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2,331,700
3D amplified MRI (aMRI).
Amplified MRI (aMRI) has been introduced as a new method of detecting and visualizing pulsatile brain motion in 2D. Here, we improve aMRI by introducing a novel 3D aMRI approach.</AbstractText>3D aMRI was developed and tested for its ability to amplify sub-voxel motion in all three directions. In addition, 3D aMRI was qualitatively compared to 2D aMRI on multi-slice and 3D (volumetric) balanced steady-state free precession cine data and phase contrast (PC-MRI) acquired on healthy volunteers at 3T. Optical flow maps and 4D animations were produced from volumetric 3D aMRI data.</AbstractText>3D aMRI exhibits better image quality and fewer motion artifacts compared to 2D aMRI. The tissue motion was seen to match that of PC-MRI, with the predominant brain tissue displacement occurring in the cranial-caudal direction. Optical flow maps capture the brain tissue motion and display the physical change in shape of the ventricles by the relative movement of the surrounding tissues. The 4D animations show the complete brain tissue and cerebrospinal fluid (CSF) motion, helping to highlight the "piston-like" motion of the ventricles.</AbstractText>Here, we introduce a novel 3D aMRI approach that enables one to visualize amplified cardiac- and CSF-induced brain motion in striking detail. 3D aMRI captures brain motion with better image quality than 2D aMRI and supports a larger amplification factor. The optical flow maps and 4D animations of 3D aMRI may open up exciting applications for neurological diseases that affect the biomechanics of the brain and brain fluids.</AbstractText>&#xa9; 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.</CopyrightInformation>
2,331,701
Choroid plexus cyst causing acute hydrocephalus and transtentorial herniation: report of a rare case and its successful neuroendoscopic treatment.
Choroid plexus cysts (CPC) are a frequent incidental neuroimaging finding and completely asymptomatic in the vast majority of cases. We hereby describe a rare case of acute hydrocephalus secondary to a CPC, atypical in size, location and presentation, which required urgent neuroendoscopic management. There are very few reported cases of CPC causing obstructive hydrocephalus. The authors present the case of a previously healthy 2-year-old boy with severe symptoms of acute intracranial hypertension, triventricular hydrocephalus, and left ventricle exclusion after placement of a right external ventricular drain. Magnetic resonance imaging (MRI) showed a very subtle gadolinium enhancement in the anterior region of the third ventricle and foramen of Monro (FM). An emergency neuroendoscopic exploration was performed, where a big cyst was found in the choroid plexus near the FM. The foramen was completely unblocked by thoroughly fenestrating and coagulating the cyst, and a preventive endoscopic septum pellucidotomy was done in the same procedure. The patient completely resolved his symptoms, without neurological morbidity or requirement of a cerebrospinal fluid shunt placement. It is important to consider this infrequent presentation in cases of acute or intermittent obstructive hydrocephalus without apparent cause, bearing in mind its difficult detection in neuroimaging studies and the possibility of effective neuroendoscopic treatment.
2,331,702
Development of the mammalian cortical hem and its derivatives: the choroid plexus, Cajal-Retzius cells and hippocampus.
The dorsal medial region of the developing mammalian telencephalon plays a central role in the patterning of the adjacent brain regions. This review describes the development of this specialized region of the vertebrate brain, called the <i>cortical hem</i>, and the formation of the various cells and structures it gives rise to, including the choroid plexus, Cajal-Retzius cells and the hippocampus. We highlight the ontogenic processes that create these different forebrain derivatives from their shared embryonic origin and discuss the key signalling pathways and molecules that influence the patterning of the cortical hem. These include BMP, Wnt, FGF and Shh signalling pathways acting with Homeobox factors to carve the medial telencephalon into district progenitor regions, which in turn give rise to the choroid plexus, dentate gyrus and hippocampus. We then link the formation of the lateral ventricle choroid plexus with embryonic and postnatal neurogenesis in the hippocampus.
2,331,703
Hydrocephalus Induced by Intraventricular Peroxiredoxin-2: The Role of Macrophages in the Choroid Plexus.
The choroid plexus (CP) is the primary source of cerebrospinal fluid in the central nervous system. Recent evidence indicates that inflammatory pathways at the CP may be involved in hydrocephalus development. Peroxiredoxin 2 (Prx2) is a major component of red blood cells. Extracellular Prx2 is proinflammatory, and its release after red blood cell lysis may contribute to hydrocephalus after intraventricular hemorrhage. This study aimed to identify alterations in CP macrophages and dendritic cells following intracerebroventricular Prx2 injection and investigate the relationship between macrophages/dendritic cells and hydrocephalus. There were two parts to this study. In the first part, adult male Sprague-Dawley rats received an intracerebroventricular injection of Prx2 or saline. In the second part, Prx2 was co-injected with clodronate liposomes or control liposomes. All animals were euthanized at 24 h after magnetic resonance imaging. Immunohistochemistry was used to evaluate macrophages in CP, magnetic resonance imaging to quantify hydrocephalus, and histology to assess ventricular wall damage. The intracerebroventricular injection of Prx2 not only increased the OX-6 positive cells, but it also altered their location in the CP and immunophenotype. Co-injecting clodronate liposomes with Prx2 decreased the number of macrophages and simultaneously attenuated Prx2-induced hydrocephalus and ventricular wall damage. These results suggest that CP macrophages play an essential role in CP inflammation-induced hydrocephalus. These macrophages may be a potential therapeutic target in post-hemorrhagic hydrocephalus.
2,331,704
Predicting intraventricular hemorrhage growth with a machine learning-based, radiomics-clinical model.
We constructed a radiomics-clinical model to predict intraventricular hemorrhage (IVH) growth after spontaneous intracerebral hematoma. The model was developed using a training cohort (N=626) and validated with an independent testing cohort (N=270). Radiomics features and clinical predictors were selected using the least absolute shrinkage and selection operator (LASSO) method and multivariate analysis. The radiomics score (Rad-score) was calculated through linear combination of selected features multiplied by their respective LASSO coefficients. The support vector machine (SVM) method was used to construct the model. IVH growth was experienced by 13.4% and 13.7% of patients in the training and testing cohorts, respectively. The Rad-score was associated with severe IVH and poor outcome. Independent predictors of IVH growth included hypercholesterolemia (odds ratio [OR], 0.12 [95%CI, 0.02-0.90]; p=0.039), baseline Graeb score (OR, 1.26 [95%CI, 1.16-1.36]; p&lt;0.001), time to initial CT (OR, 0.70 [95%CI, 0.58-0.86]; p&lt;0.001), international normalized ratio (OR, 4.27 [95%CI, 1.40, 13.0]; p=0.011), and Rad-score (OR, 2.3 [95%CI, 1.6-3.3]; p&lt;0.001). In the training cohort, the model achieved an AUC of 0.78, sensitivity of 0.83, and specificity of 0.66. In the testing cohort, AUC, sensitivity, and specificity were 0.71, 0.81, and 0.64, respectively. This radiomics-clinical model thus has the potential to predict IVH growth.
2,331,705
Limiting Brain Shift in Malignant Hemispheric Infarction by Decompressive Craniectomy.
Decompressive craniectomy (DC) improves functional outcomes in selected patients with malignant hemispheric infarction (MHI), but variability in the surgical technique and occasional complications may be limiting the effectiveness of this procedure. Our aim was to evaluate predefined perioperative CT measurements for association with post-DC midline brain shift in patients with MHI.</AbstractText>At two medical centers we identified 87 consecutive patients with MHI and DC between January 2007 and December 2019. We used our previously tested methods to measure the craniectomy surface area, extent of transcalvarial brain herniation, thickness of tissues overlying the craniectomy, diameter of the cerebral ventricle atrium contralateral to the stroke, extension of infarction beyond the craniectomy edges, and the pre and post-DC midline brain shifts. To avoid potential confounding from medical treatments and additional surgical procedures, we excluded patients with the first CT delayed &gt;30 hours post-DC, resection of infarcted brain, or insertion of an external ventricular drain during DC. The primary outcome in multiple linear regression analysis was the postoperative midline brain shift.</AbstractText>We analyzed 72 qualified patients. The average midline brain shift decreased from 8.7 mm pre-DC to 5.4 post-DC. The only factors significantly associated with post-DC midline brain shift at the p&lt;0.01 level were preoperative midline shift (coefficient 0.32, standard error 0.10, p=0.002) and extent of transcalvarial brain herniation (coefficient -0.20, standard error 0.05, p &lt;0.001).</AbstractText>In patients with MHI and DC, smaller post-DC midline shift is associated with smaller pre-DC midline brain shift and greater transcalvarial brain herniation. This knowledge may prove helpful in assessing DC candidacy and surgical success. Additional studies to enhance the surgical success of DC are warranted.</AbstractText>Copyright &#xa9; 2021 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,331,706
The extreme anterior interhemispheric transcallosal approach for pure aqueduct tumors: surgical technique and case series.
Purely aqueductal tumors represent a rare but distinct entity of neoplasms with characteristic morphology and clinical presentation. This study aims to describe the extreme anterior interhemispheric transcallosal approach as a surgical option for purely aqueductal tumors in the upper part of the cerebral aqueduct and present the surgical results. Prospectively collected data of 4 patients undergoing the extreme anterior interhemispheric transcallosal approach for purely aqueductal tumors in the upper cerebral aqueduct was analyzed. The technique is a variation of the anterior interhemispheric transcallosal approach. The callosotomy is placed at the transition between the body and genu of the corpus callosum, allowing an approach steep enough to reach through the foramen of Monro to the upper cerebral aqueduct without opening the choroidal fissure. All patients had preoperative, and intraoperative or immediate postoperative 3-T magnetic resonance imaging, and underwent examination at admission, after surgery, at discharge, and 3&#xa0;months postoperatively. Patient data are reported according to common descriptive statistics. All patients harbored low-grade gliomas causing hydrocephalus. Complete resection was achieved without mortality or morbidity. All patients recovered and presented neurologically intact at the 3-month postoperative follow-up. None had recurrence or needed adjuvant therapy. The extreme anterior interhemispheric transcallosal approach proved to be effective and safe. This approach does not require manipulation of the choroidal fissure or disrupt healthy brain parenchyma (except for a small callosotomy). We propose it as an option for removing a purely aqueductal tumor in the upper cerebral aqueduct with associated hydrocephalus.
2,331,707
Transcranial sonographic assessment of the third ventricle in neuro-ICU patients to detect hydrocephalus: a diagnostic reliability pilot study.
Transcranial sonography is a point-of-care tool recommended in intensive care units (ICU) to monitor brain injured patients. Objectives of the study was to assess feasibility and reliability of the third ventricle (V3) diameter measurement using transcranial sonography (TCS) compared to brain computed-tomography (CT), the gold standard measurement, and to measure the TCS learning curve.</AbstractText>prospective study, in a 16-bed neurological ICU in an academic hospital. Every consecutive brain injured adult patient, who required a brain CT and TCS monitoring were included. The V3 diameter was blindly measured by TCS and CT. Intraclass correlation coefficient (ICC) and Bland-Altman plot were used to assess the reliability and agreement between TCS and CT V3 measurements. Diagnosis performance of the V3 diameter using TCS to detect hydrocephalus was measured. Absolute difference between V3 measurement by residents and experts was measured consecutively to assess the learning curve.</AbstractText>Among the 100 patients included in the study, V3 diameter could be assessed in 87 patients (87%) from at least one side of the skull. Both temporal windows were available in 70 patients (70%). The ICC between V3 diameter measured by TCS and CT was 0.90 [95% CI 0.84-0.93] on the right side, and 0.92 [0.88-0.95] on the left side. In Bland-Altman analysis, mean difference, standard deviation, 95% limits of agreement were 0.36, 1.52,&#x2009;-&#xa0;2.7 to 3.3&#xa0;mm, respectively, on the right side; 0.25, 1.47, -&#xa0;2.7 to 3.1&#xa0;mm, respectively, on the left side. Among the 35 patients with hydrocephalus, V3 diameters could be measured by TCS in 31 patients (89%) from at least one side. Hydrocephalus was, respectively, excluded, confirmed, or inconclusive using TCS in 35 (40%), 25 (29%) and 27 (31%) of the 87 assessable patients. After 5 measurements, every resident reached a satisfactory measurement compared to the expert operator.</AbstractText>TCS allows rapid, simple and reliable V3 diameter measurement compared with the gold standard in neuro-ICU patients. Aside from sparing irradiating procedures and transfers to the radiology department, it may especially increase close patient monitoring to detect clinically occult hydrocephalus earlier. Further studies are needed to measure the potential clinical benefit of this method.</AbstractText>ClinicalTrials.gov ID: NCT02830269.</AbstractText>
2,331,708
Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.
To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly.</AbstractText>In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES.</AbstractText>Included in the study were 62 fetuses with a gestational age ranging between 12 and 37&#x2009;weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) &lt;&#x2009;3rd</sup> centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption.</AbstractText>This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. &#xa9; 2021 International Society of Ultrasound in Obstetrics and Gynecology.</AbstractText>&#xa9; 2021 International Society of Ultrasound in Obstetrics and Gynecology.</CopyrightInformation>
2,331,709
Choroid Plexus and Drug Removal Mechanisms.
Timely and efficient removal of xenobiotics and metabolites from the brain is crucial in maintaining the homeostasis and normal function of the brain. The choroid plexus (CP) forms the blood-cerebrospinal fluid barrier and vitally removes drugs and wastes from the brain through several co-existing clearance mechanisms. The CP epithelial (CPE) cells synthesize and secrete the cerebrospinal fluid (CSF). As the CSF passes through the ventricular and subarachnoid spaces and eventually drains into the general circulation, it collects and removes drugs, toxins, and metabolic wastes from the brain. This bulk flow of the CSF serves as a default and non-selective pathway for the removal of solutes and macromolecules from the brain interstitium. Besides clearance by CSF bulk flow, the CPE cells express several multispecific membrane transporters to actively transport substrates from the CSF side into the blood side. In addition, several phase I and II drug-metabolizing enzymes are expressed in the CPE cells, which enzymatically inactivate a broad spectrum of reactive or toxic substances. This review summarizes our current knowledge of the functional characteristics and key contributors to the various clearance pathways in the CP-CSF system, overviewing recent developments in our understanding of CSF flow dynamics and the functional roles of CP uptake and efflux transporters in influencing CSF drug concentrations.
2,331,710
Unilateral Tension Pneumocephalus of the Sylvian Fissure: A Rare Neurosurgical Complication.
Tension pneumocephalus is an uncommon complication of neurosurgical procedures. We report a patient who presented with headache, vomiting, left hemiparesis and rhinorrhea 30 days after correction of a recurrent nasal cerebrospinal fluid fistula and shunt placement. A computed tomography scan revealed a massive collection of air with air-fluid level in the right sylvian fissure and midline shift. A right pterional craniotomy was performed and a small corticectomy resulted in evacuation of air from the sylvian fissure. A dural graft from the previous surgery was recognized to be acting as a ball-valve mechanism, trapping air from the nasal cavity. It was removed and the cranial defect was corrected with a split calvarial bone graft. Follow-up brain computed tomography revealed complete resolution of pneumocephalus. After surgery there was progressive improvement of neurological symptoms over 10 days, and the patient was asymptomatic after 1 month of follow-up.
2,331,711
Reliability and sensitivity of two whole-brain segmentation approaches included in FreeSurfer - ASEG and SAMSEG.
Accurate and reliable whole-brain segmentation is critical to longitudinal neuroimaging studies. We undertake a comparative analysis of two subcortical segmentation methods, Automatic Segmentation (ASEG) and Sequence Adaptive Multimodal Segmentation (SAMSEG), recently provided in the open-source neuroimaging package FreeSurfer 7.1, with regard to reliability, bias, sensitivity to detect longitudinal change, and diagnostic sensitivity to Alzheimer's disease. First, we assess intra- and inter-scanner reliability for eight bilateral subcortical structures: amygdala, caudate, hippocampus, lateral ventricles, nucleus accumbens, pallidum, putamen and thalamus. For intra-scanner analysis we use a large sample of participants (n&#xa0;=&#xa0;1629) distributed across the lifespan (age range&#xa0;=&#xa0;4-93 years) and acquired on a 1.5T Siemens Avanto (n&#xa0;=&#xa0;774) and a 3T Siemens Skyra (n&#xa0;=&#xa0;855) scanners. For inter-scanner analysis we use a sample of 24 participants scanned on the day with three models of Siemens scanners: 1.5T Avanto, 3T Skyra and 3T Prisma. Second, we test how each method detects volumetric age change using longitudinal follow up scans (n&#xa0;=&#xa0;491 for Avanto and n&#xa0;=&#xa0;245 for Skyra; interscan interval&#xa0;=&#xa0;1-10 years). Finally, we test sensitivity to clinically relevant change. We compare annual rate of hippocampal atrophy in cognitively normal older adults (n&#xa0;=&#xa0;20), patients with mild cognitive impairment (n&#xa0;=&#xa0;20) and Alzheimer's disease (n&#xa0;=&#xa0;20). We find that both ASEG and SAMSEG are reliable and lead to the detection of within-person longitudinal change, although with notable differences between age-trajectories for most structures, including hippocampus and amygdala. In summary, SAMSEG yields significantly lower differences between repeated measures for intra- and inter-scanner analysis without compromising sensitivity to changes and demonstrating ability to detect clinically relevant longitudinal changes.
2,331,712
CLEC5A knockdown protects against cardiac dysfunction after myocardial infarction by suppressing macrophage polarization, NLRP3 inflammasome activation, and pyroptosis.
Increasing evidence has shown that the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptotic cell death play vital roles in the pathophysiology of myocardial infarction (MI), a common cardiovascular disease characterized by cardiac dysfunction. C-type lectin member 5A (CLEC5A) has been reported to be strongly associated with activation of the NLRP3 inflammasome and pyroptosis. In this study, an in&#xa0;vivo MI model was established by ligation of the left anterior descending coronary artery in male C57BL/6 mice, and CLEC5A knockdown was further achieved by intra-myocardial injection of adenovirus delivering shRNA-CLEC5A. CLEC5A was found to be highly expressed in the left ventricle of MI mice, while CLEC5A knockdown alleviated cardiac dysfunction in MI mice. In addition, MI-induced classical activation of macrophages was significantly inhibited after CLEC5A silencing. Additionally, CLEC5A knockdown dramatically inhibited MI-triggered activation of NLRP3 inflammasome, pyroptosis, and NF-&#x3ba;B signaling in the left ventricle of mice. In&#xa0;vitro experiments further validated that CLEC5A knockdown suppressed M1 polarization in LPS/IFN&#x3b3;-stimulated RAW264.7 cells and inhibited the polarized RAW264.7-induced activation of NLRP3 inflammasome/pyroptosis signaling in co-cultured cardiomyocytes. In conclusion, CLEC5A knockdown protects against MI-induced cardiac dysfunction by regulating macrophage polarization, NLRP3 inflammasome, and cell pyroptosis.
2,331,713
A mid-ventricular variant of Takotsubo syndrome: was it triggered by insular cortex damage?
Takotsubo syndrome (TTS) is a transient cardiomyopathy that is often associated with cerebrovascular diseases. Earlier studies have supported the concept that the cardiovascular system is regulated by a central autonomic network (CAN) consisting of the insular cortex (IC), anterior cingulate gyrus and amygdala. We report the case of a 79-year-old female diagnosed with a mid-ventricular variant of TTS concomitant with right IC ischaemic stroke. After 12&#xa0;h of hospitalization, she experienced a sudden collapse. Rapid cardiopulmonary resuscitation resulted in a return of spontaneous circulation. Subsequent left ventriculography revealed akinesis in the mid-portion of the left ventricle with vigorous contraction of the basal and apex segment. Two weeks after admission, cardiac ultrasound showed improved left ventricular contraction. Right IC ischaemia in this patient might have been associated with a dysregulation of the CAN and subsequent increased sympathetic nervous system activity that triggered TTS.
2,331,714
Persistent fontanelles in Chihuahuas. Part II: Association with craniocervical junction abnormalities, syringomyelia, and ventricular volume.
Persistent fontanelles (PFs) are, in Chihuahuas, almost ubiquitous. Furthermore, Chihuahuas are predisposed to other craniomorphological abnormalities, including syringomyelia (SM), ventriculomegaly, and craniocervical junction (CCJ) overcrowding resulting in neural tissue deviation. It is, however, undetermined if PFs are more common in dogs with these structural abnormalities, and their etiology is unknown.</AbstractText><AbstractText Label="HYPOTHESIS/OBJECTIVES" NlmCategory="OBJECTIVE">Persistent fontanelles are more numerous and larger in Chihuahuas with low body weight, older age, SM, dilated fourth ventricle, ventriculomegaly, and CCJ overcrowding.</AbstractText>Fifty client-owned Chihuahuas.</AbstractText>Cross-sectional study evaluating the association of both the number of cranial sutures affected by PFs (NAS) and total fontanelle area (TFA), based on computed tomography with SM, fourth ventricle dilatation, lateral ventricle volume, and extent of neural tissue compression at the CCJ based on magnetic resonance images.</AbstractText>The NASs was higher and TFA larger in dogs with low body weight (NAS: P&#xa0;=&#xa0;.007; 95% confidence interval [CI]&#xa0;=&#xa0;0.384-0.861; TFA: P&#xa0;=&#xa0;.002; 95% CI&#xa0;=&#xa0;-1.91 to -0.478), larger lateral ventricles (NAS: P&#x2009;&#x2264;&#x2009;.001; 95% CI&#xa0;=&#xa0;1.04-1.15; TFA: P&#x2009;&#x2264;&#x2009;.001; 95% CI&#xa0;=&#xa0;0.099-0.363), and more severe neural tissue compression at the CCJ (NAS: P&#x2009;&#x2264;&#x2009;.001; 95% CI&#xa0;=&#xa0;1.26-2.06; TFA: P&#xa0;=&#xa0;.03; 95% CI&#xa0;=&#xa0;0.066-1.13). Similarly, dogs with SM (NAS: P&#xa0;=&#xa0;.004; 95% CI&#xa0;=&#xa0;1.26-3.32; TFA: mean&#x2009;&#xb1;&#x2009;SD, 130&#x2009;&#xb1;&#x2009;217&#x2009;mm2</sup> ; P&#xa0;=&#xa0;.05) had higher NAS and larger TFA than did dogs without SM (43.7&#x2009;&#xb1;&#x2009;61.0&#x2009;mm2</sup> ). Age was not associated with NAS (P&#xa0;=&#xa0;.81; 95% CI&#xa0;=&#xa0;0.989-1.01) or TFA (P&#xa0;=&#xa0;.33; 95% CI&#xa0;=&#xa0;-0.269 to 0.092).</AbstractText>Persistent fontanelles are associated with small size, SM, ventriculomegaly, and CCJ overcrowding.</AbstractText>&#xa9; 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.</CopyrightInformation>
2,331,715
Psychosis and Dandy-Walker syndrome: a case report and review of the literature.
Dandy-Walker syndrome (DWS) is a group of brain malformations which sometimes present with psychotic symptoms. We present the case of a patient diagnosed with Dandy-Walker variant who presented with schizophrenia-like psychosis. A man in his 30s was admitted to an acute psychiatric unit presenting with persecutory delusions, auditory hallucinations and violent behaviour. The MRI performed showed the typical alterations of Dandy-Walker variant: vermian hypoplasia and cystic dilatation of the fourth ventricle. He also suffered from mild intellectual disability. After being treated with olanzapine 10&#x2009;mg/d for a month, his psychotic symptoms greatly improved and he was discharged. In conclusion, DWS may cause psychosis through a dysfunction in the circuit connecting prefrontal, thalamic and cerebellar areas. The association between these two conditions may contribute to the understanding of the aetiopathogenesis of schizophrenia.
2,331,716
Saved by anticoagulants: Incidental discovery of a misplaced defibrillator lead 6&#xa0;years after implantation. Inadvertent lead placement inside the left ventricular cavity.
Device insertion is a common cardiovascular procedure. Devices are implanted into the right heart, acting as a safeguard against systemic thromboembolism. Lead insertion into the left ventricle is rare, but carries dangerous consequences of thromboembolic events. Diagnosis and intervention of an inadvertently placed lead is essential. This is a case of a defibrillator lead inadvertently inserted into the left cavity, discovered 6 years after implantation.
2,331,717
3D Reconstruction of the Morpho-Functional Topography of the Human Vagal Trigone.
The Vagal Trigone, often referred to as Ala Cinerea, is a triangular-shaped area of the floor of the fourth ventricle that is strictly involved in the network of chardiochronotropic, baroceptive, respiratory, and gastrointestinal control systems of the medulla oblongata. While it is frequently identified as the superficial landmark for the underlying Dorsal Motor Nucleus of the Vagus, this correspondence is not univocal in anatomical literature and is often oversimplified in neuroanatomy textbooks and neurosurgical atlases. As the structure represents an important landmark for neurosurgical procedures involving the floor of the fourth ventricle, accurate morphological characterization is required to avoid unwanted side effects (e.g., bradychardia, hypertension) during neuorphysiological monitoring and cranial nerve nuclei stimulation in intraoperative settings. The aim of this study was to address the anatomo-topographical relationships of the Vagal Trigone with the underlying nuclei. For this purpose, we have conducted an anatomo-microscopical examination of serial sections deriving from 54 Human Brainstems followed by 3D reconstruction and rendering of the specimens. Our findings indicate that the Vagal Trigone corresponds only partially with the Dorsal Motor Nucleus of the Vagus, while most of its axial profile is occupied by the dorsal regions of the Solitary Tract Nucleus. Furthermore, basing on literature and our findings we speculate that the neuroblasts of the Dorsal Motor Nucleus of the Vagus undergo neurobiotaxic migration induced by the neuroblasts of the dorsolaterally located solitary tract nucleus, giving rise to the Ala Cinerea, a topographically defined area for parasympathetic visceral control.
2,331,718
Poly (L-lactic acid) nanofibrous scaffolds support the proliferation and neural differentiation of mouse neural stem and progenitor cells.
