Biol Psychiatry</MedlineTA><NlmUniqueID>0213264</NlmUniqueID><ISSNLinking>0006-3223</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Brain Stimul. 2020 Sep - Oct;13(5):1226-1231</RefSource><PMID Version="1">32442625</PMID></CommentsCorrections><CommentsCorrections RefType="CommentIn"><RefSource>Biol Psychiatry. 2021 Feb 15;89(4):e13-e14</RefSource><PMID Version="1">32768146</PMID></CommentsCorrections><CommentsCorrections RefType="CommentIn"><RefSource>Biol Psychiatry. 2021 Feb 15;89(4):e15-e16</RefSource><PMID Version="1">32768147</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003865" MajorTopicYN="Y">Depressive Disorder, Major</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004565" MajorTopicYN="Y">Electroconvulsive Therapy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D066128" MajorTopicYN="N">Gray Matter</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008279" MajorTopicYN="N">Magnetic Resonance Imaging</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Antidepressant</Keyword><Keyword MajorTopicYN="N">Biomarker</Keyword><Keyword MajorTopicYN="N">Brain</Keyword><Keyword MajorTopicYN="N">Depression</Keyword><Keyword MajorTopicYN="N">ECT</Keyword><Keyword MajorTopicYN="N">Magnetic resonance imaging</Keyword><Keyword MajorTopicYN="N">Neuroimaging</Keyword></KeywordList><InvestigatorList><Investigator ValidYN="Y"><LastName>Erchinger</LastName><ForeName>Vera Jane</ForeName><Initials>VJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Haavik</LastName><ForeName>Jan</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Evjenth Sørhaug</LastName><ForeName>Ole Johan</ForeName><Initials>OJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jørgensen</LastName><ForeName>Martin B</ForeName><Initials>MB</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bolwig</LastName><ForeName>Tom G</ForeName><Initials>TG</Initials></Investigator><Investigator ValidYN="Y"><LastName>Magnusson</LastName><ForeName>Peter</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cano</LastName><ForeName>Marta</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Pujol</LastName><ForeName>Jesús</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Menchón</LastName><ForeName>José M</ForeName><Initials>JM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Petrides</LastName><ForeName>Georgios</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Sienaert</LastName><ForeName>Pascal</ForeName><Initials>P</Initials></Investigator></InvestigatorList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>2</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>7</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>7</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>9</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>1</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>9</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31561859</ArticleId><ArticleId IdType="doi">10.1016/j.biopsych.2019.07.010</ArticleId><ArticleId IdType="pii">S0006-3223(19)31543-4</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31561226</PMID><DateRevised><Year>2019</Year><Month>09</Month><Day>27</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0715</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Sep</Month><Day>27</Day></PubDate></JournalIssue><Title>Journal of neurosurgery. Pediatrics</Title><ISOAbbreviation>J Neurosurg Pediatr</ISOAbbreviation></Journal>Intracisternal BioGlue injection in the fetal lamb: a novel model for creation of obstructive congenital hydrocephalus without additional chemically induced neuroinflammation.<Pagination><StartPage>1</StartPage><EndPage>11</EndPage><MedlinePgn>1-11</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3171/2019.6.PEDS19141</ELocationID><ELocationID EIdType="pii" ValidYN="Y">2019.6.PEDS19141</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">The authors hypothesized that new agents such as BioGlue would be as efficacious as kaolin in the induction of hydrocephalus in fetal sheep.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">This study was performed in 34 fetal lambs randomly divided into 2 studies. In the first study, fetuses received kaolin, BioGlue (2.0 mL), or Onyx injected into the cisterna magna, or no injection (control group) between E85 and E90. In the second study, fetuses received 2.0-mL or 2.5-mL injections of BioGlue into the cisterna magna between E85 and E90. Fetuses were monitored using ultrasound to assess lateral ventricle size and progression of hydrocephalus. The fetuses were delivered (E120-E125) and euthanized for histological analysis. Selected brain sections were stained for ionized calcium binding adaptor 1 (Iba1) and glial fibrillary acidic protein (GFAP) to assess the presence and activation of microglia and astroglia, respectively. Statistical comparisons were performed with Student's t-test for 2 determinations and ANOVA 1-way and 2-way repeated measures for multiple determinations.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">At 30 days after injection, the lateral ventricles were larger in all 3 groups that had undergone injection than in controls (mean diameter in controls 3.76 ± 0.05 mm, n = 5). However, dilatation was greater in the fetuses injected with 2 mL of BioGlue (11.34 ± 4.76 mm, n = 11) than in those injected with kaolin (6.4 ± 0.98 mm, n = 7) or Onyx (5.7 ± 0.31 mm, n = 6) (ANOVA, *p ≤ 0.0001). Fetuses injected with 2.0 mL or 2.5 mL of BioGlue showed the same ventricle dilatation but it appeared earlier (at 10 days postinjection) in those injected with 2.5 mL. The critical threshold of ventricle dilatation was 0.1 for all the groups, and only the BioGlue 2.0 mL and BioGlue 2.5 mL groups exceeded this critical value (at 30 days and 18 days after injection, respectively) (ANOVA, *p ≤ 0.0001). Moderate to severe hydrocephalus with corpus callosum disruption was observed in all experimental groups. All experimental groups showed ventriculomegaly with significant microgliosis and astrogliosis in the subventricular zone around the lateral ventricles. Only kaolin resulted in significant microgliosis in the fourth ventricle area (ANOVA, *p ≤ 0.005).</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">The results of these studies demonstrate that BioGlue is more effective than Onyx or kaolin for inducing hydrocephalus in the fetal lamb and results in a volume-related response by obstructive space-occupancy without local neuroinflammatory reaction. This novel use of BioGlue generates a model with potential for new insights into hydrocephalus pathology and the development of therapeutics in obstructive hydrocephalus. In addition, this model allows for the study of acute and chronic obstructive hydrocephalus by using different BioGlue volumes for intracisternal injection.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Oria</LastName><ForeName>Marc</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>1Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Duru</LastName><ForeName>Soner</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>1Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scorletti</LastName><ForeName>Federico</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>1Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>3Department of Pediatric Surgery, Hospital Bambino Gesu, Rome, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vuletin</LastName><ForeName>Fernando</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>4Department of Pediatric Surgery, Pontificia Universidad Católica de Chile, Santiago, Chile; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Encinas</LastName><ForeName>Jose L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>5Department of Pediatric Surgery, Hospital La Paz, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Correa-Martín</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>2Jesus Usón Minimally Invasive Surgery Centre (JUMISC), Caceres, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bakri</LastName><ForeName>Kenan</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>1Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jones</LastName><ForeName>Helen N</ForeName><Initials>HN</Initials><AffiliationInfo><Affiliation>1Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sanchez-Margallo</LastName><ForeName>Francisco M</ForeName><Initials>FM</Initials><AffiliationInfo><Affiliation>2Jesus Usón Minimally Invasive Surgery Centre (JUMISC), Caceres, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peiro</LastName><ForeName>Jose L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>1Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>09</Month><Day>27</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Neurosurg Pediatr</MedlineTA><NlmUniqueID>101463759</NlmUniqueID><ISSNLinking>1933-0707</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">BPD = biparietal diameter</Keyword><Keyword MajorTopicYN="N">BSA = bovine serum albumin</Keyword><Keyword MajorTopicYN="N">BioGlue</Keyword><Keyword MajorTopicYN="N">CHSS = Cincinnati Hydrocephalus Severity Scale</Keyword><Keyword MajorTopicYN="N">GFAP = glial fibrillary acidic protein</Keyword><Keyword MajorTopicYN="N">HC = head circumference</Keyword><Keyword MajorTopicYN="N">Iba1 = ionized calcium binding adaptor 