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2,328,600 | Effect of Central Injection of Neostigmine on the Bacterial Endotoxin Induced Suppression of GnRH/LH Secretion in Ewes during the Follicular Phase of the Estrous Cycle. | Induced by a bacterial infection, an immune/inflammatory challenge is a potent negative regulator of the reproduction process in females. The reduction of the synthesis of pro-inflammatory cytokine is considered as an effective strategy in the treatment of inflammatory induced neuroendocrine disorders. Therefore, the effect of direct administration of acetylcholinesterase inhibitor-neostigmine-into the third ventricle of the brain on the gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretions under basal and immune stress conditions was evaluated in this study. In the study, 24 adult, 2-years-old Blackhead ewes during the follicular phase of their estrous cycle were used. Immune stress was induced by the intravenous injection of LPS <i>Escherichia coli</i> in a dose of 400 ng/kg. Animals received an intracerebroventricular injection of neostigmine (1 mg/animal) 0.5 h before LPS/saline treatment. It was shown that central administration of neostigmine might prevent the inflammatory-dependent decrease of GnRH/LH secretion in ewes and it had a stimulatory effect on LH release. This central action of neostigmine is connected with its inhibitory action on local pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)α synthesis in the hypothalamus, which indicates the importance of this mediator in the inhibition of GnRH secretion during acute inflammation. |
2,328,601 | Folate Receptor α-Modified Nanoparticles for Targeting of the Central Nervous System. | Effective and timely delivery of therapeutic agents from the systemic circulation to the central nervous system (CNS) is often precluded by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). A new pathway of folate uptake mediated by folate receptor alpha (FRα, molecular weight of 28.29 kg mol<sup>-1</sup>) occurring in various epithelial cells of the CNS (e.g., choroid plexus) was described. Aiming to investigate this mechanism for the delivery of nanomedicines to the CNS, in this work, we initially produced nanoparticles (NPs) made of a highly hydrophobic poly(ethylene glycol)-<i>b</i>-poly(ε-caprolactone) (PEG-<i>b</i>-PCL) block copolymer functionalized with an amine moiety in the edge of the PEG block by a simple nanoprecipitation method. Hydrophilic PEG blocks migrated to the NP surface during formation, exposing primary amine groups that were used to conjugate the targeting ligand, FRα. The size of the NPs was in the 58-98 nm range and standard deviation (S.D., a measure of the size population peak width) of 26-41 nm, as measured by dynamic light scattering (DLS). The FRα conjugation yield ranged between 50% and 75% (determined indirectly by the bicinchoninic acid protein assay). Pristine and FRα-modified NPs showed good compatibility with primary human choroid plexus epithelial cells (HCPEpiCs). The uptake of FRα-conjugated NPs by HCPEpiCs was qualitatively evaluated in vitro using inverted optical fluorescence and confocal microscopy. FRα-modified NPs were internalized by HCPEpiCs to a greater extent than the unmodified counterparts. Then, their permeability was characterized in standard and inverted HCPEpiC monolayers. In both cases, NPs surface modified with the FRα and complexed to folic acid (FA) showed significantly higher apparent permeability coefficient (<i>P</i><sub>app</sub>) values than the pristine ones. Finally, the biodistribution of unmodified and FRα-FA-modified NPs following intravenous (i.v.) administration was compared in ICR mice. Results indicated that conjugation of the FRα-FA complex to the NP surface promotes higher accumulation in the brain, highlighting the promise of FRα-FA-modified NPs to serve as a platform for the targeting of active molecules to the CNS from the systemic circulation. |
2,328,602 | [Penetrative needling improves neurological function by up-regulating expression of autophagy related protein LC3 in rats with hemorrhagic stroke]. | To observe the effect of penetrative needling from "Baihui" (GV20) to "Qubin" (GB7) on neurological function and expression of autophagy related protein microtubule-associated protein, light chain 3 (LC3) in rats with hemorrhagic stroke, so as to explore its mechanism underlying improvement of hemorrhagic stroke.</AbstractText>A total of 120 male SD rats were randomly divided into sham operation, model, non-acupoint, acupuncture and medication (Rapamycin) groups which were further divided into two time-point subgroups (3, 7 days after modeling, n</i>=12/subgroup). The intracerebral hemorrhage model was established by injection of the rat's auto-blood (50 μL) into the putaman region. Penetrative needling from GV20 to GB7 or sham acupoints (about 1 cm beside GV20 and GB7) was conducted for 30 min, twice daily for 7 days. For rats of the medication group, Rapamycin solution (7 μmol/L) was injected into the right lateral ventricle. The neurological functions (locomotor and balance deficits) were evaluated according to suspended wire test (0-6 points) and horizontal board walking test (0-6 points). Immunohistochemistry and Western blot were used to detect the expression of total LC3 and expression of LC3-Ⅰ and LC3-Ⅱ proteins in the ischemic penumbra region of brain tissue, respectively.</AbstractText>After modeling, the neurological function scores were significantly decreased on day 3 and 7, the levels of LC3-Ⅱ/Ⅰ and LC3 protein on day 3 and 7 were significantly increased in the model group relevant to the sham operation group (P</i><0.05). Following the interventions, the neurological function scores as well as LC3-Ⅱ/Ⅰ and LC3 protein expression were significantly increased in both acupuncture and medication groups compared with the model group (P</i><0.05). The effect of Rapamycin was obviously stronger than that of penetrative needling in up-regulating the expression of LC3-Ⅱ/Ⅰ and LC3 protein (P</i><0.05).</AbstractText>Penetrative needling can improve neurologic function in hemorrhagic stroke rats, which is related with its effect in up-regulating the expression of autophagy-related protein LC3.</AbstractText> |
2,328,603 | Fatal Postpartum Hemorrhage in Diffuse Midline Glioma with H3-K27M Mutation. | Management of pregnant women with brain tumors necessitates difficult decision-making especially for estimating or preventing its intratumoral hemorrhage. A 26-year-old, 19-week pregnant woman complaining of headache and vomiting was admitted to our hospital. Magnetic resonance imaging (MRI) revealed hydrocephalus and a mass lesion without contrast enhancement extending from the left thalamus. To resolve severe symptoms, a ventriculoperitoneal shunt was inserted, and a biopsy was taken via the right ventricle. Pathological examination suggested diffuse or pilocytic astrocytoma, but subsequent genetic analysis revealed the diagnosis of midline glioma with H3-K27M mutation. The patient opted not to terminate the pregnancy, and MRIs conducted every four weeks revealed no change in tumor aspect. The patient delivered a healthy baby by cesarean section, and postpartum day 1 was uneventful. However, she was found in a coma due to a massive intratumoral hemorrhage on postpartum day 2 and died 3 weeks after the hemorrhage. This is the first case report of diffuse midline glioma with H3-K27M mutation in a pregnant woman followed by fatal hemorrhage. It highlights the necessity of careful clinical management and frequent neuroimaging during the entire perinatal period, even if the tumor has hypovascularity or low proliferative potential on radiological or pathological findings. |
2,328,604 | NRXN1 is associated with enlargement of the temporal horns of the lateral ventricles in psychosis. | Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the genetic underpinnings of these structural brain modifications, we performed genome-wide association analyses (GWAS) on 60 quantitative structural brain MRI phenotypes in a sample of 777 subjects (483 cases and 294 controls pooled together). Genotyping was performed with the Illumina PsychChip microarray, followed by imputation to the 1000 genomes multiethnic reference panel. Enlargement of the Temporal Horns of Lateral Ventricles (THLV) is associated with an intronic SNP of the gene NRXN1 (rs12467877, P = 6.76E-10), which accounts for 4.5% of the variance in size. Enlarged THLV is associated with psychosis in this sample, and with reduction of the hippocampus and enlargement of the choroid plexus and caudate. Eight other suggestively significant associations (P < 5.5E-8) were identified with THLV and 5 other brain structures. Although rare deletions of NRXN1 have been previously associated with psychosis, this is the first report of a common SNP variant of NRXN1 associated with enlargement of the THLV in psychosis. |
2,328,605 | Left Interhemispheric Craniotomy for Resection of Cavernous Malformation: 2-Dimensional Operative Video. | Thalamic cavernous malformations pose variable surgical challenges given that the location and size of the lesion often determine the approach surgical trajectory. The patient in this case has a large thalamic cavernous malformation that results in a mass effect on the third ventricle and directly abuts the lateral ventricle. A small interhemispheric craniotomy is performed to allow for an anterior interhemispheric transcallosal approach to the lesion. The lateral ventricle is accessed, and the septum is removed to enhance visualization of the surgical field. A small rim of normal parenchyma on the lateral margin of the thalamus is transgressed, and the cavernous malformation is entered. The lesion is removed in a piecemeal manner. Use of counter traction assists with the piecemeal removal. The lighted suction is critical during inspection and manipulation of the lesion within the resection cavity given the limited lighting deep within the cavity. The lesion was removed completely, and postoperative imaging confirms gross total resection. The patient gave informed consent for surgery and video recording. The institutional review board approval was deemed unnecessary. Used with permission from the Barrow Neurological Institute. |
2,328,606 | Endoscopic resection of the third ventricular epidermoid cysts: A case review and review of literature. | Epidermoid cysts are benign, congenital lesions that originate from ectodermal cells, they are most commonly found in the cerebellopontine angle, but rarely in the ventricular system. There is limited literature regarding the different microsurgical techniques utilized to approach these lesions.</AbstractText>A 63-year-old female with a recurrent third ventricular epidermoid cyst underwent gross total resection utilizing an endoscopic technique. We also reviewed the various endoscopic/microsurgical approaches and outcomes reported in literature.</AbstractText>We identified 15 cases, including our own. Nine of these were managed using microsurgical techniques, while six cases (including ours) were treated endoscopically; gross total resection was achieved in 10/15 cases (67%). Most commonly, surgeons utilized the interhemispheric transcallosal approach (five cases). Tumor recurrence was seen in two cases. Complications attributed to these resections included: disorders of the hypothalamic-pituitary axis (3) - diabetes insipidus, galactorrhea, and hypopituitarism; tumor recurrence (2); aseptic meningitis (1); and a transient Korsakoff syndrome (1).</AbstractText>Epidermoid cysts of the third ventricle are exceedingly rare, and surgical resection is generally well tolerated. Microsurgical transcortical, transcallosal, and endoscopic approaches each have advantages and disadvantages, and are associated with unique procedure-specific complications. Continuing technological improvement would favor endoscopic approaches for resection of tumors of the third ventricle in the future.</AbstractText> |
2,328,607 | Minimizing cortical disturbance to access ventricular subependymoma - A novel approach utilizing spinal minimally invasive tubular retractor system. | Subependymomas are rare benign tumors found primarily in the lateral and fourth ventricles. Patients become symptomatic when the tumor obstructs cerebrospinal fluid pathways. We present a novel minimally invasive technique for lateral ventricular subependymoma resection.</AbstractText>A 57-year-old male presented after a period of progressive ataxia, right upper extremity tremor, and syncopal events. Emergent non-contrast computed tomography of the brain demonstrated a lobulated mass in the left lateral ventricle causing moderate-to-severe obstructive hydrocephalus. Emergent ventriculostomy was placed as a temporizing measure. Subsequent magnetic resonance imaging (MRI) illustrated a large benign appearing mass causing obstruction of the left foramen of Monroe. A small craniotomy was performed utilizing previous ventriculostomy twist hole. The left lateral ventricle was accessed through sequential dilation of ventriculostomy tract using a minimally invasive spine surgery tubular system. Tumor was resected en bloc under microscopic assistance. The patient had an excellent outcome with return to baseline mental status and was discharged from the hospital postoperative day 1. Follow-up MRI demonstrated gross total resection of the mass and decreasing lateral ventricle hydrocephalus with minimal cortical disturbance.</AbstractText>A minimally invasive tubular system approach to ventricular tumors can be utilized to minimize cortical resection and brain retraction. Minimally invasive surgery also has the potential to decrease the length of stay and enhance postoperative recovery.</AbstractText> |
2,328,608 | Extraventricular neurocytoma with ganglioid differentiation of the sellar and parasellar regions in an elderly patient: A case report. | Extraventricular neurocytoma (EVN) is a rare variant of central neurocytoma which arises outside of the ventricular system. Diffuse ganglioid differentiation is a characteristic seen in a subset of these tumors which has an uncertain prognostic significance. Typically, EVN presents in children and young adults. Given the rarity of this tumor, the natural history and response to treatments remain unclear.</AbstractText>We present a case of EVN with diffuse ganglioid differentiation in a 70-year-old male which arose in the midline parasellar region and extended into the third ventricle. This is the oldest such patient reported. Despite prior reports that extremes of age are associated with more aggressive behavior, the tumor in this case did not exhibit such an aggressive course.</AbstractText>In this report, we review the natural history and clinical course of this patient and summarize the literature regarding this rare pathological entity. Our patient responded well to therapy despite older age, ganglioid differentiation, and higher mitotic index.</AbstractText> |
2,328,609 | Third ventricle World Health Organization Grade II meningioma presenting with intraventricular hemorrhage and obstructive hydrocephalus: A case report and literature review. | Third ventricular meningiomas are exceedingly rare intracranial tumors that may present with intraventricular hemorrhage.</AbstractText>The patient is 46-year-old who initially presented with obstructive hydrocephalus from a presumed vascular lesion and who was treated with endoscopic third ventriculostomy. He presented 3 years later with acute intraventricular hemorrhage and hydrocephalus. The hemorrhage was evacuated and the third ventricular tumor was resected, and the patient made an excellent recovery. Histopathological analysis identified the tumor as the World Health Organization Grade II meningioma.</AbstractText>Third ventricular meningioma is a rare tumor that may present with hemorrhage and obstructive hydrocephalus. Surgical resection can be helpful for this rare presentation of intracranial meningioma.</AbstractText> |
2,328,610 | The cerebellar peduncle as localization of a recurrent atypical plexus papilloma: A case report. | Choroid plexus papillomas (CPPs) are infrequently encountered brain tumors with the majority originating in the ventricular system. Rarely, CPP occurs outside of the ventricles.</AbstractText>We report the case of a recurrent CPP that initially originated within the fourth ventricle, though years later it recurred in the left middle cerebellar peduncle.</AbstractText>Patients with cerebellar plexus papilloma need long-term follow-up comprising regular magnetic resonance imagings since, in patients with a history of CPP, any new mild symptomatology, even years after the initial presentation, may be an early sign of tumor recurrence.</AbstractText> |
2,328,611 | Neuronal precursor cells with dopaminergic commitment in the rostral migratory stream of the mouse. | Neuroblasts born in the subventricular zone of adult mammals migrate via the rostral migratory stream into the granular cell layer or periglomerular layer of the olfactory bulb to differentiate into interneurons. To analyze if new neurons in the granular cell layer or periglomerular layer have different origins, we inserted a physical barrier into the rostral migratory stream, depleted cell proliferation with cytarabine infusions, labeled newborn cells with bromodeoxyuridine, and sacrificed mice after short-term (0, 2, or 14 days) or long-term (55 or 105 days) intervals. After short-term survival, the subventricular zone and rostral migratory stream rapidly repopulated with bromodeoxyuridine<sup>+</sup> cells after cytarabine-induced depletion. Nestin, glial fibrillary acidic protein and the PAX6 were expressed in bromodeoxyuridine<sup>+</sup> cells within the rostral migratory stream downstream of the physical barrier. After long-term survival after physical barrier implantation, bromodeoxyuridine<sup>+</sup> neurons were significantly reduced in the granular cell layer, but bromodeoxyuridine<sup>+</sup> and dopaminergic neurons in the periglomerular layer remained unaffected by the physical barrier. Thus, newborn neurons for the granular cell layer are mainly recruited from neural stem cells located in the subventricular zone, but new neurons for the periglomerular layer with dopaminergic predisposition can rise as well from neuronal stem or precursor cells in the rostral migratory stream. |
2,328,612 | Effects of a single bout of exercise on mitochondria-mediated apoptotic signaling in rat cardiac and skeletal muscles. | This study aimed to determine the effects of a single bout exercise on mitochondria-mediated apoptotic signaling in cardiac and skeletal muscles. Fischer 344 rats (4 months old) were randomly divided into the control or a single bout of exercise group (n=10 each). The rats performed a single bout of treadmill exercise for 60 min. Mitochondria-mediated apoptotic signaling (e.g., Bax, Bcl-2, mitochondrial permeability transition pore [mPTP] opening, cytochrome c, and cleaved caspase-3) was measured in cardiac (e.g., left ventricle) and skeletal (e.g., soleus and white gastrocnemius) muscles. A single bout of exercise significantly decreased mPTP opening sensitivity in all tissues. However, a single bout of exercise did not show any statistical differences in Bax, Bcl-2, cytochrome c, and cleaved caspase-3 in all tissues measured. A single bout of exercise did not show definite results on characteristics of mitochondria-mediated apoptotic signaling. Therefore, further research is necessary to provide a more mechanistic understanding of the apoptosis pathway. |
2,328,613 | Thalamus Cavernous Malformation Resection of via Contralateral Anterior Interhemispheric Transcallosal Approach: Two-Dimensional Operative Video. | Thalamic cavernous malformations (CM) are highly challenging surgically. In this illustrative video (Video 1), we present the case of a 36-year-old man with a CM at the left medial thalamus, which was successfully treated by a contralateral anterior interhemispheric transcallosal approach. Informed consent was obtained from the patient. Preoperative imaging demonstrated that the CM appeared to have reached the pial surface superiorly and medially, and diffusion tensor imaging showed the pyramidal tracts to be traveling laterally to the CM. Based on the "Two-point" principle and to avoid pyramidal tract impingement, an anterior interhemispheric transcallosal approach was chosen. Furthermore, to avoid excessive retraction on the ipsilateral hemisphere, we selected the contralateral trajectory over the ipsilateral trajectory. The head was positioned with the right side down; thus, the space between the right hemisphere and the falx could expand because of gravity autoretraction, which could minimize the need of retraction during the interhemispheric dissection. A small incision on the corpus callosum was performed under the guidance of neuronavigation, and the left ventricle was subsequently entered. After a thin layer of hemosiderin-stained pia was opened on the superior surface of the left thalamus, some sandlike old hemorrhagic component was removed for decompression, and the lesion was carefully dissected away from the normal parenchyma within the surrounding gliosis boundary. The CM was removed en bloc, and the deep venous anomaly was well protected. The patient did not experience any intraoperative changes shown by electrophysiologic monitoring, and he recovered well postoperatively. |