The distribution and growth of cells on nanofibrous scaffolds seem to be an indispensable precondition in cell tissue engineering. The potential use of biomaterial scaffolds in neural stem cell therapy is increasingly attracting attention.</AbstractText>In this study, we produced porous nanofibrous scaffolds fabricated from random poly-L-lactic acid (PLLA) to support neurogenic differentiation of neural stem and progenitor cells (NSPCs), isolated from the subventricular zone (SVZ) of the adult mouse brain.</AbstractText>The viability and proliferation of the NSPCs on the nanofibrous PLLA scaffold were also tested by nuclear staining with 4, 6-diamidino-2-phenylindole dihydrochloride (DAPI), 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and scanning electron microscopy (SEM). To investigate the differentiation potential of NSPCs on the scaffolds, the cells were treated with a neurogenic differentiation medium, and immunostaining was done to detect neuronal and glial cells after 14 and 21&#xa0;days of cultivation. Furthermore, the morphology of differentiated cells on the scaffold was examined using SEM.</AbstractText>The DAPI staining revealed the proliferation of NSPCs onto the surface of the nanofibrous PLLA scaffold. DAPI-positive cells were counted on days 2 and 5 after cultivation. The mean number of cells in each microscopic field was significantly (p&#xa0;&lt;&#xa0;.05) increased (51&#xa0;&#xb1;&#xa0;19 on day 2 compared to 77&#xa0;&#xb1;&#xa0;25 cells on day 5). The results showed that the cell viability on PLLA scaffolds significantly increased compared to control groups. Moreover, cell viability was significantly increased 5&#xa0;days after culturing (262.3&#xa0;&#xb1;&#xa0;50.2) as compared to 2&#xa0;days culture in Vitro (174.2&#xa0;&#xb1;&#xa0;28.3, p&#xa0;&lt;&#xa0;.05). Scanning electron micrographs also showed that the NSPCs adhered and differentiated on PLLA scaffolds. We found that the neural cell markers, microtubule-associated protein 2 (MAP2) and glial &#xfb01;brillary acidic protein (GFAP), were expressed in NSPCs seeded on random PLLA scaffolds after 21&#xa0;days of cultivation.</AbstractText>These results suggest that the PLLA nano-scaffolds, due to their biocompatible property, are an appropriate structure for the proliferation, differentiation, and normal growth of NSPCs.</AbstractText>&#xa9; 2021 International Society for Developmental Neuroscience.</CopyrightInformation>
2,331,719
Cortical spectral matching and shape and volume analysis of the fetal brain pre- and post-fetal surgery for spina bifida: a retrospective study.
A retrospective study was performed to study the effect of fetal surgery on brain development measured by MRI in fetuses with myelomeningocele (MMC).</AbstractText>MRI scans of 12 MMC fetuses before and after surgery were compared to 24 age-matched controls without central nervous system abnormalities. An automated super-resolution reconstruction technique generated isotropic brain volumes to mitigate 2D MRI fetal motion artefact. Unmyelinated white matter, cerebellum and ventricles were automatically segmented, and cerebral volume, shape and cortical folding were thereafter quantified. Biometric measures were calculated for cerebellar herniation level (CHL), clivus-supraocciput angle (CSO), transverse cerebellar diameter (TCD) and ventricular width (VW). Shape index (SI), a mathematical marker of gyrification, was derived. We compared cerebral volume, surface area and SI before and after MMC fetal surgery versus controls. We additionally identified any relationship between these outcomes and biometric measurements.</AbstractText>MMC ventricular volume/week (mm3</sup>/week) increased after fetal surgery (median: 3699, interquartile range (IQR): 1651-5395) compared to controls (median: 648, IQR: 371-896); P&#x2009;=&#x2009;0.015. The MMC SI is higher pre-operatively in all cerebral lobes in comparison to that in controls. Change in SI/week in MMC fetuses was higher in the left temporal lobe (median: 0.039, IQR: 0.021-0.054), left parietal lobe (median: 0.032, IQR: 0.023-0.039) and right occipital lobe (median: 0.027, IQR: 0.019-0.040) versus controls (P&#x2009;=&#x2009;0.002 to 0.005). Ventricular volume (mm3</sup>) and VW (mm) (r&#x2009;=&#x2009;0.64), cerebellar volume and TCD (r&#x2009;=&#x2009;0.56) were moderately correlated.</AbstractText>Following fetal myelomeningocele repair, brain volume, shape and SI were significantly different from normal in most cerebral layers. Morphological brain changes after fetal surgery are not limited to hindbrain herniation reversal. These findings may have neurocognitive outcome implications and require further evaluation.</AbstractText>&#xa9; 2021. The Author(s).</CopyrightInformation>
2,331,720
A cellular and spatial map of the choroid plexus across brain ventricles and ages.
The choroid plexus (ChP) in each brain ventricle produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. Here, we construct a single-cell and spatial atlas of each ChP in the developing, adult, and aged mouse brain. We delineate diverse cell types, subtypes, cell states, and expression programs in epithelial and mesenchymal cells across ages and ventricles. In the developing ChP, we predict a common progenitor pool for epithelial and neuronal cells, validated by lineage tracing. Epithelial and fibroblast cells show regionalized expression by ventricle, starting at embryonic stages and persisting with age, with a dramatic transcriptional shift with maturation, and a smaller shift in each aged cell type. With aging, epithelial cells upregulate host-defense programs, and resident macrophages upregulate interleukin-1&#x3b2; (IL-1&#x3b2;) signaling genes. Our atlas reveals cellular diversity, architecture and signaling across ventricles during development, maturation, and aging of the ChP-brain barrier.
2,331,721
Rivaroxaban versus warfarin for the management of left ventricle thrombus.
Rivaroxaban has been recently introduced for the management of non-valvular intra-cardiac thrombosis with variable results. We aimed to compare the results of the off-label use of rivaroxaban versus warfarin in the management of patients with left ventricle (LV) thrombus. This research is a retrospective study conducted on 63 patients who had LV thrombus from January to December 2016. We compared patients treated with warfarin (n=35) to patients who had rivaroxaban (n=28), and study outcomes were time to thrombus resolution, bleeding, stroke, and mortality.</AbstractText>The median duration of treatment was 9.5 (25th-75th percentiles: 6-32.5) months for rivaroxaban and 14 (3-41) months for warfarin. Thrombus resolution occurred in 24 patients in the warfarin group (68.6%) and 20 patients in the rivaroxaban group (71.4%). The median time to resolution in the warfarin group was 9 (4-20) months and 3 (2-11.5) months in the rivaroxaban group. Thrombus resolution was significantly faster in patients on rivaroxaban (p= 0.019). Predictors of thrombus resolution were thrombus surface area (HR: 1.21; CI 95% (1.0-1.46); p= .048) and the use of rivaroxaban (HR: 1.92; CI 95% (1.01-3.65); p= 0.048). There was no difference in stroke, bleeding, and mortality between both groups.</AbstractText>Rivaroxaban was as effective and safe as warfarin in managing patients with left ventricle thrombus. Larger randomized clinical trials are recommended to confirm our findings.</AbstractText>
2,331,722
Application of contrast-enhanced magnetic resonance imaging in the assessment of blood-cerebrospinal fluid barrier integrity.
VERHEGGEN, I.C.M., W. Freeze, J. de Jong, J. Jansen, A. Postma, M. van Boxtel, F. Verhey and W. Backes. The application of contrast-enhanced MRI in the assessment of blood-cerebrospinal fluid barrier integrity. Choroid plexus epithelial cells form a barrier that enables active, bidirectional exchange between the blood plasma and cerebrospinal fluid (CSF), known as the blood-CSF barrier (BCSFB). Through its involvement in CSF composition, the BCSFB maintains homeostasis in the central nervous system. While the relation between blood-brain barrier disruption, aging and neurodegeneration is extensively studied using contrast-enhanced MRI, applying this technique to investigate BCSFB disruption in age-related neurodegeneration has received little attention. This review provides an overview of the current status of contrast-enhanced MRI to assess BCSFB permeability. Post-contrast ventricular gadolinium enhancement has been used to indicate BCSFB permeability. Moreover, new techniques highly sensitive to low gadolinium concentrations in the CSF, for instance heavily T2-weighted imaging with cerebrospinal fluid suppression, seem promising. Also, attempts are made at using other contrast agents, such as manganese ions or very small superparamagnetic iron oxide particles, that seem to be cleared from the brain at the choroid plexus. Advancing and applying new developments such as these could progress the assessment of BCSFB integrity.
2,331,723
MRI to detect and localize the area postrema in multiple sclerosis: The role of 3D-DIR and 3D-FLAIR.
Area postrema (AP) is a highly vascularized paired 2 mm-long anatomical structure, localized on the dorsal inferior surface of the medulla oblongata, at the caudal end of the fourth-ventricle. AP is principally affected in AP syndrome, which is commonly associated with autoimmune inflammatory diseases, including essentially neuromyelitis optica spectrum disorder (NMOSD). The aim of this study is to assess the best cerebral MRI sequences and planes for AP detection in order to assist or aid in the diagnosis of difficult NMOSD cases.</AbstractText>3DT1, 2DT2, 3D-fluid-attenuated inversion recovery (3DFLAIR), and 3D-double inversion recuperation (3DDIR), routinely used in inflammatory diseases, were analyzed and scored based on quality (0-2), and ability to detect AP in each plane (0 = no detection, 1 = probable detection, 2 = obvious detection). Based on image availability, subjects were divided into three groups: Group-1, including 100 randomly selected subjects with 3DT1 and 3DFLAIR, Group-2, including 30 multiple sclerosis (MS) patients from the "Observatoire Fran&#xe7;ais de la Scl&#xe9;rose En Plaques" (OFSEP) with 3DT1, 3DFLAIR, and 3DDIR, and Group-3, including 164 OFSEP MS patients with 3DFLAIR and 2DT2.</AbstractText>AP was undetectable on 3DT1 and 2DT2. AP was detected in 87% of 3DFLAIR in Group-1, 90% in Group-2, and 90% in Group-3. AP was also detected in 100% of 3DDIR images in the axial plane.</AbstractText>As evidenced, AP was easily assessed on 3DDIR and 3DFLAIR emphasizing the importance of adding these sequences to NMOSD MRI-protocols. Moreover, the most effective imaging plane in identifying AP was the axial plane.</AbstractText>&#xa9; 2021 American Society of Neuroimaging.</CopyrightInformation>
2,331,724
The black rim susceptibility sign in the MRI evaluation of intracranial colloid cysts.
Colloid cysts are relatively rare intracranial lesions located in the rostral aspect of third ventricle. They may produce acute hydrocephalus, brain herniation, and death. On conventional MRI, the appearance of a colloid cyst varies depending on its composition. Small isointense cysts can be missed. The purpose of this study is to introduce a new sign, "black rim susceptibility" sign for the accurate diagnosis of colloid cyst on susceptibility weighted imaging (SWI).</AbstractText>A retrospective case-control study consisted of 100 MRI brain scans (19 cases and 81 controls) performed from January 2012 to September 2018. Two fellowship trained neuroradiologists individually interpreted SWI sequences for the presence of the "black rim susceptibility" sign (thin rim of dark signal along the periphery of a rounded, hyperintense focus).</AbstractText>The sample was 43% male and 57% female, with an average age of 51.8 &#xb1; 17.7. Out of 19 cases, 9 had undergone surgery in which pathology had confirmed colloid cyst. Sensitivity, specificity, and accuracy for reader 1 was 94.8%, 98.8%, and 98% and for reader 2 was 89.5%, 100%, and 98%, respectively. Positive predictive value and negative predictive value for reader 1 was 94.7% and 98.8% and for reader 2 was 100% and 97.6%, respectively. Interrater correlation between the two readers was calculated with kappa of 0.93.</AbstractText>The black rim susceptibility appearance of colloid cyst on SWI is a novel description and an effective sign that can be used by radiologists for accurate diagnosis.</AbstractText>&#xa9; 2021 American Society of Neuroimaging.</CopyrightInformation>
2,331,725
Brown Vialetto Van Laere syndrome: presenting with left ventricular non-compaction and mimicking mitochondrial disorders.
Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare, treatable neurodegenerative disorder with a variable clinical presentation, caused by mutations in three different riboflavin transporter genes.</AbstractText>An 11-year-old-boy presented with respiratory insufficiency and a rapidly progressive muscle weakness. He was the fifth child of a consanguineous marriage with a medical history of hearing loss. He was peripherally week with a reduced muscle tone. Upper extremity muscles were effected more than lower limbs. He deteriorated rapidly and became quadriplegic. Brain magnetic resonance imaging and magnetic resonance spectroscopy were normal. Echocardiography revealed left ventricular non-compaction. A homozygous c.1088C &gt; T (p.363L) missense mutation was identified in SLC52A2 gene. Significant clinical improvement was seen with high dose riboflavin.</AbstractText>This is the first reported BVVLS case presented with left ventricle-non compaction which may be caused by a secondary respiratory chain deficiency. Riboflavin transporter deficiencies should be considered in the differential diagnosis of mitochondrial disorders and secondary respiratory chain deficiencies should be thought during the follow-up of BVVLS.</AbstractText>
2,331,726
Development of a Prognostic Model to Predict Mortality after Traumatic Brain Injury in Intensive Care Setting in a Developing Country.
<b>Objectives</b> &#x2003;We aimed to develop a prognostic model for the prediction of in-hospital mortality in patients with traumatic brain injury (TBI) admitted to the neurosurgery intensive care unit (ICU) of our institute. <b>Materials and Methods</b> &#x2003;The clinical and computed tomography scan data of consecutive patients admitted after a diagnosis TBI in ICU were reviewed. Construction of the model was done by using all the variables of Corticosteroid Randomization after Significant Head Injury and International Mission on Prognosis and Analysis of Clinical Trials in TBI models. The endpoint was in-hospital mortality. <b>Results</b> &#x2003;A total of 243 patients with TBI were admitted to ICU during the study period. The in-hospital mortality was 15.3%. On multivariate analysis, the Glasgow coma scale (GCS) at admission, hypoxia, hypotension, and obliteration of the third ventricle/basal cisterns were significantly associated with mortality. Patients with hypoxia had eight times, with hypotensions 22 times, and with obliteration of the third ventricle/basal cisterns three times more chance of death. The TBI score was developed as a sum of individual points assigned as follows: GCS score 3 to 4 (+2 points), 5 to 12 (+1), hypoxia (+1), hypotension (+1), and obliteration third ventricle/basal cistern (+1). The mortality was 0% for a score of "0" and 85% for a score of "4." <b>Conclusion</b> &#x2003;The outcome of patients treated in ICU was based on common admission variables. A simple clinical grading score allows risk stratification of patients with TBI admitted in ICU.
2,331,727
Blood-brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2&#xa0;weeks.
Repeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood-brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3&#xa0;days per week for 2&#xa0;weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2&#xa0;weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits.
2,331,728
Efficacy of Intact Cord Resuscitation Compared to Immediate Cord Clamping on Cardiorespiratory Adaptation at Birth in Infants with Isolated Congenital Diaphragmatic Hernia (CHIC).
Resuscitation at birth of infants with Congenital Diaphragmatic Hernia (CDH) remains highly challenging because of severe failure of cardiorespiratory adaptation at birth. Usually, the umbilical cord is clamped immediately after birth. Delaying cord clamping while the resuscitation maneuvers are started may: (1) facilitate blood transfer from placenta to baby to augment circulatory blood volume; (2) avoid loss of venous return and decrease in left ventricle filling caused by immediate cord clamping; (3) prevent initial hypoxemia because of sustained uteroplacental gas exchange after birth when the cord is intact. The aim of this trial is to evaluate the efficacy of intact cord resuscitation compared to immediate cord clamping on cardiorespiratory adaptation at birth in infants with isolated CDH. The Congenital Hernia Intact Cord (CHIC) trial is a prospective multicenter open-label randomized controlled trial in two balanced parallel groups. Participants are randomized either immediate cord clamping (the cord will be clamped within the first 15 s after birth) or to intact cord resuscitation group (umbilical cord will be kept intact during the first part of the resuscitation). The primary end-point is the number of infants with APGAR score &lt;4 at 1 min or &lt;7 at 5 min. One hundred eighty participants are expected for this trial. To our knowledge, CHIC is the first study randomized controlled trial evaluating intact cord resuscitation on newborn infant with congenital diaphragmatic hernia. Better cardiorespiratory adaptation is expected when the resuscitation maneuvers are started while the cord is still connected to the placenta.
2,331,729
Role of &#x3b1;2-Adrenoceptor Subtypes in Suppression of L-Type Ca<sup>2+</sup> Current in Mouse Cardiac Myocytes.
Sarcolemmal &#x3b1;2 adrenoceptors (&#x3b1;2-AR), represented by &#x3b1;2A, &#x3b1;2B and &#x3b1;2C isoforms, can safeguard cardiac muscle under sympathoadrenergic surge by governing Ca<sup>2+</sup> handling and contractility of cardiomyocytes. Cardiomyocyte-specific targeting of &#x3b1;2-AR would provide cardiac muscle-delimited stress control and enhance the efficacy of cardiac malfunction treatments. However, little is known about the specific contribution of the &#x3b1;2-AR subtypes in modulating cardiomyocyte functions. Herein, we analyzed the expression profile of &#x3b1;2A, &#x3b1;2B and &#x3b1;2C subtypes in mouse ventricle and conducted electrophysiological antagonist assay evaluating the contribution of these isoforms to the suppression of L-type Ca<sup>2+</sup> current (<i>I</i><sub>CaL</sub>). Patch-clamp electro-pharmacological studies revealed that the &#x3b1;2-agonist-induced suppression of <i>I</i><sub>CaL</sub> involves mainly the &#x3b1;2C, to a lesser extent the &#x3b1;2B, and not the &#x3b1;2A isoforms. RT-qPCR evaluation revealed the presence of <i>adra2b</i> and <i>adra2c</i> (&#x3b1;2B and &#x3b1;2C isoform genes, respectively), but was unable to identify the expression of <i>adra2a</i> (&#x3b1;2A isoform gene) in the mouse left ventricle. Immunoblotting confirmed the presence only of the &#x3b1;2B and the &#x3b1;2C proteins in this tissue. The identified &#x3b1;2-AR isoform-linked regulation of <i>I</i><sub>CaL</sub> in the mouse ventricle provides an important molecular substrate for the cardioprotective targeting.
2,331,730
Preoperative Devascularization of Choroid Plexus Tumors: Specific Issues about Anatomy and Embolization Technique.
(1) Background: Surgical treatment of choroid plexus tumors is challenging, burdened by a notable risk of bleeding. Neoadjuvant chemotherapy and preoperative embolization have been attempted, with encouraging results; however, the consensus on these procedures is lacking. (2) Methods: We present a case of a 10-month-old girl who underwent preoperative embolization of a hemorrhagic choroid plexus carcinoma of the lateral ventricle via the anterior choroidal artery, followed by total resection. (3) Results: The endovascular procedure was successfully completed, despite the rectification of the anterior choroidal artery associated with the absence of flow proximal to the plexal point. Minimal bleeding was observed during resection and the patient remained neurologically intact. (4) Conclusions: The time from entrance to exit in the anterior choroidal artery should be monitored and regarded as a potential 'occlusion time' in this specific group of patients. Nevertheless, our case supports the feasibility and effectiveness of preoperative embolization of a choroid plexus carcinoma of the lateral ventricle via the anterior choroidal artery, without complications. Furthermore, we suggest the use of a fast-embolic agent, such as N-butyl cyanoacrylate glue, as the preferred agent for this specific pathology and patient population.
2,331,731
Hemodynamic Forces Regulate Cardiac Regeneration-Responsive Enhancer Activity during Ventricle Regeneration.
Cardiac regenerative capacity varies widely among vertebrates. Zebrafish can robustly regenerate injured hearts and are excellent models to study the mechanisms of heart regeneration. Recent studies have shown that enhancers are able to respond to injury and regulate the regeneration process. However, the mechanisms to activate these regeneration-responsive enhancers (RREs) remain poorly understood. Here, we utilized transient and transgenic analysis combined with a larval zebrafish ventricle ablation model to explore the activation and regulation of a representative RRE. <i>lepb</i>-linked enhancer sequence (<i>LEN</i>) directed enhanced green fluorescent protein (EGFP) expression in response to larval ventricle regeneration and such activation was attenuated by hemodynamic force alteration and mechanosensation pathway modulation. Further analysis revealed that Notch signaling influenced the endocardial <i>LEN</i> activity as well as endogenous <i>lepb</i> expression. Altogether, our work has established zebrafish models for rapid characterization of cardiac RREs in vivo and provides novel insights on the regulation of <i>LEN</i> by hemodynamic forces and other signaling pathways during heart regeneration.
2,331,732
Feasibility, Reproducibility and Validation of Right Ventricular Volume and Function Assessment Using Three-Dimensional Echocardiography.
Three-dimensional echocardiography (3DE) is advised for right ventricular (RV) assessment. Data regarding the optimal acquisition settings and optimization are still scarce. We aimed to evaluate the feasibility, reproducibility and validation of 3DE for RV volume and function assessment, using cardiac magnetic resonance (CMR) as gold standard. Thirty healthy volunteers and 36 consecutive patients were prospectively included. CMR was performed in the latter. Standard apical four-chamber view (A4CV), focused A4CV and modified A4CV were used for 3DE RV acquisition. Feasibility (and the effect of changes in settings) was evaluated. Intra and interobserver analyses were performed by three observers (expert vs. novice). RV parameters by echocardiography were compared to CMR. Feasibility of acquisition was 16.7% for A4CV, 80.0% for focused A4CV and 16.7% for modified A4CV. Changes in settings had no significant influence on feasibility and further analysis. Intraobserver variability was good in both expert and novice, interobserver variability was good between experienced observers. Compared to CMR, 3DE volumes were significantly lower with fair to moderate correlation (EDV: 91.1 &#xb1; 24.4 mL vs. 144.3 &#xb1; 43.0 mL (<i>p</i> &lt; 0.001), r = 0.653 and ESV: 48.1 &#xb1; 16.4 mL vs. 60.4 &#xb1; 21.2 mL (<i>p</i> &lt; 0.001), r = 0.530, by multi-beat 3DE and CMR respectively). These findings suggest that standardization is needed in order to implement this technique in clinical practice, thus further studies are required.
2,331,733
Diagnostic Classification and Biomarker Identification of Alzheimer's Disease with Random Forest Algorithm.
Random Forest (RF) is a bagging ensemble model and has many important advantages, such as robustness to noise, an effective structure for complex multimodal data and parallel computing, and also provides important features that help investigate biomarkers. Despite these benefits, RF is not used actively to predict Alzheimer's disease (AD) with brain MRIs. Recent studies have reported RF's effectiveness in predicting AD, but the test sample sizes were too small to draw any solid conclusions. Thus, it is timely to compare RF with other learning model methods, including deep learning, particularly with large amounts of data. In this study, we tested RF and various machine learning models with regional volumes from 2250 brain MRIs: 687 normal controls (NC), 1094 mild cognitive impairment (MCI), and 469 AD that ADNI (Alzheimer's Disease Neuroimaging Initiative database) provided. Three types of features sets (63, 29, and 22 features) were selected, and classification accuracies were computed with RF, Support vector machine (SVM), Multi-layer perceptron (MLP), and Convolutional neural network (CNN). As a result, RF, MLP, and CNN showed high performances of 90.2%, 89.6%, and 90.5% with 63 features. Interestingly, when 22 features were used, RF showed the smallest decrease in accuracy, -3.8%, and the standard deviation did not change significantly, while MLP and CNN yielded decreases in accuracy of -6.8% and -4.5% with changes in the standard deviation from 3.3% to 4.0% for MLP and 2.1% to 7.0% for CNN, indicating that RF predicts AD more reliably with fewer features. In addition, we investigated the importance of the features that RF provides, and identified the hippocampus, amygdala, and inferior lateral ventricle as the major contributors in classifying NC, MCI, and AD. On average, AD showed smaller hippocampus and amygdala volumes and a larger volume of inferior lateral ventricle than those of MCI and NC.
2,331,734
A Systematic Review on the Correlations between Left Atrial Strain and Cardiovascular Outcomes in Chronic Kidney Disease Patients.
Left atrial strain (LASr) represents a relatively new but promising technique for left atrial and left ventricle function evaluation. LASr was strongly linked to myocardial fibrosis and endocardial thickness, suggesting the utility of LASr in subclinical cardiac dysfunction detection. As CKD negatively impacts cardiovascular risk and mortality, underlying structural and functional abnormalities of cardiac remodeling are widely investigated. LASr could be used in LV diastolic dysfunction grading with an excellent discriminatory power. Our objectives were to assess the impact and existing correlations between LASr and cardiovascular outcomes, as reported in clinical trials, including patients with CKD. We searched PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials for full-text papers. As reported in clinical studies, LASr was associated with adverse cardiovascular outcomes, including cardiovascular death and major adverse cardiovascular events (HR 0.89, 95% CI, 0.84-0.93, <i>p</i> &lt; 0.01), paroxysmal atrial fibrillation (OR 0.847, 95% CI, 0.760-0.944, <i>p</i> = 0.003), reduced exercise capacity (AUC 0.83, 95% CI, 0.78-0.88, <i>p</i> &lt; 0.01), diastolic dysfunction (<i>p</i> &lt; 0.05), and estimated pulmonary capillary wedge pressure (<i>p</i> &lt; 0.001). Despite limitations attributed to LA deformation imaging (image quality, inter-observer variability, software necessity, learning curve), LASr constitutes a promising marker for cardiovascular events prediction and risk evaluation in patients with CKD.
2,331,735
3D Imaging and Quantitative Characterization of Mouse Capillary Coronary Network Architecture.