1</Keyword><Keyword MajorTopicYN="N">JUMISC = Jesus Usón Minimally Invasive Surgery Centre</Keyword><Keyword MajorTopicYN="N">LVD = lateral ventricle diameter</Keyword><Keyword MajorTopicYN="N">Onyx</Keyword><Keyword MajorTopicYN="N">SVZ = subventricular zone</Keyword><Keyword MajorTopicYN="N">congenital hydrocephalus</Keyword><Keyword MajorTopicYN="N">experimental model</Keyword><Keyword MajorTopicYN="N">fetal lamb</Keyword><Keyword MajorTopicYN="N">kaolin</Keyword><Keyword MajorTopicYN="N">neuroinflammation</Keyword><Keyword MajorTopicYN="N">ventriculomegaly</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>3</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>6</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>9</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>9</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>9</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31561226</ArticleId><ArticleId IdType="doi">10.3171/2019.6.PEDS19141</ArticleId><ArticleId IdType="pii">2019.6.PEDS19141</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31561218</PMID><DateRevised><Year>2020</Year><Month>06</Month><Day>05</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0693</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Sep</Month><Day>27</Day></PubDate></JournalIssue><Title>Journal of neurosurgery</Title><ISOAbbreviation>J Neurosurg</ISOAbbreviation></Journal>Cerebrospinal fluid disturbances after transcallosal surgery: incidence and predictive factors. | Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response.</AbstractText>Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites.</AbstractText>Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean ± SD of 1.04 ± 1.03% (Cohen's d = 1.01, p < .001) and the subcortical gray matter volume increased by 1.47 ± 1.05% (d = 1.40, p < .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation ρ = -.44, p < .001), while total white matter volume remained unchanged (d = -0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome.</AbstractText>The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.</AbstractText>Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,565 | Intraoperative measurement of intraventricular pressure in dogs with communicating internal hydrocephalus. | Collapse of the lateral cerebral ventricles after ventriculo-peritoneal drainage is a fatal complication in dogs with internal hydrocephalus. It occurs due to excessive outflow of cerebrospinal fluid into the peritoneal cavity (overshunting). In most shunt systems, one-way valves with different pressure settings regulate flow into the distal catheter to avoid overshunting. The rationale for the choice of an appropriate opening pressure is a setting at the upper limit of normal intracranial pressure in dogs. However, physiological intraventricular pressure in normal dogs vary between 5 and 12 mm Hg. Furthermore, we hypothesise that intraventricular pressure in hydrocephalic dogs might differ from pressure in normal dogs and we also consider that normotensive hydrocephalus exists in dogs, as in humans. In order to evaluate intraventricular pressure in hydrocephalic dogs, twenty-three client owned dogs with newly diagnosed communicating internal hydrocephalus were examined before implantation of a ventriculo-peritoneal shunt using a single use piezo-resistive strain-gauge sensor (MicroSensor ICP probe). Ventricular volume and brain volume were measured before surgery, based on magnetic resonance images. Total ventricular volume was calculated and expressed in relation to the total volume of the brain, including the cerebrum, cerebellum, and brainstem (ventricle-brain index). Multiple logistic regression analysis was performed to assess the influence of the covariates "age", "gender", "duration of clinical signs", "body weight", and "ventricle-brain index" on intraventricular pressure. The mean cerebrospinal fluid pressure in the hydrocephalic dogs was 8.8 mm Hg (standard deviation 4.22), ranging from 3-18 mm Hg. The covariates "age", (P = 0.782), "gender" (P = 0.162), "body weight", (P = 0.065), or ventricle-brain index (P = 0.27)" were not correlated with intraventricular pressure. The duration of clinical signs before surgery, however, was correlated with intraventricular pressure (P< 0.0001). Dogs with internal hydrocephalus do not necessarily have increased intraventricular pressure. Normotensive communicating hydrocephalus exists in dogs. |
2,328,566 | Left ventricular mechanics in the acute phase of Takotsubo cardiomyopathy: distinctive ballooning patterns translate into different diastolic properties. | Although apical and midventricular Takotsubo cardiomyopathies (TTCs) share common triggers and pathophysiological features, little is known about the potential differences in left ventricular (LV) mechanistic properties between these TTC phenotypes. We sought to investigate whether LV systolic and/or diastolic function, as assessed invasively by left heart catheterization (LHC), differ according to ballooning patterns in the acute phase of TTC. One hundred and fourteen TTC patients were retrospectively identified between January 2009 and December 2015 at the University Hospital of Strasbourg, France. A comprehensive list of LV quantitative parameters was derived from LHC analysis for each patient. We examined 2 groups of patients according to ballooning patterns in the acute phase of TTC: patients with apical ballooning ("Apical group"; n = 76) and those with midventricular ballooning ("Midventricular group"; n = 38). LV minimal diastolic pressure (8.72 ± 6.72 vs. 5.02 ± 6.08 mmHg; p = 0.004), LV end diastolic pressure (23.11 ± 8.32 vs. 18.84 ± 8.06 mmHg; p = 0.01), and LV diastolic stiffness (LV stiffness 1: 0.29 ± 0.23 vs. 18.84 ± 8.06 mmHg/mL; p = 0.04-LV stiffness 2: 0.16 ± 0.08 vs. 0.12 ± 0.05 mmHg/mL; p = 0.005) were significantly higher in patients with apical TTC than in the midventricular group. Concomitantly, these findings were associated with significantly higher BNP levels in the apical group (923.91 ± 1164.53 vs. 418.71 ± 557.75 pg/mL; p = 0.004) than in the midventricular group. In the acute phase of stress cardiomyopathy, the classic apical form of TTC is associated with poorer diastolic function compared to the midventricular ballooning variant, as assessed through direct invasive hemodynamic measurements using LHC. |
2,328,567 | Gut microbiota regulates cardiac ischemic tolerance and aortic stiffness in obesity. | The gut microbiota has emerged as an important regulator of host physiology, with recent data suggesting a role in modulating cardiovascular health. The present study determined if gut microbial signatures could transfer cardiovascular risk phenotypes between lean and obese mice using cecal microbiota transplantation (CMT). Pooled cecal contents collected from obese leptin-deficient (Ob) mice or C57Bl/6j control (Con) mice were transplanted by oral gavage into cohorts of recipient Ob and Con mice maintained on identical low-fat diets for 8 wk (<i>n</i> = 9-11/group). Cardiovascular pathology was assessed as the degree of arterial stiffness (aortic pulse wave velocity) and myocardial infarct size following a 45/120 min ex vivo global cardiac ischemia-reperfusion protocol. Gut microbiota was characterized by 16S rDNA sequencing, along with measures of intestinal barrier function and cecal short-chain fatty acid (SCFA) composition. Following CMT, the gut microbiota of recipient mice was altered to resemble that of the donors. Ob CMT to Con mice increased arterial stiffness, left ventricular (LV) mass, and myocardial infarct size, which were associated with greater gut permeability and reduced cecal SCFA concentrations. Conversely, Con CMT to Ob mice increased cecal SCFA, reduced LV mass, and attenuated myocardial infarct size, with no effects on gut permeability or arterial stiffness. Collectively, these data demonstrate that obesity-related changes in the gut microbiota, independent of dietary manipulation, regulate hallmark measures of cardiovascular pathology in mice and highlight the potential of microbiota-targeted therapeutics for reducing cardiovascular pathology and risk in obesity.<b>NEW & NOTEWORTHY</b> These data are the first to demonstrate that cecal microbiota transplantation (CMT) can alter cardiovascular pathology in lean and obese mice independent from alterations in dietary intake. Myocardial infarct size was reduced in obese mice receiving lean CMT and worsened in lean mice receiving obese CMT. Lean mice receiving obese CMT also displayed increased aortic stiffness. These changes were accompanied by alterations in short-chain fatty acids and gut permeability. |