2,328,614 | An Alternative Route to the Posterior Half of the Third Ventricle: The Transoccipital Horn Approach. Technical Note. | Lesions arising or abutting in the posterior half of the third ventricle are approached through established routes to avoid damage of essential brain structures. Occasionally, the features of the lesion require rethinking these traditional routes and tailoring the surgical approach to cause fewer debilitating sequelae to the patient. We introduce a modification of previously described transcortical approaches to lesions of the posterior third ventricle. The technique and possible indications are discussed.</AbstractText>Two cases of posterior third ventricle tumors are presented. In both patients, a small posterior fossa and large tentorial veins located along the surgical route, as well as the position of the lesion underneath the internal cerebral veins, encouraged the concept of a novel transoccipital horn approach that was developed to access the tumor with less postoperative deficits.</AbstractText>Both lesions were removed with transitory postoperative visual deficits.</AbstractText>The transoccipital horn approach is a feasible alternative to other surgical routes to the posterior part of the third ventricle in cases of particularly challenging anatomy and tumor characteristics. It allows reaching the lesion along its major axis, fully exploiting the natural space created by the tumor in its growth and avoiding the internal cerebral veins.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,615 | Laser Interstitial Thermal Therapy to the Posterior Fossa: Challenges and Nuances. | Posterior fossa tumors are rare in adults and pose a challenge to treat due to the bony contour of the posterior fossa, complex anatomical structures including deep venous sinuses, and the proximity of the fourth ventricle and brain stem. We describe our experience with laser interstitial thermal therapy (LITT) for the management of brain metastases and radiation necrosis of the posterior fossa.</AbstractText>We retrospectively analyzed 13 patients with metastases and radiation necrosis of the posterior fossa managed with LITT.</AbstractText>Thirteen patients with histopathologically confirmed radiation necrosis (n = 5) and metastases (n = 8) of the posterior fossa underwent LITT. The median preoperative tumor was 4.66 cm3</sup>, and median postoperative ablation cavity volume was 6.29 cm3</sup>. The median volume of the ablation cavity was decreased to 2.90 cm3</sup> at a 9-month follow-up. The median volume of peritumoral edema was 12.25 cm3</sup>, which fell to a median of 5.77 cm3</sup> at 1-month follow-up. The median progression-free survival was 7 months (range, 3-14 months) and the mean overall survival was 40 months (range, 2-49 months) after LITT. There were no intraoperative complications. One patient experienced palsy of the seventh and eighth cranial nerves on follow-up, attributable to LITT.</AbstractText>Lesions of the posterior fossa are challenging to treat given their proximity to the dura and venous sinuses. Our findings demonstrate that LITT ablation may be a safe and feasible option for metastases and radiation necrosis of the posterior fossa. Larger studies are needed to confirm the efficacy of this approach.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,616 | Temporary bronchial stenting for airway compression in the interstage palliation of functional single ventricle. | The Norwood procedure is the first of three palliative surgical procedures offered for hypoplastic left heart syndrome (HLHS). Due to the small size of the thorax and proximity of airway and vascular structures, compression of the airway is possible following the Norwood procedure. We describe the management of an infant with HLHS following Stage I surgical palliation who developed refractory respiratory failure secondary to severe left bronchial compression. |
2,328,617 | Virtual three-dimensional model for preoperative planning in a complex case of a double outlet right ventricle. | A 3-year-old child with a complex variant of double outlet right ventricle achieved a successful biventricular repair after detailed delineation of the intracardiac anatomy on multimodality imaging. A virtual three-dimensional (3D) model based on computed tomography was used successfully in the absence of an actual 3D-printed model. This case report seeks to highlight and hence increase the utilization of the virtual 3D model in resource-limited settings. |
2,328,618 | Intracranial lymphatic drainage discharges iron from the ventricles and reduce the occurrence of chronic hydrocephalus after intraventricular hemorrhage in rats. | <b>Background:</b> The discovery of intracranial lymphatic system provides a new theory about cerebrospinal fluid circulation. In order to investigate the role of lymphatic drainage in hydrocephalus after intraventricular hemorrhage (IVH), three parts of experiments were performed.<b>Methods:</b> IVH model was produced by 200ul autologous blood injection into lateral ventricle of SD male rats. Perls Prussian blue reaction was used to confirm the ability of iron drainage through deep cervical lymph nodes (DCLNs) in part I. The part II measured the volume of ventricles by MR scanner , and the part III compared the ferritin level of area surrounding ventricles by Western blotting after IVH.<b>Results:</b> The ability of iron drainage through DCLNs was confirmed. DCLNs-excised rats got a 19.6% higher incidence of hydrocephalus than DCLNs-preserved rats at day 28 after IVH. And DCLNs-excised group showed higher ferritin level than DCLNs-preserved group at day 3 after IVH.<b>Conclusion:</b> The whole experiments revealed the role of intracranial lymphatic system in discharging iron out of central nervous system at acute phase of IVH, and proved the function in alleviating and avoiding hydrocephalus at chronic phase after IVH. |
2,328,619 | Restitution and Stability of Human Ventricular Action Potential at High and Variable Pacing Rate. | Despite the key role of beat-to-beat action potential (AP) variability in the onset of ventricular arrhythmias at high pacing rate, the knowledge of the involved dynamics and of effective prognostic parameters is largely incomplete. Electrical restitution (ER), the way AP duration (APD) senses changes in preceding cycle length (CL), has been used to monitor transition to arrhythmias. The use of standard ER (sER), though, is controversial, not always suitable for in vivo and only rarely for clinical applications. By means of simulations on a human ventricular AP model, I investigate the dynamics of APD at high pacing rate under sinusoidally, saw-tooth, and randomly variable pacing CLs. AP sequences were compared in terms of beat-to-beat restitution (btb-ER) and of the collections of sER curves generated from each beat. A definition of APD stability is also proposed, based on successive APD changes introduced in an AP sequence by a premature beat. The explored CL range includes values leading to APD alternans under constant pacing. Three different types of response to CL variability were found, corresponding to progressively higher rate of beat-to-beat CL changes. Low rates (∼1 ms/beat) generate a btb-ER dominated by steady-state rate dependence of APD (type 1), intermediate rates (∼5 ms/beat) lead to a btb-ER similar to a single sER (type 2), and high rates (∼20 ms/beat) to hysteretic btb-ER under periodic pacing and to a vertically spread btb-ER in the case of random pacing (type 3). Stability of AP repolarization always increases with the rate of CL changes. Thus, rather than looking at sER slope, which requires additional interventions during the recording of cardiac electrical activity, this study provides rationale for the use of btb-ER representations as predictors of repolarization stability under extreme pacing conditions, known to be critical for the arrhythmia development. |
2,328,620 | Deficiency of Mitochondrial Aspartate-Glutamate Carrier 1 Leads to Oligodendrocyte Precursor Cell Proliferation Defects Both In Vitro and In Vivo. | Aspartate-Glutamate Carrier 1 (AGC1) deficiency is a rare neurological disease caused by mutations in the solute carrier family 25, member 12 (<i>SLC25A12</i>) gene, encoding for the mitochondrial aspartate-glutamate carrier isoform 1 (AGC1), a component of the malate-aspartate NADH shuttle (MAS), expressed in excitable tissues only. AGC1 deficiency patients are children showing severe hypotonia, arrested psychomotor development, seizures and global hypomyelination. While the effect of AGC1 deficiency in neurons and neuronal function has been deeply studied, little is known about oligodendrocytes and their precursors, the brain cells involved in myelination. Here we studied the effect of AGC1 down-regulation on oligodendrocyte precursor cells (OPCs), using both in vitro and in vivo mouse disease models. In the cell model, we showed that a reduced expression of AGC1 induces a deficit of OPC proliferation leading to their spontaneous and precocious differentiation into oligodendrocytes. Interestingly, this effect seems to be related to a dysregulation in the expression of trophic factors and receptors involved in OPC proliferation/differentiation, such as Platelet-Derived Growth Factor α (PDGFα) and Transforming Growth Factor βs (TGFβs). We also confirmed the OPC reduction in vivo in AGC1-deficent mice, as well as a proliferation deficit in neurospheres from the Subventricular Zone (SVZ) of these animals, thus indicating that AGC1 reduction could affect the proliferation of different brain precursor cells. These data clearly show that AGC1 impairment alters myelination not only by acting on N-acetyl-aspartate production in neurons but also on OPC proliferation and suggest new potential therapeutic targets for the treatment of AGC1 deficiency. |
2,328,621 | High-Frame-Rate Tri-Plane Echocardiography With Spiral Arrays: From Simulation to Real-Time Implementation. | Major cardiovascular diseases (CVDs) are associated with (regional) dysfunction of the left ventricle. Despite the 3-D nature of the heart and its dynamics, the assessment of myocardial function is still largely based on 2-D ultrasound imaging, thereby making diagnosis heavily susceptible to the operator's expertise. Unfortunately, to date, 3-D echocardiography cannot provide adequate spatiotemporal resolution in real-time. Hence, tri-plane imaging has been introduced as a compromise between 2-D and true volumetric ultrasound imaging. However, tri-plane imaging typically requires high-end ultrasound systems equipped with fully populated matrix array probes embedded with expensive and little flexible electronics for two-stage beamforming. This article presents an advanced ultrasound system for real-time, high frame rate (HFR), and tri-plane echocardiography based on low element count sparse arrays, i.e., the so-called spiral arrays. The system was simulated, experimentally validated, and implemented for real-time operation on the ULA-OP 256 system. Five different array configurations were tested together with four different scan sequences, including multi-line and planar diverging wave transmission. In particular, the former can be exploited to achieve, in tri-plane imaging, the same temporal resolution currently used in clinical 2-D echocardiography, at the expenses of contrast (-3.5 dB) and signal-to-noise ratio (SNR) (-8.7 dB). On the other hand, the transmission of planar diverging waves boosts the frame rate up to 250 Hz, but further compromises contrast (-10.5 dB), SNR (-9.7 dB), and lateral resolution (+46%). In conclusion, despite an unavoidable loss in image quality and sensitivity due to the limited number of elements, HFR tri-plane imaging with spiral arrays is shown to be feasible in real-time and may enable real-time functional analysis of all left ventricular segments of the heart. |
2,328,622 | Fourth Ventricle Enlargement in Chiari Malformation Type I. | How Chiari malformation type I (CM-I) affects posterior fossa brain structures and produces various symptoms remains unclear. The fourth ventricle is surrounded by critical structures required for normal function. The foramen of Magendie can be obstructed in CM-I; therefore, fourth ventricle changes may occur. To test this hypothesis, we assessed fourth ventricle volume in CM-I compared with healthy controls.</AbstractText>Using our database from 2007-2016, we studied 72 patients with CM-I and 30 age-matched healthy control subjects. Fourth and lateral ventricle volumes and posterior fossa volumes (PFV) were assessed and correlated with clinical signs and symptoms. Statistical analysis was performed.</AbstractText>Patients with CM-I had larger fourth ventricle volumes compared with control subjects (1.31 vs. 0.95 mL; P = 0.012). There were no differences in lateral ventricle volume or PFV. CM-I fourth ventricle volume was associated with tonsillar descent (P = 0.030). CM-I fourth ventricle volume variance was larger than healthy controls (F71,29</sub> = 8.33; P < 0.0001). Patients with CM-I with severe signs and symptoms had a significantly larger fourth ventricle than patients with CM-I with mild signs and symptoms (1.565 vs. 1.015 mL; P = 0.0002).</AbstractText>The fourth ventricle can be enlarged in CM-I independent of lateral ventricle size and is associated with greater tonsillar descent. Most importantly, fourth ventricle enlargement was associated with a worse clinical and radiographic presentation independent of PFV. Fourth ventricle enlargement can affect critical structures and may be a mechanism contributing to symptoms unexplained by tonsil descent. Fourth ventricle enlargement is a useful adjunct in assessing CM-I.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,623 | [Quantitative study on the development of fetal ventricles and cisterna magna in second and third trimesters with MRI]. | <b>Objective:</b> To analyze the changes of growth and development of normal fetal ventricles and cisterna magna with gestational age(GA) and the correlation with fetal gender in the second and third trimester,and establish the MR prenatal diagnosis reference standards. <b>Methods:</b> A total of 633 fetuses (mean GA (27.0±4.1) weeks (18.9-40.6 weeks))without central nervous system abnormalities were retrospectively collected from the Obstetrics and Gynecology Hospital of Fudan University from June 2012 to August 2017. The lateral ventricle trigonometric width (LVTW), third ventricle width (TVW), fourth ventricle width (FVW), anterior-posterior diameter of the fourth ventricle(APDFV), cavum septum pellucidum width (CSPW) and cisterna magna width (CMW) were obtained in the standard measure planes on MR image.The correlation between the biometrics and GA and the correlation between the biometrics and fetal gender were analyzed respectively, and the normal reference values of the biometrics were calculated. <i>Spearman</i> correlation analysis, <i>Pearson</i> correlation analysis,linear regression analysis, independent samples <i>t</i>-test and paired samples <i>t</i>-test were used for statistic analysis. <b>Results:</b> (1)Fetal LLVTW,RLVTW,TVW,CSPW and CMW in second and third trimesters were correlated with GA at medium and low levels(the correlation coefficient <i>r</i> were 0.311, 0.277, 0.207, 0.226, 0.295, respectively, all <i>P<</i>0.01). FVW and APDFV were statistically correlated with GA, and the linear regression equations were as follows: y=0.022×GA-0.043 (adjusted <i>R</i>(2)=0.642); y=0.018×GA-0.159 (adjusted <i>R</i>(2)=0.690). (2)Fetal LLVTW,RLVTW,FVW,APDFV and CSPW were not correlated with fetal gender in second and third trimesters(<i>r=</i>-0.078,-0.057,-0.087,-0.004 and 0.024, <i>P=</i>0.124,0.258,0.085,0.931 and 0.618, all <i>P></i>0.05). TVW and CMW were statistically correlated with fetal gender(<i>r=-</i>0.310, -0.180, <i>P=</i>0.000, 0.006, all <i>P<</i>0.05). (3) The mean values of LLVTW and RLVTW were (0.71±0.13) cm and (0.68±0.13) cm, respectively, and significant difference was found between them(<i>t=</i>3.180, <i>P=</i>0.002). The mean value of CSPW was (0.59±0.15) cm. And the mean values of male and female fetuses for TVW and CMW were (0.17±0.05) cm, (0.16±0.06) cm and (0.68±0.15) cm, (0.58±0.15) cm, respectively. The corresponding prenatal MRI diagnostic criteria were as follows: LLVTW 1.1 cm, RLVTW 1.0 cm, CSPW 1.0 cm, TVW 0.3 cm, CMW (male 1.1 cm, female 1.0 cm). <b>Conclusions:</b> The normal fetal ventricles and cisterna magna are increased with the GA in the second and third trimesters. TVW and CMW are related to fetal gender. The establishment of normal reference values of fetal ventricles and cisterna magna based on GA and fetal gender are conducive to enhance the accuracy of MRI prenatal diagnosis.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ma</LastName><ForeName>X L</ForeName><Initials>XL</Initials><AffiliationInfo><Affiliation>Department of Radiology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>G F</ForeName><Initials>GF</Initials></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>X Z</ForeName><Initials>XZ</Initials></Author><Author ValidYN="Y"><LastName>Tian</LastName><ForeName>X M</ForeName><Initials>XM</Initials></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Q</ForeName><Initials>Q</Initials></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>M H</ForeName><Initials>MH</Initials></Author><Author ValidYN="Y"><LastName>Zhong</LastName><ForeName>T</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>N</ForeName><Initials>N</Initials></Author></AuthorList><Language>chi</Language><GrantList CompleteYN="Y"><Grant><GrantID>SHDC12014130</GrantID><Agency>Key Programs for New Technology Development of Municipal Hospitals of Shanghai, China</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Zhonghua Yi Xue Za Zhi</MedlineTA><NlmUniqueID>7511141</NlmUniqueID><ISSNLinking>0376-2491</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002946" MajorTopicYN="Y">Cisterna Magna</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005865" MajorTopicYN="N">Gestational Age</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008279" MajorTopicYN="N">Magnetic Resonance Imaging</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011247" MajorTopicYN="N">Pregnancy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011263" MajorTopicYN="N">Pregnancy Trimester, Third</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012016" MajorTopicYN="N">Reference Values</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016216" MajorTopicYN="Y">Ultrasonography, Prenatal</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="chi"><b>目的：</b> 分析中晚孕期正常胎儿脑室和后颅窝池生长发育随孕周的变化规律及与胎儿性别的相关性，并制定磁共振（MR）产前诊断参考标准。<b>方法：</b> 回顾性分析2012年6月至2017年8月在复旦大学附属妇产科医院影像科行磁共振成像（MRI）检查无中枢神经系统异常的胎儿共633例，平均孕周18.9~40.6（27.0±4.1）周。在MRI图像标准层面测量胎儿侧脑室三角区宽度（LVTW）、第三脑室宽度（TVW）、第四脑室宽度（FVW）、第四脑室前后径（APDFV）、透明隔间腔宽度（CSPW）以及小脑延髓池宽度（CMW）。分析各指标与孕周及胎儿性别的相关性，并计算各指标正常参考值。各指标与胎儿性别的相关性采用<i>Spearman</i>相关分析，与孕周的相关性采用<i>Pearson</i>相关分析，与孕周高度相关性指标进一步行回归分析，男女胎儿组间各测量指标及孕周均值比较采用两独立样本<i>t</i>检验，左、右侧脑室宽度（LLVTW、RLVTW）均值比较采用配对样本<i>t</i>检验。<b>结果：</b> （1）中晚孕期胎儿LLVTW、RLVTW、TVW、CSPW及CMW分别与孕周呈中、低度相关（相关系数<i>r</i>值分别0.311、0.277、0.207、0.226、0.295，均<i>P<</i>0.01）；FVW及APDFV均与孕周显著线性相关（<i>r=</i>0.802、0.831，均<i>P=</i>0.000），线性回归方程分别为：y=0.022×孕周-0.043（调整<i>R</i>(2)=0.642）；y=0.018×孕周-0.159（调整<i>R</i>(2)=0.690）。（2）LLVTW、RLVTW、FVW、APDFV、CSPW均与胎儿性别不相关（<i>r=</i>-0.078、-0.057、-0.087、-0.004、0.024，<i>P=</i>0.124、0.258、0.085、0.931、0.618，均<i>P></i>0.05）；TVW、CMW与胎儿性别相关（<i>r=</i>-0.310、-0.180，<i>P=</i>0.000、0.006，均<i>P<</i>0.05）。（3）LLVTW、RLVTW均值分别为（0.71±0.13）cm、（0.68±0.13）cm，两者差异有统计学意义（<i>t=</i>3.180，<i>P=</i>0.002）；CSPW均值为（0.59±0.15）cm，TVW及CMW男、女胎儿均值分别为：（0.17±0.05）cm、（0.16±0.06）cm和（0.68±0.15）cm、（0.58±0.15）cm。相应MRI产前诊断标准分别为：LLVTW 1.1 cm，RLVTW 1.0 cm，CSPW 1.0 cm，TVW 0.3 cm，CMW（男1.1 cm，女1.0 cm）。<b>结论：</b> 中晚孕期正常胎儿脑室及后颅窝池均随孕周增加表现出不同程度增长趋势，TVW及CMW与胎儿性别相关。依据孕周及胎儿性别间差异分别制定脑室及后颅窝池的正常参考值，可为MRI产前诊断提供准确参考。. |
2,328,624 | Sensitivity Analysis of a Left Ventricle Model in the Context of Intraventricular Dyssynchrony. | The objective of the current study was to propose a sensitivity analysis of a 3D left ventricle model in order to assess the influence of parameters on myocardial mechanical dispersion. A finite element model of LV electro-mechanical activity was proposed and a screening method was used to evaluate the sensitivity of model parameters on the standard deviation of time to peak strain. Results highlight the importance of propagation parameters associated with septal and lateral segments activation. Simulated curves were compared to myocardial strains, obtained from echocardiography of one healthy subject and one patient diagnosed with intraventricular dyssynchrony and coronary artery disease. Results show a close match between simulation and clinical strains and illustrate the model ability to reproduce myocardial strains in the context of intraventricular dyssynchrony. |