Characterization of the cardiac capillary network structure is of critical importance to understand the normal coronary functional properties and coronary microvascular diseases. The aim of our study was to establish an accessible methodology for 3D imaging and 3D processing to quantitatively characterize the capillary coronary network architecture in mice. Experiments were done on C57BL/6J mice. 3D imaging was performed by light sheet microscopy and confocal microscopy on iDISCO+ optical cleared hearts after labelling of the capillary endothelium by lectin injection. 3D images were processed with the open source software ImageJ. Non-visual image segmentation was based of the frequency distribution of the voxel greyscale values, followed by skeletonization and distance mapping. Capillary networks in left and right ventricles and septum were characterized by the volume network density, the fractal dimension, the number of segments and nodes and their ratio, the total network length, and the average length, diameter, and tortuosity of the segments. Scale-dependent parameter values can be impacted by the resolution limit of the 3D imaging technique. The proposed standardized methodology for 3D image processing is easily accessible for a biologist in terms of investment and difficulty level, and allows the quantification of the 3D capillary architecture and its statistical comparison in different conditions.
2,331,736
Semi-Lethal Primary Ciliary Dyskinesia in Rats Lacking the <i>Nme7</i> Gene.<ELocationID EIdType="pii" ValidYN="Y">3810</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/ijms22083810</ELocationID><Abstract><AbstractText><i>NME7</i> (non-metastatic cells 7, nucleoside diphosphate kinase 7) is a member of a gene family with a profound effect on health/disease status. NME7 is an established member of the ciliome and contributes to the regulation of the microtubule-organizing center. We aimed to create a rat model to further investigate the phenotypic consequences of <i>Nme7</i> gene deletion. The CRISPR/Cas9 nuclease system was used for the generation of Sprague Dawley <i>Nme7</i> knock-out rats targeting the exon 4 of the <i>Nme7</i> gene. We found the homozygous <i>Nme7</i> gene deletion to be semi-lethal, as the majority of SD<i><sup>Nme7</sup></i><sup>-/-</sup> pups died prior to weaning. The most prominent phenotypes in surviving SD<i><sup>Nme7</sup></i><sup>-/-</sup> animals were hydrocephalus, situs inversus totalis, postnatal growth retardation, and sterility of both sexes. Thinning of the neocortex was histologically evident at 13.5 day of gestation, dilation of all ventricles was detected at birth, and an external sign of hydrocephalus, i.e., doming of the skull, was usually apparent at 2 weeks of age. Heterozygous SD<i><sup>Nme7</sup></i><sup>+/-</sup> rats developed normally; we did not detect any symptoms of primary ciliary dyskinesia. The transcriptomic profile of liver and lungs corroborated the histological findings, revealing defects in cell function and viability. In summary, the knock-out of the rat <i>Nme7</i> gene resulted in a range of conditions consistent with the presentation of primary ciliary dyskinesia, supporting the previously implicated role of the centrosomally located <i>Nme7</i> gene in ciliogenesis and control of ciliary transport.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>&#x160;edov&#xe1;</LastName><ForeName>Lucie</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital, 128 00 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bukov&#xe1;</LastName><ForeName>Ivana</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ba&#x17e;antov&#xe1;</LastName><ForeName>Pavla</ForeName><Initials>P</Initials><Identifier Source="ORCID">0000-0002-4221-1370</Identifier><AffiliationInfo><Affiliation>Institute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital, 128 00 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petrezs&#xe9;lyov&#xe1;</LastName><ForeName>Silvia</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0003-3054-540X</Identifier><AffiliationInfo><Affiliation>Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prochazka</LastName><ForeName>Jan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>&#x160;koln&#xed;kov&#xe1;</LastName><ForeName>Elena</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital, 128 00 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zudov&#xe1;</LastName><ForeName>Dagmar</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>V&#x10d;el&#xe1;k</LastName><ForeName>Josef</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Molecular Endocrinology, Institute of Endocrinology, 116 94 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Makovick&#xfd;</LastName><ForeName>Pavol</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Biology, Faculty of Education, J. Selye University, 945 01 Komarno, Slovakia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bendlov&#xe1;</LastName><ForeName>B&#x11b;la</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Molecular Endocrinology, Institute of Endocrinology, 116 94 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>&#x160;eda</LastName><ForeName>Ond&#x159;ej</ForeName><Initials>O</Initials><Identifier Source="ORCID">0000-0001-8498-5895</Identifier><AffiliationInfo><Affiliation>Institute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital, 128 00 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sedlacek</LastName><ForeName>Radislav</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>17-13491S</GrantID><Agency>Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky</Agency><Country/></Grant><Grant><GrantID>Progres Q25/LF1</GrantID><Agency>Univerzita Karlova v Praze</Agency><Country/></Grant><Grant><GrantID>RVO64165</GrantID><Agency>Ministerstvo Zdravotnictv&#xed; Cesk&#xe9; Republiky</Agency><Country/></Grant><Grant><GrantID>RVO 68378050, LM2018126 and OP RDI CZ.1.05 / 2.1.00 / 19.0395 and CZ.1.05 / 1.1.00 / 02.0109</GrantID><Agency>Ministerstvo &#x160;kolstv&#xed;, Ml&#xe1;de&#x17e;e a T&#x11b;lov&#xfd;chovy</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>04</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Int J Mol Sci</MedlineTA><NlmUniqueID>101092791</NlmUniqueID><ISSNLinking>1422-0067</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>EC 2.7.4.6</RegistryNumber><NameOfSubstance UI="D009701">Nucleoside-Diphosphate Kinase</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002923" MajorTopicYN="N">Cilia</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000648" MajorTopicYN="N">ultrastructure</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002925" MajorTopicYN="N">Ciliary Motility Disorders</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020869" MajorTopicYN="N">Gene Expression Profiling</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055785" MajorTopicYN="N">Gene Knockdown Techniques</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005804" MajorTopicYN="Y">Genes, Lethal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D056726" MajorTopicYN="N">Genetic Association Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="Y">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005838" MajorTopicYN="N">Genotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009701" MajorTopicYN="N">Nucleoside-Diphosphate Kinase</DescriptorName><QualifierName UI="Q000172" MajorTopicYN="Y">deficiency</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010641" MajorTopicYN="N">Phenotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055647" MajorTopicYN="N">Rats, Transgenic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059467" MajorTopicYN="N">Transcriptome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055114" MajorTopicYN="N">X-Ray Microtomography</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Nme7</Keyword><Keyword MajorTopicYN="N">cilia</Keyword><Keyword MajorTopicYN="N">hydrocephalus</Keyword><Keyword MajorTopicYN="N">infertility</Keyword><Keyword MajorTopicYN="N">knock-out rat</Keyword></KeywordList><CoiStatement>The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>2</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2021</Year><Month>4</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>4</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>4</Month><Day>30</Day><Hour>1</Hour><Minute>4</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>5</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>5</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33916973</ArticleId><ArticleId IdType="pmc">PMC8067621</ArticleId><ArticleId IdType="doi">10.3390/ijms22083810</ArticleId><ArticleId IdType="pii">ijms22083810</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Afzelius B.A. A human syndrome caused by immotile cilia. Science. 1976;193:317&#x2013;319. doi: 10.1126/science.1084576.</Citation><ArticleIdList><ArticleId IdType="doi">10.1126/science.1084576</ArticleId><ArticleId IdType="pubmed">1084576</ArticleId></ArticleIdList></Reference><Reference><Citation>Reiter J.F., Leroux M.R. Genes and molecular pathways underpinning ciliopathies. Nat. Rev. Mol. Cell Biol. 2017;18:533&#x2013;547. doi: 10.1038/nrm.2017.60.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrm.2017.60</ArticleId><ArticleId IdType="pmc">PMC5851292</ArticleId><ArticleId IdType="pubmed">28698599</ArticleId></ArticleIdList></Reference><Reference><Citation>Desvignes T., Pontarotti P., Fauvel C., Bobe J. Nme protein family evolutionary history, a vertebrate perspective. BMC Evol. Biol. 2009;9:256. doi: 10.1186/1471-2148-9-256.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/1471-2148-9-256</ArticleId><ArticleId IdType="pmc">PMC2777172</ArticleId><ArticleId IdType="pubmed">19852809</ArticleId></ArticleIdList></Reference><Reference><Citation>Puts G.S., Leonard M.K., Pamidimukkala N.V., Snyder D.E., Kaetzel D.M. Nuclear functions of NME proteins. Lab. Investig. 2018;98:211&#x2013;218. doi: 10.1038/labinvest.2017.109.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/labinvest.2017.109</ArticleId><ArticleId IdType="pmc">PMC6136249</ArticleId><ArticleId IdType="pubmed">29058704</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu P., Choi Y.K., Qi R.Z. NME7 is a functional component of the gamma-tubulin ring complex. Mol. Biol. Cell. 2014;25:2017&#x2013;2025. doi: 10.1091/mbc.e13-06-0339.</Citation><ArticleIdList><ArticleId IdType="doi">10.1091/mbc.e13-06-0339</ArticleId><ArticleId IdType="pmc">PMC4072575</ArticleId><ArticleId IdType="pubmed">24807905</ArticleId></ArticleIdList></Reference><Reference><Citation>Lai C.K., Gupta N., Wen X., Rangell L., Chih B., Peterson A.S., Bazan J.F., Li L., Scales S.J. Functional characterization of putative cilia genes by high-content analysis. Mol. Biol. Cell. 2011;22:1104&#x2013;1119. doi: 10.1091/mbc.e10-07-0596.</Citation><ArticleIdList><ArticleId IdType="doi">10.1091/mbc.e10-07-0596</ArticleId><ArticleId IdType="pmc">PMC3069013</ArticleId><ArticleId IdType="pubmed">21289087</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang C.H., Ma N., Lin Y.T., Wu C.C., Hsiao M., Lu F.L., Yu C.C., Chen S.Y., Lu J. A shRNA functional screen reveals Nme6 and Nme7 are crucial for embryonic stem cell renewal. Stem Cells. 2012;30:2199&#x2013;2211. doi: 10.1002/stem.1203.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/stem.1203</ArticleId><ArticleId IdType="pubmed">22899353</ArticleId></ArticleIdList></Reference><Reference><Citation>Romani P., Ignesti M., Gargiulo G., Hsu T., Cavaliere V. Extracellular NME proteins: A player or a bystander? Lab. Investig. 2018;98:248&#x2013;257. doi: 10.1038/labinvest.2017.102.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/labinvest.2017.102</ArticleId><ArticleId IdType="pubmed">29035383</ArticleId></ArticleIdList></Reference><Reference><Citation>Heit J.A., Armasu S.M., Asmann Y.W., Cunningham J.M., Matsumoto M.E., Petterson T.M., De Andrade M. A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q. J. Thromb. Haemost. 2012;10:1521&#x2013;1531. doi: 10.1111/j.1538-7836.2012.04810.x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1538-7836.2012.04810.x</ArticleId><ArticleId IdType="pmc">PMC3419811</ArticleId><ArticleId IdType="pubmed">22672568</ArticleId></ArticleIdList></Reference><Reference><Citation>Lindstrom S., Wang L., Smith E.N., Gordon W., van Hylckama Vlieg A., de Andrade M., Brody J.A., Pattee J.W., Haessler J., Brumpton B.M., et al. Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism. Blood. 2019;134:1645&#x2013;1657. doi: 10.1182/blood.2019000435.</Citation><ArticleIdList><ArticleId IdType="doi">10.1182/blood.2019000435</ArticleId><ArticleId IdType="pmc">PMC6871304</ArticleId><ArticleId IdType="pubmed">31420334</ArticleId></ArticleIdList></Reference><Reference><Citation>Herrera-Rivero M., Stoll M., Hegenbarth J.C., Ruhle F., Limperger V., Junker R., Franke A., Hoffmann P., Shneyder M., Stach M., et al. Single- and Multimarker Genome-Wide Scans Evidence Novel Genetic Risk Modifiers for Venous Thromboembolism. Thromb. Haemost. 2021 doi: 10.1055/s-0041-1723988.</Citation><ArticleIdList><ArticleId IdType="doi">10.1055/s-0041-1723988</ArticleId><ArticleId IdType="pubmed">33592630</ArticleId></ArticleIdList></Reference><Reference><Citation>Giri A., Hellwege J.N., Keaton J.M., Park J., Qiu C., Warren H.R., Torstenson E.S., Kovesdy C.P., Sun Y.V., Wilson O.D., et al. Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. Nat. Genet. 2019;51:51&#x2013;62. doi: 10.1038/s41588-018-0303-9.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41588-018-0303-9</ArticleId><ArticleId IdType="pmc">PMC6365102</ArticleId><ArticleId IdType="pubmed">30578418</ArticleId></ArticleIdList></Reference><Reference><Citation>Hoffmann T.J., Ehret G.B., Nandakumar P., Ranatunga D., Schaefer C., Kwok P.Y., Iribarren C., Chakravarti A., Risch N. Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation. Nat. Genet. 2017;49:54&#x2013;64. doi: 10.1038/ng.3715.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/ng.3715</ArticleId><ArticleId IdType="pmc">PMC5370207</ArticleId><ArticleId IdType="pubmed">27841878</ArticleId></ArticleIdList></Reference><Reference><Citation>Mendez-Giraldez R., Gogarten S.M., Below J.E., Yao J., Seyerle A.A., Highland H.M., Kooperberg C., Soliman E.Z., Rotter J.I., Kerr K.F., et al. GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals. Sci. Rep. 2017;7:17075. doi: 10.1038/s41598-017-17136-0.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41598-017-17136-0</ArticleId><ArticleId IdType="pmc">PMC5719082</ArticleId><ArticleId IdType="pubmed">29213071</ArticleId></ArticleIdList></Reference><Reference><Citation>Van Setten J., Verweij N., Mbarek H., Niemeijer M.N., Trompet S., Arking D.E., Brody J.A., Gandin I., Grarup N., Hall L.M., et al. Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits. Eur. J. Hum. Genet. 2019;27:952&#x2013;962. doi: 10.1038/s41431-018-0295-z.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41431-018-0295-z</ArticleId><ArticleId IdType="pmc">PMC6777533</ArticleId><ArticleId IdType="pubmed">30679814</ArticleId></ArticleIdList></Reference><Reference><Citation>Sedova L., Skolnikova E., Hodulova M., Vcelak J., Seda O., Bendlova B. Expression profiling of Nme7 interactome in experimental models of metabolic syndrome. Physiol. Res. 2018;67(Suppl. 3):S543&#x2013;S550. doi: 10.33549/physiolres.934021.</Citation><ArticleIdList><ArticleId IdType="doi">10.33549/physiolres.934021</ArticleId><ArticleId IdType="pubmed">30484681</ArticleId></ArticleIdList></Reference><Reference><Citation>Reish O., Aspit L., Zouella A., Roth Y., Polak-Charcon S., Baboushkin T., Benyamini L., Scheetz T.E., Mussaffi H., Sheffield V.C., et al. A Homozygous Nme7 Mutation Is Associated with Situs Inversus Totalis. Hum. Mutat. 2016;37:727&#x2013;731. doi: 10.1002/humu.22998.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/humu.22998</ArticleId><ArticleId IdType="pmc">PMC6066188</ArticleId><ArticleId IdType="pubmed">27060491</ArticleId></ArticleIdList></Reference><Reference><Citation>Vogel P., Read R., Hansen G.M., Freay L.C., Zambrowicz B.P., Sands A.T. Situs inversus in Dpcd/Poll-/-, Nme7-/-, and Pkd1l1-/- mice. Vet. Pathol. 2010;47:120&#x2013;131. doi: 10.1177/0300985809353553.</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/0300985809353553</ArticleId><ArticleId IdType="pubmed">20080492</ArticleId></ArticleIdList></Reference><Reference><Citation>Vogel P., Read R.W., Hansen G.M., Payne B.J., Small D., Sands A.T., Zambrowicz B.P. Congenital hydrocephalus in genetically engineered mice. Vet. Pathol. 2012;49:166&#x2013;181. doi: 10.1177/0300985811415708.</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/0300985811415708</ArticleId><ArticleId IdType="pubmed">21746835</ArticleId></ArticleIdList></Reference><Reference><Citation>Yu Y., Fuscoe J.C., Zhao C., Guo C., Jia M., Qing T., Bannon D.I., Lancashire L., Bao W., Du T., et al. A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nat. Commun. 2014;5:3230. doi: 10.1038/ncomms4230.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/ncomms4230</ArticleId><ArticleId IdType="pmc">PMC3926002</ArticleId><ArticleId IdType="pubmed">24510058</ArticleId></ArticleIdList></Reference><Reference><Citation>Fagerberg L., Hallstrom B.M., Oksvold P., Kampf C., Djureinovic D., Odeberg J., Habuka M., Tahmasebpoor S., Danielsson A., Edlund K., et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol. Cell Proteom. 2014;13:397&#x2013;406. doi: 10.1074/mcp.M113.035600.</Citation><ArticleIdList><ArticleId IdType="doi">10.1074/mcp.M113.035600</ArticleId><ArticleId IdType="pmc">PMC3916642</ArticleId><ArticleId IdType="pubmed">24309898</ArticleId></ArticleIdList></Reference><Reference><Citation>Kriegstein A., Alvarez-Buylla A. The glial nature of embryonic and adult neural stem cells. Annu. Rev. Neurosci. 2009;32:149&#x2013;184. doi: 10.1146/annurev.neuro.051508.135600.</Citation><ArticleIdList><ArticleId IdType="doi">10.1146/annurev.neuro.051508.135600</ArticleId><ArticleId IdType="pmc">PMC3086722</ArticleId><ArticleId IdType="pubmed">19555289</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang X., Zhou Y., Wang J., Tseng I.C., Huang T., Zhao Y., Zheng Q., Gao Y., Luo H., Zhang X., et al. SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis. J. Neurosci. 2016;36:12586&#x2013;12597. doi: 10.1523/JNEUROSCI.1620-16.2016.</Citation><ArticleIdList><ArticleId IdType="doi">10.1523/JNEUROSCI.1620-16.2016</ArticleId><ArticleId IdType="pmc">PMC5157104</ArticleId><ArticleId IdType="pubmed">27974614</ArticleId></ArticleIdList></Reference><Reference><Citation>Murtha L.A., Yang Q., Parsons M.W., Levi C.R., Beard D.J., Spratt N.J., McLeod D.D. Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats. Fluids Barriers CNS. 2014;11:12. doi: 10.1186/2045-8118-11-12.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/2045-8118-11-12</ArticleId><ArticleId IdType="pmc">PMC4057524</ArticleId><ArticleId IdType="pubmed">24932405</ArticleId></ArticleIdList></Reference><Reference><Citation>De Jesus D.F., Orime K., Kaminska D., Kimura T., Basile G., Wang C.H., Haertle L., Riemens R., Brown N.K., Hu J., et al. Parental metabolic syndrome epigenetically reprograms offspring hepatic lipid metabolism in mice. J. Clin. Investig. 2020;130:2391&#x2013;2407. doi: 10.1172/JCI127502.</Citation><ArticleIdList><ArticleId IdType="doi">10.1172/JCI127502</ArticleId><ArticleId IdType="pmc">PMC7190992</ArticleId><ArticleId IdType="pubmed">32250344</ArticleId></ArticleIdList></Reference><Reference><Citation>Masuzaki R., Zhao S., Valerius M.T., Tsugawa D., Oya Y., Ray K.C., Karp S.J. SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration. J. Biol. Chem. 2016;291:3346&#x2013;3358. doi: 10.1074/jbc.M115.703264.</Citation><ArticleIdList><ArticleId IdType="doi">10.1074/jbc.M115.703264</ArticleId><ArticleId IdType="pmc">PMC4751379</ArticleId><ArticleId IdType="pubmed">26703468</ArticleId></ArticleIdList></Reference><Reference><Citation>Monti-Rocha R., Cramer A., Gaio Leite P., Antunes M.M., Pereira R.V.S., Barroso A., Queiroz-Junior C.M., David B.A., Teixeira M.M., Menezes G.B., et al. SOCS2 Is Critical for the Balancing of Immune Response and Oxidate Stress Protecting Against Acetaminophen-Induced Acute Liver Injury. Front. Immunol. 2018;9:3134. doi: 10.3389/fimmu.2018.03134.</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fimmu.2018.03134</ArticleId><ArticleId IdType="pmc">PMC6349694</ArticleId><ArticleId IdType="pubmed">30723477</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang Y., Nakajima T., Gonzalez F.J., Tanaka N. PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice. Int. J. Mol. Sci. 2020;21:2061. doi: 10.3390/ijms21062061.</Citation><ArticleIdList><ArticleId IdType="doi">10.3390/ijms21062061</ArticleId><ArticleId IdType="pmc">PMC7139552</ArticleId><ArticleId IdType="pubmed">32192216</ArticleId></ArticleIdList></Reference><Reference><Citation>Zadjali F., Santana-Farre R., Vesterlund M., Carow B., Mirecki-Garrido M., Hernandez-Hernandez I., Flodstrom-Tullberg M., Parini P., Rottenberg M., Norstedt G., et al. SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. FASEB J. 2012;26:3282&#x2013;3291. doi: 10.1096/fj.12-205583.</Citation><ArticleIdList><ArticleId IdType="doi">10.1096/fj.12-205583</ArticleId><ArticleId IdType="pubmed">22562833</ArticleId></ArticleIdList></Reference><Reference><Citation>Bukowy-Bieryllo Z., Rabiasz A., Dabrowski M., Pogorzelski A., Wojda A., Dmenska H., Grzela K., Sroczynski J., Witt M., Zietkiewicz E. Truncating mutations in exons 20 and 21 of OFD1 can cause primary ciliary dyskinesia without associated syndromic symptoms. J. Med. Genet. 2019;56:769&#x2013;777. doi: 10.1136/jmedgenet-2018-105918.</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/jmedgenet-2018-105918</ArticleId><ArticleId IdType="pubmed">31366608</ArticleId></ArticleIdList></Reference><Reference><Citation>Wallmeier J., Nielsen K.G., Kuehni C.E., Lucas J.S., Leigh M.W., Zariwala M.A., Omran H. Motile ciliopathies. Nat. Rev. Dis. Primers. 2020;6:77. doi: 10.1038/s41572-020-0209-6.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41572-020-0209-6</ArticleId><ArticleId IdType="pubmed">32943623</ArticleId></ArticleIdList></Reference><Reference><Citation>Ghosh S., Das P.J., McQueen C.M., Gerber V., Swiderski C.E., Lavoie J.P., Chowdhary B.P., Raudsepp T. Analysis of genomic copy number variation in equine recurrent airway obstruction (heaves) Anim. Genet. 2016;47:334&#x2013;344. doi: 10.1111/age.12426.</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/age.12426</ArticleId><ArticleId IdType="pubmed">26932307</ArticleId></ArticleIdList></Reference><Reference><Citation>Pejler G. The emerging role of mast cell proteases in asthma. Eur. Respir. J. 2019;54 doi: 10.1183/13993003.00685-2019.</Citation><ArticleIdList><ArticleId IdType="doi">10.1183/13993003.00685-2019</ArticleId><ArticleId IdType="pubmed">31371445</ArticleId></ArticleIdList></Reference><Reference><Citation>Koh I.U., Choi N.H., Lee K., Yu H.Y., Yun J.H., Kong J.H., Kim H.J., Lee S., Kim S.C., Kim B.J., et al. Obesity susceptible novel DNA methylation marker on regulatory region of inflammation gene: Results from the Korea Epigenome Study (KES) BMJ Open Diabetes Res. Care. 2020;8:e001338. doi: 10.1136/bmjdrc-2020-001338.</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/bmjdrc-2020-001338</ArticleId><ArticleId IdType="pmc">PMC7422660</ArticleId><ArticleId IdType="pubmed">32788176</ArticleId></ArticleIdList></Reference><Reference><Citation>Mandal J., Roth M., Papakonstantinou E., Fang L., Savic S., Tamm M., Stolz D. Adrenomedullin mediates pro-angiogenic and pro-inflammatory cytokines in asthma and COPD. Pulm. Pharmacol. Ther. 2019;56:8&#x2013;14. doi: 10.1016/j.pupt.2019.01.006.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.pupt.2019.01.006</ArticleId><ArticleId IdType="pubmed">30690080</ArticleId></ArticleIdList></Reference><Reference><Citation>Taylor B.J., Snyder E.M., Richert M.L., Wheatley C.M., Chase S.C., Olson L.J., Johnson B.D. Effect of beta2-adrenergic receptor stimulation on lung fluid in stable heart failure patients. J. Heart Lung Transplant. 2017;36:418&#x2013;426. doi: 10.1016/j.healun.2016.09.008.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.healun.2016.09.008</ArticleId><ArticleId IdType="pmc">PMC5362291</ArticleId><ArticleId IdType="pubmed">27863863</ArticleId></ArticleIdList></Reference><Reference><Citation>Sironen A., Shoemark A., Patel M., Loebinger M.R., Mitchison H.M. Sperm defects in primary ciliary dyskinesia and related causes of male infertility. Cell. Mol. Life Sci. 2020;77:2029&#x2013;2048. doi: 10.1007/s00018-019-03389-7.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00018-019-03389-7</ArticleId><ArticleId IdType="pmc">PMC7256033</ArticleId><ArticleId IdType="pubmed">31781811</ArticleId></ArticleIdList></Reference><Reference><Citation>Terre B., Lewis M., Gil-Gomez G., Han Z., Lu H., Aguilera M., Prats N., Roy S., Zhao H., Stracker T.H. Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice. Development. 2019;146 doi: 10.1242/dev.162628.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.162628</ArticleId><ArticleId IdType="pmc">PMC6503982</ArticleId><ArticleId IdType="pubmed">30936178</ArticleId></ArticleIdList></Reference><Reference><Citation>Marshall C.B., Mays D.J., Beeler J.S., Rosenbluth J.M., Boyd K.L., Guasch G.L.S., Shaver T.M., Tang L.J., Liu Q., Shyr Y., et al. p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network. Cell Rep. 2016;14:2289&#x2013;2300. doi: 10.1016/j.celrep.2016.02.035.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.celrep.2016.02.035</ArticleId><ArticleId IdType="pmc">PMC4794398</ArticleId><ArticleId IdType="pubmed">26947080</ArticleId></ArticleIdList></Reference><Reference><Citation>N&#xfa;nez-Oll&#xe9; M., Jung C., Terr&#xe9; B., Balsiger N.A., Plata C., Roset R., Pardo-Pastor C., Garrido M., Rojas S., Alameda F., et al. Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility. Oncotarget. 2017;8:99261&#x2013;99273. doi: 10.18632/oncotarget.21818.</Citation><ArticleIdList><ArticleId IdType="doi">10.18632/oncotarget.21818</ArticleId><ArticleId IdType="pmc">PMC5725090</ArticleId><ArticleId IdType="pubmed">29245899</ArticleId></ArticleIdList></Reference><Reference><Citation>Terre B., Piergiovanni G., Segura-Bayona S., Gil-Gomez G., Youssef S.A., Attolini C.S., Wilsch-Brauninger M., Jung C., Rojas A.M., Marjanovic M., et al. GEMC1 is a critical regulator of multiciliated cell differentiation. EMBO J. 2016;35:942&#x2013;960. doi: 10.15252/embj.201592821.</Citation><ArticleIdList><ArticleId IdType="doi">10.15252/embj.201592821</ArticleId><ArticleId IdType="pmc">PMC5207319</ArticleId><ArticleId IdType="pubmed">26933123</ArticleId></ArticleIdList></Reference><Reference><Citation>Kurkowiak M., Zietkiewicz E., Witt M. Recent advances in primary ciliary dyskinesia genetics. J. Med. Genet. 2015;52:1&#x2013;9. doi: 10.1136/jmedgenet-2014-102755.</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/jmedgenet-2014-102755</ArticleId><ArticleId IdType="pmc">PMC4285891</ArticleId><ArticleId IdType="pubmed">25351953</ArticleId></ArticleIdList></Reference><Reference><Citation>Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402&#x2013;408. doi: 10.1006/meth.2001.1262.</Citation><ArticleIdList><ArticleId IdType="doi">10.1006/meth.2001.1262</ArticleId><ArticleId IdType="pubmed">11846609</ArticleId></ArticleIdList></Reference><Reference><Citation>Kramer A., Green J., Pollard J., Jr., Tugendreich S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics. 2014;30:523&#x2013;530. doi: 10.1093/bioinformatics/btt703.</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/bioinformatics/btt703</ArticleId><ArticleId IdType="pmc">PMC3928520</ArticleId><ArticleId IdType="pubmed">24336805</ArticleId></ArticleIdList></Reference><Reference><Citation>Schneider C.A., Rasband W.S., Eliceiri K.W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods. 2012;9:671&#x2013;675. doi: 10.1038/nmeth.2089.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nmeth.2089</ArticleId><ArticleId IdType="pmc">PMC5554542</ArticleId><ArticleId IdType="pubmed">22930834</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">34038055</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK570710</ArticleId><ArticleId IdType="doi">10.36255/exonpublications.gliomas.2021.chapter13</ArticleId></ArticleIdList><Book><Publisher><PublisherName>Exon Publications</PublisherName><PublisherLocation>Brisbane (AU)</PublisherLocation></Publisher><BookTitle book="cod9780645001747">Gliomas</BookTitle><PubDate><Year>2021</Year><Month>04</Month><Day>30</Day></PubDate><AuthorList Type="editors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Debinski</LastName><ForeName>Waldemar</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Brain Tumor Center of Excellence, Wake Forest Baptist, Medical Center Comprehensive Cancer Center, Winston Salem, NC, USA</Affiliation></AffiliationInfo></Author></AuthorList><Isbn>9780645001747</Isbn><ELocationID EIdType="doi">10.36255/exonpublications.gliomas.2021</ELocationID><Medium>Internet</Medium></Book><LocationLabel Type="chapter">Chapter 13</LocationLabel><ArticleTitle book="cod9780645001747" part="Ch13">Glioneuronal Tumors: Insights into a Rare Tumor Entity