2,328,568 | [Progress in cerebrospinal fluid proteome technology and its clinical application]. | Cerebrospinal fluid surrounds and supports the central nervous system, including the ventricles and subarachnoid spaces. Cerebrospinal fluid should be an important source of biomarkers for central nervous system diseases because it is in direct contact with the central nervous system. Many studies are reported on cerebrospinal fluid proteomics, highlighting many recent progresses. Here, we review recent advances in proteomics technology and clinical application of cerebrospinal fluid.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Linpeng</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Key Laboratory of Prevention and Cure for the Plateau Environmental Damage of PLA, The 940th Hospital of PLA Joint Logistics Support Force, Lanzhou 730050, Gansu, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Pharmacy, Lanzhou University, Lanzhou 730000, Gansu, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Pengcheng</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jin</LastName><ForeName>Wanjun</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Key Laboratory of Prevention and Cure for the Plateau Environmental Damage of PLA, The 940th Hospital of PLA Joint Logistics Support Force, Lanzhou 730050, Gansu, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, Gansu, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ma</LastName><ForeName>Huiping</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Key Laboratory of Prevention and Cure for the Plateau Environmental Damage of PLA, The 940th Hospital of PLA Joint Logistics Support Force, Lanzhou 730050, Gansu, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, Gansu, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jing</LastName><ForeName>Linlin</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Key Laboratory of Prevention and Cure for the Plateau Environmental Damage of PLA, The 940th Hospital of PLA Joint Logistics Support Force, Lanzhou 730050, Gansu, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jia</LastName><ForeName>Zhengping</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Key Laboratory of Prevention and Cure for the Plateau Environmental Damage of PLA, The 940th Hospital of PLA Joint Logistics Support Force, Lanzhou 730050, Gansu, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Pharmacy, Lanzhou University, Lanzhou 730000, Gansu, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>chi</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Sheng Wu Gong Cheng Xue Bao</MedlineTA><NlmUniqueID>9426463</NlmUniqueID><ISSNLinking>1000-3061</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002556">Cerebrospinal Fluid Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D020543">Proteome</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D015415" MajorTopicYN="N">Biomarkers</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002556" MajorTopicYN="N">Cerebrospinal Fluid Proteins</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020543" MajorTopicYN="N">Proteome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D040901" MajorTopicYN="Y">Proteomics</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="chi">脑脊液 (CSF) 围绕并支持中枢神经系统 (CNS)，包括脑室和蛛网膜下腔，由于脑脊液与中枢神经系统直接接触，所以其是寻找中枢神经系统疾病生物标记物的重要来源。国内外学者开展了大量CSF 蛋白质组学的研究工作，并取得了较大进展。文中综述了近年来CSF 蛋白质组学技术及临床应用研究进展。. |
2,328,569 | Ratio of fetal choroid plexus to head size: simple sonographic marker of open spina bifida at 11-13 weeks' gestation. | To measure the ratio of choroid plexus (CP) size to head size in normal fetuses and to compare it to that in fetuses with open spina bifida (OSB) and quantify the subjective sign of a 'dry brain'.</AbstractText>This was a retrospective study of ultrasound images, obtained during first-trimester screening between 11 and 13 weeks of gestation, from 34 fetuses with OSB and 160 normal fetuses. From the hospital databases, we retrieved images of the fetal head in the transventricular axial plane. We measured the areas of both CPs and the head and calculated the ratio between them. We also measured the longest diameter of each CP and calculated their mean (CP length), and measured the occipitofrontal diameter (OFD) and calculated the ratio of CP length to OFD. Measurements from the OSB fetuses were plotted on crown-rump length (CRL) reference ranges constructed using data from the normal fetuses, and Z-scores were calculated.</AbstractText>In the normal fetuses, the CP area increased, while the ratios of CP area to head area and CP length to OFD decreased, with increasing CRL. In 30 of the 34 (88%) fetuses with OSB, both ratios were increased significantly and the CPs filled the entirety of the head, giving the impression of a dry brain. In these cases, the borders of the lateral ventricles could not be identified.</AbstractText>At 11-13 weeks, the majority of fetuses with OSB have reduced fluid in the lateral ventricles such that the CPs fill the head. The dry brain sign is easily visualized during routine first-trimester ultrasound examination while measuring the biparietal diameter, and can be quantified by comparing the size of the CPs to the head size. Until prospective data confirm the usefulness of this sign in screening for OSB, it should be considered as a hint to prompt the examiner to assess thoroughly the posterior fossa and spine. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.</AbstractText>Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.</CopyrightInformation> |
2,328,570 | Shunt Failure-The First 30 Days. | Incontrovertible predictors of shunt malfunction remain elusive.</AbstractText>To determine predictors of shunt failure within 30 d of index surgery.</AbstractText>This was a single-center retrospective cohort study from January 2010 through November 2016. Using a ventricular shunt surgery research database, clinical and procedural variables were procured. An "index surgery" was defined as implantation of a new shunt or revision or augmentation of an existing shunt system. The primary outcome was shunt failure of any kind within the first 30 days of index surgery. Bivariate models were created, followed by a final multivariable logistic regression model using a backward-forward selection procedure.</AbstractText>Our dataset contained 655 unique patients with a total of 1206 operations. The median age for the cohort at the time of first shunt surgery was 4.6 yr (range, 0-28; first and third quartile, .37 and 11.8, respectively). The 30-day failure rates were 12.4% when analyzing the first-index operation only (81/655), and 15.7% when analyzing all-index operations (189/1206). Small or slit ventricles at the time of index surgery and prior ventricular shunt operations were found to be significant covariates in both the "first-index" (P < .01 and P = .05, respectively) and "all-index" (P = .02 and P < .01, respectively) multivariable models. Intraventricular hemorrhage at the time of index surgery was an additional predictor in the all-index model (P = .01).</AbstractText>This study demonstrates that only 3 variables are predictive of 30-day shunt failure when following established variable selection procedures, 2 of which are potentially under direct control of the surgeon.</AbstractText>Copyright © 2019 by the Congress of Neurological Surgeons.</CopyrightInformation> |
2,328,571 | An Integrative Transcriptome Analysis Reveals Consistently Dysregulated Long Noncoding RNAs and Their Transcriptional Regulation Relationships in Heart Failure. | Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are emerging as important regulators involved in diseases, including heart failure (HF). In this study, we used microarray profiles to examine the transcriptome of lncRNAs in left ventricle samples derived from HF patients. We designed a custom pipeline to reannotate lncRNAs from microarray data and identified a set of consistently dysregulated lncRNAs in HF across the three independent cohorts. In total, 84 lncRNAs were found to be consistently dysregulated in at least two cohorts. By using a rank aggregation method, we integrated correlated protein-coding genes of the consistently dysregulated lncRNAs derived from HF samples and characterized their biological functions based on the correlated genes. The transcriptional regulation relationships of these lncRNAs ranged from 104 to 261, suggesting their important regulatory functions. Among the conserved lncRNAs, <i>AC018647.1</i> and <i>AC009113.1</i> showed significant dysregulation across all three cohorts. Our results showed that the two lncRNAs were involved in development-associated and cardiac cycle-associated functions. |
2,328,572 | Combination of HGF and IGF-1 promotes connexin 43 expression and improves ventricular arrhythmia after myocardial infarction through activating the MAPK/ERK and MAPK/p38 signaling pathways in a rat model. | In this study, we hypothesized that the combination of hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) alters the expression of connexin 43 (Cx43) and results in a reduced frequency of induced ventricular arrhythmia in rats after myocardial infarction (MI) and explored the preliminary mechanisms involved.</AbstractText>Cardiomyocytes were cultured in vitro</i> in medium with PBS, HGF, IGF-1, GFs (HGF + IGF-1), HGF + p38 inhibitor, HGF + ERK inhibitor, IGF-1 + p38 inhibitor or IGF-1 + ERK inhibitor. The expression of Cx43 was tested by real-time PCR and Western blotting after 48 hours. MI was induced in 48 male Sprague-Dawley rats. The rats were randomly divided into four groups and received an injection of PBS, HGF, IGF-1 or GFs into the infarct border zone two weeks after MI. Six weeks after injection, the expression levels of Cx43 and programmed stimulation-induced ventricular arrhythmias were examined.</AbstractText>In vitro</i>, the expression of Cx43 mRNA and the Cx43 protein in cardiomyocytes was higher in the HGF, IGF-1, and GFs groups than in the PBS group. GFs had a combinatorial effect on the Cx43 mRNA level but not on the Cx43 protein level. There was a significant reduction in Cx43 mRNA and Cx43 protein levels in the IGF-1 + p38 inhibitor group and IGF-1 + ERK inhibitor group compared to the IGF-1 group. In vivo, programmed stimulation significantly decreased the frequency of ventricular arrhythmia in the GFs, HGF and IGF-1 groups, and this effect was accompanied by increased immunohistochemical staining for Cx43, myocardial Cx43 protein levels and Cx43 mRNA levels in the infarct border zone of the left ventricle compared with those in the PBS group. The combinatorial effect of GFs on Cx43 expression was only observed at the mRNA level.</AbstractText>Both HGF and IGF-1 enhanced the expression of Cx43 and improved induced ventricular arrhythmia in rats with MI. Both synergistic and antagonistic effects of HGF and IGF-1 were not observed. In addition, IGF-1 may function through the MAPK/p38 and ERK1/2 signaling pathways to regulate Cx43 expression.</AbstractText> |