2,328,625 | Dynamics of centriole amplification in centrosome-depleted brain multiciliated progenitors. | Reproductive and respiratory organs, along with brain ventricles, are lined by multiciliated epithelial cells (MCC) that generate cilia-powered fluid flows. MCC hijack the centrosome duplication pathway to form hundreds of centrioles and nucleate motile cilia. In these cells, the large majority of procentrioles are formed associated with partially characterized organelles called deuterosomes. We recently challenged the paradigm that deuterosomes and procentrioles are formed de novo by providing data, in brain MCC, suggesting that they are nucleated from the pre-existing centrosomal younger centriole. However, the origin of deuterosomes and procentrioles is still under debate. Here, we further question centrosome importance for deuterosome and centriole amplification. First, we provide additional data confirming that centriole amplification occurs sequentially from the centrosomal region, and that the first procentriole-loaded deuterosomes are associated with the daughter centriole or in the centrosomal centriole vicinity. Then, to further test the requirement of the centrosome in deuterosome and centriole formation, we depleted centrosomal centrioles using a Plk4 inhibitor. We reveal unexpected limited consequences in deuterosome/centriole number in absence of centrosomal centrioles. Notably, in absence of the daughter centriole only, deuterosomes are not seen associated with the mother centriole. In absence of both centrosomal centrioles, procentrioles are still amplified sequentially and with no apparent structural defects. They seem to arise from a focal region, characterized by microtubule convergence and pericentriolar material (PCM) assembly. The relevance of deuterosome association with the daughter centriole as well as the role of the PCM in the focal and sequential genesis of centrioles in absence of centrosomal centrioles are discussed. |
2,328,626 | Hydrocephalus with Ventricular Papillary Structure Induced by Aggressive Intracranial Dural Arteriovenous Fistulas. | A 76-year-old man presented with progressive dementia, gait disturbance, and urinary incontinence for 1 year. Computed tomography scan revealed nonobstructive hydrocephalus, but abnormal papillary structures at the ventricular wall were noted. Before cerebrospinal fluid (CSF) diversion surgery for hydrocephalus, we performed magnetic resonance angiography and magnetic resonance venography, which revealed multiple engorged vessels over the ventricular wall and bilateral hemispheres. Digital subtraction angiography revealed 2 dural arteriovenous fistulas (DAVFs) at the left transverse-sigmoid sinus and superior sagittal sinus. Signs of angioarchitecture characteristic of cerebral venous hypertension (CVH) were noted, including cortical vein regurgitation and severe pseudophlebitic pattern. DAVFs with CVH might be a factor contributing to acquired hydrocephalus. DAVFs should be considered when patients with hydrocephalus exhibit abnormal papillary structures at the ventricular wall. Performing CSF diversion surgery for hydrocephalus before downgrading or curing such aggressive DAVFs may lead to major complications. |
2,328,627 | hGFAP-Positive Stem Cells Depend on Brg1 for Proper Formation of Cerebral and Cerebellar Structures. | Brahma-related gene 1 (Brg1) is one of the two mutually exclusive catalytic subunits of the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. Several roles of Brg1 have been described including acting as a tumor suppressor but also functioning in neural stem cell (NSC) maintenance, neural crest development, or differentiation of oligodendrocytes and Schwann cells. Here, we generated human glial fibrillary acidic protein (hGFAP)-cre::Brg1fl/fl mice to analyze the function of Brg1 in multipotential NSCs during late stages of neural development. hGFAP-cre::Brg1fl/fl mice died approximately 2 weeks after birth. Macroscopic examination revealed a severe hydrocephalus and a decreased brain weight caused by the loss of Brg1. The cerebellum of hGFAP-cre::Brg1fl/fl mice displayed disorganized cortical layers as well as a massive hypoplasia due to a dramatically reduced number of granule neurons. The cerebrum presented with less proliferative and more apoptotic precursor cells in the subventricular zone (SVZ). Furthermore, the cerebral cortex stood out with significantly thinned upper layers and with impressive dendrite pathology. Finally, the hippocampus was severely underdeveloped with only a sparse number of detectable neurons. We conclude that NSCs depend on Brg1 to give rise to major essential brain structures including the cerebellum, the cerebral cortex, and the hippocampus. |
2,328,628 | CGRP derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis. | Aberrant activation of cardiac fibroblasts leads to cardiac fibrosis, and evolving evidences suggest that endogenous bioactive substances derived from cardiac fibroblasts regulate cardiac fibroblasts activation in an autocrine/paracrine manner. Here we first presented evidence that cardiac fibroblasts can synthesize and secrete calcitonin gene-related peptide (CGRP), therefore, this study aimed to investigate the role of cardiac fibroblasts-derived CGRP in cardiac fibroblasts activation and its regulative mechanism.</AbstractText>The abundantly expression of CGRP in rat, mouse, and human myocardium allowed us to explore the cellular origin of CGRP, and found that the cardiac CGRP was mainly derived from cardiac fibroblasts. Activating TRPA1 with a specific agonist allyl isothiocyanate promoted the synthesis and secretion of CGRP, as well as intracellular Ca2+. These effects were reversed by TRPA1-specific antagonist HC030031 and Ca2+ chelator BAPTA-AM. TGF-β1 was applied to induce the activation of cardiac fibroblasts, and found that TGF-β1 can increase the mRNA expression and secretion levels of CGRP in cardiac fibroblasts. Either CGRP8-37 (CGRP receptor antagonist) or α-CGRP small interfering RNA (siRNA) aggravated TGF-β1-induced proliferation, differentiation, collagen production, and instigated inflammation in cardiac fibroblasts. Moreover, TGF-β1-induced NF-κB activation including IκBα phosphorylation and p65 nuclear translocation were also promoted by CGRP8-37 and α-CGRP siRNA. NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) reversed the effects of CGRP8-37 on NF-κB activation. The promotive effects of CGRP8-37 on TGF-β1-induced activation of cardiac fibroblasts were all reversed by PDTC. Monocrotaline (MCT) induces pulmonary arterial hypertension, progressively leading to right ventricular fibrosis. This model of cardiac fibrosis was developed here to test the potentially beneficial effects of TRPA1 activation in vivo. The non-toxic TRPA1 agonist Cinnamaldehyde (CA) inhibited MCT-induced elevation in right ventricle systolic pressure, RV/LV + S, and right ventricular collagen accumulation, as well as down-regulation of CGRP. CA increased the synthesis and secretion of CGRP, and inhibited TGF-β1-induced activation in cardiac fibroblasts.</AbstractText>Our data suggested an autocrine role for cardiac fibroblasts-derived CGRP in suppressing activation of cardiac fibroblasts through inhibiting NF-κB activation. Increasing autocrine CGRP by activating TRPA1 can ameliorate cardiac fibrosis. These findings support the notion that CGRP derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis.</AbstractText>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.</CopyrightInformation> |
2,328,629 | Temperature-Responsive Polymersomes of Poly(3-methyl-<i>N</i>-vinylcaprolactam)-<i>block</i>-poly(<i>N</i>-vinylpyrrolidone) To Decrease Doxorubicin-Induced Cardiotoxicity. | Despite being one of the most potent chemotherapeutics, doxorubicin (DOX) facilitates cardiac toxicity by irreversibly damaging the cardiac muscle as well as severely dysregulating the immune system and impairing the resolution of cardiac inflammation. Herein, we report synthesis and aqueous self-assembly of nanosized polymersomes from temperature-responsive poly(3-methyl-<i>N</i>-vinylcaprolactam)-<i>block</i>-poly(<i>N</i>-vinylpyrrolidone) (PMVC-PVPON) diblock copolymers and demonstrate their potential to minimize DOX cardiotoxicity compared to liposomal DOX. RAFT polymerization of vinylpyrrolidone and 3-methyl-<i>N</i>-vinylcaprolactam, which are structurally similar monomers but have drastically different hydrophobicity, allows decreasing the cloud point of PMVC<i><sub>m</sub></i>-PVPON<i><sub>n</sub></i> copolymers below 20 °C. The lower critical solution temperature (LCST) of the PMVC<sub>58</sub>-PVPON<i><sub>n</sub></i> copolymer varied from 19.2 to 18.6 and to 15.2 °C by decreasing the length of the hydrophilic PVPON<i><sub>n</sub></i> block from <i>n</i> = 98 to <i>n</i> = 65 and to <i>n</i> = 20, respectively. The copolymers assembled into stable vesicles at room temperature when PVPON polymerization degrees were 65 and 98. Anticancer drug DOX was entrapped with high efficiency into the aqueous PMVC<sub>58</sub>-PVPON<sub>65</sub> polymersomal core surrounded by the hydrophobic temperature-sensitive PMVC shell and the hydrophilic PVPON corona. Unlike many liposomal, micellar, or synthetic drug delivery systems, these polymersomes exhibit an exceptionally high loading capacity of DOX (49%) and encapsulation efficiency (95%) due to spontaneous loading of the drug at room temperature from aqueous DOX solution. We also show that C57BL/6J mice injected with the lethal dose of DOX at 15 mg kg<sup>-1</sup> did not survive the 14 day treatment, resulting in 100% mortality. The DOX-loaded PMVC<sub>58</sub>-PVPON<sub>65</sub> polymersomes did not cause any mortality in mice indicating that they can be used for successful DOX encapsulation. The gravimetric analyses of the animal organs from mice treated with liposome-encapsulated DOX (Lipo-DOX) and PMVC<sub>58</sub>-PVPON<sub>65</sub> polymersomes (Poly-DOX) revealed that the Lipo-DOX injection caused some toxicity manifesting as decreased body weight compared to Poly-DOX and saline control. Masses of the left ventricle of the heart, lung, and spleen reduced in the Lipo-DOX-treated mice compared to the nontoxic saline control, while no significant decrease of those masses was observed for the Poly-DOX-treated mice. Our results provide evidence for superior stability of synthetic polymersomes in vivo and show promise for the development of next-generation drug carriers with minimal side effects. |
2,328,630 | The association between 24-h blood pressure patterns and left ventricular mechanics. | We sought to investigate left ventricular (LV) mechanics in the recently diagnosed hypertensive patients with different 24-h blood pressure (BP) patterns (dipping, nondipping, extreme dipping and reverse dipping).</AbstractText>The current cross-sectional study included 209 hypertensive patients who underwent 24-h ambulatory BP monitoring and comprehensive two-dimensional echocardiographic examination including multilayer strain analysis.</AbstractText>There was no difference in 24-h and daytime BP values between four groups. Night-time BP significantly and gradually increased from extreme dippers, across dippers and nondippers, to reverse dippers. LV global longitudinal and circumferential strains were greater in dippers and extreme dippers than in nondippers and reverse dippers. This was also found for endocardial and epicardial LV longitudinal and circumferential strains. Multivariate logistic regression analysis demonstrated that nondipping and reverse dipping patterns were associated with reduced LV longitudinal strain [odds ratio (OR) 1.71 (95% confidence interval (CI): 1.10-5.61) and OR 2.50 (95% CI: 1.31-6.82), respectively] independently of age, sex, 24-h SBP, LV mass index and E/è. Only the reverse dipping BP pattern was independently of clinical and echocardiographic parameters related with reduced LV circumferential strain [OR 1.90 (95% CI: 1.10-4.80)].</AbstractText>Nondipping and reverse dipping BP patterns had stronger impact on LV mechanics compared with patients with dipping and extreme dipping BP patterns in hypertensive population. LV functional and mechanical remodeling deteriorated from extreme dippers and dippers, to nondippers and reverse dippers.</AbstractText> |
2,328,631 | Natural History of Ventriculomegaly in Fetal Agenesis of the Corpus Callosum. | To assess the natural evolution of the size of the fetal lateral ventricles throughout pregnancy in fetuses with callosal anomalies.</AbstractText>Cases of fetal callosal anomalies were retrospectively classified as isolated or complex based on the presence of other structural or genetic anomalies. Longitudinal ultrasound studies were reviewed, and postnatal outcomes were retrieved for isolated cases.</AbstractText>In 135 fetuses, those who first presented after 24 weeks' gestation were more likely to have ventriculomegaly (n = 58 of 68 [85%]) than those who presented before 24 weeks (n = 39 of 67 [58%]; P < .001). In 79 cases that had longitudinal follow-up, the mean increase in ventricular width was 0.6 mm/wk, without a significant difference between isolated and complex cases (mean ± SD, 0.6 ± 1.5 versus 0.6 ± 1.1 mm; P = .45).</AbstractText>Callosal anomalies are associated with progressive ventriculomegaly on prenatal ultrasound imaging, without a difference between isolated and complex anomalies. This feature should be considered part of the disease spectrum. The consequence of progressive ventriculomegaly on the long-term neurodevelopmental outcome is still unknown, and further studies should be aimed at obtaining long-term follow-up of these cases.</AbstractText>© 2019 by the American Institute of Ultrasound in Medicine.</CopyrightInformation> |
2,328,632 | Long-range fibre damage in small vessel brain disease affects aphasia severity. | We sought to determine the underlying pathophysiology relating white matter hyperintensities to chronic aphasia severity. We hypothesized that: (i) white matter hyperintensities are associated with damage to fibres of any length, but to a higher percentage of long-range compared to mid- and short-range intracerebral white matter fibres; and (ii) the number of long-range fibres mediates the relationship between white matter hyperintensities and chronic post-stroke aphasia severity. We measured the severity of periventricular and deep white matter hyperintensities and calculated the number and percentages of short-, mid- and long-range white matter fibres in 48 individuals with chronic post-stroke aphasia. Correlation and mediation analyses were performed to assess the relationship between white matter hyperintensities, connectome fibre-length measures and aphasia severity as measured with the aphasia quotient of the Western Aphasia Battery-Revised (WAB-AQ). We found that more severe periventricular and deep white matter hyperintensities correlated with a lower proportion of long-range fibres (r = -0.423, P = 0.003 and r = -0.315, P = 0.029, respectively), counterbalanced by a higher proportion of short-range fibres (r = 0.427, P = 0.002 and r = 0.285, P = 0.050, respectively). More severe periventricular white matter hyperintensities also correlated with a lower proportion of mid-range fibres (r = -0.334, P = 0.020), while deep white matter hyperintensities did not correlate with mid-range fibres (r = -0.169, P = 0.250). Mediation analyses revealed: (i) a significant total effect of periventricular white matter hyperintensities on WAB-AQ (standardized beta = -0.348, P = 0.008); (ii) a non-significant direct effect of periventricular white matter hyperintensities on WAB-AQ (P > 0.05); (iii) significant indirect effects of more severe periventricular white matter hyperintensities on worse aphasia severity mediated in parallel by fewer long-range fibres (effect = -6.23, bootstrapping: standard error = 2.64, 95%CI: -11.82 to -1.56) and more short-range fibres (effect = 4.50, bootstrapping: standard error = 2.59, 95%CI: 0.16 to 10.29). We conclude that small vessel brain disease seems to affect chronic aphasia severity through a change of the proportions of long- and short-range fibres. This observation provides insight into the pathophysiology of small vessel brain disease, and its relationship with brain health and chronic aphasia severity. |
2,328,633 | Air gun wound: bihemispheric penetrating brain injury in a paediatric patient. | Air guns are classified as low-velocity missiles and they usually considered safe and harmless. Despite that fact, air guns still can make serious or life-threatening injuries. Most of air gun injuries occur in paediatric population. A 2-year-old boy was shot in the forehead withan air gun accidentally. Skull radiography and non-contrast CT scan of the head were performed and showed penetrating bihemispheric brain injury from the left frontal to right occipital lobes at the level of the lateral ventricle with a metal-density foreign body at the right occipital. A projectile was successfully extracted via craniotomy, without complications. Air guns have the potential to cause fatal, life-threatening injury especially in children. Imaging is crucial for the evaluation of wound ballistics. Understanding about the mechanism of projectiles and wound ballistics is very helpful for radiologists to conceptualize these injuries when interpreting these cases. The role of radiology in ballistic wound cases is critical and important, both for clinical and forensic settings. |
2,328,634 | Association of Cavum Septum Pellucidum and Cavum Vergae With Cognition, Mood, and Brain Volumes in Professional Fighters. | Many studies have investigated the imaging findings showing sequelae of repetitive head trauma, with mixed results.</AbstractText>To determine whether fighters (boxers and mixed martial arts fighters) with cavum septum pellucidum (CSP) and cavum vergae (CV) have reduced volumes in various brain structures or worse clinical outcomes on cognitive and mood testing.</AbstractText><AbstractText Label="DESIGN, SETTING, AND PARTICIPANTS">This cohort study assessed participants from the Professional Fighters Brain Health Study. Data were collected from April 14, 2011, to January 17, 2018, and were analyzed from September 1, 2018, to May 23, 2019. This study involved a referred sample of 476 active and retired professional fighters. Eligible participants were at least 18 years of age and had at least a fourth-grade reading level. Healthy age-matched controls with no history of trauma were also enrolled.</AbstractText>Presence of CSP, CV, and their total (additive) length (CSPV length).</AbstractText>Information regarding depression, impulsivity, and sleepiness among study participants was obtained using the Patient Health Questionnaire depression scale, Barrett Impulsiveness Scale, and the Epworth Sleepiness Scale. Cognition was assessed using raw scores from CNS Vital Signs. Volumes of various brain structures were measured via magnetic resonance imaging.</AbstractText>A total of 476 fighters (440 men, 36 women; mean [SD] age, 30.0 [8.2] years [range, 18-72 years]) and 63 control participants (57 men, 6 women; mean [SD] age, 30.8 [9.6] years [range, 18-58 years]) were enrolled in the study. Compared with fighters without CV, fighters with CV had significantly lower mean psychomotor speed (estimated difference, -11.3; 95% CI, -17.4 to -5.2; P = .004) and lower mean volumes in the supratentorium (estimated difference, -31 191 mm3; 95% CI, -61 903 to -479 mm3; P = .05) and other structures. Longer CSPV length was associated with lower processing speed (slope, -0.39; 95% CI, -0.49 to -0.28; P < .001), psychomotor speed (slope, -0.43; 95% CI, -0.53 to -0.32; P < .001), and lower brain volumes in the supratentorium (slope, -1072 mm3 for every 1-mm increase in CSPV length; 95% CI, -1655 to -489 mm3; P < .001) and other structures.</AbstractText>This study suggests that the presence of CSP and CV is associated with lower regional brain volumes and cognitive performance in a cohort exposed to repetitive head trauma.</AbstractText> |
2,328,635 | The comparison of the impact of arterial stiffness and central pressure on left ventricular geometry and diastolic function. | This study was performed to compare the associations of brachial-ankle pulse wave velocity (baPWV) and central blood pressure (CBP) measurements with left ventricular (LV) geometry and diastolic function.</AbstractText>A total of 77 subjects (64.5 ± 10.8 years, 67.5% females) without documented cardiovascular disease were prospectively recruited. All subjects underwent transthoracic echocardiography, baPWV and noninvasive measurement of CBP on the same day.</AbstractText>In simple linear correlation analyses, neither baPWV nor CBP was associated with LV mass index or relative wall thickness (P</i> > 0.05 for each). Although baPWV significantly correlated with septal e´ velocity in simple linear correlation analyses (r</i> = 0.258, P</i> = 0.025), the significance was lost after controlling for potential confounder (P</i> = 0.881). In simple linear correlation analyses, central systolic blood pressure (CSBP) and central pulse pressure (CPP) significantly correlated with both septal e´ velocity or E/e´ (P</i> <  0.05 for each); however, neither central diastolic nor mean arterial pressures was associated with both septal e´ velocity and E/e´ (P</i> > 0.05 for each). After controlling for confounders, including age, sex and body mass index, CSBP correlated with septal e´ velocity (β</i> = - 0.258, P</i> = 0.025), but not with E/e´ (P</i> = 0.074). CPP correlated with both septal e´ velocity (β</i> = - 0.300, P</i> = 0.014) and E/e´ (β</i> = 0.428, P</i> = 0.002) in the same multivariable model.</AbstractText>In subjects without documented cardiovascular disease, CSBP and CPP may be more strongly associated with LV diastolic function than baPWV. Further studies with a larger sample size are needed to confirm our results.</AbstractText> |