<i>NME7</i> (non-metastatic cells 7, nucleoside diphosphate kinase 7) is a member of a gene family with a profound effect on health/disease status. NME7 is an established member of the ciliome and contributes to the regulation of the microtubule-organizing center. We aimed to create a rat model to further investigate the phenotypic consequences of <i>Nme7</i> gene deletion. The CRISPR/Cas9 nuclease system was used for the generation of Sprague Dawley <i>Nme7</i> knock-out rats targeting the exon 4 of the <i>Nme7</i> gene. We found the homozygous <i>Nme7</i> gene deletion to be semi-lethal, as the majority of SD<i><sup>Nme7</sup></i><sup>-/-</sup> pups died prior to weaning. The most prominent phenotypes in surviving SD<i><sup>Nme7</sup></i><sup>-/-</sup> animals were hydrocephalus, situs inversus totalis, postnatal growth retardation, and sterility of both sexes. Thinning of the neocortex was histologically evident at 13.5 day of gestation, dilation of all ventricles was detected at birth, and an external sign of hydrocephalus, i.e., doming of the skull, was usually apparent at 2 weeks of age. Heterozygous SD<i><sup>Nme7</sup></i><sup>+/-</sup> rats developed normally; we did not detect any symptoms of primary ciliary dyskinesia. The transcriptomic profile of liver and lungs corroborated the histological findings, revealing defects in cell function and viability. In summary, the knock-out of the rat <i>Nme7</i> gene resulted in a range of conditions consistent with the presentation of primary ciliary dyskinesia, supporting the previously implicated role of the centrosomally located <i>Nme7</i> gene in ciliogenesis and control of ciliary transport.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>&#x160;edov&#xe1;</LastName><ForeName>Lucie</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital, 128 00 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bukov&#xe1;</LastName><ForeName>Ivana</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ba&#x17e;antov&#xe1;</LastName><ForeName>Pavla</ForeName><Initials>P</Initials><Identifier Source="ORCID">0000-0002-4221-1370</Identifier><AffiliationInfo><Affiliation>Institute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital, 128 00 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petrezs&#xe9;lyov&#xe1;</LastName><ForeName>Silvia</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0003-3054-540X</Identifier><AffiliationInfo><Affiliation>Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prochazka</LastName><ForeName>Jan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>&#x160;koln&#xed;kov&#xe1;</LastName><ForeName>Elena</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital, 128 00 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zudov&#xe1;</LastName><ForeName>Dagmar</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>V&#x10d;el&#xe1;k</LastName><ForeName>Josef</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Molecular Endocrinology, Institute of Endocrinology, 116 94 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Makovick&#xfd;</LastName><ForeName>Pavol</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Biology, Faculty of Education, J. Selye University, 945 01 Komarno, Slovakia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bendlov&#xe1;</LastName><ForeName>B&#x11b;la</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Molecular Endocrinology, Institute of Endocrinology, 116 94 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>&#x160;eda</LastName><ForeName>Ond&#x159;ej</ForeName><Initials>O</Initials><Identifier Source="ORCID">0000-0001-8498-5895</Identifier><AffiliationInfo><Affiliation>Institute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital, 128 00 Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sedlacek</LastName><ForeName>Radislav</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i., 252 50 Vestec, Czech Republic.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>17-13491S</GrantID><Agency>Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky</Agency><Country/></Grant><Grant><GrantID>Progres Q25/LF1</GrantID><Agency>Univerzita Karlova v Praze</Agency><Country/></Grant><Grant><GrantID>RVO64165</GrantID><Agency>Ministerstvo Zdravotnictv&#xed; Cesk&#xe9; Republiky</Agency><Country/></Grant><Grant><GrantID>RVO 68378050, LM2018126 and OP RDI CZ.1.05 / 2.1.00 / 19.0395 and CZ.1.05 / 1.1.00 / 02.0109</GrantID><Agency>Ministerstvo &#x160;kolstv&#xed;, Ml&#xe1;de&#x17e;e a T&#x11b;lov&#xfd;chovy</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>04</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Int J Mol Sci</MedlineTA><NlmUniqueID>101092791</NlmUniqueID><ISSNLinking>1422-0067</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>EC 2.7.4.6</RegistryNumber><NameOfSubstance UI="D009701">Nucleoside-Diphosphate Kinase</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002923" MajorTopicYN="N">Cilia</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000648" MajorTopicYN="N">ultrastructure</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002925" MajorTopicYN="N">Ciliary Motility Disorders</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020869" MajorTopicYN="N">Gene Expression Profiling</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055785" MajorTopicYN="N">Gene Knockdown Techniques</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005804" MajorTopicYN="Y">Genes, Lethal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D056726" MajorTopicYN="N">Genetic Association Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="Y">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005838" MajorTopicYN="N">Genotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009701" MajorTopicYN="N">Nucleoside-Diphosphate Kinase</DescriptorName><QualifierName UI="Q000172" MajorTopicYN="Y">deficiency</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010641" MajorTopicYN="N">Phenotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055647" MajorTopicYN="N">Rats, Transgenic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059467" MajorTopicYN="N">Transcriptome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055114" MajorTopicYN="N">X-Ray Microtomography</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Nme7</Keyword><Keyword MajorTopicYN="N">cilia</Keyword><Keyword MajorTopicYN="N">hydrocephalus</Keyword><Keyword MajorTopicYN="N">infertility</Keyword><Keyword MajorTopicYN="N">knock-out rat</Keyword></KeywordList><CoiStatement>The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>2</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2021</Year><Month>4</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>4</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>4</Month><Day>30</Day><Hour>1</Hour><Minute>4</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>5</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>5</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33916973</ArticleId><ArticleId IdType="pmc">PMC8067621</ArticleId><ArticleId IdType="doi">10.3390/ijms22083810</ArticleId><ArticleId IdType="pii">ijms22083810</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Afzelius B.A. A human syndrome caused by immotile cilia. Science. 1976;193:317&#x2013;319. doi: 10.1126/science.1084576.</Citation><ArticleIdList><ArticleId IdType="doi">10.1126/science.1084576</ArticleId><ArticleId IdType="pubmed">1084576</ArticleId></ArticleIdList></Reference><Reference><Citation>Reiter J.F., Leroux M.R. Genes and molecular pathways underpinning ciliopathies. Nat. Rev. Mol. Cell Biol. 2017;18:533&#x2013;547. doi: 10.1038/nrm.2017.60.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrm.2017.60</ArticleId><ArticleId IdType="pmc">PMC5851292</ArticleId><ArticleId IdType="pubmed">28698599</ArticleId></ArticleIdList></Reference><Reference><Citation>Desvignes T., Pontarotti P., Fauvel C., Bobe J. Nme protein family evolutionary history, a vertebrate perspective. BMC Evol. Biol. 2009;9:256. doi: 10.1186/1471-2148-9-256.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/1471-2148-9-256</ArticleId><ArticleId IdType="pmc">PMC2777172</ArticleId><ArticleId IdType="pubmed">19852809</ArticleId></ArticleIdList></Reference><Reference><Citation>Puts G.S., Leonard M.K., Pamidimukkala N.V., Snyder D.E., Kaetzel D.M. Nuclear functions of NME proteins. Lab. Investig. 2018;98:211&#x2013;218. doi: 10.1038/labinvest.2017.109.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/labinvest.2017.109</ArticleId><ArticleId IdType="pmc">PMC6136249</ArticleId><ArticleId IdType="pubmed">29058704</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu P., Choi Y.K., Qi R.Z. NME7 is a functional component of the gamma-tubulin ring complex. Mol. Biol. Cell. 2014;25:2017&#x2013;2025. doi: 10.1091/mbc.e13-06-0339.</Citation><ArticleIdList><ArticleId IdType="doi">10.1091/mbc.e13-06-0339</ArticleId><ArticleId IdType="pmc">PMC4072575</ArticleId><ArticleId IdType="pubmed">24807905</ArticleId></ArticleIdList></Reference><Reference><Citation>Lai C.K., Gupta N., Wen X., Rangell L., Chih B., Peterson A.S., Bazan J.F., Li L., Scales S.J. Functional characterization of putative cilia genes by high-content analysis. Mol. Biol. Cell. 2011;22:1104&#x2013;1119. doi: 10.1091/mbc.e10-07-0596.</Citation><ArticleIdList><ArticleId IdType="doi">10.1091/mbc.e10-07-0596</ArticleId><ArticleId IdType="pmc">PMC3069013</ArticleId><ArticleId IdType="pubmed">21289087</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang C.H., Ma N., Lin Y.T., Wu C.C., Hsiao M., Lu F.L., Yu C.C., Chen S.Y., Lu J. A shRNA functional screen reveals Nme6 and Nme7 are crucial for embryonic stem cell renewal. Stem Cells. 2012;30:2199&#x2013;2211. doi: 10.1002/stem.1203.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/stem.1203</ArticleId><ArticleId IdType="pubmed">22899353</ArticleId></ArticleIdList></Reference><Reference><Citation>Romani P., Ignesti M., Gargiulo G., Hsu T., Cavaliere V. Extracellular NME proteins: A player or a bystander? Lab. Investig. 2018;98:248&#x2013;257. doi: 10.1038/labinvest.2017.102.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/labinvest.2017.102</ArticleId><ArticleId IdType="pubmed">29035383</ArticleId></ArticleIdList></Reference><Reference><Citation>Heit J.A., Armasu S.M., Asmann Y.W., Cunningham J.M., Matsumoto M.E., Petterson T.M., De Andrade M. A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q. J. Thromb. Haemost. 2012;10:1521&#x2013;1531. doi: 10.1111/j.1538-7836.2012.04810.x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1538-7836.2012.04810.x</ArticleId><ArticleId IdType="pmc">PMC3419811</ArticleId><ArticleId IdType="pubmed">22672568</ArticleId></ArticleIdList></Reference><Reference><Citation>Lindstrom S., Wang L., Smith E.N., Gordon W., van Hylckama Vlieg A., de Andrade M., Brody J.A., Pattee J.W., Haessler J., Brumpton B.M., et al. Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism. Blood. 2019;134:1645&#x2013;1657. doi: 10.1182/blood.2019000435.</Citation><ArticleIdList><ArticleId IdType="doi">10.1182/blood.2019000435</ArticleId><ArticleId IdType="pmc">PMC6871304</ArticleId><ArticleId IdType="pubmed">31420334</ArticleId></ArticleIdList></Reference><Reference><Citation>Herrera-Rivero M., Stoll M., Hegenbarth J.C., Ruhle F., Limperger V., Junker R., Franke A., Hoffmann P., Shneyder M., Stach M., et al. Single- and Multimarker Genome-Wide Scans Evidence Novel Genetic Risk Modifiers for Venous Thromboembolism. Thromb. Haemost. 2021 doi: 10.1055/s-0041-1723988.</Citation><ArticleIdList><ArticleId IdType="doi">10.1055/s-0041-1723988</ArticleId><ArticleId IdType="pubmed">33592630</ArticleId></ArticleIdList></Reference><Reference><Citation>Giri A., Hellwege J.N., Keaton J.M., Park J., Qiu C., Warren H.R., Torstenson E.S., Kovesdy C.P., Sun Y.V., Wilson O.D., et al. Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. Nat. Genet. 2019;51:51&#x2013;62. doi: 10.1038/s41588-018-0303-9.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41588-018-0303-9</ArticleId><ArticleId IdType="pmc">PMC6365102</ArticleId><ArticleId IdType="pubmed">30578418</ArticleId></ArticleIdList></Reference><Reference><Citation>Hoffmann T.J., Ehret G.B., Nandakumar P., Ranatunga D., Schaefer C., Kwok P.Y., Iribarren C., Chakravarti A., Risch N. Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation. Nat. Genet. 2017;49:54&#x2013;64. doi: 10.1038/ng.3715.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/ng.3715</ArticleId><ArticleId IdType="pmc">PMC5370207</ArticleId><ArticleId IdType="pubmed">27841878</ArticleId></ArticleIdList></Reference><Reference><Citation>Mendez-Giraldez R., Gogarten S.M., Below J.E., Yao J., Seyerle A.A., Highland H.M., Kooperberg C., Soliman E.Z., Rotter J.I., Kerr K.F., et al. GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals. Sci. Rep. 2017;7:17075. doi: 10.1038/s41598-017-17136-0.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41598-017-17136-0</ArticleId><ArticleId IdType="pmc">PMC5719082</ArticleId><ArticleId IdType="pubmed">29213071</ArticleId></ArticleIdList></Reference><Reference><Citation>Van Setten J., Verweij N., Mbarek H., Niemeijer M.N., Trompet S., Arking D.E., Brody J.A., Gandin I., Grarup N., Hall L.M., et al. Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits. Eur. J. Hum. Genet. 2019;27:952&#x2013;962. doi: 10.1038/s41431-018-0295-z.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41431-018-0295-z</ArticleId><ArticleId IdType="pmc">PMC6777533</ArticleId><ArticleId IdType="pubmed">30679814</ArticleId></ArticleIdList></Reference><Reference><Citation>Sedova L., Skolnikova E., Hodulova M., Vcelak J., Seda O., Bendlova B. Expression profiling of Nme7 interactome in experimental models of metabolic syndrome. Physiol. Res. 2018;67(Suppl. 3):S543&#x2013;S550. doi: 10.33549/physiolres.934021.</Citation><ArticleIdList><ArticleId IdType="doi">10.33549/physiolres.934021</ArticleId><ArticleId IdType="pubmed">30484681</ArticleId></ArticleIdList></Reference><Reference><Citation>Reish O., Aspit L., Zouella A., Roth Y., Polak-Charcon S., Baboushkin T., Benyamini L., Scheetz T.E., Mussaffi H., Sheffield V.C., et al. A Homozygous Nme7 Mutation Is Associated with Situs Inversus Totalis. Hum. Mutat. 2016;37:727&#x2013;731. doi: 10.1002/humu.22998.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/humu.22998</ArticleId><ArticleId IdType="pmc">PMC6066188</ArticleId><ArticleId IdType="pubmed">27060491</ArticleId></ArticleIdList></Reference><Reference><Citation>Vogel P., Read R., Hansen G.M., Freay L.C., Zambrowicz B.P., Sands A.T. Situs inversus in Dpcd/Poll-/-, Nme7-/-, and Pkd1l1-/- mice. Vet. Pathol. 2010;47:120&#x2013;131. doi: 10.1177/0300985809353553.</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/0300985809353553</ArticleId><ArticleId IdType="pubmed">20080492</ArticleId></ArticleIdList></Reference><Reference><Citation>Vogel P., Read R.W., Hansen G.M., Payne B.J., Small D., Sands A.T., Zambrowicz B.P. Congenital hydrocephalus in genetically engineered mice. Vet. Pathol. 2012;49:166&#x2013;181. doi: 10.1177/0300985811415708.</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/0300985811415708</ArticleId><ArticleId IdType="pubmed">21746835</ArticleId></ArticleIdList></Reference><Reference><Citation>Yu Y., Fuscoe J.C., Zhao C., Guo C., Jia M., Qing T., Bannon D.I., Lancashire L., Bao W., Du T., et al. A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nat. Commun. 2014;5:3230. doi: 10.1038/ncomms4230.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/ncomms4230</ArticleId><ArticleId IdType="pmc">PMC3926002</ArticleId><ArticleId IdType="pubmed">24510058</ArticleId></ArticleIdList></Reference><Reference><Citation>Fagerberg L., Hallstrom B.M., Oksvold P., Kampf C., Djureinovic D., Odeberg J., Habuka M., Tahmasebpoor S., Danielsson A., Edlund K., et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol. Cell Proteom. 2014;13:397&#x2013;406. doi: 10.1074/mcp.M113.035600.</Citation><ArticleIdList><ArticleId IdType="doi">10.1074/mcp.M113.035600</ArticleId><ArticleId IdType="pmc">PMC3916642</ArticleId><ArticleId IdType="pubmed">24309898</ArticleId></ArticleIdList></Reference><Reference><Citation>Kriegstein A., Alvarez-Buylla A. The glial nature of embryonic and adult neural stem cells. Annu. Rev. Neurosci. 2009;32:149&#x2013;184. doi: 10.1146/annurev.neuro.051508.135600.</Citation><ArticleIdList><ArticleId IdType="doi">10.1146/annurev.neuro.051508.135600</ArticleId><ArticleId IdType="pmc">PMC3086722</ArticleId><ArticleId IdType="pubmed">19555289</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang X., Zhou Y., Wang J., Tseng I.C., Huang T., Zhao Y., Zheng Q., Gao Y., Luo H., Zhang X., et al. SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis. J. Neurosci. 2016;36:12586&#x2013;12597. doi: 10.1523/JNEUROSCI.1620-16.2016.</Citation><ArticleIdList><ArticleId IdType="doi">10.1523/JNEUROSCI.1620-16.2016</ArticleId><ArticleId IdType="pmc">PMC5157104</ArticleId><ArticleId IdType="pubmed">27974614</ArticleId></ArticleIdList></Reference><Reference><Citation>Murtha L.A., Yang Q., Parsons M.W., Levi C.R., Beard D.J., Spratt N.J., McLeod D.D. Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats. Fluids Barriers CNS. 2014;11:12. doi: 10.1186/2045-8118-11-12.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/2045-8118-11-12</ArticleId><ArticleId IdType="pmc">PMC4057524</ArticleId><ArticleId IdType="pubmed">24932405</ArticleId></ArticleIdList></Reference><Reference><Citation>De Jesus D.F., Orime K., Kaminska D., Kimura T., Basile G., Wang C.H., Haertle L., Riemens R., Brown N.K., Hu J., et al. Parental metabolic syndrome epigenetically reprograms offspring hepatic lipid metabolism in mice. J. Clin. Investig. 2020;130:2391&#x2013;2407. doi: 10.1172/JCI127502.</Citation><ArticleIdList><ArticleId IdType="doi">10.1172/JCI127502</ArticleId><ArticleId IdType="pmc">PMC7190992</ArticleId><ArticleId IdType="pubmed">32250344</ArticleId></ArticleIdList></Reference><Reference><Citation>Masuzaki R., Zhao S., Valerius M.T., Tsugawa D., Oya Y., Ray K.C., Karp S.J. SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration. J. Biol. Chem. 2016;291:3346&#x2013;3358. doi: 10.1074/jbc.M115.703264.</Citation><ArticleIdList><ArticleId IdType="doi">10.1074/jbc.M115.703264</ArticleId><ArticleId IdType="pmc">PMC4751379</ArticleId><ArticleId IdType="pubmed">26703468</ArticleId></ArticleIdList></Reference><Reference><Citation>Monti-Rocha R., Cramer A., Gaio Leite P., Antunes M.M., Pereira R.V.S., Barroso A., Queiroz-Junior C.M., David B.A., Teixeira M.M., Menezes G.B., et al. SOCS2 Is Critical for the Balancing of Immune Response and Oxidate Stress Protecting Against Acetaminophen-Induced Acute Liver Injury. Front. Immunol. 2018;9:3134. doi: 10.3389/fimmu.2018.03134.</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fimmu.2018.03134</ArticleId><ArticleId IdType="pmc">PMC6349694</ArticleId><ArticleId IdType="pubmed">30723477</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang Y., Nakajima T., Gonzalez F.J., Tanaka N. PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice. Int. J. Mol. Sci. 2020;21:2061. doi: 10.3390/ijms21062061.</Citation><ArticleIdList><ArticleId IdType="doi">10.3390/ijms21062061</ArticleId><ArticleId IdType="pmc">PMC7139552</ArticleId><ArticleId IdType="pubmed">32192216</ArticleId></ArticleIdList></Reference><Reference><Citation>Zadjali F., Santana-Farre R., Vesterlund M., Carow B., Mirecki-Garrido M., Hernandez-Hernandez I., Flodstrom-Tullberg M., Parini P., Rottenberg M., Norstedt G., et al. SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. FASEB J. 2012;26:3282&#x2013;3291. doi: 10.1096/fj.12-205583.</Citation><ArticleIdList><ArticleId IdType="doi">10.1096/fj.12-205583</ArticleId><ArticleId IdType="pubmed">22562833</ArticleId></ArticleIdList></Reference><Reference><Citation>Bukowy-Bieryllo Z., Rabiasz A., Dabrowski M., Pogorzelski A., Wojda A., Dmenska H., Grzela K., Sroczynski J., Witt M., Zietkiewicz E. Truncating mutations in exons 20 and 21 of OFD1 can cause primary ciliary dyskinesia without associated syndromic symptoms. J. Med. Genet. 2019;56:769&#x2013;777. doi: 10.1136/jmedgenet-2018-105918.</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/jmedgenet-2018-105918</ArticleId><ArticleId IdType="pubmed">31366608</ArticleId></ArticleIdList></Reference><Reference><Citation>Wallmeier J., Nielsen K.G., Kuehni C.E., Lucas J.S., Leigh M.W., Zariwala M.A., Omran H. Motile ciliopathies. Nat. Rev. Dis. Primers. 2020;6:77. doi: 10.1038/s41572-020-0209-6.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41572-020-0209-6</ArticleId><ArticleId IdType="pubmed">32943623</ArticleId></ArticleIdList></Reference><Reference><Citation>Ghosh S., Das P.J., McQueen C.M., Gerber V., Swiderski C.E., Lavoie J.P., Chowdhary B.P., Raudsepp T. Analysis of genomic copy number variation in equine recurrent airway obstruction (heaves) Anim. Genet. 2016;47:334&#x2013;344. doi: 10.1111/age.12426.</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/age.12426</ArticleId><ArticleId IdType="pubmed">26932307</ArticleId></ArticleIdList></Reference><Reference><Citation>Pejler G. The emerging role of mast cell proteases in asthma. Eur. Respir. J. 2019;54 doi: 10.1183/13993003.00685-2019.</Citation><ArticleIdList><ArticleId IdType="doi">10.1183/13993003.00685-2019</ArticleId><ArticleId IdType="pubmed">31371445</ArticleId></ArticleIdList></Reference><Reference><Citation>Koh I.U., Choi N.H., Lee K., Yu H.Y., Yun J.H., Kong J.H., Kim H.J., Lee S., Kim S.C., Kim B.J., et al. Obesity susceptible novel DNA methylation marker on regulatory region of inflammation gene: Results from the Korea Epigenome Study (KES) BMJ Open Diabetes Res. Care. 2020;8:e001338. doi: 10.1136/bmjdrc-2020-001338.</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/bmjdrc-2020-001338</ArticleId><ArticleId IdType="pmc">PMC7422660</ArticleId><ArticleId IdType="pubmed">32788176</ArticleId></ArticleIdList></Reference><Reference><Citation>Mandal J., Roth M., Papakonstantinou E., Fang L., Savic S., Tamm M., Stolz D. Adrenomedullin mediates pro-angiogenic and pro-inflammatory cytokines in asthma and COPD. Pulm. Pharmacol. Ther. 2019;56:8&#x2013;14. doi: 10.1016/j.pupt.2019.01.006.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.pupt.2019.01.006</ArticleId><ArticleId IdType="pubmed">30690080</ArticleId></ArticleIdList></Reference><Reference><Citation>Taylor B.J., Snyder E.M., Richert M.L., Wheatley C.M., Chase S.C., Olson L.J., Johnson B.D. Effect of beta2-adrenergic receptor stimulation on lung fluid in stable heart failure patients. J. Heart Lung Transplant. 2017;36:418&#x2013;426. doi: 10.1016/j.healun.2016.09.008.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.healun.2016.09.008</ArticleId><ArticleId IdType="pmc">PMC5362291</ArticleId><ArticleId IdType="pubmed">27863863</ArticleId></ArticleIdList></Reference><Reference><Citation>Sironen A., Shoemark A., Patel M., Loebinger M.R., Mitchison H.M. Sperm defects in primary ciliary dyskinesia and related causes of male infertility. Cell. Mol. Life Sci. 2020;77:2029&#x2013;2048. doi: 10.1007/s00018-019-03389-7.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00018-019-03389-7</ArticleId><ArticleId IdType="pmc">PMC7256033</ArticleId><ArticleId IdType="pubmed">31781811</ArticleId></ArticleIdList></Reference><Reference><Citation>Terre B., Lewis M., Gil-Gomez G., Han Z., Lu H., Aguilera M., Prats N., Roy S., Zhao H., Stracker T.H. Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice. Development. 2019;146 doi: 10.1242/dev.162628.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.162628</ArticleId><ArticleId IdType="pmc">PMC6503982</ArticleId><ArticleId IdType="pubmed">30936178</ArticleId></ArticleIdList></Reference><Reference><Citation>Marshall C.B., Mays D.J., Beeler J.S., Rosenbluth J.M., Boyd K.L., Guasch G.L.S., Shaver T.M., Tang L.J., Liu Q., Shyr Y., et al. p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network. Cell Rep. 2016;14:2289&#x2013;2300. doi: 10.1016/j.celrep.2016.02.035.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.celrep.2016.02.035</ArticleId><ArticleId IdType="pmc">PMC4794398</ArticleId><ArticleId IdType="pubmed">26947080</ArticleId></ArticleIdList></Reference><Reference><Citation>N&#xfa;nez-Oll&#xe9; M., Jung C., Terr&#xe9; B., Balsiger N.A., Plata C., Roset R., Pardo-Pastor C., Garrido M., Rojas S., Alameda F., et al. Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility. Oncotarget. 2017;8:99261&#x2013;99273. doi: 10.18632/oncotarget.21818.</Citation><ArticleIdList><ArticleId IdType="doi">10.18632/oncotarget.21818</ArticleId><ArticleId IdType="pmc">PMC5725090</ArticleId><ArticleId IdType="pubmed">29245899</ArticleId></ArticleIdList></Reference><Reference><Citation>Terre B., Piergiovanni G., Segura-Bayona S., Gil-Gomez G., Youssef S.A., Attolini C.S., Wilsch-Brauninger M., Jung C., Rojas A.M., Marjanovic M., et al. GEMC1 is a critical regulator of multiciliated cell differentiation. EMBO J. 2016;35:942&#x2013;960. doi: 10.15252/embj.201592821.</Citation><ArticleIdList><ArticleId IdType="doi">10.15252/embj.201592821</ArticleId><ArticleId IdType="pmc">PMC5207319</ArticleId><ArticleId IdType="pubmed">26933123</ArticleId></ArticleIdList></Reference><Reference><Citation>Kurkowiak M., Zietkiewicz E., Witt M. Recent advances in primary ciliary dyskinesia genetics. J. Med. Genet. 2015;52:1&#x2013;9. doi: 10.1136/jmedgenet-2014-102755.</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/jmedgenet-2014-102755</ArticleId><ArticleId IdType="pmc">PMC4285891</ArticleId><ArticleId IdType="pubmed">25351953</ArticleId></ArticleIdList></Reference><Reference><Citation>Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402&#x2013;408. doi: 10.1006/meth.2001.1262.</Citation><ArticleIdList><ArticleId IdType="doi">10.1006/meth.2001.1262</ArticleId><ArticleId IdType="pubmed">11846609</ArticleId></ArticleIdList></Reference><Reference><Citation>Kramer A., Green J., Pollard J., Jr., Tugendreich S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics. 2014;30:523&#x2013;530. doi: 10.1093/bioinformatics/btt703.</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/bioinformatics/btt703</ArticleId><ArticleId IdType="pmc">PMC3928520</ArticleId><ArticleId IdType="pubmed">24336805</ArticleId></ArticleIdList></Reference><Reference><Citation>Schneider C.A., Rasband W.S., Eliceiri K.W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods. 2012;9:671&#x2013;675. doi: 10.1038/nmeth.2089.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nmeth.2089</ArticleId><ArticleId IdType="pmc">PMC5554542</ArticleId><ArticleId IdType="pubmed">22930834</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">34038055</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK570710</ArticleId><ArticleId IdType="doi">10.36255/exonpublications.gliomas.2021.chapter13</ArticleId></ArticleIdList><Book><Publisher><PublisherName>Exon Publications</PublisherName><PublisherLocation>Brisbane (AU)</PublisherLocation></Publisher><BookTitle book="cod9780645001747">Gliomas</BookTitle><PubDate><Year>2021</Year><Month>04</Month><Day>30</Day></PubDate><AuthorList Type="editors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Debinski</LastName><ForeName>Waldemar</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Brain Tumor Center of Excellence, Wake Forest Baptist, Medical Center Comprehensive Cancer Center, Winston Salem, NC, USA</Affiliation></AffiliationInfo></Author></AuthorList><Isbn>9780645001747</Isbn><ELocationID EIdType="doi">10.36255/exonpublications.gliomas.2021</ELocationID><Medium>Internet</Medium></Book><LocationLabel Type="chapter">Chapter 13</LocationLabel><ArticleTitle book="cod9780645001747" part="Ch13">Glioneuronal Tumors: Insights into a Rare Tumor Entity</ArticleTitle><Language>eng</Language><AuthorList Type="authors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Krauze</LastName><ForeName>Andra Valentina</ForeName><Initials>AV</Initials><AffiliationInfo><Affiliation>Division of Radiation Oncology and Developmental Radiotherapeutics, BC Cancer Surrey, University of British Columbia, Vancouver, Canada</Affiliation></AffiliationInfo></Author></AuthorList><PublicationType UI="D016454">Review</PublicationType><Abstract>Glioneuronal tumors are a group of rare neoplasms made up of neural and glial components in heterogenous proportions, generally exhibiting WHO grade I clinical behavior. These tumors affect infants, children and young adults, but are also described in adults and the elderly. They are strongly associated with seizures. Tumor subtypes described under the umbrella of glioneuronal tumors are actively evolving but to date comprise central, extraventricular and lipo- neurocytoma, desmoplastic infantile astrocytoma and ganglioglioma, diffuse leptomeningeal glioneuronal tumor, dysembryoplastic neuroepithelial tumor, papillary glioneuronal tumor, rosette-forming glioneuronal tumor of the fourth ventricle, rosetted glioneuronal tumor with neuropil-like islands, gangliocytoma, ganglioglioma, anaplastic ganglioglioma and paraganglioma. They vary in radiographic appearance, with some exhibiting large heterogenous solid/cystic masses. With large scale genetic and molecular analyses ongoing, classification continues to evolve. Seizure management and surgical resection represent the cornerstones of management, with the use of systemic agents and radiation lacking conclusive results. Optimal management requires multidisciplinary discussion including neuro-oncological and neuro-surgical expertise due to both the rarity of these tumors and the lack of evidence with data confined to small retrospective series and reviews.