2,328,573 | Patients with chronic mild or moderate traumatic brain injury have abnormal brain enlargement. | <b>Introduction:</b> Much less is known about brain volume abnormalities in patients with chronic mild or moderate traumatic brain injury (TBI) compared with patients with more severe injury. Commercially available software methods including NeuroQuant® are being used increasingly to assess MRI brain volume in patients with TBI.<b>Methods:</b> 50 patients with mild or moderate TBI were compared to the NeuroQuant® normal control database (<i>n</i> = thousands) with respect to MRI brain volume.<b>Results:</b> The patients had many areas of abnormal enlargement and fewer areas of atrophy, including abnormally small cerebral white matter (CWM) limited to the first 10 months after injury. Examination of correlations within the patient group between CWM volume and volumes of the abnormally enlarged regions showed multiple significant negative correlations, indicating that CWM atrophy correlated with enlargement of the other regions.<b>Discussion:</b> The finding of many regions of abnormal brain enlargement was relatively new, although a couple of previous studies of patients with mild TBI found similar but more limited findings. The cause of the abnormal enlargement was unknown, but possibilities included: (1) hyperactivity and hypertrophy; or (2) chronic neuro-inflammation and edema.<b>Abbreviations:</b> ADNI: Alzheimer's Disease Neuroimaging Initiative; CWM: cerebral white matter; GM: cerebral cortical gray matter; ICC: intraclass correlations coefficient; IFT: infratentorial; MRI: magnetic resonance imaging; mTBI: mild TBI; NQ: NeuroQuant®; SCN: subcortical nuclei; t0: time of injury; t1: time of first NeuroQuanted MRI scan after injury; t2: time of second NeuroQuanted MRI scan after injury; TBI: traumatic brain injury; VBR: ventricle-to-brain ratio; WBP: whole-brain parenchyma. |
2,328,574 | Morpholino Studies in Xenopus Brain Development. | Antisense morpholino oligonucleotides (MOs) have become a valuable method to knockdown protein levels, to block with mRNA splicing and to interfere with miRNA function. MOs are widely used to alter gene expression in development of Xenopus and Zebrafish, where they are typically injected into the fertilized egg or blastomeres. Here we present methods to use electroporation to target delivery of MOs to the central nervous system of Xenopus laevis or Xenopus tropicalis tadpoles. Briefly, MO electroporation is accomplished by injecting MO solution into the brain ventricle and driving the MOs into cells of the brain with current passing between 2 platinum plate electrodes, positioned on either side of the target brain area. The method is relatively straightforward and uses standard equipment found in many neuroscience labs. A major advantage of electroporation is that it allows spatial and temporal control of MO delivery and therefore knockdown. Co-electroporation of MOs with cell type-specific fluorescent protein expression plasmids allows morphological analysis of cellular phenotypes. Furthermore, co-electroporation of MOs with rescuing plasmids allows assessment of specificity of the knockdown and phenotypic outcome. By combining MO-mediated manipulations with sophisticated assays of neuronal function, such as electrophysiological recording, behavioral assays, or in vivo time-lapse imaging of neuronal development, the functions of specific proteins and miRNAs within the developing nervous system can be elucidated. These methods can be adapted to apply antisense morpholinos to study protein and RNA function in a variety of complex tissues. |
2,328,575 | Interrater and Intrarater Reliability of the Colloid Cyst Risk Score. | The Colloid Cyst Risk Score (CCRS) was developed to identify symptomatic patients and stratify risk of hydrocephalus among patients with colloid cysts. Its components consider patient age, cyst diameter, presence/absence of headache, fluid-attenuated inversion recovery (FLAIR) hyperintensity, and location within the third ventricle.</AbstractText>To independently evaluate the inter- and intrarater reliability of the CCRS.</AbstractText>Patients with a colloid cyst were identified from billing records and radiology archives. Three independent raters reviewed electronic medical records to determine age, presence/absence of headache, cyst diameter (mm), FLAIR hyperintensity, and risk zone location. Raters made 53 observations, including 5 repeat observations.Fleiss' generalized kappa (κ) was calculated for all of the nominal criteria, whereas Kendall's coefficient of concordance (W) and the intraclass correlation coefficient (ICC) were calculated for the overall score.</AbstractText>Total CCRS score demonstrated extremely strong agreement (W = 0.83) using Kendall's W coefficient and good agreement (ICC = 0.74) using the ICC (P < .001). For interrater reliability of individual criteria, age (κ = 1.00) and FLAIR hyperintensity (κ = 0.89) demonstrated near perfect agreement. Axial diameter (κ = 0.63) demonstrated substantial agreement, whereas agreement was moderate for risk zone (κ = 0.51) and fair for headache (κ = 0.26). Intrarater reliability for total CCRS score was extremely strong using Kendall's W, good to excellent using ICC, and fair to substantial using weighted kappa.</AbstractText>The CCRS has good inter- and intrarater reliability when tested in an independent sample of patients, though strength of agreement varies among individual criteria. The validity of the CCRS requires independent evaluation.</AbstractText>Copyright © 2019 by the Congress of Neurological Surgeons.</CopyrightInformation> |
2,328,576 | Integrated Metabolomics-DNA Methylation Analysis Reveals Significant Long-Term Tissue-Dependent Directional Alterations in Aminoacyl-tRNA Biosynthesis in the Left Ventricle of the Heart and Hippocampus Following Proton Irradiation. | In this study, an untargeted metabolomics approach was used to assess the effects of proton irradiation (1 Gy of 150 MeV) on the metabolome and DNA methylation pattern in the murine hippocampus and left ventricle of the heart 22 weeks following exposure using an integrated metabolomics-DNA methylation analysis. The integrated metabolomics-DNA methylation analysis in both tissues revealed significant alterations in aminoacyl-tRNA biosynthesis, but the direction of change was tissue-dependent. Individual and total amino acid synthesis were downregulated in the left ventricle of proton-irradiated mice but were upregulated in the hippocampus of proton-irradiated mice. Amino acid tRNA synthetase methylation was mostly downregulated in the hippocampus of proton-irradiated mice, whereas no consistent methylation pattern was observed for amino acid tRNA synthetases in the left ventricle of proton-irradiated mice. Thus, proton irradiation causes long-term changes in the left ventricle and hippocampus in part through methylation-based epigenetic modifications. Integrated analysis of metabolomics and DNA methylation is a powerful approach to obtain converging evidence of pathways significantly affected. This in turn might identify biomarkers of the radiation response, help identify therapeutic targets, and assess the efficacy of mitigators directed at those targets to minimize, or even prevent detrimental long-term effects of proton irradiation on the heart and the brain. |
2,328,577 | Multimodality Imaging of Right Ventricular Pseudoaneurysm Caused by Blunt Chest Trauma. | Right ventricular pseudoaneurysm is a rare but fatal complication of blunt chest trauma. Different imaging modalities including transthoracic echocardiogram, gated-CT angiography and cardiac MR can provide useful anatomic and functional information that can make the diagnosis and guide management. Surgical treatment is needed to avoid fatal outcome. (<b>Level of Difficulty: Beginner.</b>). |