2,328,636 | A descriptive report of the selenium distribution in tissues from pigs with mulberry heart disease (MHD). | Mulberry Heart Disease (MHD) is a condition affecting mainly young pigs in excellent body condition. Feed efficient pigs showing high average daily gains are more likely to be affected. MHD has been described as a challenge in Norwegian pig production over the last decade despite abundant supplies of vitamin E, and selenium (Se) close to the upper limits set by the EU. From 2015 to 2017, samples from documented MHD field cases were collected and compared with controls regarding post mortem findings and Se concentrations in numerous internal and external organs were determined in order to characterize the Se distribution, and to identify any differences between MHD cases and controls.</AbstractText>Eight MHD cases from commercial farms and a pet pig producer located in the South West and East of Norway, and three control animals originating from these farms were included in this study. MHD cases and controls were weaned pigs with an average bodyweight (BW) of 17 kg (range 9 to 46 kg BW), with the exception of one pet piglet (Mangalica, 6 kg BW) that had only received sow milk. Selenium was determined in samples from the cardiovascular, digestive, immune, endocrine, integumentary, muscular, respiratory and urinary systems using inductively coupled plasma mass spectrometry (QQQ ICP-MS). All pigs with MHD suffered sudden deaths. Control animals were euthanized without being bled prior to necropsy and sampling. Significantly different mean Se concentrations between MHD cases and controls were found in cardiac samples as well as almost all skeletal muscles (P</i> < 0.05).</i> Based on the samples from ten different muscles (except the cardiac samples), mean Se concentrations in MHD cases were 0.34 (0.01) mg/ kg DM compared with 0.65 (0.02) mg/ kg DM in control pigs (P</i> < 0.0001). In cardiac samples, mean Se concentrations from MHD cases were 0.87 (0.02) mg/ kg DM vs. 1.12 (0.04) mg/ kg DM (P</i> < 0.0001). Additionally, significantly lower Se concentrations compared with controls were found in the liver as well as the caecum, duodenum, gastric ventricle, jejunum, kidney, skin and thymus samples.</AbstractText>Based on the present work, the current common practice regarding tissue analyses in MHD cases could be refined to include other organs than liver and heart. The evident differences in mean Se concentrations in 9 out of 10 samples from the muscular system, could make such samples relevant for complementary measurements of Se concentrations to help confirm the MHD diagnosis. We find it interesting that although our limited number of sampled pigs are different in terms of genetics, size and feeding regimes, the variation of Se concentrations in a given organ was low between MHD cases. Since this report includes a limited number of MHD cases and controls, our results should be corroborated by a controlled, larger study.</AbstractText> |
2,328,637 | Central Neurocytoma Presenting with Bleed and Obstructive Hydrocephalus: A Rare Presentation. | Central neurocytomas (CNs) occur typically in the lateral ventricle, adjacent to the septum pellucidum and foramen of Monro. The clinical presentation varies and many are incidentally detected. Incidence of spontaneous hemorrhage at presentation is rare. We hereby report a case of the intraventricular lesion with bleed which was operated on an emergency basis as it caused obstructive hydrocephalus and the patient was in altered sensorium. The exact cause of hemorrhage in CNs is not known, and the previously discussed explanations are discussed. |
2,328,638 | Endoscopic resection of an intraventricular cavernoma: a case report. | Cerebral cavernous malformations occur in 0.5% of the population. They consist of thin-walled vessels and can be found as congenital or sporadic lesions. Most of them are asymptomatic, however, due to their anatomical features blood leakage into the surrounding tissue can cause severe neurological symptoms. Although risk of bleeding is low, symptomatic lesions should be treated, with microsurgical resection being the therapy of choice for surgically accessible cavernomas. Intraventricular cavernous malformations are a rare subtype, and due to their anatomical localization, they are eligible for endoscopic surgery. However, there are only a few reports on endoscopic resection of intraventricular cavernomas to be found in the literature. We report the case of a 48-year-old woman who suffers from multiple cerebral cavernous malformations. Since the first diagnosis, several of these cavernomas had been removed in open microsurgical interventions. Most recently, a new lesion arose intraventricularly, adjacent to the ependymal wall of the right lateral ventricle. In follow-up, cranial MR imaging microbleeding and an increasing size were detected. Eventually, the lesion was endoscopically removed. Presurgery the patient suffered from right-sided sensibility loss and gait disturbances as a consequence of prior surgeries. Postsurgery, no new neurological symptoms could be found. We here present MR images and intraoperative pictures as well as a short video of the resection itself. In our opinion, endoscopic resection of intraventricular cavernomas should be considered in selected cases. |
2,328,639 | Psychotic experiences in childhood are associated with increased structural integrity of the left arcuate fasciculus - A population-based case-control study. | Around 1 in 5 children under 13 years old experience sub-clinical psychotic experiences (PEs) like hallucinations and delusions. While PEs in childhood are a significant risk factor for adult psychotic disorders, the majority of those experiencing childhood PEs do not develop a psychotic disorder. Individual differences in regional brain maturation rates may be responsible for this age-related and often transient emergence of PEs. Fronto-temporal association tracts undergo extensive maturation and myelination throughout childhood and adolescence, thus we focus on individual differences in one such tract, the arcuate fasciculus. A normative population-based sample of children (aged 11-13) attended a clinical interview and MRI (n = 100), 25 of whom were identified as reporting strong PEs. This group had reduced mean and radial diffusivity in the arcuate fasciculus compared with a group of matched controls (n = 25) who reported no PEs. The group difference was greater in the left hemisphere than the right. Mediation analyses showed that this group difference was driven predominantly by perceptual disturbances and an along-tract analysis showed that the group difference was greatest approximately halfway between the frontal and temporal termination points of the tract (adjacent to the left lateral ventricle). This study is the first to investigate links between arcuate fasciculus diffusivity and psychotic experiences in a population sample of children. |
2,328,640 | Delayed clearance of cerebrospinal fluid tracer from choroid plexus in idiopathic normal pressure hydrocephalus. | Impaired clearance of amyloid-β from choroid plexus is one proposed mechanism behind amyloid deposition in Alzheimer's disease. The present study examined whether clearance from choroid plexus of a cerebrospinal fluid tracer, serving as a surrogate marker of a metabolic waste product, is altered in idiopathic normal pressure hydrocephalus (iNPH), one sub-type of dementia. In a prospective observational study of close to healthy individuals (reference cohort; REF) and individuals with iNPH, we performed standardized T1-weighted magnetic resonance imaging scans before and through 24 h after intrathecal administration of a cerebrospinal fluid tracer (the magnetic resonance imaging contrast agent gadobutrol). Changes in normalized T1 signal within the choroid plexus and cerebrospinal fluid of lateral ventricles were quantified using FreeSurfer. The normalized T1 signal increased to maximum within choroid plexus and cerebrospinal fluid of lateral ventricles 6-9 h after intrathecal gadobutrol in both the REF and iNPH cohorts (enrichment phase). Peak difference in normalized T1 signals between REF and iNPH individuals occurred after 24 h (clearance phase). The results gave evidence for gadobutrol resorption from cerebrospinal fluid by choroid plexus, but with delay in iNPH patients. Whether choroid plexus has a role in iNPH pathogenesis in terms of delayed clearance of amyloid-β remains to be shown. |
2,328,641 | Temporal Horn Choroid Plexus Papilloma Presenting with Seizures in Adulthood: Clinical Case Report and Review of the Literature. | Choroid plexus papillomas (CPPs) are benign World Health Organization grade I tumors that comprise 2%-4% of all brain tumors among children and less than 1% of brain tumors in adults. Most adult cases occur in the fourth ventricle, with only 1 previous report describing an adult patient with a temporal horn CPP.</AbstractText>We report a rare case of a temporal horn CPP presenting in an adult with seizures. We performed a minimally invasive subtemporal approach for gross total resection of the lesion.</AbstractText>CPP presenting in the temporal horn is rare among adults. We discuss the surgical nuances of the subtemporal approach for resection and review the literature regarding adult presentation of CPP and the treatment strategies for adult CPP.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,642 | Functions of subventricular zone neural precursor cells in stroke recovery. | The proliferation and ectopic migration of neural precursor cells (NPCs) in response to ischemic brain injury was first reported two decades ago. Since then, studies of brain injury-induced subventricular zone cytogenesis, primarily in rodent models, have provided insight into the cellular and molecular determinants of this phenomenon and its modulation by various factors. However, despite considerable correlational evidence-and some direct evidence-to support contributions of NPCs to behavioral recovery after stroke, the causal mechanisms have not been identified. Here we discuss the subventricular zone cytogenic response and its possible roles in brain injury and disease, focusing on rodent models of stroke. Emerging evidence suggests that NPCs can modulate harmful responses and enhance reparative responses to neurologic diseases. We speculatively identify four broad functions of NPCs in the context of stroke: cell replacement, cytoprotection, remodeling of residual tissue, and immunomodulation. Thus, NPCs may have pleiotropic functions in supporting behavioral recovery after stroke. |
2,328,643 | A good choice for the patients with prior failed ventriculoperitoneal shunt treatment of suprasellar arachnoid cysts: endoscopic fenestration. | To investigate the effectiveness of endoscopic fenestration in the patients with prior failed ventriculoperitoneal (VP) shunt treatment of suprasellar arachnoid cysts (SACs). Between 2012 and 2018, four pediatric patients of SACs with previous failed VP shunt treatment were surgically treated using endoscopic ventriculocystocisternostomy (VCC) in our hospital. The clinical symptoms, imaging data, and surgical outcomes were collected and analyzed retrospectively. A literature review is provided with regard to the reasons of shunt failure and surgical outcome of further endoscopic fenestration in the previously reported patients of SACs with prior failed VP shunt. For the 4 cases, the initial clinical symptoms relieved or even disappeared after shunt placement, but, respectively, recurred 2, 6, 11, and 6 months later. MR scans were conducted when the clinical symptoms reappeared and showed a cyst had greatly enlarged after shunt placement. Furthermore, VP shunt-related slit ventricle was also demonstrated in 3 cases. Clinical improvement and cysts shrinkage occurred in all 4 patients after VCC. Slit ventricle and hydrocephalus were also resolved. Three patients had their shunt apparatus removed after VCC, and another patient's guardian refused to remove the shunt apparatus. Subdural hematoma occurred in one case after shunt apparatus removal. Four patients have been stable during follow-up period (mean follow-up 26.5 months). All the three patients whose VP shunt were removed were shunt independence. There were 24 patients who underwent endoscopic fenestration as an alternative to the failed VP shunt treatment in the published reports. Added our 4 patients to the published group, the effective rate of endoscopic fenestration for SACs following previous failed VP shunt treatment was approximately 93% (26/28). Of the 24 patients, the shunt apparatuses were in situ or reimplantation in 9 patients due to shunt dependence. The correction to recognize the SAC is the first condition to select the optimal management philosophy. The analysis of the series suggests endoscopic operation is still an effective and safe option in the SAC patients with previous failed VP shunt, and the shunt apparatus can be removed for some patients. The short interval time between shunt operation and endoscopic fenestration is conductive to return patients to the shunt-free state. |
2,328,644 | Refractory epilepsy associated with ventriculoperitoneal shunt over-drainage: case report. | Epilepsy and intracranial pressure (ICP) can be interrelated. While shunt malfunction is recognized as a cause of seizures, shunt over-drainage is seldom reported as such. We report a child who had undergone ventriculoperitoneal shunt insertion at the age of 6 months following an excision of a left ventricle choroid plexus papilloma, who developed refractory epilepsy since the age of 3 years. An MRI showed small ventricles. The child presented with acute hydrocephalus due to proximal shunt malfunction at the age of 11 years and was treated with an endoscopic third ventriculostomy. Following the procedure, the seizures abated. Our case suggests that intractable epilepsy may be related to intracranial hypotension. Potential treatments for shunt over-drainage may be indicated even in the absence of classic over-drainage symptoms, in the presence of refractory epilepsy. |
2,328,645 | Aortic erosion occurring in over 5 years after Amplatzer septal Occluder implantation for secundum atrial septal defect: a case report.<Pagination><StartPage>159</StartPage><MedlinePgn>159</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">159</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1186/s13019-019-0982-z</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Aortic erosion is a serious complication that usually occurs shortly after Amplazter Septal Occluder (ASO) implantation for atrial septal defect (ASD).</AbstractText><AbstractText Label="CASE PRESENTATION" NlmCategory="METHODS">A seven-year-old girl was diagnosed with secundum ASD without symptoms. Transesophageal echocardiography (TEE) showed a defect of 20 mm in diameter in the fossa ovalis without aortic rim. An ASO device of 24 mm in diameter was selected and electively implanted. The "A-shape" of the device was confirmed by intraoperative TEE, a landmark finding indicating the proper implantation of ASO in patients without aortic rim. After an uneventful postoperative course of 5 years and 10 months, she was transferred to our unit due to cardiogenic shock. Her echocardiogram in emergency room showed pericardial effusion with collapsed right ventricle. Given her history of ASO and the observation of the sequentially increasing pericardial effusion, we diagnosed her with acute cardiac tamponade due to aortic erosion. Emergency pericardiotomy was then performed to improve the hemodynamic condition. Fresh clots were found, so we immediately prepared the cardiopulmonary bypass circuit and explored the damage to the aorta, in which the clots had accumulated. Bleeding suddenly started when the clots were removed. We then inserted the cannulae for perfusion and venous drainage. The clots were removed, and tears were found in both the lateral side of the ascending aorta and the right atrial wall. Intraoperative TEE showed that an edge of the ASO device was directly touching the aortic wall and the Doppler color-flow imaging showed blood flow through this lesion. The erosive lacerations of both the ascending aorta and right atrium were detected from the inside after achieving cardioplegic cardiac arrest. The ascending aorta was obliquely incised, and the laceration was closed from inside the aortic root. The postoperative course was uneventful. She has been doing well for 5 years since the surgery.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">We experienced and successfully treated a rare case of acute cardiac tamponade caused by aortic erosion 5 years and 10 months after ASO implantation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Onakatomi</LastName><ForeName>Yasuko</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Surgery, Kanagawa Children's Medical Center, Yokohama, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Asou</LastName><ForeName>Toshihide</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Surgery, Kanagawa Children's Medical Center, Yokohama, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Takeda</LastName><ForeName>Yuko</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Surgery, Kanagawa Children's Medical Center, Yokohama, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ueda</LastName><ForeName>Hideaki</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Kanagawa Children's Medical Center, Yokohama, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goda</LastName><ForeName>Motohiko</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Surgery, Yokohama City University, Fukuura 3-9, Kanazawa-ku, Yokohama, Kanagawa, 236-0008, Japan. gogomotto@gmail.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Masuda</LastName><ForeName>Munekata</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Cardiovascular Surgery, Yokohama City University, Fukuura 3-9, Kanazawa-ku, Yokohama, Kanagawa, 236-0008, Japan.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>09</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Cardiothorac Surg</MedlineTA><NlmUniqueID>101265113</NlmUniqueID><ISSNLinking>1749-8090</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001013" MajorTopicYN="N">Aorta, Thoracic</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="Y">diagnostic imaging</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001018" MajorTopicYN="N">Aortic Diseases</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006328" MajorTopicYN="N">Cardiac Catheterization</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020878" MajorTopicYN="N">Device Removal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017548" MajorTopicYN="N">Echocardiography, Transesophageal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005500" MajorTopicYN="N">Follow-Up Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006344" MajorTopicYN="N">Heart Septal Defects, Atrial</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011183" MajorTopicYN="N">Postoperative Complications</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012086" MajorTopicYN="N">Reoperation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055989" MajorTopicYN="N">Septal Occluder Device</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014656" MajorTopicYN="N">Vascular Surgical Procedures</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Amplazter septal occluder</Keyword><Keyword MajorTopicYN="N">Aortic rim</Keyword><Keyword MajorTopicYN="N">Atrial septal defect</Keyword><Keyword MajorTopicYN="N">Cardiac tamponade</Keyword><Keyword MajorTopicYN="N">Erosion</Keyword></KeywordList><CoiStatement>The authors declare that they have no competing interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>7</Month><Day>8</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>9</Month><Day>2</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>9</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>9</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>12</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31492164</ArticleId><ArticleId IdType="pmc">PMC6728993</ArticleId><ArticleId IdType="doi">10.1186/s13019-019-0982-z</ArticleId><ArticleId IdType="pii">10.1186/s13019-019-0982-z</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>McElhinney DB, Quartermain MD, Kenny D, Alboliras E, Amin Z. 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Cathe cardiovasc interv. 2013;82:592–584. doi: 10.1002/ccd.25158.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/ccd.25158</ArticleId><ArticleId IdType="pubmed">23172721</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31491755</PMID><DateRevised><Year>2019</Year><Month>09</Month><Day>06</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0715</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Sep</Month><Day>06</Day></PubDate></JournalIssue><Title>Journal of neurosurgery. Pediatrics</Title><ISOAbbreviation>J Neurosurg Pediatr</ISOAbbreviation></Journal>A 12-year single-center retrospective analysis of antisiphon devices to prevent proximal ventricular shunt obstruction for hydrocephalus. | Aortic erosion is a serious complication that usually occurs shortly after Amplazter Septal Occluder (ASO) implantation for atrial septal defect (ASD).</AbstractText>A seven-year-old girl was diagnosed with secundum ASD without symptoms. Transesophageal echocardiography (TEE) showed a defect of 20 mm in diameter in the fossa ovalis without aortic rim. An ASO device of 24 mm in diameter was selected and electively implanted. The "A-shape" of the device was confirmed by intraoperative TEE, a landmark finding indicating the proper implantation of ASO in patients without aortic rim. After an uneventful postoperative course of 5 years and 10 months, she was transferred to our unit due to cardiogenic shock. Her echocardiogram in emergency room showed pericardial effusion with collapsed right ventricle. Given her history of ASO and the observation of the sequentially increasing pericardial effusion, we diagnosed her with acute cardiac tamponade due to aortic erosion. Emergency pericardiotomy was then performed to improve the hemodynamic condition. Fresh clots were found, so we immediately prepared the cardiopulmonary bypass circuit and explored the damage to the aorta, in which the clots had accumulated. Bleeding suddenly started when the clots were removed. We then inserted the cannulae for perfusion and venous drainage. The clots were removed, and tears were found in both the lateral side of the ascending aorta and the right atrial wall. Intraoperative TEE showed that an edge of the ASO device was directly touching the aortic wall and the Doppler color-flow imaging showed blood flow through this lesion. The erosive lacerations of both the ascending aorta and right atrium were detected from the inside after achieving cardioplegic cardiac arrest. The ascending aorta was obliquely incised, and the laceration was closed from inside the aortic root. The postoperative course was uneventful. She has been doing well for 5 years since the surgery.</AbstractText>We experienced and successfully treated a rare case of acute cardiac tamponade caused by aortic erosion 5 years and 10 months after ASO implantation.</AbstractText> |