2,331,737
Cerebellar Glioependymal Cyst.
Glioependymal cyst (GEC) is an uncommonly observed clinical entity in the posterior cranial fossa. A 36-year-old female with cystic lesion in the right cerebellum was hospitalized for evaluating headache and dizziness. Brain images showed a well-defined, ovoid mass adjacent to the fourth ventricle. After drainage and excision of the cyst, the patient became symptom free. Pathology examination disclosed low cuboidal epithelium and glial cells in the cyst wall. The radiological features, neurological manifestations, and the operations for GECs of the present localization are described in this short communication.
2,331,738
Identification of intracranial hemorrhage progression by transcranial point-of-care ultrasound in a patient with prior hemicraniectomy: a case report.
Transcranial ultrasound has been described as a tool to identify intracranial pathology, however, it is seldom used in the adult patient population due to poor imaging windows and rapid availability of more advanced imaging such as CT and MRI. We report a unique population in which transcranial ultrasound may be beneficial: those with a history of hemicraniectomy. We present a case of a 65-year-old male with a history of hemicraniectomy who suffered head trauma after a fall from his wheelchair. An initial non-contrast head CT scan identified an intracranial hemorrhage. Point-of-care bedside transcranial ultrasound was able to identify the progression of intracranial hemorrhage, which was confirmed by interval head CT. This prompted repeat CT imaging followed by neurosurgical intervention with the placement of an external ventricular drain in the right lateral ventricle. While ultrasound is unlikely to replace the need for more advanced imaging in these patients, point-of-care transcranial ultrasound may be a useful tool that can be employed rapidly at the bedside for interval screening in patients with hemicraniectomy and concern for new or worsening intracranial hemorrhage.
2,331,739
Echocardiographic Diagnosis of Double-Chambered Left Ventricle in an Infant.
&#x2022; DCLV is a very rare entity. &#x2022; Diagnosis is challenging because of overlapping features with similar entities. &#x2022; Distinguishing among these entities is critical because of differences in prognosis. &#x2022; Echocardiography is considered sufficient for the diagnosis. &#x2022; In critically ill patients awaiting transplantation, diagnosis can add complexity.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hoda</LastName><ForeName>Mehar</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Pediatric Cardiology, Department of Pediatrics, University of Texas Southwestern, Dallas, Texas.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arar</LastName><ForeName>Yousef</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Pediatric Cardiology, Department of Pediatrics, University of Texas Southwestern, Dallas, Texas.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thankavel</LastName><ForeName>Poonam</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Division of Pediatric Cardiology, Department of Pediatrics, University of Texas Southwestern, Dallas, Texas.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ikemba</LastName><ForeName>Catherine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Division of Pediatric Cardiology, Department of Pediatrics, University of Texas Southwestern, Dallas, Texas.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>02</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>CASE (Phila)</MedlineTA><NlmUniqueID>101700477</NlmUniqueID><ISSNLinking>2468-6441</ISSNLinking></MedlineJournalInfo><OtherAbstract Type="Publisher" Language="eng">[Figure: see text]
2,331,740
Central administration of afzelin extracted from Ribes fasciculatum improves cognitive and memory function in a mouse model of dementia.
Neurodegenerative disorders are characterized by the decline of cognitive function and the progressive loss of memory. The dysfunctions of the cognitive and memory system are closely related to the decreases in brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) signalings. Ribes fasciculatum, a medicinal plant grown in diverse countries, has been reported to pharmacological effects for autoimmune diseases and aging recently. Here we found that afzelin is a major compound in Ribes fasciculatum. To further examine its neuroprotective effect, the afzelin (100&#xa0;ng/&#xb5;l, three times a week) was administered into the third ventricle of the hypothalamus of C57BL/6 mice for one month and scopolamine was injected (i.p.) to these mice to impair cognition and memory before each behavior experiment. The electrophysiology to measure long-term potentiation and behavior tests for cognitive and memory functions were performed followed by investigating related molecular signaling pathways. Chronic administration of afzelin into the brain ameliorated synaptic plasticity and cognitive/memory behaviors in mice given scopolamine. Studies of mice's hippocampi revealed that the response of afzelin was accountable for the restoration of the cholinergic systems and molecular signal transduction via CREB-BDNF pathways. In conclusion, the central administration of afzelin leads to improved neurocognitive and neuroprotective effects on synaptic plasticity and behaviors partly through the increase in CREB-BDNF signaling.
2,331,741
Super-Resolution of Cardiac MR Cine Imaging using Conditional GANs and Unsupervised Transfer Learning.
High-resolution (HR), isotropic cardiac Magnetic Resonance (MR) cine imaging is challenging since it requires long acquisition and patient breath-hold times. Instead, 2D balanced steady-state free precession (SSFP) sequence is widely used in clinical routine. However, it produces highly-anisotropic image stacks, with large through-plane spacing that can hinder subsequent image analysis. To resolve this, we propose a novel, robust adversarial learning super-resolution (SR) algorithm based on conditional generative adversarial nets (GANs), that incorporates a state-of-the-art optical flow component to generate an auxiliary image to guide image synthesis. The approach is designed for real-world clinical scenarios and requires neither multiple low-resolution (LR) scans with multiple views, nor the corresponding HR scans, and is trained in an end-to-end unsupervised transfer learning fashion. The designed framework effectively incorporates visual properties and relevant structures of input images and can synthesise 3D isotropic, anatomically plausible cardiac MR images, consistent with the acquired slices. Experimental results show that the proposed SR method outperforms several state-of-the-art methods both qualitatively and quantitatively. We show that subsequent image analyses including ventricle segmentation, cardiac quantification, and non-rigid registration can benefit from the super-resolved, isotropic cardiac MR images, to produce more accurate quantitative results, without increasing the acquisition time. The average Dice similarity coefficient (DSC) for the left ventricular (LV) cavity and myocardium are 0.95 and 0.81, respectively, between real and synthesised slice segmentation. For non-rigid registration and motion tracking through the cardiac cycle, the proposed method improves the average DSC from 0.75 to 0.86, compared to the original resolution images.
2,331,742
Abdominal Imaging of Children and Young Adults With Fontan Circulation: Pathophysiology and Surveillance.
<b>OBJECTIVE.</b> The Fontan procedure has significantly improved the survival in children with a functional single ventricle, but it is associated with chronically elevated systemic venous pressure that leads to multisystemic complications. Imaging plays an important role in assessing these complications and guiding management. The pathophysiology, imaging modalities, and current surveillance recommendations are discussed and illustrated. <b>CONCLUSION.</b> Significant improvement in survival of patients with Fontan circulation is associated with ongoing cardiac and extracardiac comorbidities and multisystemic complications. The liver and intestines are particularly vulnerable to damage. In addition, this patient population has been shown to be at increased risk of certain malignancies such as hepatocellular carcinoma and neuroendocrine tumors. Familiarity with imaging findings of Fontan-associated liver disease and other abdominal complications of the Fontan circulation is essential for radiologists because we are likely to encounter these patients in our general practice.
2,331,743
Oncocytic papillary cystadenoma of the larynx: comparative study of ten cases and review of the literature.
Oncocytic papillary cystadenomas (OPCs) of the larynx are rare benign cystic lesions that usually present as supraglottic masses arising from the laryngeal ventricles. OPCs are found in patients older than 60&#xa0;years, with a female predominance. Symptoms vary from asymptomatic to hoarseness, dyspnea, and dysphagia; often, they mimic a laryngocele. The treatment is surgical. Diagnosis is based on histopathologic examination.</AbstractText>Surgical records for laryngeal masses diagnosed between 2005 and 2020 were searched retrospectively.</AbstractText>Ten patients were identified and included in the study. OPCs predominantly occurred in women (9/10), and the mean age at presentation was 73&#xa0;years. Most patients (8/10) presented with hoarseness and were smokers. OPCs were localized in the ventricle in eight out of ten patients. Surgical treatment was performed in all cases, mostly using transoral endolaryngeal approach (9/10). Histopathologic examination revealed oncocytic cyst or oncocytic papillary cystadenoma (the former term being the older synonym for OPC).</AbstractText>OPCs present a separate clinicopathologic entity, distinct from other cystic laryngeal lesions. They have a characteristic location, age and sex group, microscopic appearance, and potential for local recurrence.</AbstractText>&#xa9; 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</CopyrightInformation>
2,331,744
Fabry Disease p.M290I Mutation is Related to Organ Involvement: A Case Report.
Fabry disease (FD) is an X-linked hereditary disease. It results from mutations in the GLA gene, leading to deficient activity of the enzyme alpha-galactosidase A&#xa0;(&#x3b1;-Gal A) and progressive accumulation of undegraded glycosphingolipids in cell lysosomes. Enzyme replacement therapy (ERT) can improve&#xa0;the natural course of this disease, but an early diagnosis is crucial for a successful treatment. We describe the case of a female diagnosed with chronic proteinuric kidney disease in the postpartum period. Despite receiving optimal medical treatment, the disease progressed and she started renal replacement therapy (RRT) with peritoneal dialysis (PD). Five years later, she was enrolled in a pilot screening study for FD, and the heterozygous mutation c.870G&gt;C (p.Met290Ile; M290I) in exon six of the GLA gene was found. The family screening revealed the presence of this mutation in the patient's father and daughter. The proband did not meet the criteria for a definitive FD diagnosis, but she remained under follow-up at our nephrology metabolic diseases consultation, as the mutation was described as pathogenic and associated with a classic FD phenotype. Later that same year, reassessment exams revealed a worsening left ventricle mass index (LVMi), a new ischemic cerebral lesion, and a substantial increase in serum globotriaosylsphingosine (LysoGb3) levels. These clinical changes led to a decision to initiate ERT. p.M290I is a previously known but poorly described GLA mutation. To our knowledge, this is the first report of p.M290I mutation-associated disease activity that offers strong evidence of its pathogenicity.
2,331,745
Hippocampal insulin resistance and the Sirtuin 1 signaling pathway in diabetes-induced cognitive dysfunction.
In the peripheral nervous system, the activation of Sirtuin 1 can improve insulin resistance; however, the role played by Sirtuin 1 in the central nervous system remains unknown. In this study, rat models of diabetes mellitus were generated by a single injection of streptozotocin. At 8 weeks after streptozotocin injection, the Morris water maze test and western blot assays confirmed that the diabetic model rats had learning and memory deficits, insulin resistance, and Sirtuin 1 expression could be detected in the hippocampus. Insulin and the insulin receptor inhibitor S961 were intranasally administered to investigate the regulatory effects of insulin signaling on Sirtuin 1. The results showed that insulin administration improved the impaired cognitive function of diabetic model rats and increased the expression levels of phosphorylated insulin receptor, phosphorylated insulin receptor substrate 1, and Sirtuin 1 in the hippocampus. Conversely, S961 administration resulted in more severe cognitive dysfunction and reduced the expression levels of phosphorylated insulin receptor, phosphorylated insulin receptor substrate 1, and Sirtuin 1. The Sirtuin 1 activator SRT2104 and the inhibitor Sirtinol were injected into the lateral ventricle, which revealed that the activation of Sirtuin 1 increased the expression levels of target of rapamycin complex 1, phosphorylated cAMP-response element-binding protein, and brain-derived neurotrophic factor. Hippocampal dendritic length and spine density also increased in response to Sirtuin 1 activation. In contrast, Sirtinol decreased the expression levels of target of rapamycin complex 1, phosphorylated cAMP-response element-binding protein, and brain-derived neurotrophic factor and damaged the dendritic structure. These findings suggest that the Sirtuin 1 signaling pathway plays an important role in the development of insulin resistance-related cognitive deficits in diabetic rats. This study was approved by the Animal Ethics Welfare Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine (approval No. ZYFY201811207) in November 2018.
2,331,746
Choroid plexus perfusion in sickle cell disease and moyamoya vasculopathy: Implications for glymphatic flow.
Cerebrospinal fluid (CSF) and interstitial fluid exchange have been shown to increase following pharmacologically-manipulated increases in cerebral arterial pulsatility, consistent with arterial pulsatility improving CSF circulation along perivascular glymphatic pathways. The choroid plexus (CP) complexes produce CSF, and CP activity may provide a centralized indicator of perivascular flow. We tested the primary hypothesis that elevated cortical cerebral blood volume and flow, present in sickle cell disease (SCD), is associated with fractionally-reduced CP perfusion relative to healthy adults, and the supplementary hypothesis that reduced arterial patency, present in moyamoya vasculopathy, is associated with elevated fractional CP perfusion relative to healthy adults. Participants (n&#x2009;=&#x2009;75) provided informed consent and were scanned using a 3-Tesla arterial-spin-labeling MRI sequence for CP and cerebral gray matter (GM) perfusion quantification. ANOVA was used to calculate differences in CP-to-GM perfusion ratios between groups, and regression analyses applied to evaluate the dependence of the CP-to-GM perfusion ratio on group after co-varying for age and sex. ANOVA yielded significant (p&#x2009;&lt;&#x2009;0.001) group differences, with CP-to-GM perfusion ratios increasing between SCD (ratio&#x2009;=&#x2009;0.93&#x2009;&#xb1;&#x2009;0.28), healthy (ratio&#x2009;=&#x2009;1.04&#x2009;&#xb1;&#x2009;0.32), and moyamoya (ratio&#x2009;=&#x2009;1.29&#x2009;&#xb1;&#x2009;0.32) participants, which was also consistent with regression analyses. Findings are consistent with CP perfusion being inversely associated with cortical perfusion.
2,331,747
Phenanthrene alters the electrical activity of atrial and ventricular myocytes of a polar fish, the Navaga cod.
Oil and gas exploration in the Arctic can result in the release of polycyclic aromatic hydrocarbons (PAHs) into relatively pristine environments. Following the recent spill of approximately 17 500 tonnes of diesel fuel in Norilsk, Russia, May 2020, our study focussed on the effects of phenanthrene, a low molecular weight PAH found in diesel and crude oil, on the isolated atrial and ventricular myocytes from the heart of the polar teleost, the Navaga cod (Eleginus nawaga). Acute exposure to phenanthrene in navaga cardiomyocytes caused significant action potential (AP) prolongation, confirming the proarrhythmic effects of this pollutant. We show AP prolongation was due to potent inhibition of the main repolarising current, I<sub>Kr</sub>, with an IC<sub>50</sub> value of ~2&#xa0;&#xb5;M. We also show a potent inhibitory effect (~55%) of 1&#xa0;&#xb5;M phenanthrene on the transient I<sub>Kr</sub> currents that protects the heart from early-after-depolarizations and arrhythmias. These data, along with more minor effects on inward sodium (I<sub>Na</sub>) (~17% inhibition at 10&#xa0;&#xb5;M) and calcium (I<sub>Ca</sub>) (~17% inhibition at 30&#xa0;&#xb5;M) currents, and no effects on inward rectifier (I<sub>K1</sub> and I<sub>KAch</sub>) currents, demonstrate the cardiotoxic effects exerted by phenanthrene on the atrium and ventricle of navaga cod. Moreover, we report the first data that we are aware of on the impact of phenanthrene on atrial myocyte function in any fish species.
2,331,748
Modified models to distinguish central nervous system demyelinating diseases with brain lesions.
Brain lesions in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are indistinguishable from those with relapsing-remitting multiple sclerosis (RRMS) and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-Ab NMOSD).</AbstractText>Patients with MOGAD, RRMS, and AQP4-Ab NMOSD with abnormal brain lesions were retrospectively reviewed and divided into training and validation sets. Discriminatory models using brain images and demographics were generated to identify optimal predictors using orthogonal partial least square discriminant analysis after principal component analysis (PCA) of clinico-radiological data without a diagnosis. Constructed models were tested in an independent cohort.</AbstractText>PCA of 51 brain scans and demographics from patients (13 MOGAD, 24 RRMS, and 14 AQP4-Ab NMOSD) demonstrated that RRMS was distinct from antibody-mediated conditions. The best predictors between MOGAD and AQP4-Ab NMOSD were poorly demarcated lesions, large abnormalities (both predictive for MOGAD), female sex, disease duration, linear lesions adjacent to the lateral ventricle, and cerebellum involvement (all predictive for MOGAD). Periventricular, ovoid/round, juxtacortical, and callosal lesions; Dawson's fingers; T1 hypointensity (all predictive for RRMS); and fluffy as well as large lesions (for MOGAD) were the best predictors of MOGAD and RRMS. RRMS versus MOGAD and RRMS versus AQP4-Ab NMOSD models exhibited a high predictive value and perfect accuracy (100%), which was validated in an independent cohort. The model of patients with AQP4-Ab NMOSD and MOGAD exhibited lower predictive power but still achieved an accuracy of 90%.</AbstractText>Brain MRI characteristics combined with demographics enables the distinction of MOGAD from RRMS and AQP4-Ab NMOSD. Fluffy and large lesions are relatively specific MRI characteristics in patients with MOGAD with brain abnormalities in Asian countries.</AbstractText>Copyright &#xa9; 2021. Published by Elsevier B.V.</CopyrightInformation>
2,331,749
Estimates of locus coeruleus function with functional magnetic resonance imaging are influenced by localization approaches and the use of multi-echo data.
The locus coeruleus (LC) plays a central role in regulating human cognition, arousal, and autonomic states. Efforts to characterize the LC's function in humans using functional magnetic resonance imaging have been hampered by its small size and location near a large source of noise, the fourth ventricle. We tested whether the ability to characterize LC function is improved by employing neuromelanin-T1 weighted images (nmT1) for LC localization and multi-echo functional magnetic resonance imaging (ME-fMRI) for estimating intrinsic functional connectivity (iFC). Analyses indicated that, relative to a probabilistic atlas, utilizing nmT1 images to individually localize the LC increases the specificity of seed time series and clusters in the iFC maps. When combined with independent components analysis (ME-ICA), ME-fMRI data provided significant improvements in the temporal signal to noise ratio and DVARS relative to denoised single echo data (1E-fMRI). The effects of acquiring nmT1 images and ME-fMRI data did not appear to only reflect increases in power: iFC maps for each approach overlapped only moderately. This is consistent with findings that ME-fMRI offers substantial advantages over 1E-fMRI acquisition and denoising. It also suggests that individually identifying LC with nmT1 scans is likely to reduce the influence of other nearby brainstem regions on estimates of LC function.
2,331,750
Robot-guided Ventriculoperitoneal Shunt in Slit-like Ventricles.