2,328,578 | Long tunnel external ventricular drain: an adjunct in the management of patients with infection associated hydrocephalus. | <b>Objective:</b> To evaluate the safety and efficacy of long tunnelled external ventricular drains (LTEVD) as a temporizing measure in patients with ventriculitis/meningitis requiring cerebrospinal fluid (CSF) diversion in whom immediate shunt surgery is not feasible.<b>Methods:</b> A retrospective review of the records of 15 patients with ventriculitis/meningitis, in whom an LTEVD was inserted, was performed to evaluate its safety, new onset CSF infection and need for permanent CSF diversion.<b>Results:</b> 15 patients with ventriculitis/meningitis had 16 LTEVDs placed between May 2006 and December 2016. There were 10 males and 5 females, their mean age being 16.5 years (range, 8 months-50 years). The mean duration of CSF drainage was 15.6 days (range, 4 to 44 days). Of the 16 LTEVDs that were inserted, two (13.3% - one CSF infection and one wound infection) developed new infection after 44 and 17 days of continuous CSF drainage respectively. The LTEVDs were removed and permanent CSF diversion procedures were performed in 10 patients during the same admission and in one patient later. At a mean follow up of 11.6 months (range 2-40 months), 8 of the 11 patients who underwent a permanent CSF diversion procedure had no clinical features of meningitis/ventriculitis.<b>Conclusion:</b> LTEVDs are an effective method of temporary CSF diversion in patients requiring the same for more than 5 days. These drains have a low infection rate when placed up to four weeks making them a safe and efficacious adjunct in management of ventriculitis/meningitis associated hydrocephalus. |
2,328,579 | Alterations in the Structural and Functional Connectivity of the Visuomotor Network of Children With Periventricular Leukomalacia. | Children born preterm with periventricular leukomalacia (PVL) demonstrate increased difficulties with tasks requiring visuomotor integration. The visuomotor integration network encompasses brain regions within frontal, parietal, and occipital cortices. Because of their proximity to the lateral ventricle the underlying white matter pathways are at a high risk of damage following PVL-related hypoxic-ischemic white matter injury. This study provides an exploratory analysis of the structural and functional connections within the visuomotor integration network, along with an a priori evaluation of the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and frontal aslant tract. For each pathway, tracts within both hemispheres revealed decreased volume and number of reconstructed fibers and an increase in quantitative anisotropy and generalized fractional anisotropy. The connectivity results also indicate that there may be changes to both the structural integrity and functional integration of neural networks involved with visuomotor integration functions in children with PVL. |
2,328,580 | Sex-Dependent QRS Guidelines for Cardiac Resynchronization Therapy Using Computer Model Predictions. | Cardiac resynchronization therapy (CRT) is an important treatment for heart failure. Low female enrollment in clinical trials means that current CRT guidelines may be biased toward males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex differences in the left ventricle (LV) size could provide an explanation for the improved female response at lower QRSd. We aimed to test if sex differences in CRT response at lower QRSd thresholds are explained by differences in LV size and hence predict sex-specific guidelines for CRT. We investigated the effect that LV size sex difference has on QRSd between male and females in 1093 healthy individuals and 50 CRT patients using electrophysiological computer models of the heart. Simulations on the healthy mean shape models show that LV size sex difference can account for 50-100% of the sex difference in baseline QRSd in healthy individuals. In the CRT patient cohort, model simulations predicted female-specific guidelines for CRT, which were 9-13 ms lower than current guidelines. Sex differences in the LV size are able to account for a significant proportion of the sex difference in QRSd and provide a mechanistic explanation for the sex difference in CRT response. Simulations accounting for the smaller LV size in female CRT patients predict 9-13 ms lower QRSd thresholds for female CRT guidelines. |
2,328,581 | PV-LVNet: Direct left ventricle multitype indices estimation from 2D echocardiograms of paired apical views with deep neural networks. | Accurate direct estimation of the left ventricle (LV) multitype indices from two-dimensional (2D) echocardiograms of paired apical views, i.e., paired apical four-chamber (A4C) and two-chamber (A2C), is of great significance to clinically evaluate cardiac function. It enables a comprehensive assessment from multiple dimensions and views. Yet it is extremely challenging and has never been attempted, due to significantly varied LV shape and appearance across subjects and along cardiac cycle, the complexity brought by the paired different views, unexploited inter-frame indices relatedness hampering working effect, and low image quality preventing segmentation. We propose a paired-views LV network (PV-LVNet) to automatically and directly estimate LV multitype indices from paired echo apical views. Based on a newly designed Res-circle Net, the PV-LVNet robustly locates LV and automatically crops LV region of interest from A4C and A2C sequence with location module and image resampling, then accurately and consistently estimates 7 different indices of multiple dimensions (1D, 2D & 3D) and views (A2C, A4C, and union of A2C+A4C) with indices module. The experiments show that our method achieves high performance with accuracy up to 2.85mm mean absolute error and internal consistency up to 0.974 Cronbach's α for the cardiac indices estimation. All of these indicate that our method enables an efficient, accurate and reliable cardiac function diagnosis in clinical. |
2,328,582 | Characterization of boscalid-induced oxidative stress and neurodevelopmental toxicity in zebrafish embryos. | Boscalid is a widely used fungicide in agriculture and has been frequently detected in both environments and agricultural products. However, evidence on the neurotoxic effect of boscalid is scarce. In this study, zebrafish served as an animal model to investigate the toxic effects and mechanisms of boscalid on aquatic vertebrates or higher animals. And we unravelled that boscalid induced developmental defects associated with oxidative stress. Developmental defects, including head deformity, hypopigmentation, decreased number of newborn neurons, structural defects around the ventricle, enlarged intercellular space in the brain, and nuclear concentration, were observed in zebrafish embryos after boscalid exposure at 48 hpf. Interestingly, we found that boscalid might directly induce oxidative stress and alter the activity of ATPase, which in turn disrupted the expression of genes involved in neurodevelopment and transmitter-transmitting signalings and melanocyte differentiation and melanin synthesis signalings. Ultimately, the differentiation of nerve cells and melanocytes were both impacted and the synthesis of melanin was inhibited, leading to morphological abnormalities. Additionally, exposure to boscalid led to less and imbalance motion and altered tendency of locomotor in larval fish. Collectively, our results provide new evidences for a comprehensive assessment of its toxicity and a warning for its residues in environment and agricultural products. |
2,328,583 | Visual versus Verbal Working Memory in Statistically Determined Patients with Mild Cognitive Impairment: On behalf of the Consortium for Clinical and Epidemiological Neuropsychological Data Analysis (CENDA). | Previous research in mild cognitive impairment (MCI) suggests that visual episodic memory impairment may emerge before analogous verbal episodic memory impairment. The current study examined working memory (WM) test performance in MCI to assess whether patients present with greater visual versus verbal WM impairment. WM performance was also assessed in relation to hippocampal occupancy (HO), a ratio of hippocampal volume to ventricular dilation adjusted for demographic variables and intracranial volume.</AbstractText>Jak et al. (2009) (The American Journal of Geriatric Psychiatry, 17, 368-375) and Edmonds, Delano-Wood, Galasko, Salmon, & Bondi (2015) (Journal of Alzheimer's Disease, 47(1), 231-242) criteria classify patients into four groups: little to no cognitive impairment (non-MCI); subtle cognitive impairment (SCI); amnestic MCI (aMCI); and a combined mixed/dysexecutive MCI (mixed/dys MCI). WM was assessed using co-normed Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span Backwards and Wechsler Memory Scale-IV (WMS-IV) Symbol Span Z-scores.</AbstractText>Between-group analyses found worse WMS-IV Symbol Span and WAIS-IV Digit Span Backwards performance for mixed/dys MCI compared to non-MCI patients. Within-group analyses found no differences for non-MCI patients; however, all other groups scored lower on WMS-IV Symbol Span than WAIS-IV Digit Span Backwards. Regression analysis with HO as the dependent variable was statistically significant for WMS-IV Symbol Span performance. WAIS-IV Digit Span Backwards performance failed to reach statistical significance.</AbstractText>Worse WMS-IV Symbol Span performance was observed in patient groups with measurable neuropsychological impairment and better WMS-IV Symbol Span performance was associated with higher HO ratios. These results suggest that visual WM may be particularly sensitive to emergent illness compared to analogous verbal WM tests.</AbstractText> |