2,328,646 | Geranylgeraniol prevents statin-induced skeletal muscle fatigue without causing adverse effects in cardiac or vascular smooth muscle performance. | The administration of geranylgeranyl pyrophosphate (GGPP) (or its precursor, geranylgeraniol [GGOH]) has been shown by several in vitro studies to be capable of abrogating statin-induced myotoxicity. Nonetheless, the potential of GGPP repletion to prevent statin-associated muscle symptoms (SAMS) in vivo is yet to be investigated. Therefore, this study aimed to evaluate the ability of GGOH to prevent SAMS in rodents. Female Wistar rats (12 weeks of age) were randomised to 1 of 4 treatment groups: control, control with GGOH, simvastatin or simvastatin with GGOH. Ex vivo assessment of force production was conducted in skeletal muscles of varying fiber composition. Ex vivo left ventricular performance and blood vessel function was also assessed to determine if the administration of GGOH caused adverse changes in these parameters. Statin administration was associated with reduced force production in fast-twitch glycolytic muscle, but coadministration with GGOH completely abrogated this effect. Additionally, GGOH improved the performance of muscles not adversely affected by simvastatin (ie, those with a greater proportion of slow-twitch oxidative fibers), and increased force production in the control animals. Neither control nor statin-treated rodents given GGOH exhibited adverse changes in cardiac function. Vascular relaxation was also maintained following treatment with GGOH. The findings of this study demonstrate that GGOH can prevent statin-induced skeletal muscle fatigue in rodents without causing adverse changes in cardiovascular function. Further studies to elucidate the exact mechanisms underlying the effects observed in this investigation are warranted. |
2,328,647 | Gender Differences in Characteristics and Outcome in Primary Intraventricular Hemorrhage. | Primary intraventricular hemorrhage (PIVH) is a rare type of Intracerebral Hemorrhage (ICH), which is poorly understood. This study aimed to investigate gender differences in patients' characteristics, management and outcome at discharge and 90 days after PIVH.</AbstractText>Consecutive patients with PIVH from a single center in China were enrolled over a 7- year period. Gender differences in demographics, risk factors, etiological subtypes, treatment, and outcomes were examined. The logistic regression models were used in the study to identify the predictors of poor outcome.</AbstractText>In total, 174 patients were analyzed, and 77 (44.3%) of them were women. Women with PIVH were younger (p = 0.047), with lower systolic and diastolic blood pressure (p = 0.02 and p = 0.004, respectively). They had more cases caused by Moyamoya disease (p = 0.038). There were fewer patients with hypertension (p = 0.008), smoking (p＜0.001), chronic alcoholism (p＜0.001), harbored lower hemoglobin (p＜0.001) and Absolute Monocyte Count (AMC) (p = 0.04) at admission compared with men. There were no differences between female and male patients regarding the mortality and poor outcome in the multivariable-adjusted models ((OR = 0.57; 95% CI, 0.15-2.14) and (OR = 0.86; 95% CI, 0.32-2.37), respectively). In subgroup analysis after adjustment, the gender specific independent predictors for unfavorable outcome were higher with a Graeb score (OR = 1.78; 95% CI, 1.01-3.13) or AMC (OR = 9.66; 95% CI, 1.20-12.87) in women, and lower Glasgow coma scale (GCS) score (OR = 0.64; 95% CI, 0.47-0.87) or acute hydrocephalus (OR = 0.17; 95% CI, 0.03-0.86) in men.</AbstractText>Women with PIVH exhibit some distinctive baseline features compared with men. The gender difference of the PIVH does not appear to affect the neurological outcome. The predictors of poor outcomes are Graeb score and AMC in women and GCS score and acute hydrocephalus in men.</AbstractText>Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.</CopyrightInformation> |
2,328,648 | The Internal Cerebral Vein: New Classification of Branching Patterns Based on CTA. | The internal cerebral vein begins at the foramen of Monro by the union of the thalamostriate and the anterior septal veins. The lateral direct vein is its other major tributary. Numerous researchers have reported differences in internal cerebral vein branching patterns but did not classify them. Hence, the objectives of this study were to evaluate the anatomy of the internal cerebral vein and its primary tributaries and classify them depending on their course patterns using CTA.</AbstractText>Head CTAs of 250 patients were evaluated in this study, in which we identified the number and termination of the anterior septal vein and the lateral direct vein. The course of the lateral direct vein and its influence on the number of thalamostriate veins and their diameters and courses were assessed. The anterior septal vein-internal cerebral vein junctions and their locations in relation to the foramen of Monro also were evaluated.</AbstractText>We classified internal cerebral vein branching patterns into 4 types depending on the presence of an extra vessel draining the striatum. Most commonly, the internal cerebral vein continued further as 1 thalamostriate vein (77%). The lateral direct veins were identified in 22% of the hemispheres, and usually they terminated at the middle third of the internal cerebral vein (65.45%). The most common location of the anterior septal vein-internal cerebral vein junction was anterior (57.20%), with the anterior septal vein terminating at the venous angle.</AbstractText>Detailed knowledge of the anatomy of the deep cerebral veins is of great importance in neuroradiology and neurosurgery because iatrogenic injury to the veins may result in basal nuclei infarcts. A classification of internal cerebral vein branching patterns may aid clinicians in planning approaches to the third and lateral ventricles.</AbstractText>© 2019 by American Journal of Neuroradiology.</CopyrightInformation> |
2,328,649 | Heterogeneity of Neural Stem Cells in the Ventricular-Subventricular Zone. | In this chapter, heterogeneity is explored in the context of the ventricular-subventricular zone, the largest stem cell niche in the mammalian brain. This niche generates up to 10,000 new neurons daily in adult mice and extends over a large spatial area with dorso-ventral and medio-lateral subdivisions. The stem cells of the ventricular-subventricular zone can be subdivided by their anatomical position and transcriptional profile, and the stem cell lineage can also be further subdivided into stages of pre- and post-natal quiescence and activation. Beyond the stem cells proper, additional differences exist in their interactions with other cellular constituents of the niche, including neurons, vasculature, and cerebrospinal fluid. These variations in stem cell potential and local interactions are discussed, as well as unanswered questions within this system. |
2,328,650 | Isolated, Subtle Neurological Abnormalities in Mild Cognitive Impairment Types. | Des anomalies neurologiques subtiles et isolées associées à différents types de déficience cognitive légère. Contexte: Des anomalies neurologiques à la fois subtiles et isolées sont fréquemment observées chez les personnes vieillissantes. Elles ont été associées à la maladie des petits vaisseaux du cerveau (cerebral small vessel disease) et à une atrophie des structures sous-corticales chez des sujets âgés en santé sur les plans neurologique et cognitif. Objectif: Étudier la fréquence de ces anomalies dans le cas de différents types de déficience cognitive légère ; évaluer, pour chaque type de déficience, la relation transversale entre ces anomalies et des hyper-signaux de la substance blanche, des lacunes cérébrales, l’atrophie du noyau caudé et l’élargissement des ventricules. Méthodes: Au total, 1250 sujets atteints de différents types de déficience cognitive légère ont été inclus dans notre analyse et ont passé un examen d’IRM du cerveau. On a évalué les hyper-signaux de la substance blanche à l’aide de deux échelles d’évaluation visuelle. À noter que les lacunes cérébrales ont également été évaluées. Du côté de l’atrophie du noyau caudé et de l’élargissement des ventricules, ces anomalies ont été mesurées respectivement au moyen de l’index bicaudé (bicaudate ratio) et du ratio volumique ventricule-cerveau (lateral ventricles to brain ratio). Enfin, les génotypes associés à l’apolipoprotéine E (ApoE) ont été examinés. Fait à souligner, des examens neurologiques de routine portant sur les signes du système nerveux central, sur les signes du cervelet et sur les réflexes archaïques ont été utilisés pour tenter de cerner les anomalies évoquées ci-dessus. Des éléments de la partie III de l’échelle UPDRS (Unified Parkinson’s Disease Rating Scale) ont été par ailleurs mis à profit pour évaluer les anomalies regroupées au sein de la catégorie des signes bénins de la maladie de Parkinson. Les liens entre ces anomalies et les résultats aux examens d’IRM ont été déterminés à l’aide d’une analyse de régression logistique. Résultats: Ces anomalies neurologiques à la fois subtiles et isolées augmentent en fonction de l’âge et sont présentes parmi tous les types de déficience cognitive légère, en particulier dans ces domaines multiples et chez les sujets porteurs de l’allèle ϵ4 du gène de l’ApoE. On a vu également qu’elles sont associées à des hyper-signaux de la substance blanche, à des lacunes cérébrales, à l’atrophie du noyau caudé et à l’élargissement des ventricules. Conclusion: Cette étude démontre que les processus vasculaires et atrophiques des structures corticales et sous-corticales contribuent à l’apparition d’anomalies neurologiques à la fois subtiles et isolées. Des études prospectives de longue haleine basées sur la population sont toutefois nécessaires pour mieux comprendre le rôle de ces anomalies dans l’évolution des cas de déficience cognitive légère vers la démence. |
2,328,651 | RBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury. | Hypoxic ischemia (HI) is an acute brain threat across all age groups. Therapeutic hypothermia ameliorates resulting injury in neonates but its side effects prevent routine use in adults. Hypothermia up-regulates a small protein subset that includes RNA-binding motif protein 3 (RBM3), which is neuroprotective under stressful conditions. Here we show how RBM3 stimulates neuronal differentiation and inhibits HI-induced apoptosis in the two areas of persistent adult neurogenesis, the subventricular zone (SVZ) and the subgranular zone (SGZ), while promoting neural stem/progenitor cell (NSPC) proliferation after HI injury only in the SGZ. RBM3 interacts with IGF2 mRNA binding protein 2 (IMP2), elevates its expression and thereby stimulates IGF2 release in SGZ but not SVZ-NSPCs. In summary, we describe niche-dependent regulation of neurogenesis after adult HI injury via the novel RBM3-IMP2-IGF2 signaling pathway. |
2,328,652 | Subcortical heterotopic gray matter brain malformations: Classification study of 107 individuals. | To better evaluate the imaging spectrum of subcortical heterotopic gray matter brain malformations (subcortical heterotopia [SUBH]), we systematically reviewed neuroimaging and clinical data of 107 affected individuals.</AbstractText>SUBH is defined as heterotopic gray matter, located within the white matter between the cortex and lateral ventricles. Four large brain malformation databases were searched for individuals with these malformations; data on imaging, clinical outcomes, and results of molecular testing were systematically reviewed and integrated with all previously published subtypes to create a single classification system.</AbstractText>Review of the databases revealed 107 patients with SUBH, the large majority scanned during childhood (84%), including more than half before 4 years (59%). Although most individuals had cognitive or motor disability, 19% had normal development. Epilepsy was documented in 69%. Additional brain malformations were common and included abnormalities of the corpus callosum (65/102 [64%]), and, often, brainstem or cerebellum (47/106 [44%]). Extent of the heterotopic gray matter brain malformations (unilateral or bilateral) did not influence the presence or age at onset of seizures. Although genetic testing was not systematically performed in this group, the sporadic occurrence and frequent asymmetry suggests either postzygotic mutations or prenatal disruptive events. Several rare, bilateral forms are caused by mutations in genes associated with cell proliferation and polarity (EML1</i>, TUBB</i>, KATNB1, CENPJ</i>, GPSM2</i>).</AbstractText>This study reveals a broad clinical and imaging spectrum of heterotopic malformations and provides a framework for their classification.</AbstractText>Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.</CopyrightInformation> |
2,328,653 | [Hematoma Expansion within 24 hours of Hypertensive Intracerebral Hemorrhage and Its Association with Signs on Nonenhanced Computed Tomography]. | To explore the correlation between hematoma expansion within 24 hours of hypertensive intracerebral hemorrhage and signs on nonenhanced computed tomography(NECT). Methods The clinical data and CT images of 185 patients with hypertensive intracerebral hemorrhage were retrospectively analyzed.The differences in CT parameters were compared between the expansion group and the unexpanded group.Binary logistic regression analysis was performed on the indicators with statistical significance between the two groups to identify the potential correlation between CT parameters and hematoma expansion.The roles of blend sign,lobulation sign,and black hole sign in predicting early hematoma expansion were assessed. Results The CT quantitative data including initial volume,maximum diameter,minimum diameter,maximum CT value,mean CT value,difference between maximum diameter and minimum diameter showed no significant difference between these two group(all <i>P</i>>0.05).CT qualitative data including blend sign,lobulation sign,and black hole sign were significantly different(<i>P</i><0.05)but the differences became not significant after the hematoma broke into the ventricles.Binary logistic regression analysis showed that blend sign,lobulation sign,and black hole sign were independent risk factors for early hematoma expansion,with sensitivity,specificity,positive predictive value,and negative predictive value of the combined signs and the early hematoma expansion calculated by the four-fold table method being 78.4%,59.0%,42.1%,and 87.8%,respectively,and the Youden index was 0.374.Its Youden index was closer to 1 than the blend sign,the black hole sign,and the lobulation sign. Conclusion The blend sign,lobulation sign,and black hole sign in NECT can be used to predict hematoma expansion within 24 hours after hypertensive cerebral hemorrhage. |
2,328,654 | Identification and Characterization of a Transcribed Distal Enhancer Involved in Cardiac Kcnh2 Regulation. | The human ether-a-go-go-related gene KCNH2 encodes the voltage-gated potassium channel underlying I<sub>Kr</sub>, a current critical for the repolarization phase of the cardiac action potential. Mutations in KCNH2 that cause a reduction of the repolarizing current can result in cardiac arrhythmias associated with long-QT syndrome. Here, we investigate the regulation of KCNH2 and identify multiple active enhancers. A transcribed enhancer ∼85 kbp downstream of Kcnh2 physically contacts the promoters of two Kcnh2 isoforms in a cardiac-specific manner in vivo. Knockdown of its ncRNA transcript results in reduced expression of Kcnh2b and two neighboring mRNAs, Nos3 and Abcb8, in vitro. Genomic deletion of the enhancer, including the ncRNA transcription start site, from the mouse genome causes a modest downregulation of both Kcnh2a and Kcnh2b in the ventricles. These findings establish that the regulation of Kcnh2a and Kcnh2b is governed by a complex regulatory landscape that involves multiple partially redundantly acting enhancers. |
2,328,655 | Impact of the cerebrospinal fluid-mask algorithm on the diagnostic performance of <sup>123</sup>I-Ioflupane SPECT: an investigation of parkinsonian syndromes. | A cerebrospinal fluid (CSF)-mask algorithm has been developed to reduce the adverse influence of CSF-low-counts on the diagnostic utility of the specific binding ratio (SBR) index calculated with Southampton method. We assessed the effect of the CSF-mask algorithm on the diagnostic performance of the SBR index for parkinsonian syndromes (PS), including Parkinson's disease, and the influence of cerebral ventricle dilatation on the CSF-mask algorithm.</AbstractText>We enrolled 163 and 158 patients with and without PS, respectively. Both the conventional SBR (non-CSF-mask) and SBR corrected with the CSF-mask algorithm (CSF-mask) were calculated from 123</sup>I-Ioflupane single-photon emission computed tomography (SPECT) images of these patients. We compared the diagnostic performance of the corresponding indices and evaluated whether the effect of the CSF-mask algorithm varied according to the extent of ventricle dilatation, as assessed with the Evans index (EI). A receiver-operating characteristics (ROC) analysis was used for statistical analyses.</AbstractText>ROC analyses demonstrated that the CSF-mask algorithm performed better than the non-CSF-mask (no correction, area under the curve [AUC] = 0.917 [95% confidence interval (CI) 0.887-0.947] vs. 0.895 [95% CI 0.861-0.929], p < 0.001; attenuation correction, AUC = 0.930 [95% CI 0.902-0.957] vs. 0.903 [95% CI 0.870-0.936], p < 0.001). When not corrected for attenuation, no significant difference in the AUC was observed in the low EI group between the non-CSF-mask and CSF-mask algorithms (0.927 [95% CI 0.877-0.978] vs. 0.942 [95% CI 0.898-0.986], p = 0.11); in the middle and high EI groups, the CSF-mask algorithm performed better than the non-CSF-mask algorithm (middle EI group, AUC = 0.894 [95% CI 0.825-0.963] vs. 0.872 [95% CI 0.798-0.947], p < 0.05; high EI group, AUC = 0.931 [95% CI 0.883-0.978] vs. 0.900 [95% CI 0.840-0.961], p < 0.01). When corrected for attenuation, significant differences in the AUC were observed in all three EI groups (low EI group, AUC = 0.961 [95% CI 0.924-0.998] vs. 0.942 [95% CI 0.895-0.988], p < 0.05; middle EI group, AUC = 0.905 [95% CI 0.843-0.968] vs. 0.872 [95% CI 0.800-0.944], p < 0.005; high EI group, AUC = 0.954 [95% CI 0.917-0.991] vs. 0.917 [95% CI 0.862-0.973], p < 0.005).</AbstractText>The CSF-mask algorithm improved the performance of the SBR index in informing the diagnosis of PS, especially in cases with ventricle dilatation.</AbstractText> |