Ventriculoperitoneal shunt (VPS) is the most common procedure used in the management of hydrocephalus regardless of the etiology. The standard free-hand technique is used for the placement of VPS in patients with enlarged ventricles. In patients with very small ventricles, CSF access through ventriculostomy becomes challenging and free-hand technique may be associated with high failure rates. In these situations, stereotactic-guided VPS becomes very useful.</AbstractText>To validate and describe the technique of robotic-guided VPS in cases with very small ventricles.</AbstractText>Three patients underwent VPS with robotic guidance between 2016 and 2019. One patient with a diagnosis of occipital meningocele, who later developed recalcitrant CSF leak from the operative site, and two other patients were diagnosed with idiopathic intracranial hypertension (IIH). Plain CT brain with 1-mm slice thickness acquired prior to the surgery was uploaded into the ROSA machine (Zimmer Biomet Warsaw, Indiana). The trajectory for the VPS is created on the robotic software presurgery. The patient is placed in the supine position with head turned to the side contralateral to VPS insertion and fixed with Mayfield clamp. Registration of the patient is done with the robot. The placement of the VPS is commenced with the robotic arm in the predetermined trajectory.</AbstractText>Ventricle was hit in a single attempt in all the cases. CSF leak stopped in the case with meningocele; headache, and visual acuity improved in both the cases of IIH.</AbstractText>Robotic-guidance provides a safe and accurate method of VPS placement even in the presence of slit-like ventricles.</AbstractText>
2,331,751
GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats.
The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) in neuropathic pain. Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase (CBHRP) was used to label the CSF-CN. Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN. Chronic constriction injury of sciatic nerve (CCI) rat model was used to duplicate the neuropathic pain. Pain behavior was scored to determine the analgesic effects of GluN2B antagonist Ro 25-6981 and BDNF neutralizing antibody on CCI rats. GluN2B and BDNF were expressed in the CSF-CN and their expression was up-regulated in CCI rats. Intra-lateral ventricle injection of GluN2B antagonist Ro 25-6981 or BDNF neutralizing antibody notably alleviated thermal hyperalgesia and mechanical allodynia in CCI rats. Moreover, the increased expression of BDNF protein in CCI rats was reversed by intra-lateral ventricle injection of Ro 25-6981. These results suggest that GluN2B and BDNF are expressed in the CSF-CN and alteration of GluN2B-BDNF pathway in the CSF-CN is involved in the modulation of the peripheral neuropathic pain.
2,331,752
Myocardial infarct late after Fontan-type surgery in pulmonary atresia and intact ventricular septum: a must-know complication! About a case report.
Coronary abnormalities are frequent in pulmonary atresia and intact ventricular septum, mainly in patients with a very diminutive right ventricle. They severely impact on early and late prognosis. We describe an 8-year-old girl who presented with myocardial ischaemia, late after uneventful Fontan completion. The importance of precise delineation of the coronary anatomy upon initial assessment and during follow-up is emphasised.
2,331,753
Effect of chronic intracerebroventricular administration of an aromatase inhibitor on the expression of socio-sexual behaviors in male Japanese quail.
Aromatase converts androgens into estrogens in the brain of vertebrates including humans. This enzyme is also expressed in other tissues where its action may result in negative effects on human health (e.g., promotion of tumor growth). To prevent these effects, aromatase inhibitors were developed and are currently used to block human estrogen-dependent tumors. In vertebrates including quail, aromatase is expressed in a highly conserved set of interconnected brain nuclei known as the social behavior network. This network is directly implicated in the expression of a large range of social behaviors. The primary goal of this study was to characterize in Japanese quail the potential impact of brain aromatase on sexual behavior, aggressiveness and social motivation (i.e., tendency to approach and stay close to conspecifics). An additional goal was to test the feasibility and effectiveness of long-term delivery of an aromatase inhibitor directly into the third ventricle via Alzet&#x2122; osmotic minipumps using male sexual behavior as the aromatase dependent measure. We demonstrate that this mode of administration results in the strongest inhibition of both copulatory behavior and sexual motivation ever observed in this species, while other social behaviors were variably affected. Sexual motivation and the tendency to approach a group of conspecifics including females clearly seem to depend on brain aromatase, but the effects of central estrogen production on aggressive behavior and on the motivation to approach males remain less clear.
2,331,754
Canine presumed glial brain tumours treated with radiotherapy: Is there an inferior outcome in tumours contacting the subventricular zone?
Post-treatment outcome in canine glial tumours is described with a broad range of survival times between 2 and 28&#x2009;months. After surgery or radiation therapy, the tumours may progress locally or spread within the central nervous system. It is unknown if tumour- or patient-specific factors influence prognosis. In humans, glioblastoma involving the subventricular zone has been found to recur distantly, with shortened time to progression and overall survival. We included 32 dogs irradiated for a presumptive primary glial brain tumour in this retrospective cohort study. Tumours were grouped relative to subventricular zone contact and overt ventricular invasion assessing pre-treatment magnetic resonance images. Median time to progression (TTP) for all cases was 534&#x2009;days (95%CI, 310-758), with a significantly shorter TTP in dogs with lesions at the subventricular zone (median TTP, 260 vs. 687&#x2009;days; p&#xa0;=&#xa0;.049). Tumours at the subventricular zone progressed more often (p&#xa0;=&#xa0;.001), and more likely as CNS-metastasis (52.9% vs. 13.3%, p&#xa0;=&#xa0;.028). Median overall survival (OS) was 489&#x2009;days (95%CI, 147-831) and median tumour-specific survival 609&#x2009;days (95%CI, 382-835). Involvement of the subventricular zone was significantly associated with a shorter tumour-specific survival (median, 306 vs. 719&#x2009;days; p&#xa0;=&#xa0;.044). Glial tumours contacting the subventricular zone in dogs have a shorter tumour-specific survival and a higher rate of progression and CNS-metastasis. Despite local tumour control, metastasis must be considered and should prompt further treatment approaches.
2,331,755
Sex-dependent vulnerability of fetal nonhuman primate cardiac mitochondria to moderate maternal nutrient reduction.
Poor maternal nutrition in pregnancy affects fetal development, predisposing offspring to cardiometabolic diseases. The role of mitochondria during fetal development on later-life cardiac dysfunction caused by maternal nutrient reduction (MNR) remains unexplored. We hypothesized that MNR during gestation causes fetal cardiac bioenergetic deficits, compromising cardiac mitochondrial metabolism and reserve capacity. To enable human translation, we developed a primate baboon model (Papio spp.) of moderate MNR in which mothers receive 70% of control nutrition during pregnancy, resulting in intrauterine growth restriction (IUGR) offspring and later exhibiting myocardial remodeling and heart failure at human equivalent &#x223c;25 years. Term control and MNR baboon offspring were necropsied following cesarean-section, and left ventricle (LV) samples were collected. MNR adversely impacted fetal cardiac LV mitochondria in a sex-dependent fashion. Increased maternal plasma aspartate aminotransferase, creatine phosphokinase (CPK), and elevated cortisol levels in MNR concomitant with decreased blood insulin in male fetal MNR were measured. MNR resulted in a two-fold increase in fetal LV mitochondrial DNA (mtDNA). MNR resulted in increased transcripts for several respiratory chain (NDUFB8, UQCRC1, and cytochrome c) and adenosine triphosphate (ATP) synthase proteins. However, MNR fetal LV mitochondrial complex I and complex II/III activities were significantly decreased, possibly contributing to the 73% decreased ATP content and increased lipid peroxidation. MNR fetal LV showed mitochondria with sparse and disarranged cristae dysmorphology. Conclusion: MNR disruption of fetal cardiac mitochondrial fitness likely contributes to the documented developmental programming of adult cardiac dysfunction, indicating a programmed mitochondrial inability to deliver sufficient energy to cardiac tissues as a chronic mechanism for later-life heart failure.
2,331,756
Arterial hypertension and remodelling of the right ventricle.
In the case of long-term and physiological loads (e.g. during pregnancy or regular athletics training), reversible morphological changes occur in the heart - cardiomyocytes undergo hypertrophy; however, this is not accompanied by impairment of left ventricular function or myocyte metabolism. However, in the course of various pathological processes, as time goes by, gradually permanent morphological changes occur. These changes are referred to as remodelling of the heart muscle, which, regardless of the primary cause, can lead to the development of chronic heart failure.</AbstractText>The study was performed on post-mortem material of 35 human hearts obtained from forensic sections and anatomopathological sections of people who died of non-cardiac causes (mainly traffic accidents, suicide attempts, strokes, acute infections); material was fixed in a 4% formalin solution. The hearts were subjected to macro- and microscopic assessment. During microscopic assessment the features of remodelling were evaluated.</AbstractText>In vivo and echocardiographic tests, as well as macroscopic evaluation of post-mortem material, suggest the presence of some kind of right ventricular muscle remodelling; however, classic microscopic observations, presented in this study, do not provide such unambiguous evidence. Thus, the question arises: why and how the right ventricular function is disturbed, sometimes at early stages of arterial hypertension.</AbstractText>
2,331,757
Cell population analysis of the adult murine subependymal neurogenic lineage by flow cytometry.
This protocol provides a flow-cytometry-based procedure to classify and isolate all cells of the adult rodent subependymal zone (SEZ) neurogenic lineage, without the need for reporter mice, into different cell populations, including three neural stem cell (NSC) fractions with molecular signatures that are coherent with single-cell transcriptomics. Additionally, their cycling behavior can be assessed by means of 5-ethynyl-2'-deoxyuridine (EdU) incorporation. Our method allows the isolation of different NSC fractions and the functional assay of their cycling heterogeneity and quiescence-activation transitions. For complete details on the use, execution, and outcomes of this protocol, please refer to Belenguer et&#xa0;al. (2021).
2,331,758
Human Cord Blood Derived Unrestricted Somatic Stem Cells Restore Aquaporin Channel Expression, Reduce Inflammation and Inhibit the Development of Hydrocephalus After Experimentally Induced Perinatal Intraventricular Hemorrhage.
Intraventricular hemorrhage (IVH) is a severe complication of preterm birth associated with cerebral palsy, intellectual disability, and commonly, accumulation of cerebrospinal fluid (CSF). Histologically, IVH leads to subependymal gliosis, fibrosis, and disruption of the ependymal wall. Importantly, expression of aquaporin channels 1 and 4 (AQP1 and AQP4) regulating respectively, secretion and absorption of cerebrospinal fluids is altered with IVH and are associated with development of post hemorrhagic hydrocephalus. Human cord blood derived unrestricted somatic stem cells (USSCs), which we previously demonstrated to reduce the magnitude of hydrocephalus, as having anti-inflammatory, and beneficial behavioral effects, were injected into the cerebral ventricles of rabbit pups 18 h after glycerol-induced IVH. USSC treated IVH pups showed a reduction in ventricular size when compared to control pups at 7 and 14 days (both, <i>P</i> &lt; 0.05). Histologically, USSC treatment reduced cellular infiltration and ependymal wall disruption. In the region of the choroid plexus, immuno-reactivity for AQP1 and ependymal wall AQP4 expression were suppressed after IVH but were restored following USSC administration. Effects were confirmed by analysis of mRNA from dissected choroid plexus and ependymal tissue. Transforming growth factor beta (TGF-&#x3b2;) isoforms, connective tissue growth factor (CTGF) and matrix metalloprotease-9 (MMP-9) mRNA, as well as protein levels, were significantly increased following IVH and restored towards normal with USSC treatment (<i>P</i> &lt; 0.05). The anti-inflammatory cytokine Interleukin-10 (IL-10) mRNA was reduced in IVH, but significantly recovered after USSC injection (<i>P</i> &lt; 0.05). In conclusion, USSCs exerted anti-inflammatory effects by suppressing both TGF-&#x3b2; specific isoforms, CTGF and MMP-9, recovered IL-10, restored aquaporins expression towards baseline, and reduced hydrocephalus. These results support the possibility of the use of USSCs to reduce IVH consequences in prematurity.
2,331,759
Insulin-like Growth Factors may be Markers of both Traumatic Brain Injury and Fear-Related Stress.
Insulin-like growth factors (IGF) are potent neurotrophic and neurorepair factors that were recently proposed as biomarkers of traumatic brain injury (TBI) and associated psychiatric comorbidities, in particular post-traumatic stress disorder (PSTD). We tested the hypothesis that the IGF system is differentially deregulated in the acute and early chronic stages of TBI, and under acute stress. Plasma and brain IGF1 and IGF2 levels were evaluated in mice 3&#xa0;weeks and 3&#xa0;days after a controlled cortical impact (CCI)-induced mild-to-moderate TBI. The effects of conditioned fear on IGF levels and its interaction with TBI (TBI followed, 3&#xa0;weeks later, by fear-inducing procedures) were also evaluated. In the plasma, IGF1 decreased 3&#xa0;weeks post-TBI only (-9%), whereas IGF2 remained unaffected. In the brain, IGF1 increased only in the cortex and hippocampus at 3&#xa0;weeks post-TBI (up to +650%). At 3&#xa0;days, surpringly, this increase was more diffuse and more important in sham (craniotomized) animals. Additionally, IGF2 immunostaining in brain ventricles was reorganized in TBI animals at both post-TBI stages. Conditioned fear exposure did not influence the effects of early chronic TBI on plasma IGF1 levels, but reduced plasma IGF2 (-6%) levels. It also dampened the effects of TBI on brain IGF systems, but brain IGF1 level and IGF2 tissue distribution remained statistically different from controls under these conditions. In co-exposed animals, DNA methylation increased at the hippocampal Igf1 gene promoter. These results show that blood IGF1 and IGF2 are most reduced in the early chronic phase of TBI and after exposure to a stressful event, and that the brain IGF system is up-regulated after TBI, and more so in the acute phase.
2,331,760
The natriuretic peptide system in heart failure: Diagnostic and therapeutic implications.
Natriuretic peptides, which are activated in heart failure, play an important cardioprotective role. The most notable of the cardioprotective natriuretic peptides are atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are abundantly expressed and secreted in the atrium and ventricles, respectively, and C-type natriuretic peptide (CNP), which is expressed mainly in the vasculature, central nervous system, and bone. ANP and BNP exhibit antagonistic effects against angiotensin II via diuretic/natriuretic actions, vasodilatory actions, and inhibition of aldosterone secretion, whereas CNP is involved in the regulation of vascular tone and blood pressure, among other roles. ANP and BNP are of particular interest with respect to heart failure, as their levels, most notably BNP and N-terminal proBNP-a cleavage product produced when proBNP is processed to mature BNP-are increased in patients with heart failure. Furthermore, the identification of natriuretic peptides as sensitive markers of cardiac load has driven significant research into their physiological roles in cardiovascular homeostasis and disease, as well as their potential use as both biomarkers and therapeutics. In this review, I discuss the physiological functions of the natriuretic peptide family, with a particular focus on the basic research that has led to our current understanding of its roles in maintaining cardiovascular homeostasis, and the pathophysiological implications for the onset and progression of heart failure. The clinical significance and potential of natriuretic peptides as diagnostic and/or therapeutic agents are also discussed.
2,331,761
2-Methoxyestradiol Attenuates the Development and Retards the Progression of Hypoxia-And Alpha-Naphthylthiourea-Induced Pulmonary Hypertension.
Pulmonary arterial hypertension (PH), a progressive, incurable, and deadly disease, predominantly develops in women. Growing body of evidence suggest that dysregulated estradiol (E2) metabolism influences the development of PH and that some of the biological effects of E2 are mediated by its major non-estrogenic metabolite, 2-metyhoxyestradiol (2ME). The objective of this study was to examine effects of 2ME in chronic hypoxia (CH)-induced PH and alpha-naphthylthiourea (ANTU)-induced acute lung injury and PH. In addition, we investigated the effects of exposure to different levels of CH on development of PH. Chronic exposure to 15% or 10% oxygen produced similar increases in right ventricle peak systolic pressure (RVPSP) and pulmonary vascular remodeling, but oxygen concentration-dependent increase in hematocrit. Notably, right ventricle (RV) hypertrophy correlated with level of hypoxia and hematocrit, rather than with magnitude of RVPSP. The latter suggests that, in addition to increased afterload, hypoxia (via increased hematocrit) significantly contributes to RV hypertrophy in CH model of PH. In CH-PH rats, preventive and curative 2ME treatments reduced both elevated RVPSP and pulmonary vascular remodeling. Curative treatment with 2ME was more effective in reducing hematocrit and right ventricular hypertrophy, as compared to preventive treatment. Single ANTU injection produced lung injury, i.e., increased lungs weight and induced pleural effusion. Treatment with 2ME significantly reduced pleural effusion and, more importantly, eliminated acute mortality induced by ANTU (33% vs 0%, ANTU vs. ANTU+2ME group). Chronic treatment with ANTU induced PH and RV hypertrophy and increased lungs weight. 2-ME significantly attenuated severity of disease (i.e., reduced RVPSP, RV hypertrophy and pulmonary vascular injury). This study demonstrates that 2ME has beneficial effects in chronic hypoxia- and acute lung injury-induced PH and provides preclinical justification for clinical evaluation of 2ME in pulmonary hypertension.
2,331,762
Inverted Takotsubo Cardiomyopathy as an Early Complication After Liver Transplantation.
BACKGROUND Takotsubo cardiomyopathy (TTC) is a cardiac syndrome characterized by transient left ventricle (LV) dysfunction, typically showing apical ballooning due to apical akinesis with preserved basal segment contractility. The inverted form is very uncommon and is characterized by basal segment hypokinesis or akinesis and normal LV apical segment contractility. CASE REPORT We describe the case of a 49-year-old woman who developed inverted TTC after orthotopic liver transplantation. On day 1 (D1), dyspnea and oliguria suddenly appeared. A chest X-ray showed pulmonary edema, and echocardiography showed severe systolic LV dysfunction with an estimated ejection fraction of approximately 25% and akinesis of basal and midventricular LV segments, normal apical segment contractility, and mild mitral regurgitation. Elevated troponin T, creatine kinase-MB, and N-terminal pro B-type natriuretic peptide were found in the blood sample. Suspected inverted takotsubo cardiomyopathy was confirmed by left ventriculography, with normal apical part motion, akinesis in the other LV parts, and negative coronary angiography. The echocardiographic findings returned to normal on D14, and the patient was discharged from the hospital on D19 with normal LV motion and an ejection fraction of 65%. The transplanted liver function was excellent. CONCLUSIONS Organ transplantation is connected with a great emotional stress because the patient's life depends on the death of another person. Therefore, we have to think about the possibility of stress cardiomyopathy even after liver transplantation, because early diagnosis and treatment can be life-saving for the patient. To our knowledge, this is the first described case of inverted takotsubo cardiomyopathy after liver transplantation.
2,331,763
Low b-value diffusion tensor imaging for measuring pseudorandom flow of cerebrospinal fluid.
Cerebrospinal fluid (CSF) plays an important role in the clearance system of the brain. Recently, low b-value diffusion tensor imaging (low-b DTI) has been reported to be useful in the observation of CSF flow; however, the precise flow property observed by low-b DTI has not been fully investigated. Accordingly, a mathematical framework of low-b DTI is proposed for investigating CSF and clarifying its pseudorandom flow.</AbstractText>The framework will show that the limit of the diffusion tensor as b-value decreases to zero approximately represents the covariance of the velocity distribution of the CSF's pseudorandom flow.</AbstractText>The low b-value diffusion tensor (DTL</sub> ) of whole-brain CSF was obtained using diffusion-weighted echo-planar imaging. Seven healthy volunteers were scanned for intersubject analysis; three of the volunteers was consecutively scanned for repeatability analysis. Obtained DTL</sub> was visually assessed by ellipsoid-representation map and was statistically evaluated by calculating mean diffusivity (MD) and fractional anisotropy (FA) in regions of interest (ROIs) representing intensive pseudorandom flow.</AbstractText>Obtained DTL</sub> consistently shows large and anisotropic diffusivity in some segments of CSF, typically the ROIs around the foramen of Monro, the aqueduct, the prepontine cistern, the middle cerebral artery, and the Sylvian fissure throughout the study. The statistical analysis shows high repeatability and consistently high MD and FA in all the ROIs for all the volunteers.</AbstractText>From the viewpoint of the proposed framework, the high and anisotropic DTL</sub> in the ROIs indicates large covariance of velocity distribution, which represents intensive pseudorandom flows of CSF.</AbstractText>&#xa9; 2021 International Society for Magnetic Resonance in Medicine.</CopyrightInformation>
2,331,764
Brain Ependymoma in an African Grey Parrot (<i>Psittacus erithacus erithacus</i>).
A 14-year-old unsexed African grey parrot (<i>Psittacus erithacus erithacus</i>) was presented with a 12-hour history of neurological signs and vomiting. The external physical examination of the patient revealed lethargy, moderate hypothermia, a head tilt, and horizontal nystagmus. Whole-body radiographic imaging and blood biochemistry parameters were unremarkable, and a serological test to detect bornavirus was negative. A computed tomography scan of the bird revealed a large cystic lesion located on the fourth ventricle of the brain. In spite of treatment (nonsteroidal anti-inflammatory drugs and antibiotic and antiparasitic therapy), the parrot's health continued to decline, and it was euthanatized 12 days after presentation. A complete postmortem examination was performed on the patient's brain. Histopathological interpretation of tissues submitted described a large neoformation composed of cells arranged in perivascular pseudorosettes. Hyperchromatic nuclei and marked anisokaryosis were suggestive of a malignant tumor. The tissue mass was associated with significant dilation of the fourth ventricle and a severe peripheral gliosis. The histopathological diagnosis of the neoformation was an ependymoma. Ependymomas are glial tumors of the ependymal cells that line the central canal and the ventricles of the brain and are rarely described in mammals. In birds, ependymomas were only described in budgerigars (<i>Melopsittacus undulatus</i>). In human medicine, the recommended treatment is surgical removal of the tumor when possible, followed by radiotherapy.
2,331,765
Colloid cysts of the third ventricle in children.
The rarity of colloid cysts in children makes it difficult to characterize this entity and offer meaningful advice on treatment. Infrequent case reports exist, but to date there has been no age-specific assessment. The purpose of this study was to define any differences between children and adults who are evaluated and treated for colloid cysts of the third ventricle.</AbstractText>Patients with colloid cysts were reviewed and stratified by age. Individuals &#x2264; 18 years of age were defined as pediatric patients and those &gt; 18 years of age as adults. Clinical and radiographic data, treatment, and postoperative outcomes were compared between both groups. Bivariate analysis was conducted using the Fisher exact test for categorical variables and Mann-Whitney U-test for continuous variables.</AbstractText>Of 132 endoscopic resections (121 primary, 10 secondary, and 1 tertiary) of a colloid cyst, 9 (6.8%) were performed in pediatric patients (mean age 14.1 years, range 9-18 years) and 123 (93.2%) were performed in adult patients (mean age 43.8 years, range 19-73 years). Cases were found incidentally more commonly in pediatric than adult patients (66.7% vs 37.4%, p &gt; 0.05), and pediatric patients had lower rates of hydrocephalus than adult patients (11.1% vs 63.4%, p &lt; 0.05). Acute decompensation at presentation was found in 8 adults (6.5%) but no children. Complete cyst removal (88.9% vs 90.2%, p &gt; 0.05) and length of stay (1.6 days vs 2.9 days, p &gt; 0.05) were not significantly different between the groups. Postoperative complications (6.5% in adults, 0% in children) and recurrence (2.4% in adults, 0% in children) were rare in both groups, and there were no treatment-related deaths. The mean postoperative radiological follow-up was longer in pediatric patients (45 months, range 4-89 months) than adults (44.1 months, range 1-171 months).</AbstractText>While differences exist between children and adults regarding colloid cyst presentation, these are in keeping with the predicted evolution of a slow-growing lesion. Consistent with this observation, children had lower rates of hydrocephalus and a smaller mean maximal cyst diameter. Contrary to the published literature, however, sudden deterioration was not observed in pediatric patients but occurred in adult patients. In this limited pediatric sample size, the authors have not recorded any postoperative complications or recurrences to date. These encouraging results with endoscopic removal may positively impact future decisions related to children given their protracted life expectancy and projected rates of progression.</AbstractText>
2,331,766
[Prehospital treatment of tension pneumothorax in children-which decisions do we make? : Results of a survey among German emergency physicians].
The preclinical treatment of a&#xa0;traumatic or spontaneous tension pneumothorax remains a&#xa0;particular challenge in pediatric patients. Currently recommended interventions for decompression are either finger thoracostomy or needle decompression. Due to the tiny intercostal spaces, finger thoracostomy may not be feasible in small children and surgical preparation may be necessary. In needle decompression, the risk of injuring underlying vital structures is increased because of the smaller anatomic structures. As most emergency physicians do not regularly work in pediatric trauma care, decompression of tension pneumothorax is associated with significant uncertainty; however, in this rare emergency situation, consistent and goal-oriented action is mandatory and lifesaving. An assessment of pre-existing experience and commonly used techniques therefore seems necessary to deduce the need for future education and training.</AbstractText>In this study an online survey was created to evaluate the experience and the favored prehospital treatment of tension pneumothorax in children among German emergency physicians.</AbstractText>An online survey was conducted with 43&#xa0;questions on previous experience with tension pneumothorax in children, favored decompression technique and anatomical structures in different age groups. Surveyed were the emergency physicians of the ground-based emergency medical service of the University Medical Center Mannheim, the German Air Rescue Service (DRF) and the pediatric emergency medical service of the City of Munich.</AbstractText>More than half of all respondents stated that there was uncertainty about the procedure of choice. Needle decompression was favored in smaller children and mini-thoracostomy in older children. In comparison with the literature, the thickness of the chest wall was mostly estimated correctly by the emergency medical physicians. The depth of the vital structures was underestimated at most of the possible insertion sites in all age groups. At the lateral insertion sites on the left hemithorax, however, the distance to the left ventricle was overestimated. The caliber of the needle selected for decompression tended to be too large, especially in younger children.</AbstractText>Even though having interviewed an experienced group of prehospital emergency physicians, the experience in decompression of tension pneumothorax in children is relatively scant. Knowledge of chest wall thickness and depth to vital structures is sufficient, the choice of needle calibers tends to be too large but still reasonable. For many providers a&#xa0;large amount of uncertainty about the right choice of technique and equipment arises from the challenge of decompressing a&#xa0;tension pneumothorax in children and therefore further theoretical education and regular training are required for safe performance of the procedure.</AbstractText>&#xa9; 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.</CopyrightInformation>
2,331,767
Long lasting effects of early temperature exposure on the swimming performance and skeleton development of metamorphosing Gilthead seabream (Sparus aurata L.) larvae.