2,328,584 | Echocardiographic Screening of Cardiovascular Status in Pediatric Sickle Cell Disease. | Although elevated right ventricular pressure and left ventricular diastolic dysfunction measured by echocardiogram are independent predictors of death in adults with sickle cell disease (SCD), the utility of routine echocardiographic screening in the pediatric population is controversial. We performed a 3-year retrospective review of children ≥ 10 years of age with SCD who underwent an outpatient transthoracic echocardiogram as part of a screening program. Of 172 patients referred for screening, 105 (61%) had a measurable tricuspid regurgitation jet velocity (TRV): median 2.4 m/s (IQR 2.3-2.5). Elevated right ventricular (RV) pressure (TRV ≥ 2.5 m/s, 25 mmHg), documented in 30% (32/105), was significantly associated with chronic transfusion therapy and elevated lactate dehydrogenase. Left ventricle (LV) dilation, documented in 25% (44/172), was significantly associated with lower hemoglobin, and higher reticulocyte count, lactate dehydrogenase level, and bilirubin level. There was no association between elevated right ventricular pressure or left ventricle dilation and indices of biventricular systolic or diastolic function. The one death in the cohort during the study period had normal echocardiographic findings. In conclusion, mild RV pressure elevation and LV dilation in children with SCD is associated with abnormal laboratory markers of disease severity, but not with ventricular dysfunction over the 3-year study period. |
2,328,585 | Pioglitazone treatment prior to transplantation improves the efficacy of human mesenchymal stem cells after traumatic brain injury in rats. | Traumatic brain injury is a leading cause of death and disability around the world. So far, drugs are not available to repair brain damage. Human mesenchymal stem cell (hMSC) transplantation therapy is a promising approach, although the inflammatory microenvironment of the injured brain affects the efficacy of transplanted hMSCs. We hypothesize that reducing the inflammation in the cerebral microenvironment by reducing pro-inflammatory chemokines prior to hMSC administration will improve the efficacy of hMSC therapy. In a rat model of lateral fluid percussion injury, combined pioglitazone (PG) and hMSC (combination) treatment showed less anxiety-like behavior and improved sensorimotor responses to a noxious cold stimulus. Significant reduction in brain lesion volume, neurodegeneration, microgliosis and astrogliosis were observed after combination treatment. TBI induced expression of inflammatory chemokine CCL20 and IL1-β were significantly decreased in the combination treatment group. Combination treatment significantly increased brain-derived neurotrophic factor (BDNF) level and subventricular zone (SVZ) neurogenesis. Taken together, reducing proinflammatory cytokine expression in the cerebral tissues after TBI by PG administration and prior to hMSC therapy improves the outcome of the therapy in which BDNF could have a role. |
2,328,586 | High impact of miRNA-4521 on FOXM1 expression in medulloblastoma. | Medulloblastoma, an embryonal tumor of the cerebellum/fourth ventricle, is one of the most frequent malignant brain tumors in children. Although genetic variants are increasingly used in treatment stratification, survival of high-risk patients, characterized by leptomeningeal dissemination, TP53 mutation or MYC amplification, is still poor. FOXM1, a proliferation-specific oncogenic transcription factor, is deregulated in various solid tumors, including medulloblastoma, and triggers cellular proliferation, migration and genomic instability. In tissue samples obtained from medulloblastoma patients, the significant upregulation of FOXM1 was associated with a loss of its putative regulating microRNA, miR-4521. To understand the underlying mechanism, we investigated the effect of miR-4521 on the expression of the transcription factor FOXM1 in medulloblastoma cell lines. Transfection of this microRNA reduced proliferation and invasion of several medulloblastoma cell lines and induced programmed cell death through activation of caspase 3/7. Further, downstream targets of FOXM1 such as PLK1 and cyclin B1 were significantly reduced thus affecting the cell cycle progression in medulloblastoma cell lines. In conclusion, a restoration of miRNA-4521 may selectively suppress the pathophysiological effect of aberrant FOXM1 expression and serve as a targeted approach for medulloblastoma therapy. |
2,328,587 | Effects of prenatal exposure to particulate matter air pollution on corpus callosum and behavioral problems in children. | Air pollution (AP) may affect neurodevelopment, but studies about the effects of AP on the growing human brain are still scarce. We aimed to investigate the effects of prenatal exposure to AP on lateral ventricles (LV) and corpus callosum (CC) volumes in children and to determine whether the induced brain changes are associated with behavioral problems.</AbstractText>Among the children recruited through a set of representative schools of the city of Barcelona, (Spain) in the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) study, 186 typically developing participants aged 8-12 years underwent brain MRI on the same 1.5 T MR unit over a 1.5-year period (October 2012-April 2014). Brain volumes were derived from structural MRI scans using automated tissue segmentation. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) and the criteria of the Attention Deficit Hyperactivity Disorder DSM-IV list. Prenatal fine particle (PM2.5</sub>) levels were retrospectively estimated at the mothers' residential addresses during pregnancy with land use regression (LUR) models. To determine whether brain structures might be affected by prenatal PM2.5</sub> exposure, linear regression models were run and adjusted for age, sex, intracranial volume (ICV), maternal education, home socioeconomic vulnerability index, birthweight and mothers' smoking status during pregnancy. To test for associations between brain changes and behavioral outcomes, negative binomial regressions were performed and adjusted for age, sex, ICV.</AbstractText>Prenatal PM2.5</sub> levels ranged from 11.8 to 39.5 μg/m3</sup> during the third trimester of pregnancy. An interquartile range increase in PM2.5</sub> level (7 μg/m3</sup>) was significantly linked to a decrease in the body CC volume (mm3</sup>) (β = -53.7, 95%CI [-92.0, -15.5] corresponding to a 5% decrease of the mean body CC volume) independently of ICV, age, sex, maternal education, socioeconomic vulnerability index at home, birthweight and mothers' smoking status during the third trimester of pregnancy. A 50 mm3</sup> decrease in the body CC was associated with a significant higher hyperactivity subscore (Rate Ratio (RR) = 1.09, 95%CI [1.01, 1.17) independently of age, sex and ICV. The statistical significance of these results did not survive to False Discovery Rate correction for multiple comparisons.</AbstractText>Prenatal exposure to PM2.5</sub> may be associated with CC volume decrease in children. The consequences might be an increase in behavioral problems.</AbstractText>Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,588 | Can Biomarkers Provide Right Ventricular-Specific Prognostication in the Perioperative Setting? | Since the introduction of biomarkers in the late 1980s, considerable research has been dedicated to their validation and application. As a result, many biomarkers are now commonly used in clinical practice. However, the role of biomarkers in the prediction of right ventricular failure (RVF) and in the prognostication for patients with RVF remains underexplored. Barriers include a lack of awareness of the importance of right ventricular function, especially in the perioperative setting, as well as a lack of reproducible means to assess right ventricular function in this setting. We provide an overview of biomarkers with right ventricular prognostic capabilities that could be further explored in patients expecting cardiac surgery, who are notoriously susceptible to developing RVF. We discuss biomarkers' mechanistic pathways and highlight their potential strengths and weaknesses in use in research and clinical care. |