2,328,656 | Imaging of cerebrospinal fluid flow: fundamentals, techniques, and clinical applications of phase-contrast magnetic resonance imaging. | Cerebrospinal fluid (CSF) is a dynamic compartment of the brain, constantly circulating through the ventricles and subarachnoid space. In recent years knowledge about CSF has expended due to numerous applications of phase-contrast magnetic resonance imaging (PC-MRI) in CSF flow evaluation, leading to the revision of former theories and new concepts about pathophysiology of CSF disorders, which are caused either by alterations in CSF production, absorption, or its hydrodynamics. Although alternative non-invasive techniques have emerged in recent years, PC-MRI is still a fundamental sequence that provides both qualitative and quantitative CSF assessment. PC-MRI is widely used to evaluate CSF hydrodynamics in normal pressure hydrocephalus (NPH), Chiari type I malformations (CMI), syringomyelia, and after neurosurgical procedures. In NPH precisely performed PC-MRI provides reliable clinical information useful for differential diagnosis and selection of patients benefiting from surgical operation. Patients with CMI show abnormalities in CSF dynamics within the subarachnoid space, which are pronounced even further if syringomyelia coexists. Another indication for PC-MRI may be assessment of post-surgical CSF flow normalisation. The aim of this review is to highlight the significance of CSF as a multifunctional entity, to outline both the physical and technical background of PC-MRI, and to state current applications of this technique, not only in the diagnosis of central nervous system disorders, but also in the further clinical monitoring and prognosis after treatment. |
2,328,657 | Clinical Implementation of Targeted Gene Sequencing for Malformation of Cortical Development. | Malformations of cortical development comprise phenotypically heterogeneous conditions, and the diagnostic value of genetic testing in blood still remains to be elucidated. We used targeted gene sequencing to identify malformations of cortical development caused by germline mutations and characteristics associated with pathogenic mutations.</AbstractText>A total of 81 patients with malformations of cortical development were included. Genomic DNA was isolated from peripheral blood. Ninety-six genes were assessed using a targeted next-generation sequencing panel. Single-nucleotide variants and exonic and chromosomal copy number variations were examined with our customized pipeline.</AbstractText>Genetic causes were identified from blood in 19 (23.5%) patients with malformations of cortical development; 14 patients had pathogenic or likely pathogenic single-nucleotide variants in seven genes, including DCX (n = 5), DEPDC5 (n = 2), PAFAH1B1 (n = 3), TUBA1A (n = 1), TUBA8 (n = 1), TUBB2B (n = 1), and TUBB3 (n = 1). Five patients had pathogenic copy number variations. Multifocal involvement of the lesion (tangential distribution, P < 0.001) and concurrent involvement of multiple structures such as the cortex, white matter, and ventricle (radial distribution, P = 0.003) were more commonly found in patients with identified genetic causes. Intellectual disability was also more commonly associated with pathogenic mutations (P = 0.048). In a multivariable regression analysis, both tangential and radial radiological distribution of malformations of cortical development were independently associated with positive germline test results.</AbstractText>We identified germline mutations in almost one-fourth of our patients with malformations of cortical development by using targeted gene sequencing. Germline abnormalities were more likely found in patients who had multifocal malformations of cortical development.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,658 | Positive Outcome of Endoscopic Third Ventriculostomy in Fourth Ventricular Outlet Obstruction. | We report a case of headache due to a hydrocephalus with associated syringomyelia. Magnetic resonance imaging showed a fourth ventricular outlet obstruction. An endoscopic third ventriculostomy (ETV) was performed with successful clinical and radiologic outcome. Fourth ventricular outlet obstruction is an uncommon cause of obstructive hydrocephalus, but it must be kept in mind. As far as we know, there are few reports that propose ETV as treatment. Therefore our case supports that ETV could be a successful option for the management of this condition. |
2,328,659 | First Intracranial Pressure Monitoring or First Operation: Which One Is Better? | For patients with TBI, traditional methods such as clinical examination and imaging data are the primary references used for deciding whether to operate or not. Intracranial pressure (ICP) monitoring based on lateral ventricles or parenchymal pressure is a more direct reflection of ICP. However, the research on whether the outcome results of ICP monitoring are better than results based on clinical signs and imaging is sparse. Therefore, we compared treatment results for patients with TBI based on ICP monitoring and traditional methods.</AbstractText>This retrospective study included patients with TBI admitted to our collaborative hospitals between January 1, 2012, and December 31, 2013. All patients enrolled were divided into a traditional methods group and ICP monitoring group. Follow-up treatment was determined by ICP monitoring value or traditional methods in the 2 groups. Propensity matching scores were used to ensure that baseline characteristics of patients in the 2 groups were consistent.</AbstractText>A significant association was found between the initial ICP value and neurologic deterioration (odds ratio 1.24; P < 0.001), and nonlinear correlation achieved the best fit (R2</sup> = 0.547). Both 6-month good recovery rate and favorable outcome rate were higher in the ICP monitoring group than the traditional methods group by propensity score analysis (P < 0.05).</AbstractText>For patients with TBI with cerebral contusion volume >20 mL, both 6-month good recovery rate and favorable outcome rate were significantly higher in the ICP monitoring group than the traditional methods group.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,660 | Transthyretin expression in the postischemic brain. | The unknown role of the carrier protein transthyretin (TTR) in mechanisms of functional recovery in the postischemic brain prompted us to study its expression following experimental stroke. Male C57/B6 mice (age 9 to 10 weeks) were subjected to permanent focal ischemia induced by photothrombosis (PT) and brain tissues were analyzed for ttr expression and TTR levels at 24 hours, 48 hours, 7 days and 14 days following the insult by RT-PCR, Western blot and immunohistochemistry. Fourteen days after PT, non-specific TTR-like immunoreactive globules were found in the ischemic core and surrounding peri-infarct region by immunohistochemistry that could not be allocated to DAPI positive cells. No TTR immunoreactivity was found when stainings were performed with markers for neurons (Neuronal Nuclei, NeuN), reactive astrocytes (glial fibrillary acidic protein, GFAP) or microglia (cluster of differentiation 68, CD68). In addition, we could not find TTR by immunoblotting in protein extracts obtained from the ischemic territory nor ttr expression by RT-PCR at all time points following PT. In all experiments, ttr expression in the choroid plexus and TTR in the mouse serum served as positive controls and recombinant legumain peptide as negative control. Together, our results indicate that TTR is not synthesized in brain resident cells in the ischemic infarct core and adjacent peri-infarct area. Thus, it seems unlikely that in situ synthesized TTR is involved in mechanisms of tissue reorganization during the first 14 days following PT. |
2,328,661 | [The Efficacy of the Emergent Shunt-Clamp System for Secondary Hydrocephalus Associated with Fourth Ventricle Outlet Obstruction Syndrome:A Report of Two Cases]. | Endoscopic third ventriculostomy(ETV)is the first-line treatment for fourth ventricle outlet obstruction(FVOO)-associated hydrocephalus. However, because FVOO is difficult to diagnose in the acute stage, ventriculoperitoneal shunt(VPS)is also used. Herein, we report two cases of shunted FVOO resulting in overdrainage or slit ventricle syndrome(SVS)that were treated successfully with the shunt-clamp system. In addition, we discuss the efficacy of the shunt-clamp system for FVOO-associated hydrocephalus. CASE 1:A 79-year-old man complained of severe postural headaches. One year earlier, he underwent VPS for secondary hydrocephalus associated with hemorrhagic cerebellar infarction. CT revealed that the ventricle had become slit-like. Although the shunt valve adjusted the maximum pressure, his complaint and the ventricle shape did not improve. After the on-off valve was inserted in the shunt system and clamped, his symptoms were resolved and the ventricle size was normalized. CASE 2:A 21-year-old man who complained of drowsiness, diplopia, and severe intermittent retroocular pain was admitted to our hospital. One year earlier, he underwent VPS with the shunt-clamp system for a secondary hydrocephalus after surgery for medulloblastoma. CT on admission revealed ventricle dilatation;however, the shape of the ventricle became slit-like 3 days after admission. We made a diagnosis of SVS and planned ETV. Owing to the difficulty in approaching the lateral ventricle, the shunt system was clamped 8 hours before the operation. After confirming ventricle dilatation, ETV was successfully performed. After the operation, the symptoms were resolved, and magnetic resonance imaging confirmed that the ventricle size was normalized. |
2,328,662 | [A Case of Dural Arteriovenous Fistula Involving the Superior Sagittal Sinus that Presented as a Primary Intraventricular Hemorrhage]. | We report an extremely rare case of dural arteriovenous fistula(DAVF)involving the superior sagittal sinus(SSS)that presented as a primary intraventricular hemorrhage(PIVH). A 79-year-old man who presented with disturbance of consciousness and vomiting was transferred to our hospital. The initial head CT revealed an intraventricular hemorrhage in the lateral, third, and fourth ventricles, predominantly involving the right lateral ventricle associated with obstructive hydrocephalus. CT angiography and three-dimensional rotational angiography(3D-RA)revealed SSS-DAVF with retrograde venous drainage from the cortical venous system to the subependymal venous system through engorged superficial/anastomotic/deep medullary or transcerebral veins, showing a pseudophlebitic pattern. A severe stenosis of the SSS was observed at the site just proximal to the shunting point. A varix of the right transvers caudate vein(TCV)was observed within the thickest portion of the hematoma in close contact with the wall of the right lateral ventricle. A stenosis of the branching point of the right TCV was detected on the 3D-RA image. The DAVF was completely cured after transarterial embolization. The varix gradually shrank and finally disappeared after 2 months. This is the first report of a case of PIVH due to SSS-DAVF with a subependymal varix considered as the bleeding point. Serial gadolinium-enhanced MR images clearly showed the shrinking of the varix. Our case is the second reported case of spontaneous resolution of the varix after embolization of the DAVF. The obstructive changes of the two venous outflow pathways(SSS/TCV)might further worsen the state of venous congestion in the deep medullary venous system and eventually lead to formation and rupture of the varix. |
2,328,663 | A data augmentation approach to train fully convolutional networks for left ventricle segmentation. | Left ventricle (LV) segmentation plays an important role in the diagnosis of cardiovascular diseases. The cardiac contractile function can be quantified by measuring the segmentation results of LVs. Fully convolutional networks (FCNs) have been proven to be able to segment images. However, a large number of annotated images are required to train the network to avoid overfitting, which is a challenge for LV segmentation owing to the limited small number of available training samples. In this paper, we analyze the influence of augmenting training samples used in an FCN for LV segmentation, and propose a data augmentation approach based on shape models to train the FCN from a few samples. We show that the balanced training samples affect the performance of FCNs greatly. Experiments on four public datasets demonstrate that the FCN trained by our augmented data outperforms most existing automated segmentation methods with respect to several commonly used evaluation measures. |
2,328,664 | Inverse localization of earliest cardiac activation sites from activation maps based on the viscous Eikonal equation. | In this study we propose a novel method for identifying the locations of earliest activation in the human left ventricle from activation maps measured at the epicardial surface. Electrical activation is modeled based on the viscous Eikonal equation. The sites of earliest activation are identified by solving a minimization problem. Arbitrary initial locations are assumed, which are then modified based on a shape derivative based perturbation field until a minimal mismatch between the computed and the given activation maps on the epicardial surface is achieved. The proposed method is tested in two numerical benchmarks, a generic 2D unit-square benchmark, and an anatomically accurate MRI-derived 3D human left ventricle benchmark to demonstrate potential utility in a clinical context. For unperturbed input data, our localization method is able to accurately reconstruct the earliest activation sites in both benchmarks with deviations of only a fraction of the used spatial discretization size. Further, with the quality of the input data reduced by spatial undersampling and addition of noise, we demonstrate that an accurate identification of the sites of earliest activation is still feasible. |
2,328,665 | Symptomatic cysts of the cavum septi pellucidi, cavum vergae and cavum veli interpositi: A retrospective duocentric study of 10 patients. | Cysts of the Cavum septi pellucidi (CSP), cavum vergae (CV) and cavum veli interpositi (CVI) are anterior midline intracranial findings which are typically incidental - only rarely do we encounter symptomatic cysts of this type. Only a quite small number of these cysts series have been published, controversies regarding optimal management still exist.</AbstractText>This is a retrospective study of 10 patients treated at 2 clinics between 2002-2018. 9 patients underwent surgery and 1 is under long-term monitoring. Apart from demographic data, the study analyzed symptoms, cyst size and progression over time, ventricle size, complications, and treatment modality.</AbstractText>CSP with CV was found in 8 cases with 1 case each of CSP and CVI. The study comprised 6 men and 4 women, including 4 children. The mean follow-up time was 43.4 months. The average cyst size was 20.4 mm in CSP and 19.8 mm in CV; the CVI was 33 mm. Headache was most commonly reported (70%) followed by behavioral disturbance (30%). Disturbance in memory, psychomotor development, school performance, visual acuity, and vomiting was variously noted in 20%. The prevailing symptom was headache in adults and behavioral and autonomic disturbance in children. Postoperatively, cysts had reduced by an average of 44.3% while the ventricles remained unchanged. Symptoms resolved in all cases with residual problems in patients presenting with memory loss. No complications were noted.</AbstractText>Endoscopic fenestration is the method of choice in the treatment of symptomatic midline cysts. We recommend that any further research focuses on precisely establishing their clinical presentation, particularly neuropsychological symptoms.</AbstractText>Copyright © 2019 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,328,666 | The hippocampal-to-ventricle ratio (HVR): Presentation of a manual segmentation protocol and preliminary evidence. | Disentangling age-related changes from developmental variations in hippocampal volume has proven challenging. This article presents a manual segmentation protocol for the hippocampal-to-ventricle ratio (HVR), a measure combining the assessment of hippocampal volume with surrounding ventricular volume. By providing in a single measure both a standard volumetric assessment of the hippocampus and an approximation of volume loss, based on ventricular enlargement, we believe the HVR provides a superior cross-sectional estimation of hippocampal structural integrity. In a first attempt to validate this measure, we contrasted the HVR and standard hippocampal volume in their associations with age and memory performance in two independent cohorts of healthy aging individuals. The first cohort consisted in 50 cognitively normal subjects (mean age: 66.8 years, SD: 4.96, range: 60-75 years), while the second cohort included 88 cognitively normal subjects (mean age: 65.06 years, SD: 6.42, range: 55-80 years). We showed that the manual segmentation protocol for the HVR can be implemented with high reliability. In both cohorts, the HVR showed stronger negative associations with age than standard hippocampal volume. Correlations with memory performance were also numerically superior with the HVR than standard hippocampal volume, across the two cohorts. These findings support an added benefit of using the HVR over standard hippocampal volume when examining relationships with age or memory function in aging individuals. Although further validation is required, we propose that the computation of the HVR is a promising method to improve the evaluation of hippocampal integrity from cross-sectional MR images. |
2,328,667 | Apelin-36-[L28A] and Apelin-36-[L28C(30kDa-PEG)] peptides that improve diet induced obesity are G protein biased ligands at the apelin receptor. | Apelin signalling pathways have important cardiovascular and metabolic functions. Recently, apelin-36-[L28A] and apelin-36-[L28C(30kDa-PEG)], were reported to function independent of the apelin receptor in vivo to produce beneficial metabolic effects without modulating blood pressure. We aimed to show that these peptides bound to the apelin receptor and to further characterise their pharmacology in vitro at the human apelin receptor.</AbstractText>[Pyr1</sup>]apelin-13 saturation binding experiments and competition binding experiments were performed in rat and human heart homogenates using [125</sup>I]apelin-13 (0.1 nM), and/or increasing concentrations of apelin-36, apelin-36-[L28A] and apelin-36-[L28C(30kDa-PEG)] (50pM-100μM). Apelin-36 and its analogues apelin-36-[F36A], apelin-36-[L28A], apelin-36-[L28C(30kDa-PEG)], apelin-36-[A28 A13] and [40kDa-PEG]-apelin-36 were tested in forskolin-induced cAMP inhibition and β-arrestin assays in CHO-K1 cells heterologously expressing the human apelin receptor. Bias signaling was quantified using the operational model for bias.</AbstractText>In both species, [Pyr1</sup>]apelin-13 had comparable subnanomolar affinity and the apelin receptor density was similar. Apelin-36, apelin-36-[L28A] and apelin-36-[L28C(30kDa-PEG)] competed for binding of [125</sup>I]apelin-13 with nanomolar affinities. Apelin-36-[L28A] and apelin-36-[L28C(30kDa-PEG)] inhibited forskolin-induced cAMP release, with nanomolar potencies but they were less potent compared to apelin-36 at recruiting β-arrestin. Bias analysis suggested that these peptides were G protein biased. Additionally, [40kDa-PEG]-apelin-36 and apelin-36-[F36A] retained nanomolar potencies in both cAMP and β-arrestin assays whilst apelin-36-[A13 A28] exhibited a similar profile to apelin-36-[L28C(30kDa-PEG)] in the β-arrestin assay but was more potent in the cAMP assay.</AbstractText>Apelin-36-[L28A] and apelin-36-[L28C(30kDa-PEG)] are G protein biased ligands of the apelin receptor, suggesting that the apelin receptor is an important therapeutic target in metabolic diseases.</AbstractText>Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,668 | BK channels regulate calcium oscillations in ventricular myocytes on different substrate stiffness. | Substrate stiffness is essential for cell functions, but the mechanisms by which cell sense mechanical cues are still unclear. Here we show that the frequency and the amplitude of spontaneous Ca<sup>2+</sup> oscillations were greater in chick cardiomyocytes cultured on the stiff substrates than that on the soft substrates. The spontaneous Ca<sup>2+</sup> oscillations were increased on stiff substrates. However, an eliminated dependence of the Ca<sup>2+</sup> oscillations on substrate stiffness was observed after applying blocker of the large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (BK) channels. In addition, the activity of BK channels in cardiomyocytes cultured on the stiff substrates was decreased. These results provide compelling evidences to show that BK channels are crucial in substrate stiffness-dependent regulation of the Ca<sup>2+</sup> oscillation in cardiomyocytes. |