Temperatures experienced during early ontogeny significantly influence fish phenotypes, with clear consequences for the wild and reared stocks. We examined the effect of temperature (17, 20, or 23&#xa0;&#xb0;C) during the short embryonic and yolk-sac larval period, on the swimming performance and skeleton of metamorphosing Gilthead seabream larvae. In the following ontogenetic period, all fish were subjected to common temperature (20&#xa0;&#xb0;C). The critical swimming speed of metamorphosing larvae was significantly decreased from 9.7&#x2009;&#xb1;&#x2009;0.6 TL/s (total length per second) at 17&#xa0;&#xb0;C developmental temperature (DT) to 8.7&#x2009;&#xb1;&#x2009;0.6 and 8.8&#x2009;&#xb1;&#x2009;0.7 TL/s at 20 and 23&#xa0;&#xb0;C DT respectively (p&#x2009;&lt;&#x2009;0.05). Swimming performance was significantly correlated with fish body shape (p&#x2009;&lt;&#x2009;0.05). Compared with the rest groups, fish of 17&#xa0;&#xb0;C DT presented a slender body shape, longer caudal peduncle, terminal mouth and ventrally transposed pectoral fins. Moreover, DT significantly affected the relative depth of heart ventricle (VD/TL<sub>,</sub> p&#x2009;&lt;&#x2009;0.05), which was comparatively increased at 17&#xa0;&#xb0;C DT. Finally, the incidence of caudal-fin abnormalities significantly decreased (p&#x2009;&lt;&#x2009;0.05) with the increase of DT. To our knowledge, this is the first evidence for the significant effect of DT during the short embryonic and yolk-sac larval period on the swimming performance of the later stages.
2,331,768
Recovery of the brain after intraventricular hemorrhage.
Intraventricular hemorrhage (IVH) remains a major complication of prematurity, worldwide. The severity of IVH is variable, ranging from a tiny germinal matrix bleed to a moderate-to-large ventricular hemorrhage or periventricular hemorrhagic infarction. Survivors with IVH often suffer from hydrocephalus and white matter injury. There is no tangible treatment to prevent post-hemorrhagic cerebral palsy, cognitive deficits, or hydrocephalus in these infants. White matter injury is attributed to blood-induced damage to axons and maturing oligodendrocyte precursors, resulting in reduced myelination and axonal loss. Hydrocephalus results from obstructed CSF circulation by blood clots, increased CSF production, and reduced CSF absorption by lymphatics and arachnoid villi. Several strategies to promote neurological recovery have shown promise in animal models, including the elimination of blood and blood products, alleviating cerebral inflammation and oxidative stress, as well as promoting survival and maturation of oligodendrocyte precursors. The present review integrates novel mechanisms of brain injury in IVH and the imminent therapies to alleviate post-hemorrhagic white matter injury and hydrocephalus in the survivors with IVH.
2,331,769
A longitudinal observation of brain structure between AD and FTLD.
Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are the leading causes of dementia. To better understand the disease development of cognitive function and anatomical structure in AD and FTLD, we analyzed the changes in brain volume by MRI and the psychological test results. Here, we report a dynamic observation of brain structure.</AbstractText>Thirteen patients diagnosed with probable AD by the 2011 NIA-AA criteria and eight FTLD patients diagnosed by the FTLD criteria underwent MRI at baseline. All subjects were rescanned after 5 months to 3 years of follow-up. The anatomic changes on T1-weighted imaging of each subject were measured, and the separate changes in the two groups and the differences in the changes between AD and FTLD were analyzed.</AbstractText>In AD patients, the anterior and posterior horns of the lateral ventricle and lateral fissure enlarged progressively (p&#xa0;&lt;&#xa0;0.001). The volume of the regions, including the medial and lateral temporal lobe, especially the parahippocampal gyrus, and the frontal lobe decreased significantly as the disease progressed (p&#xa0;&lt;&#xa0;0.001). Additionally, the volume of white matter in the frontal, parietal, temporal lobe and cerebellum decreased in a relatively symmetric pattern (p&#xa0;&lt;&#xa0;0.001). In FTLD patients, the anterior horn of the lateral ventricle, lateral fissure, cerebral longitudinal fissure, external space of the orbitofrontal cortex, and mesencephalon surrounding the cisterna were enlarged (p&#xa0;&lt;&#xa0;0.005), while regions including the left frontal lobe, anterior cingulate cortex, basal ganglia (especially the left basal ganglia), left lateral temporal lobe and inferior cerebellar vermis decreased as the disease progressed (p&#xa0;&lt;&#xa0;0.005). Regarding the differences between AD and FTLD, atrophy of the frontal lobe and bilateral basal ganglia was more significant in FTLD than in AD (p&#xa0;&lt;&#xa0;0.01). In addition, enlargements of the anterior horn of the lateral ventricle, left lateral fissure and interpeduncular cistern were more significant in FTLD patients than in AD patients (p &lt;&#xa0;0.01).</AbstractText>These findings suggest that AD and FTLD have distinctly different atrophy patterns: AD patients show diffuse atrophy while FTLD patients show an asymmetrical focal atrophy pattern, which might explain the relatively better and longer preservation of daily living function in FTLD patients.</AbstractText>Copyright &#xa9; 2021 Elsevier B.V. All rights reserved.</CopyrightInformation>
2,331,770
Growth in Children with a Fontan Circulation.
To evaluate growth in a population of patients with Fontan circulation.</AbstractText>We performed a cross-sectional evaluation of patients followed in our multidisciplinary Fontan clinic from January 2011 through August 2015. We reviewed the historical data, anthropometry, clinical, and laboratory studies and performed bivariate and multivariate analysis of factors associated with height z score.</AbstractText>Patients (n&#xa0;=&#xa0;210) were included in the study at median age 11.07&#xa0;years (8.3, 14.73&#xa0;years) (43% female); 138 (65%) had a dominant right systemic ventricle and 92 (44%) hypoplastic left heart syndrome. Median age at completion of Fontan circulation was 31&#xa0;months (7.6, 135.8&#xa0;months). Median height z score was -0.58 (-1.75, 0.26). Twenty-five (12%) had current or past history of protein-losing enteropathy (PLE). Median height z score for those with current or past history of PLE was -2.1 (-2.46, 1.24). Multivariate analysis revealed positive associations between height z score and body mass index z score, time since Fontan, mid-parental height, dominant systemic ventricle type, and serum alkaline phosphatase. Height correlated negatively with known genetic syndrome, PLE, use of stimulant or oral steroid medication.</AbstractText>Children with Fontan circulation have mild deficits in height, with greater deficits in those with PLE. Height z score improves with time postsurgery. Improving weight, leading to improved body mass index, may be a modifiable factor that improves growth in those who are underweight. Biochemical markers may be helpful screening tests for high-risk groups in whom to intensify interventions.</AbstractText>Copyright &#xa9; 2021 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,331,771
Bioinspired Theranostic Coordination Polymer Nanoparticles for Intranasal Dopamine Replacement in Parkinson's Disease.
Dopamine (DA) is one of the main neurotransmitters found in the central nervous system and has a vital role in the function of dopaminergic (DArgic) neurons. A progressive loss of this specific subset of cells is one of the hallmarks of age-related neurodegenerative disorders such as Parkinson's disease (PD). Symptomatic therapy for PD has been centered in the precursor l-DOPA administration, an amino acid precursor of DA that crosses the blood-brain barrier (BBB) while DA does not, although this approach presents medium- to long-term side effects. To overcome this limitation, DA-nanoencapsulation therapies are actively being searched as an alternative for DA replacement. However, overcoming the low yield of encapsulation and/or poor biodistribution/bioavailability of DA is still a current challenge. Herein, we report the synthesis of a family of neuromelanin bioinspired polymeric nanoparticles. Our system is based on the encapsulation of DA within nanoparticles through its reversible coordination complexation to iron metal nodes polymerized with a bis-imidazol ligand. Our methodology, in addition to being simple and inexpensive, results in DA loading efficiencies of up to 60%. <i>In vitro</i>, DA nanoscale coordination polymers (DA-NCPs) exhibited lower toxicity, degradation kinetics, and enhanced uptake by BE(2)-M17 DArgic cells compared to free DA. Direct infusion of the particles in the ventricle of rats <i>in vivo</i> showed a rapid distribution within the brain of healthy rats, leading to an increase in striatal DA levels. More importantly, after 4 days of nasal administrations with DA-NCPs equivalent to 200 &#x3bc;g of the free drug per day, the number and duration of apomorphine-induced rotations was significantly lower from that in either vehicle or DA-treated rats performed for comparison purposes. Overall, this study demonstrates the advantages of using nanostructured DA for DA-replacement therapy.
2,331,772
Recurrent pheochromocytoma with catecholamine cardiomyopathy and left ventricular thrombus: a case report.
Pheochromocytoma is a rare and usually benign tumor of the adrenal glands. We report a case of a 40-year-old woman with recurrent pheochromocytoma and catecholamine cardiomyopathy. She had no history of other types of tumors or connective tissue disease. She had already undergone surgery twice to remove the pheochromocytoma, which had now recurred for the second time. A thrombus in the left ventricle was also noted upon imaging examination, which dissipated after anticoagulation therapy using dabigatran, allowing the patient to opt for an elective third surgery. This paper describes the clinical outcome of using the anticoagulant dabigatran to treat left ventricular thrombosis in this rare case of recurrent pheochromocytoma, and thus further contributing to the knowledge of the clinical management of this rare and complicated disease.
2,331,773
Glomerular Filtration Dysfunction is Associated with Cardiac Adverse Remodeling in Menopausal Diabetic Chinese Women.
Previous studies have showed that nephropathy was associated with cardiac structural changes and dysfunction among diabetic adults. However, information on the association of glomerular filtration dysfunction with the cardiac adverse remodeling is still limited in menopausal diabetic women. Therefore, we investigated whether impaired glomerular filtration function is associated with the cardiac adverse remodeling in menopausal Chinese women with type 2 diabetes mellitus (DM).</AbstractText>A total of 1231 hospitalized menopausal Chinese women with type 2 DM were collected retrospectively. The cross-sectional data of echocardiography were compared among estimated glomerular filtration rate (eGFR) categorized groups.</AbstractText>In menopausal diabetic women, moderate to severe glomerular filtration dysfunction (eGFR &lt;60 mL/min per 1.73m2</sup>) was found to be associated with enlarged left-side atrioventricular chambers, increased ventricular wall thickness, decreased cardiac function and dilated right ventricle (All P</i> &lt; 0.05).</AbstractText>Glomerular filtration dysfunction is associated with cardiac adverse structural remodeling and dysfunction in menopausal Chinese women with type 2 DM.</AbstractText>&#xa9; 2021 Song et al.</CopyrightInformation>
2,331,774
MRI characteristics of syringomyelia associated with foramen magnum arachnoiditis: differentiation from Chiari malformation.
It is important to distinguish foramen magnum arachnoiditis (FMA) from Chiari malformation (CM) before surgery because the operative strategies for these diseases differ. In the current study, we compared pretreatment magnetic resonance imaging (MRI) of FMA with CM and investigated the MRI findings useful to differentiate between these diseases.</AbstractText>We retrospectively reviewed patients with FMA or CM aged&#x2009;&#x2265;&#x2009;18&#xa0;years who underwent surgeries at our institution between 2007 and 2019. The morphologies of the syrinx, neural elements, and posterior cranial fossa were preoperatively evaluated with MRI. We used the receiver operating characteristic (ROC) curve for the fourth ventricle-to-syrinx distance (FVSD).</AbstractText>Ten patients with FMAs and 179 with CMs were included. FVSD in the FMA group was significantly shorter than that in the CM group (7.5&#xa0;mm [IQR, 2.8-10&#xa0;mm] in FMA vs. 29.9&#xa0;mm [IQR, 16.3-52.9&#xa0;mm] in CM, p&#x2009;&lt;&#x2009;0.0001). The other MRI findings that showed the height, size, and length of the syrinx; size of the foramen magnum; degree of cerebellar tonsillar descent; shape of the cerebellar tonsil; and dorsal subarachnoid space at the foramen magnum differed significantly between the two groups. The ROC curve analysis showed that patients whose FVSD was less than 11&#xa0;mm could be diagnosed with FMA with a specificity of 90% and sensitivity of 96%.</AbstractText>A more cranial syrinx development (FVSD&#x2009;&lt;&#x2009;11&#xa0;mm) appears to be the characteristic MRI finding in FMA.</AbstractText>
2,331,775
Surgical management of a rare myxopapillary ependymoma of the gluteal region: A case report.
Ependymomas are rare tumors originating from neuroepithelial cells lining the wall of the ventricles or central canal of the spinal cord. While these tumors mainly occur within the central nervous system (CNS), there are occasional reports in children and young adult patients with a primary tumor occurrence outside of the CNS. Ependymomas of the sacrococcygeal region have been infrequently described in the literature with no standard of care established. We present a case report and review of the literature regarding this rare entity.</AbstractText>A 24-year-old woman presented with right gluteal pain worsened by sitting and a palpable soft tissue mass of the sacrococcygeal region. Magnetic resonance imaging revealed a 3.7 cm cystic mass centered in the right gluteal region. She underwent a biopsy at an outside institution, with histology revealing myxopapillary ependymoma. The patient was referred to our hospital and underwent an interdisciplinary neurosurgical and orthopedic oncology en bloc resection of the ependymoma, which intraoperatively appeared to originate from the coccygeal nerve.</AbstractText>In the present report, the authors demonstrate that a myxopapillary ependymoma may present as an isolated gluteal mass attached to the coccygeal nerve, without frank CNS involvement. Furthermore, an interdisciplinary approach to surgical resection of this lesion appears to represent an effective treatment modality.</AbstractText>Copyright: &#xa9; 2021 Surgical Neurology International.</CopyrightInformation>
2,331,776
Interhemispheric arachnoid cyst.
Interhemispheric arachnoid cysts are uncommon and typically associated with other midline neurodevelopmental disorders, such as complete or partial agenesis of the corpus callosum.</AbstractText>We report a case of a 27-year-old woman with worsening headache, memory deficit, and radiological progression of an interhemispheric arachnoid cyst. The treatment consisted of craniotomy for interhemispheric cyst fenestration into both the interhemispheric cistern and lateral ventricle. The postoperative course was unremarkable, with considerable clinical improvement and significant reduction in cyst size.</AbstractText>We successfully treat a patient with an enlarging arachnoid cyst and associated progressive symptoms with microsurgical fenestration.</AbstractText>Copyright: &#xa9; 2021 Surgical Neurology International.</CopyrightInformation>
2,331,777
Hydrocephalus in Mexican children with Coccidioidal Meningitis: Clinical, serological, and neuroimaging findings.
Coccidioidal meningitis (CM) is a fungal infectious disease that rarely affects children. Even in endemic areas, coccidiomycosis rarely affects the pediatric population. However, 40% of affected children develop hydrocephalus. Here, we describe the clinical, serological, and neuroimaging findings in a series of Mexican children admitted to our neurosurgical service with hydrocephalus and subsequently diagnosed with CM.</AbstractText>We report a prospective series of pediatric patients with hydrocephalus secondary to CM in an endemic area at the north of Mexico. Our report includes children with CM who were hospitalized from 2015 to 2019 in a regional hospital in Torre&#xf3;n, Coahuila. Clinical evolution was monitored for 1 year after hospital discharge.</AbstractText>Our series include five children with CM (2-17-years-old, three female), who were hospitalized for hydrocephalus and developed intracranial hypertension. The most frequent neuroimaging findings were leptomeningeal enhancement (5/5) and basal arachnoiditis (4/5), followed by asymmetric hydrocephalus (3/5), abnormalities in fourth ventricle morphology (3/5), and cerebral vasculitis (2/5). CM was diagnosed by positive serology or pathology studies. All children were initially managed with fluconazole and a shunt was placed for management of hydrocephalus. Four patients recovered without permanent neurological deficits and one subject developed persistent vegetative state. One year after hospital discharge, none of the subjects died.</AbstractText>This series contributes to the limited number of pediatric CM cases reported in the literature, and describes neuroimaging findings in the pediatric population. The cases here presented show that the identification of Coccidioides</i> as causal agent in pediatric meningitis is crucial for targeted treatment and can affect dramatically neurological prognosis. Furthermore, our report stresses that even in endemic areas pediatric coccidiomycosis represents a diagnostic challenge, which is further exacerbated by the limited availability of resources in these regions. Therefore, a positive immunoglobulin G by enzyme immunoassay is enough for diagnosis of CM in endemic areas without access to CF.</AbstractText>Copyright: &#xa9; 2021 Surgical Neurology International.</CopyrightInformation>
2,331,778
Central administration of sodium-glucose cotransporter-2 inhibitors increases food intake involving adenosine monophosphate-activated protein kinase phosphorylation in the lateral hypothalamus in healthy rats.
Sodium glucose cotransporter-2 (SGLT2) inhibitors are widely used for diabetes treatment. Although SGLT2 inhibitors have been clinically observed to increase food intake, roles or even the presence of SGLT2 in the central nervous system (CNS) has not been established. We aimed to elucidate potential functions of SGLT2 in the CNS, and the effects of CNS-targeted SGLT2 inhibitors on food intake.</AbstractText>We administered three kinds of SGLT2 inhibitors, tofogliflozin, dapagliflozin, and empagliflozin, into the lateral ventricle (LV) in rats and evaluated their effects on food intake. We also evaluated the effects of tofogliflozin administration in the third (3V) and fourth ventricle (4V). Intraperitoneal administration of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist known to suppress food intake, was combined with central tofogliflozin to elucidate whether GLP-1 signaling antagonizes the effect of central SGLT2 inhibitors on food intake. To elucidate potential molecular mechanisms mediating changes in feeding, hypothalamic areas associated with food intake regulation were harvested and analyzed after intracerebroventricular administration (ICV) of tofogliflozin.</AbstractText>Bolus ICV injection of tofogliflozin induced a robust increase in food intake starting at 1.5&#x2009;hours postinjection, and lasting for 5&#x2009;days. No effect was observed when the same dose of tofogliflozin was administered intraperitoneally. ICV dapagliflozin and empagliflozin significantly enhanced food intake, although the strength of these effects varied among drugs. Food intake was most markedly enhanced when tofogliflozin was infused into the LV. Fewer or no effects were observed with infusion into the 3V or 4V, respectively. Systemic administration of liraglutide suppressed the effect of ICV tofogliflozin on food intake. ICV tofogliflozin increased phosphorylation of AMPK and c-fos expression in the lateral hypothalamus.</AbstractText>SGLT2 inhibitors in the CNS increase food intake. SGLT2 activity in the CNS may regulate food intake through AMPK phosphorylation in the lateral hypothalamic area.</AbstractText>&#xa9; Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation>
2,331,779
Restrictive diet in a patient with irritable bowel syndrome leading to Wernicke encephalopathy.
We present a case of a woman with a past medical history of irritable bowel syndrome (IBS) and anxiety, who presents with ophthalmoplegia, ataxia and memory loss, characteristic of Wernicke encephalopathy.</AbstractText>A 64-year-old woman presented with double vision, unsteady gait and memory loss. These symptoms began after 3&#xa0;months on an unfortified restricted diet, which she initiated to alleviate IBS symptoms. Magnetic resonance imaging of the brain demonstrated hyperintense T2-weighted signal in the dorsomedial aspect of bilateral thalami, periaqueductal grey matter and around the third ventricle. The patient's visual symptoms improved significantly after thiamine supplementation, although her memory deficits persisted.</AbstractText>Although WE is often associated with chronic alcohol abuse, this case demonstrates the importance of recognizing WE in any patient with a restricted diet and subsequent timely initiation of thiamine.</AbstractText>
2,331,780
A 16-year study of longitudinal volumetric brain development in males with autism.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unknown brain etiology. Our knowledge to date about structural brain development across the lifespan in ASD comes mainly from cross-sectional studies, thereby limiting our understanding of true age effects within individuals with the disorder that can only be gained through longitudinal research. The present study describes FreeSurfer-derived volumetric findings from a longitudinal dataset consisting of 607 T1-weighted magnetic resonance imaging (MRI) scans collected from 105 male individuals with ASD (349 MRIs) and 125 typically developing male controls (258 MRIs). Participants were six to forty-five years of age at their first scan, and were scanned up to 5 times over a period of 16 years (average inter-scan interval of 3.7 years). Atypical age-related volumetric trajectories in ASD included enlarged gray matter volume in early childhood that approached levels of the control group by late childhood, an age-related increase in ventricle volume resulting in enlarged ventricles by early adulthood and reduced corpus callosum age-related volumetric increase resulting in smaller corpus callosum volume in adulthood. Larger corpus callosum volume was related to a lower (better) ADOS score at the most recent study visit for the participants with ASD. These longitudinal findings expand our knowledge of volumetric brain-based abnormalities in males with ASD, and highlight the need to continue to examine brain structure across the lifespan and well into adulthood.
2,331,781
Fully Automatic Scar Segmentation for Late Gadolinium Enhancement MRI Images in Left Ventricle with Myocardial Infarction.
Numerous methods have been published to segment the infarct tissue in the left ventricle, most of them either need manual work, post-processing, or suffer from poor reproducibility. We proposed an automatic segmentation method for segmenting the infarct tissue in left ventricle with myocardial infarction. Cardiac images of a total of 60 diseased hearts (55 human hearts and 5 porcine hearts) were used in this study. The epicardial and endocardial boundaries of the ventricles in every 2D slice of the cardiac magnetic resonance with late gadolinium enhancement images were manually segmented. The subsequent pipeline of infarct tissue segmentation is fully automatic. The segmentation results with the automatic algorithm proposed in this paper were compared to the consensus ground truth. The median of Dice overlap between our automatic method and the consensus ground truth is 0.79. We also compared the automatic method with the consensus ground truth using different image sources from different centers with different scan parameters and different scan machines. The results showed that the Dice overlap with the public dataset was 0.83, and the overall Dice overlap was 0.79. The results show that our method is robust with respect to different MRI image sources, which were scanned by different centers with different image collection parameters. The segmentation accuracy we obtained is comparable to or better than that of the conventional semi-automatic methods. Our segmentation method may be useful for processing large amount of dataset in clinic.
2,331,782
Height Versus Body Surface Area to Normalize Cardiovascular Measurements in Children Using the Pediatric Heart Network Echocardiographic Z-Score Database.
Normalizing cardiovascular measurements for body size allows for comparison among children of different ages and for distinguishing pathologic changes from normal physiologic growth. Because of growing interest to use height for normalization, the aim of this study was to develop height-based normalization models and compare them to body surface area (BSA)-based normalization for aortic and left ventricular (LV) measurements. The study population consisted of healthy, non-obese children between 2 and 18&#xa0;years of age enrolled in the Pediatric Heart Network Echo Z-Score Project. The echocardiographic study parameters included proximal aortic diameters at 3 locations, LV end-diastolic volume, and LV mass. Using the statistical methodology described in the original project, Z-scores based on height and BSA were determined for the study parameters and tested for any clinically significant relationships with age, sex, race, ethnicity, and body mass index (BMI). Normalization models based on height versus BSA were compared among underweight, normal weight, and overweight (but not obese) children in the study population. Z-scores based on height and BSA were calculated for the 5 study parameters and revealed no clinically significant relationships with age, sex, race, and ethnicity. Normalization based on height resulted in lower Z-scores in the underweight group compared to the overweight group, whereas normalization based on BSA resulted in higher Z-scores in the underweight group compared to the overweight group. In other words, increasing BMI had an opposite effect on height-based Z-scores compared to BSA-based Z-scores. Allometric normalization based on height and BSA for aortic and LV sizes is feasible. However, height-based normalization results in higher cardiovascular Z-scores in heavier children, and BSA-based normalization results in higher cardiovascular Z-scores in lighter children. Further studies are needed to assess the performance of these approaches in obese children with or without cardiac disease.
2,331,783
Collagen quantification in the ventricular walls of the heart of the common marmoset (Callithrix jacchus).
The excellent adaptability of Callithrix jacchus to life in captivity presents advantages in comparison to other nonhuman primates that are used in experimental models for biomedical research, which explains the increasing scientific interest in investigating the anatomical characteristics of this species. Owing to the relative scarcity of publications on the descriptive morphology of the heart of C. jacchus, the aim of this study was to quantify the presence of collagen in the left and right ventricular myocardium using modified picrosirius red and acid fuchsine colorimetric assays. The myocardium of the right ventricle presented a higher percentage of collagen than that of the left ventricle. No sex-related differences were observed between the groups. Interestingly, the absolute values of collagen were different depending on the method used for quantification (modified picrosirius red vs. acid fuchsine). The level of collagen quantification observed in the ventricular myocardium of C. jacchus was similar to that seen in other nonhuman primates traditionally used in experimental models of cardiac diseases.
2,331,784
Surface-in pathology in multiple sclerosis: a new view on pathogenesis?
While multiple sclerosis can affect any part of the CNS, it does not do so evenly. In white matter it has long been recognized that lesions tend to occur around the ventricles, and grey matter lesions mainly accrue in the outermost (subpial) cortex. In cortical grey matter, neuronal loss is greater in the outermost layers. This cortical gradient has been replicated in vivo with magnetization transfer ratio and similar gradients in grey and white matter magnetization transfer ratio are seen around the ventricles, with the most severe abnormalities abutting the ventricular surface. The cause of these gradients remains uncertain, though soluble factors released from meningeal inflammation into the CSF has the most supporting evidence. In this Update, we review this 'surface-in' spatial distribution of multiple sclerosis abnormalities and consider the implications for understanding pathogenic mechanisms and treatments designed to slow or stop them.