2,328,589 | VCAM-1 targeted alpha-particle therapy for early brain metastases. | Brain metastases (BM) develop frequently in patients with breast cancer. Despite the use of external beam radiotherapy (EBRT), the average overall survival is short (6 months from diagnosis). The therapeutic challenge is to deliver molecularly targeted therapy at an early stage when relatively few metastatic tumor cells have invaded the brain. Vascular cell adhesion molecule 1 (VCAM-1), overexpressed by nearby endothelial cells during the early stages of BM development, is a promising target. The aim of this study was to investigate the therapeutic value of targeted alpha-particle radiotherapy, combining lead-212 (212Pb) with an anti-VCAM-1 antibody (212Pb-αVCAM-1).</AbstractText>Human breast carcinoma cells that metastasize to the brain, MDA-231-Br-GFP, were injected into the left cardiac ventricle of nude mice. Twenty-one days after injection, 212Pb-αVCAM-1 uptake in early BM was determined in a biodistribution study and systemic/brain toxicity was evaluated. Therapeutic efficacy was assessed using MR imaging and histology. Overall survival after 212Pb-αVCAM-1 treatment was compared with that observed after standard EBRT.</AbstractText>212Pb-αVCAM-1 was taken up into early BM with a tumor/healthy brain dose deposition ratio of 6 (5.52e108 and 0.92e108) disintegrations per gram of BM and healthy tissue, respectively. MRI analyses showed a statistically significant reduction in metastatic burden after 212Pb-αVCAM-1 treatment compared with EBRT (P < 0.001), translating to an increase in overall survival of 29% at 40 days post prescription (P < 0.01). No major toxicity was observed.</AbstractText>The present investigation demonstrates that 212Pb-αVCAM-1 specifically accumulates at sites of early BM causing tumor growth inhibition.</AbstractText>© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.</CopyrightInformation> |
2,328,590 | Levodopa-responsive parkinsonism in a patient with corticobasal degeneration and bilateral choroid plexus xanthogranulomas. | Corticobasal degeneration (CBD) has substantial overlap of clinical features with other neurodegenerative diseases including Parkinson's disease (PD). Its clinical diagnostic accuracy is the lowest among the common neurodegenerative diseases, and its antemortem diagnosis is more challenging when CBD is comorbid with another brain disease. We report an elderly male patient with multiple medical conditions and a family history of essential tremor. He presented with progressive tremor that was initially thought to be essential tremor and later diagnosed as PD despite head computerized tomography showing bilateral intraventricular masses and other minor changes. The clinical diagnosis of PD was supported by his responsiveness to low-dose levodopa. However, postmortem neuropathological examination revealed CBD and bilateral choroid plexus xanthogranulomas with mild ventricular enlargement and multifocal ependymal lining injury presumably due to mild hydrocephalus. CBD is typically levodopa-unresponsive, but hydrocephalus-associated parkinsonism is commonly levodopa-responsive. We raise awareness of the present comorbidity and atypical parkinsonism due to the choroid plexus xanthogranuloma-induced hydrocephalus for the clinical diagnosis and management of parkinsonism. |
2,328,591 | Transventricular Migration of Choroid Plexus Carcinoma Causing an Intraoperative Conundrum: A Case Report with a Review of the Literature. | Migrating intracranial tumors are extremely rare occurrences in the neurosurgery literature. Introduction of any factor causing disequilibrium in cerebrospinal fluid circulation and pressure can potentially precipitate transventricular migration of pedunculated intraventricular lesions. The identification of such factors, prior to excision of intraventricular pedunculated tumors, is imperative to avoid intraoperative mismanagement. We report an extremely rare case of transventricular migration of a choroid plexus carcinoma in an infant, possibly precipitated by a ventriculoperitoneal (VP) shunt on the opposite side. This resulted in intraoperative confusion and a subsequent re-exploration of the opposite side for excision of the tumor. The literature provided only two similar occurrences in the past; however, in both cases, the migration was within the same ventricle and was documented prior to definitive resection. We report the first instance of transventricular migration of a tumor to the opposite ventricle following VP shunt which resulted in a negative intraoperative finding requiring a subsequent re-intervention on the opposite side. We believe that for any pedunculated intraventricular lesion, where an emergency management of hydrocephalus takes priority, a repeat neuroimaging is a must prior to definitive resection. |
2,328,592 | Using path signatures to predict a diagnosis of Alzheimer's disease. | The path signature is a means of feature generation that can encode nonlinear interactions in data in addition to the usual linear terms. It provides interpretable features and its output is a fixed length vector irrespective of the number of input points or their sample times. In this paper we use the path signature to provide features for identifying people whose diagnosis subsequently converts to Alzheimer's disease. In two separate classification tasks we distinguish converters from 1) healthy individuals, and 2) individuals with mild cognitive impairment. The data used are time-ordered measurements of the whole brain, ventricles and hippocampus from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We find two nonlinear interactions which are predictive in both cases. The first interaction is change of hippocampal volume with time, and the second is a change of hippocampal volume relative to the volume of the whole brain. While hippocampal and brain volume changes are well known in Alzheimer's disease, we demonstrate the power of the path signature in their identification and analysis without manual feature selection. Sequential data is becoming increasingly available as monitoring technology is applied, and the path signature method is shown to be a useful tool in the processing of this data. |
2,328,593 | Photon-counting cine-cardiac CT in the mouse. | The maturation of photon-counting detector (PCD) technology promises to enhance routine CT imaging applications with high-fidelity spectral information. In this paper, we demonstrate the power of this synergy and our complementary reconstruction techniques, performing 4D, cardiac PCD-CT data acquisition and reconstruction in a mouse model of atherosclerosis, including calcified plaque. Specifically, in vivo cardiac micro-CT scans were performed in four ApoE knockout mice, following their development of calcified plaques. The scans were performed with a prototype PCD (DECTRIS, Ltd.) with 4 energy thresholds. Projections were sampled every 10 ms with a 10 ms exposure, allowing the reconstruction of 10 cardiac phases at each of 4 energies (40 total 3D volumes per mouse scan). Reconstruction was performed iteratively using the split Bregman method with constraints on spectral rank and spatio-temporal gradient sparsity. The reconstructed images represent the first in vivo, 4D PCD-CT data in a mouse model of atherosclerosis. Robust regularization during iterative reconstruction yields high-fidelity results: an 8-fold reduction in noise standard deviation for the highest energy threshold (relative to unregularized algebraic reconstruction), while absolute spectral bias measurements remain below 13 Hounsfield units across all energy thresholds and scans. Qualitatively, image domain material decomposition results show clear separation of iodinated contrast and soft tissue from calcified plaque in the in vivo data. Quantitatively, spatial, spectral, and temporal fidelity are verified through a water phantom scan and a realistic MOBY phantom simulation experiment: spatial resolution is robustly preserved by iterative reconstruction (10% MTF: 2.8-3.0 lp/mm), left-ventricle, cardiac functional metrics can be measured from iodine map segmentations with ~1% error, and small calcifications (615 μm) can be detected during slow moving phases of the cardiac cycle. Given these preliminary results, we believe that PCD technology will enhance dynamic CT imaging applications with high-fidelity spectral and material information. |
2,328,594 | Machine Learning Methods for Automated Quantification of Ventricular Dimensions. | Medaka (<i>Oryzias latipes</i>) and zebrafish (<i>Danio rerio</i>) contribute substantially to our understanding of the genetic and molecular etiology of human cardiovascular diseases. In this context, the quantification of important cardiac functional parameters is fundamental. We have developed a framework that segments the ventricle of a medaka hatchling from image sequences and subsequently quantifies ventricular dimensions. |
2,328,595 | The relationship between ventricular volume and whole-brain irradiation dose in central nervous system germ cell tumors. | Advanced irradiation techniques, including intensity-modulated radiation therapy (IMRT), aim to limit irradiation to adjoining tissues by conforming beams to a well-defined volume. In intracranial germinomas, whole-ventricular IMRT decreases the volume of irradiation to surrounding parenchyma. This study examined the relationship between ventricular volume and radiation dose to surrounding tissue.</AbstractText>We retrospectively reviewed age, sex, ventricular and brain volume, ventricular dose, and volume of brain that received 12 Gy (V12) for patients diagnosed with germ cell tumors at our institution treated with whole-ventricular IMRT between 2002 and 2016. Variables were assessed for correlation and statistical significance.</AbstractText>Forty-seven patients were analyzed. The median whole-ventricular irradiation dose was 24 Gy with a median boost dose of 30 Gy. The median ventricular volume was 234.3 cm3</sup> , and median brain volume was 1408 cm3</sup> . There was no significant difference between mean ventricular volume of suprasellar versus pineal tumors (P = .95). The median V12 of the brain, including the ventricles, was 58.9%. The strongest correlation was between ventricular volume and V12, with an r2</sup> (coefficient of determination) of .47 (P < .001). Multiple regression analysis indicated that total boost dose and boost planning target volume significantly predicted V12 (P < .001).</AbstractText>Although whole-ventricular IMRT limited irradiation to surrounding tissue in our cohort, a significant percentage of the brain received at least 12 Gy. This study suggests that there is a positive correlation between ventricular volume and the volume of brain parenchyma receiving at least 12 Gy with an important contribution from the boost phase of treatment.</AbstractText>© 2019 Wiley Periodicals, Inc.</CopyrightInformation> |