2,328,669 | Intraventricular meningiomas frequently harbor NF2 mutations but lack common genetic alterations in TRAF7, AKT1, SMO, KLF4, PIK3CA, and TERT. | Intraventricular meningiomas (IVMs) account for less than 5% of all intracranial meningiomas; hence their molecular phenotype remains unknown. In this study, we were interested whether genetic alterations in IVMs differ from meningiomas in other locations and analyzed our institutional series with respect to clinical and molecular characteristics. A total of 25 patients with surgical removal of an IVM at our department between 1986 and 2018 were identified from our institutional database. Median progression-free survival (PFS) was 79 months (range of 2-319 months) and PFS at 5 years was 86%. Corresponding tumor tissue was available for 18 patients including one matching recurrence and was subjected to targeted panel sequencing of 130 selected genes frequently mutated in brain cancers by applying a custom hybrid capture approach on a NextSeq500 instrument. Loss of chromosome 22q and 1p occurred frequently in 89 and 44% of cases. Deleterious NF2 mutations were found in 44% of IVMs (n = 8/18). In non-NF2-mutated IVMs, previously reported genetic alterations including TRAF7, AKT1, SMO, KLF4, PIK3CA, and TERT were lacking, suggesting alternative genes in the pathogenesis of non-NF2 IVMs. In silico analysis revealed possible damaging mutations of APC, GABRA6, GSE1, KDR, and two SMO missense mutations differing from previously reported ones. Interestingly, all WHO°II IVMs (n = 3) harbored SMARCB1 and SMARCA4 mutations, indicating a role of the SWI/SNF chromatin remodeling complex in aggressive IVMs. |
2,328,670 | Surgical Management of Iatrogenic Left Ventricle Perforation by Chest Tube Insertion. | Chest tube thoracostomy is a standard procedure in every intensive care unit. Although it is regarded as a safe procedure in experienced hands, rare complications do occur. This report describes iatrogenic perforation of the left ventricle after placement of an intercostal catheter and the successful surgical management of this injury. Various operative situations that may arise in relation to iatrogenic perforation of the left ventricle are also discussed, as well as steps to manage this potentially life-threatening complication. |
2,328,671 | Tanycytic TSPO inhibition induces lipophagy to regulate lipid metabolism and improve energy balance. | Hypothalamic glial cells named tanycytes, which line the 3rd</sup> ventricle (3V), are components of the hypothalamic network that regulates a diverse array of metabolic functions for energy homeostasis. Herein, we report that TSPO (translocator protein), an outer mitochondrial protein, is highly enriched in tanycytes and regulates homeostatic responses to nutrient excess as a potential target for an effective intervention in obesity. Administration of a TSPO ligand, PK11195, into the 3V, and tanycyte-specific deletion of Tspo</i> reduced food intake and elevated energy expenditure, leading to negative energy balance in a high-fat diet challenge. Ablation of tanycytic Tspo</i> elicited AMPK-dependent lipophagy, breaking down lipid droplets into free fatty acids, thereby elevating ATP in a lipid stimulus. Our findings suggest that tanycytic TSPO affects systemic energy balance through macroautophagy/autophagy-regulated lipid metabolism, and highlight the physiological significance of TSPO in hypothalamic lipid sensing and bioenergetics in response to overnutrition.</AbstractText>3V: 3rd</sup> ventricle; ACAC: acetyl-Coenzyme A carboxylase; AGRP: agouti related neuropeptide; AIF1/IBA1: allograft inflammatory factor 1; AMPK: AMP-activated protein kinase; ARC: arcuate nucleus; Atg: autophagy related; Bafilo: bafilomycin A1</sub>; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CNS: central nervous system; COX4I1: cytochrome c oxidase subunit 4I1; FFA: free fatty acid; GFAP: glial fibrillary acidic protein; HFD: high-fat diet; ICV: intracerebroventricular; LAMP2: lysosomal-associated membrane protein 2; LD: lipid droplet; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MBH: mediobasal hypothalamus; ME: median eminence; MEF: mouse embryonic fibroblast; NCD: normal chow diet; NEFM/NFM: neurofilament medium; NPY: neuropeptide Y; OL: oleic acid; POMC: pro-opiomelanocortin-alpha; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; Rax</i>: retina and anterior neural fold homeobox; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; RER: respiratory exchange ratio; siRNA: small interfering RNA; SQSTM1: sequestosome 1; TG: triglyceride; TSPO: translocator protein; ULK1: unc-51 like kinase 1; VCO2</sub>: carbon dioxide production; VMH: ventromedial hypothalamus; VO2</sub>: oxygen consumption.</AbstractText> |
2,328,672 | Does ventricular volume affect the neurodevelopmental outcome in infants with intraventricular hemorrhage? | The aim of this study is to investigate whether ventricular volume in posthemorrhagic ventricle dilatation impacts neurodevelopmental outcome. Infants were scanned with 3D cranial ultrasound in the first few months of life, and their neurodevelopmental outcome at 4, 8, 12, and 24 months corrected age (CA) was examined.</AbstractText>Forty-nine infants who suffered an intraventricular hemorrhage (IVH) were enrolled in the study. Subjects were scanned multiple times during their stay in the neonatal intensive care unit. Images were manually segmented to measure total volume of the lateral ventricles, and the highest volume was taken. Infants with a volume ≤ 20 cc were considered low-volume (n = 33), and infants with a volume ≥ 40 cc were considered high-volume (n = 12). Developmental outcome was assessed at 4, 8, and 12 months CA with the Alberta Infant Motor Scale (AIMS) and Infant Neurological International Battery (Infanib), and at 24 months CA with the Bayley Scales of Infant Development 3e (BSID III).</AbstractText>Infants in the low-volume group had higher scores on the Infanib at 4 months CA, and on both the AIMS and Infanib at 8 and 12 months CA, even after controlling for gestational age, birth weight, and worst grade of IVH. We observed a trend where low-volume infants also scored higher on the cognitive and gross-motor subtests of the BSID III at 24 months CA.</AbstractText>Our results show that ventricular volume affects neurodevelopmental outcome in infants with IVH. This finding could guide the timing of future interventions, as earlier intervention may decrease the likelihood of adverse neurodevelopmental outcome.</AbstractText> |
2,328,673 | A Deep Learning Segmentation Approach in Free-Breathing Real-Time Cardiac Magnetic Resonance Imaging. | The purpose of this study was to segment the left ventricle (LV) blood pool, LV myocardium, and right ventricle (RV) blood pool of end-diastole and end-systole frames in free-breathing cardiac magnetic resonance (CMR) imaging. Automatic and accurate segmentation of cardiac structures could reduce the postprocessing time of cardiac function analysis.</AbstractText>We proposed a novel deep learning network using a residual block for the segmentation of the heart and a random data augmentation strategy to reduce the training time and the problem of overfitting. Automated cardiac diagnosis challenge (ACDC) data were used for training, and the free-breathing CMR data were used for validation and testing.</AbstractText>The average Dice was 0.919 (LV), 0.806 (myocardium), and 0.818 (RV). The average IoU was 0.860 (LV), 0.699 (myocardium), and 0.761 (RV).</AbstractText>The proposed method may aid in the segmentation of cardiac images and improves the postprocessing efficiency of cardiac function analysis.</AbstractText> |
2,328,674 | Fate of nanoparticles in the central nervous system after intrathecal injection in healthy mice. | Cerebrospinal fluid (CSF) is produced in the cerebral ventricles and circulates within the subarachnoid space (SAS) of the brain and spinal cord, where it exchanges with interstitial fluid of the parenchyma. The access of CSF to the entire central nervous system (CNS) makes it an attractive medium for drug delivery. However, few intrathecal (IT) therapies have reached the clinic due, in part, to limited distribution and rapid clearance. Given the success of nanoparticle (NP) carriers in prolonging circulation and improving delivery of systemically administered agents, we sought to evaluate the distribution of IT injected NPs within the CNS. We administered fluorescent, 100 nm PEGylated-NPs into the cisterna magna of healthy mice and studied their distribution along the brain and spinal cord. Our data demonstrate that NPs are capable of distributing rapidly through the SAS along the entire neuraxis with reproducible, anatomically defined patterns of delivery. NPs were well retained within the leptomeninges for over 3 weeks, showing preference for ventral surfaces and minimal penetration into the CNS parenchyma. Clearance of NPs occurred across the cribriform plate into the nasal mucosa, with a small fraction of NPs localizing with nerve roots exiting the spinal column. Larger 10 µm particles were also capable of moving through the SAS but did not achieve as widespread distribution. These studies demonstrate the ability of NPs to achieve widespread delivery along the neuraxis and highlight IT administration as a potentially significant route of administration for delivery of nanomedicine to the subarachnoid space. |
2,328,675 | Subretinal and Retrolaminar Migration of Intraocular Silicone Oil Detected on CT. | Intraocular silicone oil injection has been used to treat complicated retinal detachments, and recently its retrolaminar and intracranial migration has been reported. The purpose of this study was to document the prevalence of posterior migration of intraocular silicone oil on head CT and describe the clinical and radiologic findings.</AbstractText>This retrospective study included 57 patients with intraocular silicone oil injection who underwent unenhanced head CT between November 2008 and July 2018. All images were visually evaluated for subretinal and retrolaminar migration of intraocular silicone oil involving the anterior visual pathway (optic nerve, optic chiasm, and optic tract) and the ventricular system. Attenuation values of those structures were measured and compared with those of the contralateral or adjacent normal structures.</AbstractText>We detected subretinal and retrolaminar silicone oil migration in 7 of the 57 patients (12%), noting silicone oil at the optic nerve head (n</i> = 2), retrolaminar optic nerve (n</i> = 5), optic chiasm (n</i> = 3), optic tract (n</i> = 3), and in the lateral ventricles (n</i> = 1). Attenuation values of the structures with silicone oil migration were significantly higher than those of the control regions (optic nerve head, 69.2 ± 12.4 vs 29.8 ± 10.2 HU, P</i> < .001; retrolaminar optic nerve, 59.9 ± 11.6 vs 30.9 ± 8.6 HU, P</i> < .001; optic chiasm, 74.2 ± 11.0 vs 25.6 ± 6.9 HU, P</i> < .001; optic tract, 70.1 ± 4.7 vs 28.7 ± 7.2 HU, P</i> < .001). No significant ophthalmic or neurologic complications were documented in the patients with silicone oil migration.</AbstractText>Subretinal and retrolaminar migration of intraocular silicone oil is common. Although there were no apparent complications associated with silicone oil migration, the radiologist and clinician should be aware of this phenomenon.</AbstractText>© 2019 by American Journal of Neuroradiology.</CopyrightInformation> |
2,328,676 | Global and Regional Changes in Cortical Development Assessed by MRI in Fetuses with Isolated Nonsevere Ventriculomegaly Correlate with Neonatal Neurobehavior. | Fetuses with isolated nonsevere ventriculomegaly (INSVM) are at risk of presenting neurodevelopmental delay. However, the currently used clinical parameters are insufficient to select cases with high risk and determine whether subtle changes in brain development are present and might be a risk factor. The aim of this study was to perform a comprehensive evaluation of cortical development in INSVM by magnetic resonance (MR) imaging and assess its association with neonatal neurobehavior.</AbstractText>Thirty-two INSVM fetuses and 29 healthy controls between 26-28 weeks of gestation were evaluated using MR imaging. We compared sulci and fissure depth, cortical maturation grading of specific areas and sulci and volumes of different brain regions obtained from 3D brain reconstruction of cases and controls. Neonatal outcome was assessed by using the Neonatal Behavioral Assessment Scale at a mean of 4 ± 2 weeks after birth.</AbstractText>Fetuses with INSVM showed less profound and underdeveloped sulcation, including the Sylvian fissure (mean depth: controls 16.8 ± 1.9 mm, versus INSVM 16.0 ± 1.6 mm; P</i> = .01), and reduced global cortical grading (mean score: controls 42.9 ± 10.2 mm, versus INSVM: 37.8 ± 9.9 mm; P</i> = .01). Fetuses with isolated nonsevere ventriculomegaly showed a mean global increase of gray matter volume (controls, 276.8 ± 46.0 ×10 mm3</sup>, versus INSVM 277.5 ± 49.3 ×10 mm3</sup>, P</i> = .01), but decreased mean cortical volume in the frontal lobe (left: controls, 53.2 ± 8.8 ×10 mm3</sup>, versus INSVM 52.4 ± 5.4 ×10 mm3</sup>; P</i> = < .01). Sulcal depth and brain volumes were significantly associated with the Neonatal Behavioral Assessment Scale severity (P</i> = .005, Nagelkerke R2</sup> = 0.732).</AbstractText>INSVM fetuses showed differences in cortical development, including regions far from the lateral ventricles, that are associated with neonatal neurobehavior. These results suggest the possible use of these parameters to identify cases at higher risk of altered neurodevelopment.</AbstractText>© 2019 by American Journal of Neuroradiology.</CopyrightInformation> |
2,328,677 | Continuous intrathecal injection therapy of methotrexate is a therapeutic option in primary CNS lymphoma. | Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin's lymphoma, and its prognosis is still very poor despite the conventional therapy of high-dose methotrexate (HD-MTX) followed by whole-brain radiation therapy (WBRT). The purpose of the present study was to evaluate the survival benefit of continuous intrathecal injection therapy of methotrexate (CIT-MTX) combined with the conventional therapy. A total of 26 PCNSL patients treated with CIT-MTX were analyzed. Ten mg of methotrexate were continuously injected into the lateral ventricle via a subcutaneous port over 5 days biweekly for 5 cycles. CIT-MTX was performed with WBRT in addition to HD-MTX in 15 cases, and 11 cases with high risk for HD-MTX were treated with CIT-MTX and WBRT. The response rate of all patients was 92.3%, and median progression-free survival and median overall survival (mOS) were 59.4 months and 93.8 months, respectively. Median OS of patients treated with CIT-MTX in addition to HD-MTX and WBRT was longer than the previously reported mOS with HD-MTX and WBRT (95 vs 33 months). In cases that could not tolerate HD-MTX, mOS of patients treated with CIT-MTX and WBRT was longer than the previously reported mOS with WBRT alone (36.7 vs 18 months). There was no difference in OS between patients with cerebrospinal fluid dissemination and patients without (p = 0.83). Better prognosis in patients treated with CIT-MTX may be derived from stable concentration of methotrexate in the cerebrospinal fluid. CIT-MTX was an effective additional therapeutic option for PCNSL. |
2,328,678 | Central leukotrienes modulate fever tolerance to LPS in rats. | Leukotrienes mediate several inflammatory events such as neutrophil chemoattraction, leukocyte adhesion, and central-release of cytokines and fever. However, there is no information available about their putative role in lipopolysaccharide (LPS) tolerance. The rational of the present study was to find out if central leukotrienes are involved in the development of LPS tolerance. Thus, we inhibited central leukotriene synthesis in tolerant rats using a pharmacological tool, i.e., a selective inhibitor of leukotriene synthesis MK-886 injected into the third ventricle (3V) of rats. Body core temperature (Tb) was measured using a datalogger placed inside the abdominal cavity. A low-dose of LPS (100 μg/kg ip) was given for 4 consecutive days to induce LPS tolerance. At day 4, rats received a microinjection of MK-886 into the 3V immediately before LPS, whereas control groups were treated with vehicle (saline). We observed that LPS failed to induce plasma cytokines surges, increased hypothalamic PGE<sub>2</sub> levels and fever 3 days post LPS treatment, aptly characterizing the tolerance. When MK-886 was given to control rats treated with saline, no significant change in Tb was observed. However, a full LPS-induced fever was observed in tolerant rats pretreated with MK-886, which was associated with an enhancement in the hypothalamic PGE<sub>2</sub> levels, that were not accompanied by plasma cytokines (IL-1β, and IL-6) and PGE<sub>2</sub> surges. These data are consistent with the notion that central leukotrienes play a role in fever tolerance to LPS. |
2,328,679 | Dynamic pixel-wise weighting-based fully convolutional neural networks for left ventricle segmentation in short-axis MRI. | Left ventricle (LV) segmentation in cardiac MRI is an essential procedure for quantitative diagnosis of various cardiovascular diseases. In this paper, we present a novel fully automatic left ventricle segmentation approach based on convolutional neural networks. The proposed network fully takes advantages of the hierarchical architecture and integrate the multi-scale feature together for segmenting the myocardial region of LV. Moreover, we put forward a dynamic pixel-wise weighting strategy, which can dynamically adjust the weight of each pixel according to the segmentation accuracy of upper layer and force the pixel classifier to take more attention on the misclassified ones. By this way, the LV segmentation performance of our method can be improved a lot especially for the apical and basal slices in cine MR images. The experiments on the CAP database demonstrate that our method achieves a substantial improvement compared with other well-know deep learning methods. Beside these, we discussed two major limitations in convolutional neural networks-based semantic segmentation methods for LV segmentation. |
2,328,680 | Kaolin-induced hydrocephalus causes acetylcholinesterase activity dysfunction following hypothalamic damage in infant rats. | In hydrocephalus, the progressive accumulation of cerebrospinal fluid (CSF) causes dilatation of the lateral ventricles affecting the third ventricle and diencephalic structures such as the hypothalamus. These structures play a key role in the regulation of several neurovegetative functions by the production of the hormones. Since endocrine disturbances are commonly observed in hydrocephalic children, we investigated the impact of progressive ventricular dilation on the hypothalamus of infant rats submitted to kaolin-induced hydrocephalus. Seven-day-old infant rats were submitted to hydrocephalus induction by kaolin 20% injection method. After 14 days, the animals were decapitated and brain was collected to analyze mitochondrial function, neuronal activity by acetylcholinesterase (AChE) enzyme, oxidative damage, glial activation, and, neurotransmission-related proteins and anti-apoptotic processes in the hypothalamus. The hydrocephalic animals showed reduction in respiratory rates in the States of phosphorylation (P < 0.01) and non-phosphorylation (P < 0.05); increase in AChE activity in both the cytosol (P < 0.05) and the membrane (P < 0.01); decrease in synaptophysin (P < 0.05) and Bcl-2 (P < 0.05) contents and; increase in protein carbonyl (P < 0.01), GFAP (P < 0.01) and Iba-1 (P < 0.05) levels. The results demonstrate that ventricular dilation causes hypothalamic damage characterized by cholinergic dysfunction and suggests further investigation of the synthesis and secretion of hormones to generate new approaches and to assist in the treatment of hydrocephalic patients with hormonal alterations. |