2,331,785
Pulmonary arterial hypertension induces the release of circulating extracellular vesicles with oxidative content and alters redox and mitochondrial homeostasis in the brains of rats.
Pulmonary arterial hypertension (PAH) is characterized by increased resistance of the pulmonary vasculature and afterload imposed on the right ventricle (RV). Two major contributors to the worsening of this disease are oxidative stress and mitochondrial impairment. This study aimed to explore the effects of monocrotaline (MCT)-induced PAH on redox and mitochondrial homeostasis in the RV and brain and how circulating extracellular vesicle (EV) signaling is related to these phenomena. Wistar rats were divided into control and MCT groups (60&#x2009;mg/kg, intraperitoneal), and EVs were isolated from blood on the day of euthanasia (21 days after MCT injections). There was an oxidative imbalance in the RV, brain, and EVs of MCT rats. PAH impaired mitochondrial function in the RV, as seen by a decrease in the activities of mitochondrial complex II and citrate synthase and manganese superoxide dismutase (MnSOD) protein expression, but this function was preserved in the brain. The key regulators of mitochondrial biogenesis, namely, proliferator-activated receptor gamma coactivator 1-alpha and sirtuin 1, were poorly expressed in the EVs of MCT rats, and this result was positively correlated with MnSOD expression in the RV and negatively correlated with MnSOD expression in the brain. Based on these findings, we can conclude that the RV is severely impacted by the development of PAH, but this pathological injury may signal the release of circulating EVs that communicate with different organs, such as the brain, helping to prevent further damage through the upregulation of proteins involved in redox and mitochondrial function.
2,331,786
Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia.
Idiopathic normal pressure hydrocephalus (iNPH) is considered an age-dependent chronic communicating hydrocephalus associated with cerebrospinal fluid (CSF) malabsorption; however, the aetiology of ventricular enlargement in iNPH has not yet been elucidated. There is accumulating evidence that support the hypothesis that various alterations in CSF dynamics contribute to ventricle dilatation in iNPH. This review focuses on CSF dynamics associated with ventriculomegaly and summarises the current literature based on three potential aetiology factors: genetic, environmental and hydrodynamic. The majority of gene mutations that cause communicating hydrocephalus were associated with an abnormal structure or dysfunction of motile cilia on the ventricular ependymal cells. Aging, alcohol consumption, sleep apnoea, diabetes and hypertension are candidates for the risk of developing iNPH, although there is no prospective cohort study to investigate the risk factors for iNPH. Alcohol intake may be associated with the dysfunction of ependymal cilia and sustained high CSF sugar concentration due to uncontrolled diabetes increases the fluid viscosity which in turn increases the shear stress on the ventricular wall surface. Sleep apnoea, diabetes and hypertension are known to be associated with the impairment of CSF and interstitial fluid exchange. Oscillatory shear stress to the ventricle wall surfaces is considerably increased by reciprocating bidirectional CSF movements in iNPH. Increased oscillatory shear stress impedes normal cilia beating, leading to motile cilia shedding from the ependymal cells. At the lack of ciliary protection, the ventricular wall is directly exposed to increased oscillatory shear stress. Additionally, increased oscillatory shear stress may be involved in activating the flow-mediated dilation signalling of the ventricular wall. In conclusion, as the CSF stroke volume at the cerebral aqueduct increases, the oscillatory shear stress increases, promoting motor cilia shedding and loss of ependymal cell coverage. These are considered to be the leading causes of ventricular enlargement in iNPH.
2,331,787
Neuroprotective effects of dexpanthenol on streptozotocin-induced neuronal damage in rats.
Although the most common age-related neurodegenerative disease defined by memory loss is Alzheimer's disease (AD), only symptomatic therapies are present. A complex pathway for the AD pathogenesis that includes an increase in inflammation has recently been suggested. Since in previous animal experiments dexpanthenol has anti-inflammatory and neuroprotective activities, effects and role of dexpanthenol in an intracerebroventricular (ICV)-streptozotocin (STZ) induced sporadic-AD(memory impairment) animal model have been examined.</AbstractText>In total, 18 adult sprague-dawley rats were classified into 3 groups; control (n</i>&#x2009;=&#x2009;6), STZ&#x2009;+&#x2009;Saline (n</i>&#x2009;=&#x2009;6) and STZ&#x2009;+&#x2009;Dexpanthenol (n</i>&#x2009;=&#x2009;6). Twelve AD-induced rats through STZ-injection (3&#x2009;mg/kg) into both lateral ventricles via stereotaxy were separated into two groups five days after STZ administration: one of these groups was treated with dexpanthenol (1000&#x2009;mg/kg/day, i.p.) for 3&#x2009;weeks and the other with saline. A passive avoidance learning (PAL) test was used after treatment, followed by brain tissue extraction in all subjects. Brain levels of tumor necrosis factor-alpha (TNF-&#x3b1;) and choline acetyl transferase (ChAT) were measured and Cresyl violet staining was used to count neurons in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3).</AbstractText>It was observed that ICV-STZ significantly shortened PAL latency, increased levels of TNF-&#x3b1; in brain, decreased activity of ChAT in brain, and number of hippocampal neurons. However, dexpanthenol significantly reduced all of those STZ-induced harmful effects.</AbstractText>Dexpanthenol significantly prevented the memory deficit induced by ICV-STZ through mitigating neuronal loss in hippocampus, cholinergic deficiency and neuroinflammation in rats. These findings suggest that dexpanthenol may be beneficial for treating memory impairment.</AbstractText>
2,331,788
As above, so below: Whole transcriptome profiling demonstrates strong molecular similarities between avian dorsal and ventral pallial subdivisions.
Over the last two decades, beginning with the Avian Brain Nomenclature Forum in 2000, major revisions have been made to our understanding of the organization and nomenclature of the avian brain. However, there are still unresolved questions on avian pallial organization, particularly whether the cells above the vestigial ventricle represent distinct populations to those below it or similar populations. To test these two hypotheses, we profiled the transcriptomes of the major avian pallial subdivisions dorsal and ventral to the vestigial ventricle boundary using RNA sequencing and a new zebra finch genome assembly containing about 22,000 annotated, complete genes. We found that the transcriptomes of neural populations above and below the ventricle were remarkably similar. Each subdivision in dorsal pallium (Wulst) had a corresponding molecular counterpart in the ventral pallium (dorsal ventricular ridge). In turn, each corresponding subdivision exhibited shared gene co-expression modules that contained gene sets enriched in functional specializations, such as anatomical structure development, synaptic transmission, signaling, and neurogenesis. These findings are more in line with the continuum hypothesis of avian brain subdivision organization above and below the vestigial ventricle space, with the pallium as a whole consisting of four major cell populations (intercalated pallium, mesopallium, hyper-nidopallium, and arcopallium) instead of seven (hyperpallium apicale, interstitial hyperpallium apicale, intercalated hyperpallium, hyperpallium densocellare, mesopallium, nidopallium, and arcopallium). We suggest adopting a more streamlined hierarchical naming system that reflects the robust similarities in gene expression, neural connectivity motifs, and function. These findings have important implications for our understanding of overall vertebrate brain evolution.
2,331,789
Central nervous system lesions caused by canine distemper virus in 4 vaccinated dogs.
We examined the cerebellum and cerebrum of 4 vaccinated dogs, 3-60-mo-old, that displayed clinical signs of canine distemper virus (CDV) infection, and died 7-40&#x2009;d after developing neurologic signs. The main histologic lesions were demyelination, gliosis, meningitis, perivascular lymphocytic cuffing, and inclusion bodies. These lesions were similar in all 4 cases regardless of the time since vaccination, except that meningoencephalitis and gliosis were subacute in 3 dogs and chronic in 1 dog. However, these differences did not appear to be related to their vaccination status. Immunohistologically, a CDV-positive immunoreaction was seen mainly in astrocytes, neurons and their axons, lymphocytes around and in the blood vessels of the pia mater and choroid plexus, ependymal cells of each ventricle, and the cells of the choroid plexus. The histologic and immunohistologic changes were similar in the cerebellum and cerebrum. The genetic characterization of the virus strains in 2 of these naturally occurring canine distemper cases confirmed that they were South American wild-type strains (Kiki and Uy251) belonging to the EU1/SA1 lineage. These strains are not included in the commercial CDV vaccines available in Uruguay.
2,331,790
Smyd1 Orchestrates Early Heart Development Through Positive and Negative Gene Regulation.
SET and MYND domain-containing protein 1 (Smyd1) is a striated muscle-specific histone methyltransferase. Our previous work demonstrated that deletion of Smyd1 in either cardiomyocytes or the outflow tract (OFT) resulted in embryonic lethality at E9.5, with cardiac structural defects such as truncation of the OFT and right ventricle and impaired expansion and proliferation of the second heart field (SHF). The cardiac phenotype was accompanied by the downregulation of ISL LIM Homeobox 1 (Isl1) and upregulation of atrial natriuretic factor (ANF). However, the mechanisms of Smyd1 regulating Isl1 and ANF during embryonic heart development remain to be elucidated. Here, we employed various biochemical and molecular biological approaches including chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR), pGL3 fluorescence reporter system, and co-immunoprecipitation (CoIP) and found that Smyd1 interacted with absent small homeotic-2-like protein (ASH2L) and activated the promoter of Isl1 by trimethylating H3K4. We also found that Smyd1 associated with HDAC to repress ANF expression using trichostatin A (TSA), a deacetylase inhibitor. In conclusion, Smyd1 participates in early heart development by upregulating the expression of Isl1 and downregulating the expression of ANF.
2,331,791
Circulating biomarkers as predictors of left ventricular remodeling after myocardial infarction.
The main impact of myocardial infarction is shifting from acute mortality to adverse remodeling and chronic left ventricle dysfunction. Several circulating biomarkers are explored for better risk stratification of these patients. Biomarker testing is a very attractive idea, since it is non-invasive, not operator-dependent and widely available.</AbstractText>In the present paper we analyze data from the years 2005-2020 about circulating biomarkers of remodeling after myocardial infarction.</AbstractText>We assessed 53 articles, which examined 160 relations between biomarkers and remodeling. We analyze inclusion criteria for individual studies, time points of serum collection and remodeling assessment as well as imaging methods.</AbstractText>The main groups of assessed biomarkers included B-type natriuretic peptides, markers of cardiomyocyte injury and necrosis, markers of inflammatory response, markers of extracellular matrix turnover, microRNAs and hormones. The most common method of remodeling assessment was echocardiography and the most frequent time point for remodeling evaluation was 6 months.</AbstractText>The present analysis shows that although a relatively large number biomarkers were tested, selecting one ideal marker is still a challenge. A combination of biomarkers from different groups might be appropriate for predicting remodeling. Data presented in this analysis might be helpful for designing future studies, evaluating clinical use of an individual biomarker or a combination of different biomarkers.</AbstractText>Copyright: &#xa9; 2021 Termedia Sp. z o. o.</CopyrightInformation>
2,331,792
Primary Graft Dysfunction After Isolated Heart Transplantation&#x3000;- Incidence, Risk Factors, and Clinical Implications Based on a Single-Center Experience.
Since the international consensus on primary graft dysfunction (PGD) following heart transplantation (HT) was reported in 2014, few clinical studies have been reported. We aimed to analyze the incidence, predictive factors, and clinical implications of PGD following the International Society of Heart and Lung Transplant criteria in a single center.Methods&#x2004;and&#x2004;Results:This study enrolled 570 consecutive adult patients undergoing isolated HT between November 1992 and December 2017. Under a new set of criteria, PGD-left ventricle (PGD-LV) occurred in 35 patients (6.1%; mild, n=1 [0.2%]; moderate, n=14 [2.5%]; severe, n=20 [3.5%]), whereas PGD-right ventricle (PGD-RV) occurred in 3 (0.5%). Multivariable analysis demonstrated that preoperative admission (odds ratio [OR] 4.20; 95% confidence interval [CI] 1.24-14.26; P=0.021), preoperative extracorporeal membrane oxygenation (OR 4.03; 95% CI 1.75-9.26; P=0.001), and prolonged total ischemic time (OR 1.09; 95% CI 1.02-1.15; P=0.006) were significant predictors of moderate to severe PGD-LV. Moderate to severe PGD-LV was an independent and significant risk factor for early death (OR 55.64; 95% CI 11.65-265.73; P&lt;0.001), with its effects extending up to 3 months after HT.</AbstractText>Moderate to severe PGD-LV, as defined by the new guidelines, is an important predictor of early mortality, with effects extending up to 3 months after HT. Efforts to reduce the occurrence of moderate to severe PGD-LV may lead to better outcomes.</AbstractText>
2,331,793
Quantifying Right Ventricular Fibrosis Burden Using 3D Strain: Can Echo Approximate a Virtual Heart Biopsy?<Pagination><StartPage>1321</StartPage><EndPage>1323</EndPage><MedlinePgn>1321-1323</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jcmg.2021.02.017</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1936-878X(21)00196-0</ELocationID><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lang</LastName><ForeName>Roberto M</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA. Electronic address: rlang@medicine.bsd.uchicago.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Singh</LastName><ForeName>Amita</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016421">Editorial</PublicationType><PublicationType UI="D016420">Comment</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>04</Month><Day>14</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>JACC Cardiovasc Imaging</MedlineTA><NlmUniqueID>101467978</NlmUniqueID><ISSNLinking>1876-7591</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentOn"><RefSource>JACC Cardiovasc Imaging. 2021 Jul;14(7):1309-1320</RefSource><PMID Version="1">33744147</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D001706" MajorTopicYN="N">Biopsy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005355" MajorTopicYN="N">Fibrosis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006321" MajorTopicYN="Y">Heart</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="Y">Heart Ventricles</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011237" MajorTopicYN="N">Predictive Value of Tests</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">3D echocardiography</Keyword><Keyword MajorTopicYN="N">biopsy</Keyword><Keyword MajorTopicYN="N">fibrosis</Keyword><Keyword MajorTopicYN="N">right ventricle</Keyword></KeywordList><CoiStatement>Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>2</Month><Day>8</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>2</Month><Day>9</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>4</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>10</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>4</Month><Day>18</Day><Hour>20</Hour><Minute>35</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33865760</ArticleId><ArticleId IdType="doi">10.1016/j.jcmg.2021.02.017</ArticleId><ArticleId IdType="pii">S1936-878X(21)00196-0</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">33865608</PMID><DateRevised><Year>2021</Year><Month>05</Month><Day>27</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2173-5107</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year><Month>Apr</Month><Day>14</Day></PubDate></JournalIssue><Title>Radiologia</Title><ISOAbbreviation>Radiologia (Engl Ed)</ISOAbbreviation></Journal>Pulmonary artery obstruction index, pulmonary artery diameter and right ventricle strain as prognostic CT findings in patient with acute pulmonary embolism.
This study was designed to determine predictors of pulmonary hypertension and signs of right heart dysfunction caused by pulmonary embolism (PE) that may lead to early detection of high-risk patients. So the predictive value of pulmonary artery obstruction index (PAOI), measured by pulmonary CT angiography (PCTA) in the acute setting, in predicting the patients susceptible to PE cardiac complications was evaluated. Also two other PCTA indices, pulmonary artery diameter (PAD), and right ventricle (RV) strain, in these patients were investigated and their predictive value for cardiac complications on follow up echocardiography were demonstrated.</AbstractText>In the study 120 patients with a definite diagnosis of PE were included. The PAOI, PAD and RV strain were measured using PCTA at the time of the initial diagnosis. Transthoracic echocardiography was done 6 months after the diagnosis of PE and RV echocardiographic indices were measured. Pearson correlation was used to investigate correlation between PAOI, PAD, RV strain and signs of right heart dysfunction.</AbstractText>PAOI was strongly correlated with systolic pulmonary artery pressure (SPAP) (r=0.83), RV systolic pressure (r=0.78) and RV wall thickness (r=0.61) in long-term follow up echocardiography. A higher rate of RV dysfunction and RV dilation was detected among the patients with higher PAOI (P&lt;0.001). PAOI&#x2265;18 was strongly predictive for development of RV dysfunction. Also developments of pulmonary hypertension, RV systolic hypertension, RV dilation, RV dysfunction, and RV hypertrophy were significantly more common among patients with higher PAD and RV strain (P&lt;0.001).</AbstractText>PAOI, PAD and RV strain are sensitive and specific PCTA indices that can predict the development of long-term complications such as pulmonary hypertension and right heart dysfunction, at the time of initial PE diagnosis.</AbstractText>Copyright &#xa9; 2021 SERAM. Publicado por Elsevier Espa&#xf1;a, S.L.U. All rights reserved.</CopyrightInformation>
2,331,794
[Central neurocytomas: long-term treatment outcomes].
Central neurocytoma is a rare benign brain tumor. These tumors may be giant and accompanied by compression of ventricular system and surrounding structures. Modern treatment of brain neurocytoma includes extended resection and restoration of normal CSF circulation. Surgical treatment does not often lead to total resection of these tumors. Redo resection was preferred in patients with tumor progression for a long time. In the last decade, various authors report stereotactic irradiation for continued tumor growth to ensure local growth control. This study was aimed at evaluation of postoperative outcomes in patients with brain neurocytomas, as well as treatment of tumor progression in long-term period.</AbstractText>To analyze recurrence-free survival in patients with brain neurocytomas, risk factors of recurrence-free survival, effectiveness of various treatments for tumor progression and delayed complications.</AbstractText>Long-term postoperative follow-up data of patients with brain neurocytomas are reported in the manuscript. We analyzed recurrence-free survival and risk factors of recurrence-free survival, treatment outcomes in patients with progression of brain neurocytomas, long-term complications and their prevention.</AbstractText>Follow-up included 84 out of 115 patients with brain neurocytoma after surgical treatment in 2008-2017. Follow-up period ranged from 2 to 10 years (mean 6 years) after resection. Most patients had regression of neurological symptoms after surgery. Continued tumor growth within 12-96 months after surgery occurred in 26 (30.19%) out of 84 patients (19 cases after partial resection and 7 cases after total resection according to MRI data). Two-year recurrence-free survival was 94%, 5-year survival - 83%. Risk factors of continued tumor growth were resection quality and Ki-67 index. Redo resection was performed in 7 cases. Eleven patients underwent stereotactic irradiation for tumor progression. Indications for stereotactic irradiation of central neurocytoma are MR data on continued growth of lateral ventricle tumor without signs of ICH and CSF flow impairment. There were no cases of hemorrhage inside the residual tumor and CSF flow impairment in early postoperative period after redo resection. In all cases (n</i>=11), stereotactic irradiation (mean follow-up 2.5 years) ensured satisfactory control of tumor growth with reduction of the neoplasm in 4 cases and no tumor growth in 7 cases.</AbstractText>Resection of central neurocytoma ensures long-term recurrence-free period. The main causes of tumor recurrence are partial resection and high proliferative activity (Ki-67 index over 5%). Redo resection is advisable for tumor progression followed by CSF flow impairment. In case of continued growth of neurocytoma without signs of intracranial hypertension, stereotactic irradiation with various fractionation modes ensures effective and safe control of tumor growth.</AbstractText>
2,331,795
Heart-lung interactions in COVID-19: prognostic impact and usefulness of bedside echocardiography for monitoring of the right ventricle involvement.
Due to the SARS-CoV-2 infection-related severe pulmonary tissue damages associated with a relative specific widespread thrombotic microangiopathy, the pathophysiologic role of heart-lung interactions becomes crucial for the development and progression of right ventricular (RV) dysfunction. The high resistance in the pulmonary circulation, as a result of small vessel thrombosis and hypoxemia, is the major cause of right heart failure associated with a particularly high mortality in severe COVID-19. Timely identification of patients at high risk for RV failure, optimization of mechanical ventilation to limit its adverse effects on RV preload and afterload, avoidance of medication-related increase in the pulmonary vascular resistance, and the use of extracorporeal membrane oxygenation in refractory respiratory failure with hemodynamic instability, before RV failure develops, can improve patient survival. Since it was confirmed that the right-sided heart is particularly involved in the clinical deterioration of patients with COVID-19 and pressure overload-induced RV dysfunction plays a key role for patient outcome, transthoracic echocardiography (TTE) received increasing attention. Limited TTE focused on the right heart appears highly useful in hospitalized COVID-19 patients and particularly beneficial for monitoring of critically ill patients. In addition to detection of right-sided heart dilation and RV dysfunction, it enables assessment of RV-pulmonary arterial coupling and evaluation of RV adaptability to pressure loading which facilitate useful prognostic statements to be made. The increased use of bedside TTE focused on the right heart could facilitate more personalized management and treatment of hospitalized patients and can contribute towards reducing the high mortality associated with SARS-CoV-2 infection.
2,331,796
Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.
Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles&#xa0; and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated&#xa0;by BMI (Z&#x2009;=&#x2009;2.73, p&#x2009;=&#x2009;0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
2,331,797
Assessment of right ventricular reserve utilizing exercise provocation in systemic sclerosis.
Right ventricular (RV) capacity to adapt to increased afterload is the main determinant of outcome in pulmonary hypertension, a common morbidity seen in systemic sclerosis (SSc). We hypothesized that supine bicycle echocardiography (SBE), coupled with RV longitudinal systolic strain (RVLSS), improves detection of limitations in RV reserve in SSc. 56 SSc patients were prospectively studied during SBE with RV functional parameters compared at rest and peak stress. We further dichotomized patients based on resting RV systolic pressure (RVSP) to determine the effects of load on contractile response. Our pooled cohort analysis revealed reduced global RVLSS at rest (-16.2&#x2009;&#xb1;&#x2009;3.9%) with normal basal contractility (-25.6&#x2009;&#xb1;&#x2009;7.7%) and relative hypokinesis of the midventricular (-14.1&#x2009;&#xb1;&#x2009;6.0%) and apical (-8.9&#x2009;&#xb1;&#x2009;5.1%) segments. With exercise, global RVLSS increased significantly (p&#x2009;=&#x2009;0.0005), however despite normal basal contractility at rest, there was no further augmentation with exercise. Mid and apical RVLSS increased with exercise suggestive of RV contractile reserve. In patients with resting RVSP&#x2009;&lt;&#x2009;35&#xa0;mmHg, global and segmental RVLSS increased with exercise. In patients with resting RVSP&#x2009;&#x2265;&#x2009;35&#xa0;mmHg, global and segmental RVLSS did not increase with exercise and there was evidence of exertional RV dilation. Exercise provocation in conjunction with RVLSS identified differential regional contractile response to exercise in SSc patients. We further demonstrate the effect of increased loading conditions on RV contractile response exercise. These findings suggest subclinical impairments in RV reserve in SSc that may be missed by resting noninvasive 2DE-based assessments alone.
2,331,798
Intracerebroventricular Administration of AAV9-PHP.B SYN1-EmGFP Induces Widespread Transgene Expression in the Mouse and Monkey Central Nervous System.
Viral vectors made from adeno-associated virus (AAV) have emerged as preferred tools in basic and translational neuroscience research to introduce or modify genetic material in cells of interest. The use of viral vectors is particularly attractive in nontransgenic species, such as nonhuman primates. Injection of AAV solutions into the cerebrospinal fluid is an effective method to achieve a broad distribution of a transgene in the central nervous system. In this study, we conducted injections of AAV9-PHP.B, a recently described AAV capsid mutant, in the lateral ventricle of mice and rhesus macaques. To enhance the expression of the transgene (the tag protein emerald green fluorescent protein [EmGFP]), we used a gene promoter that confers high neuron-specific expression of the transgene, the human synapsin 1 (<i>SYN1</i>) promoter. The efficacy of the viral vector was first tested in mice. Our results show that intracerebroventricular injections of AAV9-PHP.B SYN1-EmGFP-woodchuck hepatitis virus posttranscriptional regulatory element resulted in neuronal EmGFP expression throughout the mice and monkey brains. We have provided a thorough characterization of the brain regions expressing EmGFP in both species. EmGFP was observed in neuronal cell bodies over the whole cerebral cortex and in the cerebellum, as well as in some subcortical regions, including the striatum and hippocampus. We also observed densely labeled neuropil in areas known to receive projections from these regions. Double fluorescence studies demonstrated that EmGFP was expressed by several types of neurons throughout the mouse and monkey brain. Our results demonstrate that a single injection in the lateral ventricle is an efficient method to obtain transgene expression in many cortical and subcortical regions, obviating the need of multiple intraparenchymal injections to cover large brain areas. The use of intraventricular injections of AAV9-PHP.B SYN1-EmGFP could provide a powerful approach to transduce widespread areas of the brain and may contribute to further development of methods to genetically target-specific populations of neurons.
2,331,799
The topology of ventricle surfaces and its application in the analysis of hydrocephalic ventricles: a proof-of-concept study.
The cerebral ventricles deform in a non-uniform fashion in response to increased CSF volume and/or pressure in hydrocephalic syndromes. Current research is focused on volumetric analyses, while topological analysis of ventricular surfaces remains understudied. We developed a method of quantitatively modeling the curvature of ventricular surfaces to analyze changes in ventricular surfaces in normal pressure hydrocephalus (NPH)&#xa0;and Alzheimer's disease (AD), using the left frontal horn as an example.</AbstractText>Twenty-one patients with NPH were recruited from our institution, and 21 healthy controls (HC) and patients with Alzheimer's disease (AD) were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. On T1-weighted fine-cut magnetic resonance sequences, 3D Slicer was used to segment the left frontal horn. Next, the mean curvatures at a set of points on the ventricular surface were determined. The frontal horns were scaled and centered into normalized volumes, allowing for pooling across the study subjects. The frontal horn was divided into superolateral, superomedial, inferolateral, and inferomedial surfaces, and locoregional mean curvatures were analyzed. Statistical comparisons were made between NPH, AD, and HC groups.</AbstractText>Significant differences in the mean curvature of lateral surfaces of the ventricles distinguished patterns of distortion between all three cohorts. Significant flattening of the superomedial surface discriminated NPH from HC and AD. However, significant rounding of the inferomedial surface compared to controls was a distinguishing feature of NPH alone.</AbstractText>NPH ventricles deform non-uniformly. The pattern of surface distortion may be used as an additional tool to differentiate between these hydrocephalic conditions.</AbstractText>&#xa9; 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</CopyrightInformation>