2,328,596 | Crocin Improves Cognitive Behavior in Rats with Alzheimer's Disease by Regulating Endoplasmic Reticulum Stress and Apoptosis. | To investigate the effect of crocin on the learning and memory acquisition of AD rats and its underlying mechanisms.</AbstractText>A total of 48 healthy male SD rats were randomly divided into control group, AD model group, resveratrol group, and crocin group, with 12 rats per group. AD model was established by injecting Aβ</i> 25-35</sub> to the lateral ventricle of rats, and thereafter the rats were administrated with resveratrol (40 mg/kg), crocin (40 mg/kg), or PBS daily for 14 days. Y-maze test and sucrose preference test were used to detect the learning and memory acquisition of rats. Neuronal apoptosis was detected by TUNEL staining and Western blot for apoptosis-related proteins Bax, Bcl-2, and Caspase-3. Immunofluorescence staining and Western blot tests were used to detect the expression of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in hippocampal CA1 region (Hippo) and prefrontal cortical neurons (PFC).</AbstractText>The learning and memory abilities of AD rats were significantly decreased, which was significantly rescued by resveratrol and crocin. The apoptotic cell number of Hippo and PFC neurons in AD model group was significantly higher than that in control group (P</i><0.01), while resveratrol and crocin significantly decreased the apoptotic cell number in AD group (P</i><0.01). Compared with the control group, the expression of Bcl2 in PFC and hippo of AD model group was significantly decreased (P</i><0.01), while those of Bax, Caspase3, GRP78, and CHOP were significantly increased (P</i><0.01). Resveratrol and crocin could significantly reverse the expression of these proteins in AD rats (P</i><0.05).</AbstractText>Crocin can improve the learning and memory ability of AD rats possibly by reducing endoplasmic reticulum stress and neuronal apoptosis.</AbstractText> |
2,328,597 | Copy number gain of ZEB1 mediates a double-negative feedback loop with miR-33a-5p that regulates EMT and bone metastasis of prostate cancer dependent on TGF-β signaling. | <b>Background</b>: The reciprocal repressive loop between ZEB1 and miRNAs has been extensively reported to play an important role in tumor progression and metastasis of various human tumor types. The aim of this study was to elucidate the role and the underlying mechanism of the double-negative feedback loop between ZEB1and miR-33a-5p in bone metastasis of prostate cancer (PCa). <b>Methods</b>: miR-33a-5p expression was examined in 40 bone metastatic and 165 non-bone metastatic PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-33a-5p expression and clinicopathological characteristics, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-33a-5p in bone metastasis of PCa were investigated both by EMT and the Transwell assay <i>in vitro</i>, and by a mouse model of left cardiac ventricle inoculation <i>in vivo</i>. siRNA library, real-time PCR and chromatin immunoprecipitation (ChIP) were used to identify the underlying mechanism responsible for the decreased expression of miR-33a-5p in PCa. Bioinformatics analysis, Western blotting and luciferase reporter analysis were employed to examine the relationship between miR-33a-5p and its potential targets. Clinical correlation of miR-33a-5p with its targets was examined in human PCa tissues and primary PCa cells. <b>Results</b>: miR-33a-5p expression was downregulated in PCa tissues with bone metastasis and bone-derived cells, and low expression of miR-33a-5p strongly and positively correlated with advanced clinicopathological characteristics, and shorter overall and bone metastasis-free survival in PCa patients. Upregulating miR-33a-5p inhibited, while silencing miR-33a-5p promoted EMT, invasion and migration of PCa cells. Importantly, upregulating miR-33a-5p significantly repressed bone metastasis of PC-3 cells <i>in vivo</i>. Our results further revealed that recurrent ZEB1 upregulation induced by copy number gains transcriptionally inhibited miR-33a-5p expression, contributing to the reduced expression of miR-33a-5p in bone metastatic PCa tissues. In turn, miR-33a-5p formed a double negative feedback loop with ZEB1 in target-independent manner, which was dependent on TGF-β signaling. Finally, the clinical negative correlations of miR-33a-5p with ZEB1 expression and TGF-β signaling activity were demonstrated in PCa tissues and primary PCa cells. <b>Conclusion</b>: Our findings elucidated that copy number gains of ZEB1-triggered a TGF-β signaling-dependent miR-33a-5p-mediated negative feedback loop was highly relevant to the bone metastasis of PCa. |
2,328,598 | MRI based neuroanatomical segmentation in breast cancer patients: leptomeningeal carcinomatosis vs. oligometastatic brain disease vs. multimetastastic brain disease. | Pathogenesis of brain metastases/meningeal cancer and the emotional and neurological outcomes are not yet well understood. The hypothesis of our study is that patients with leptomeningeal cancer show volumetric differences in brain substructures compared to patients with cerebral metastases.</AbstractText>Three groups consisting of female breast cancer patients prior to brain radiotherapy were compared. Leptomeningeal cancer patients (LMC Group), oligometastatic patients (1-3 brain metastases) prior to radiosurgery (OMRS Group) and patients prior to whole brain radiation (WB Group) were included. All patients had MRI imaging before treatment. T1 MRI sequences were segmented using automatic segmentation. For each patient, 14 bilateral and 11 central/median subcortical structures were tested. Overall 1127 structures were analyzed and compared between groups using age matched two-sided t-tests.</AbstractText>The average age of patients in the OMRS group was 60.8 years (± 14.7), 65.3 (± 10.3) in the LMC group and 62.6 (± 10.2) in the WB group. LMC patients showed a significantly larger fourth ventricle compared to OMRS (p = 0.001) and WB (p = 0.003). The central corpus callosum appeared smaller in the LMC group (LMC vs OMRS p = 0.01; LMC vs WB p = 0.026). The right amygdala in the WB group appeared larger compared with the OMRS (p = 0.035).</AbstractText>Differences in the size of brain substructures of the three groups were found. The results appear promising and should be taken into account for further prospective studies also involving healthy controls. The volumetrically determined size of the fourth ventricle might be a helpful diagnostic marker in the future.</AbstractText> |
2,328,599 | Model-based myocardial T1 mapping with sparsity constraints using single-shot inversion-recovery radial FLASH cardiovascular magnetic resonance. | This study develops a model-based myocardial T1 mapping technique with sparsity constraints which employs a single-shot inversion-recovery (IR) radial fast low angle shot (FLASH) cardiovascular magnetic resonance (CMR) acquisition. The method should offer high resolution, accuracy, precision and reproducibility.</AbstractText>The proposed reconstruction estimates myocardial parameter maps directly from undersampled k-space which is continuously measured by IR radial FLASH with a 4 s breathhold and retrospectively sorted based on a cardiac trigger signal. Joint sparsity constraints are imposed on the parameter maps to further improve T1 precision. Validations involved studies of an experimental phantom and 8 healthy adult subjects.</AbstractText>In comparison to an IR spin-echo reference method, phantom experiments with T1 values ranging from 300 to 1500 ms revealed good accuracy and precision at simulated heart rates between 40 and 100 bpm. In vivo T1 maps achieved better precision and qualitatively better preservation of image features for the proposed method than a real-time CMR approach followed by pixelwise fitting. Apart from good inter-observer reproducibility (0.6% of the mean), in vivo results confirmed good intra-subject reproducibility (1.05% of the mean for intra-scan and 1.17, 1.51% of the means for the two inter-scans, respectively) of the proposed method.</AbstractText>Model-based reconstructions with sparsity constraints allow for single-shot myocardial T1 maps with high spatial resolution, accuracy, precision and reproducibility within a 4 s breathhold. Clinical trials are warranted.</AbstractText> |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.