2,328,681 | Feasibility study of using one-tenth mSv radiation dose in young children chest CT with 80 kVp and model-based iterative reconstruction. | CT has become a routine imaging modality based on its excellent ability of displaying lung structures and diseases. But, how to reduce radiation dose of routine CT examination is a concern for radiologists. Our study aimed to evaluate the feasibility of using 80kVp and a model-based iterative reconstruction (MBIR) algorithm to achieve one-tenth mSv dose chest CT in infants and young children. Thirty-two cases (study group, average age 1.71 ± 1.01 years) underwent non-contrast chest CT examination at low dose with 80 kV, 4mAs and was reconstructed with MBIR (LD-MBIR) and the standard adaptive statistical iterative reconstruction (ASIR) algorithm (LD-ASIR); another group (control group) of 32 children underwent routine-dose chest CT with 100 kV and was reconstructed with ASIR only (RD-ASIR). The subjective and objective image quality of the three groups were measured and statistically compared. The radiation dose for the low dose scan was 0.09 ± 0.02 mSv, 6% of the routine dose. All LD-MBIR images were diagnostically acceptable. Compared with the RD-ASIR images, the LD-MBIR images were similar in noise in the left ventricle, muscles, lung field, on-par in displaying large airways, lung lucency and mediastinum, but were inferior in displaying lung marking, small airways and mediastinum. Thus, MBIR images with low dose in pediatric chest CT can be used in the diagnosis for lung field and air way disorders in infants and young children. |
2,328,682 | Hierarchical Template Matching for 3D Myocardial Tracking and Cardiac Strain Estimation. | Myocardial tracking and strain estimation can non-invasively assess cardiac functioning using subject-specific MRI. As the left-ventricle does not have a uniform shape and functioning from base to apex, the development of 3D MRI has provided opportunities for simultaneous 3D tracking, and 3D strain estimation. We have extended a Local Weighted Mean (LWM) transformation function for 3D, and incorporated in a Hierarchical Template Matching model to solve 3D myocardial tracking and strain estimation problem. The LWM does not need to solve a large system of equations, provides smooth displacement of myocardial points, and adapt local geometric differences in images. Hence, 3D myocardial tracking can be performed with 1.49 mm median error, and without large error outliers. The maximum error of tracking is up to 24% reduced compared to benchmark methods. Moreover, the estimated strain can be insightful to improve 3D imaging protocols, and the computer code of LWM could also be useful for geo-spatial and manufacturing image analysis researchers. |
2,328,683 | Ascl1 Balances Neuronal versus Ependymal Fate in the Spinal Cord Central Canal. | Generation of neuronal types at the right time, location, and number is essential for building a functional nervous system. Significant progress has been reached in understanding the mechanisms that govern neuronal diversity. Cerebrospinal fluid-contacting neurons (CSF-cNs), an intriguing spinal cord central canal population, are produced during advanced developmental stages, simultaneous with glial and ependymal cells. It is unknown how CSF-cNs are specified after the neurogenesis-to-gliogenesis switch. Here, we identify delayed Ascl1 expression in mouse spinal progenitors during the gliogenic phase as key in CSF-cN differentiation. With fate mappings and time-controlled deletions, we demonstrate that CSF-cNs derive from Ascl1-expressing cells and that Ascl1 triggers late neurogenesis in the amniote spinal cord. Ascl1 abrogation transforms prospective CSF-cN progenitors into ependymocytes. These results demonstrate that late spinal progenitors have the potential to produce neurons and that Ascl1 initiates CSF-cN differentiation, controlling the precise neuronal and nonneuronal composition of the spinal central canal. |
2,328,684 | Subcostal TAPSE: a retrospective analysis of a novel right ventricle function assessment method from the subcostal position in patients with sepsis. | Tricuspid annular plane systolic excursion (TAPSE) is frequently used as an objective measure of right-ventricular dysfunction. Abnormal TAPSE values are associated with poor prognosis in a number of disease states; however, the measure is not always easy to obtain in the critically ill. The purpose of this study is to assess the feasibility and accuracy of using a subcostal view and TAPSE measurement as a measure of right-ventricular dysfunction. A secondary aim was to perform a pilot study to assess whether right-ventricular dysfunction was associated with adverse outcomes including mortality.</AbstractText>Subcostal TAPSE corresponds well with TAPSE obtained from the apical window at low and moderate TAPSE values (mean difference 1.2 mm (CI 0.04-2.36; 100% data pairs < 3-mm difference for TAPSE < 19 mm; 92% had < 3 mm difference at TAPDE < 24 mm). Subcostal TAPSE is able to accurately discriminate between abnormal and normal TAPSE results (sensitivity 97.8%, specificity 87.5%). There was no association between right-ventricular (RV) dysfunction and 90-day mortality.</AbstractText>Subcostal TAPSE is a feasible and accurate alternative to conventional TAPSE from the apical view in critically ill patients. Further research is required to elucidate the relationship between RV dysfunction and outcomes in sepsis.</AbstractText> |
2,328,685 | Solitary intraventricular Hodgkin lymphoma post-transplant lymphoproliferative disease (HL-PTLD): Case report. | Lymphomas affecting the central nervous system (CNS), both primarily and secondarily, are uncommon malignancies. Immunosuppressed states, including iatrogenic immunosuppression following organ transplantation, are the most significant risk factors for developing primary CNS lymphoma (PCNSL). Post-transplant lymphoproliferative disease (PTLD) is a well described complication following bone marrow or solid organ transplantation. PTLD is usually a systemic disease with occasional CNS involvement. The incidence of CNS involvement in PTLD is low, and the majority of these cases tend to be PCNSL. Hodgkin lymphoma PTLD (HL-PTLD) constitutes only a very small percentage of PTLD. We report a rare case of a primary intraventricular CNS classical HL-PTLD in a male patient, 18 years following renal transplantation. The location allowed for safe neurosurgical intervention which resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximab-based chemotherapy regimen. Both the ventricular location of the PTLD and Hodgkin Lymphoma PTLD are themselves individually quite rare and have not previously been reported together. The unique location allowed safe neurosurgical intervention which quickly resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximab-based chemotherapy regimen. |
2,328,686 | Percutaneous retrieval of an embolized gunshot bullet from right ventricle: a case report and review of literature. | Gunshots embolizing to the heart is a rare occurrence. We report a case of percutaneous retrieval of a gunshot bullet from the right ventricle (RV) cavity of a 40-year-old lady. To the best of our knowledge, this is the first case to be reported with a right supraclavicular inlet of the bullet and successful percutaneous retrieval using a snare from the RV cavity.</AbstractText>A 40-year-old female patient was referred to our cardiac centre from a general hospital with a gunshot injury 8 days prior. On arrival, she was haemodynamically stable, there was an inlet wound at the right supraclavicular area. Transthoracic echocardiography revealed the bullet in the RV cavity. Under conscious sedation, right femoral vein access succeeded to retrieve the shot from the RV to the groin. The bullet slipped out and resnared from the right internal iliac vein and came out safely from the right femoral vein through the 24-Fr sheath. The vein was closed using a figure of 8 suture. The patient discharged home after 2 days.</AbstractText>Bullet emboli to the heart are rare, endovascular retrieval of a bullet from the right ventricular cavity is feasible and relatively safe; however, more research is required. Echocardiography during the procedure is strongly recommended to early detect any complications. Accurate use of available tools such as X-ray, echocardiography, computed tomography, and fluoroscopy is a must for precise diagnosis.</AbstractText>© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.</CopyrightInformation> |
2,328,687 | Evaluation of the global longitudinal strain and segmental strain of the right ventricle with two-dimensional speckle-tracking echocardiography with elevation of the legs. | Speckle-tracking echocardiography has shown its usefulness in the evaluation of the right ventricle (RV) in healthy subjects and in pulmonary hypertension. It is unknown whether this technique could be sensitive to assess healthy RV with increases in preload.</AbstractText>Consecutive subjects were studied without evidence of cardiopulmonary disease. They underwent speckle-tracking echocardiography in General Electric Vivid 7®</sup> equipment. The "segmental longitudinal strain" (SLS) and "global longitudinal strain" (GLS) of the RV was determined at rest and with an increase in the preload through elevation the legs to 45°.</AbstractText>We analyzed 31 subjects, 16 men and 15 women, aged 16-53 years, in which were measured SLS and GLS. Basal of the RV free wall: -29.1 ± 3.3 versus -32.7 ± 5.5%, p = 0.0002. Mid of the RV free wall: -28.6 ± 6.4 versus -31.5 ± 4.9 %, p = 0.001. Apical of the free wall of the RV: -21.9 ± 6.5 versus -23.3 ± 6.1 %, p = 0.118. Basal inferoseptum: -19.40 ± 3.2 versus -18.9 ± 3.0 %, p = 0.204. Mid inferoseptum: -19.3 ± 3.2 versus -19 ± 3.1 %, p = 0.249. Apical septum: -17.1 ± 5.1 versus -17 ± 5.4 %, p = 0.457. GLS of the RV: -23.06 ± 3.4 versus -24.5 ± 2.9 %, p = 0.002. ICC: 0.773, 95 % CI: 0.534-0.890, p < 0.001.</AbstractText>This method was sensitive to detect differences in the GLS and SLS basal and mid of the RV free wall.</AbstractText>Copyright: © 2019 Permanyer.</CopyrightInformation> |
2,328,688 | Aldosterone Jeopardizes Myocardial Insulin and β-Adrenergic Receptor Signaling <i>via</i> G Protein-Coupled Receptor Kinase 2. | Hyperaldosteronism alters cardiac function, inducing adverse left ventricle (LV) remodeling either <i>via</i> increased fibrosis deposition, mitochondrial dysfunction, or both. These harmful effects are due, at least in part, to the activation of the G protein-coupled receptor kinase 2 (GRK2). In this context, we have previously reported that this kinase dysregulates both β-adrenergic receptor (βAR) and insulin (Ins) signaling. Yet, whether aldosterone modulates cardiac Ins sensitivity and βAR function remains untested. Nor is it clear whether GRK2 has a role in this modulation, downstream of aldosterone. Here, we show <i>in vitro</i>, in 3T3 cells, that aldosterone impaired insulin signaling, increasing the negative phosphorylation of insulin receptor substrate 1 (<sup>ser307</sup>pIRS1) and reducing the activity of Akt. Similarly, aldosterone prevented the activation of extracellular signal-regulated kinase (ERK) and the production of cyclic adenosine 3',5'-monophosphate (cAMP) in response to the β<sub>1</sub>/β<sub>2</sub>AR agonist, isoproterenol. Of note, all of these effects were sizably reduced in the presence of GRK2-inhibitor CMPD101. Next, in wild-type (WT) mice undergoing chronic infusion of aldosterone, we observed a marked GRK2 upregulation that was paralleled by a substantial β1AR downregulation and augmented <sup>ser307</sup>pIRS1 levels. Importantly, in keeping with the current <i>in vitro</i> data, we found that aldosterone effects were wholly abolished in cardiac-specific GRK2-knockout mice. Finally, in WT mice that underwent 4-week myocardial infarction (MI), we observed a substantial deterioration of cardiac function and increased LV dilation and fibrosis deposition. At the molecular level, these effects were associated with a significant upregulation of cardiac GRK2 protein expression, along with a marked β1AR downregulation and increased <sup>ser307</sup>pIRS1 levels. Treating MI mice with spironolactone prevented adverse aldosterone effects, blocking GRK2 upregulation, and thus leading to a marked reduction in cardiac <sup>ser307</sup>pIRS1 levels while rescuing β1AR expression. Our study reveals that GRK2 activity is a critical player downstream of the aldosterone signaling pathway; therefore, inhibiting this kinase is an attractive strategy to prevent the cardiac structural disarray and dysfunction that accompany any clinical condition accompanied by hyperaldosteronism. |
2,328,689 | Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor β Signaling. | The X-chromosome gene USP9X encodes a deubiquitylating enzyme that has been associated with neurodevelopmental disorders primarily in female subjects. USP9X escapes X inactivation, and in female subjects de novo heterozygous copy number loss or truncating mutations cause haploinsufficiency culminating in a recognizable syndrome with intellectual disability and signature brain and congenital abnormalities. In contrast, the involvement of USP9X in male neurodevelopmental disorders remains tentative.</AbstractText>We used clinically recommended guidelines to collect and interrogate the pathogenicity of 44 USP9X variants associated with neurodevelopmental disorders in males. Functional studies in patient-derived cell lines and mice were used to determine mechanisms of pathology.</AbstractText>Twelve missense variants showed strong evidence of pathogenicity. We define a characteristic phenotype of the central nervous system (white matter disturbances, thin corpus callosum, and widened ventricles); global delay with significant alteration of speech, language, and behavior; hypotonia; joint hypermobility; visual system defects; and other common congenital and dysmorphic features. Comparison of in silico and phenotypical features align additional variants of unknown significance with likely pathogenicity. In support of partial loss-of-function mechanisms, using patient-derived cell lines, we show loss of only specific USP9X substrates that regulate neurodevelopmental signaling pathways and a united defect in transforming growth factor β signaling. In addition, we find correlates of the male phenotype in Usp9x brain-specific knockout mice, and further resolve loss of hippocampal-dependent learning and memory.</AbstractText>Our data demonstrate the involvement of USP9X variants in a distinctive neurodevelopmental and behavioral syndrome in male subjects and identify plausible mechanisms of pathogenesis centered on disrupted transforming growth factor β signaling and hippocampal function.</AbstractText>Copyright © 2019 Society of Biological Psychiatry. All rights reserved.</CopyrightInformation> |
2,328,690 | The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder. | Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.</AbstractText>We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.</AbstractText>FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.</AbstractText>Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.</AbstractText>Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,691 | Disseminated Rosette-Forming Glioneuronal Tumor with Spinal Drop Metastasis, a Uniquely Aggressive Presentation of Rare Tumor. | The rosette-forming glioneuronal tumor (RGNT) is a rare World Health Organization grade I tumor, most often originating in the fourth ventricle and characterized by a predominant glial component, as well as a neurocytic component. Despite its benign grading, there are a few documented cases of RGNT displaying more aggressive behavior with malignant characteristics.</AbstractText>Herein, we describe a uniquely aggressive presentation of RGNT in a 49-year-old man initially presenting with obstructive hydrocephalus with lesions in the right frontal lobe, fourth ventricle, and left lateral ventricle. The patient was found to have 2 distinct intracranial entities: a right frontal meningioma and disseminated intraventricular RGNT. He underwent an anatomically limited resection of the fourth ventricular lesion with fourth ventricle-to-subarachnoid space shunting. His disease progressed thereafter, with diffuse intracranial dissemination and drop metastases in the lumbar spine. He was treated with craniospinal radiation and remains on palliative care 5 months after completion of radiotherapy.</AbstractText>This case supplements and complements the handful of published cases available documenting the evolution of a particularly aggressive case of disseminated RGNT.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,692 | Developmental Retrocerebellar Cysts: A New Classification for Neuroendoscopic Management and Systematic Review. | Posterior fossa cystic malformations are diversely classified with considerable overlap without therapeutic relevance. These cysts posterior to the cerebellum, presenting in children younger than 5 years, are labeled developmental retrocerebellar cysts (DRCCs) under a new classification in relation to neuroendoscopy.</AbstractText>DRCC was categorized as type 0 for asymptomatic enlarged cistern magna and was not treated. Among symptomatic cases, cysts with a compressed fourth ventricle were labeled type 1, whereas cysts in continuity with the fourth ventricle were termed type 2. They were further categorized as subtype B if hydrocephalus was greater relative to the cyst, or otherwise as subtype A. The literature was reviewed according to PRISMA guidelines.</AbstractText>There were 13 children aged 3-48 months. Type 1A DRCC was noted in 5 patients, with onset before 6 months, 4 of whom (80%) had intracranial hypertension. All underwent suboccipital endoscopic deroofing and cisternostomy (SEDC), a new technique. Type 1B DRCC was seen in 2 patients, with onset at 8-9 months, who underwent endoscopic third ventriculostomy (ETV) + endoscopic ventriculocystostomy (EVC). Type 2A DRCC was observed in 4 patients, with onset at 5-47 months, who underwent SEDC. Type 2B DRCC was noted in 2 patients, with onset 6-8 months, who underwent ETV. With a mean follow-up of 32 months, all showed clinicoradiologic improvement. The application of our classification to other studies showed ETV/EVC to be successful in only 67% of type 1A DRCC and 72% of type 2A DRCC, compared with 100% efficacy of SEDC in our series.</AbstractText>This is probably the first ever endoscopic classification of pediatric posterior fossa cyts, elucidating pathophysiology, presentation, and treatment. Patients with type 1 DRCC present early because of extraneous compression. Among patients with type 2 DRCC, posterior fossa compliance determines the degree of hydrocephalus. The newly described SEDC seems more appropriate for types 1A and 2A DRCC. ETV is adequate in type 2B DRCC and effective with EVC in type 1B.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,693 | Pineal region metastasis with intraventricular seeding: A case report and literature review. | Tumors of the pineal region are rare, and metastatic carcinoma occurring in the pineal region is extremely rare. No previous reports have described pineal region metastasis with intraventricular seeding.</AbstractText>We report a case of a 51-year-old woman presented with a 1-week history of severe headache, nausea, and vomiting. Imaging examination revealed 2 lesions in the pineal region and the right lateral ventricle.</AbstractText>Pinealocytoma or germinoma was considered as the preoperative diagnosis. The postoperative pathological diagnosis was small cell neuroendocrine carcinoma. After bronchoscopic biopsy, small cell lung cancer was confirmed.</AbstractText>A right frontal craniotomy and a translateral ventricle approach were performed to remove 2 lesions completely. And regular radiotherapy and chemotherapy were initiated after surgery.</AbstractText>The patient was discharged from the hospital 2 weeks after operation and went to another cancer hospital for bronchoscopic biopsy, radiotherapy, and chemotherapy. Finally, the patient died 2 years after surgical treatment.</AbstractText>Metastatic tumors of the pineal region are very rare. For patients with pineal lesions, a diagnosis of a metastatic tumor should be considered. Retrograde cerebrospinal fluid circulation might be the reason for a secondary metastasis.</AbstractText> |
2,328,694 | [Protective effects of microRNA-181b on aged rats with sepsis-induced hippocampus injury in vivo]. | To investigate the protective effect of microRNA-181b (miR-181b) on aged rats with sepsis-induced hippocampus injury in vivo.</AbstractText>Seventy-five male healthy old Sprague-Dawley (SD) rats were randomly divided into five groups (n = 15) using a random number table: sham operation group (Sham group), sepsis group [cecal ligation and puncture (CLP) group], miR-181b Agomir+CLP group (Ag+CLP group), miR-181b Antagomir+CLP group (An+CLP group) and normal saline (NS) control group (NS+CLP group). Rats sepsis model was reproduced by CLP, and in Sham group, the cecum of rats was separated only after abdominal operation without ligation or perforation. The rats in Ag+CLP group were given miR-181b Agomir 10 μL via lateral ventricle at 24 hours before CLP, the rats in An+CLP group were given 10 μL miR-181b Antagomir, and those in NS+CLP group were given 10 μL NS. At 6, 12, 24 hours after CLP, 5 rats of each group were sacrificed randomly, and hippocampus were harvested. The expression of miR-181b in hippocampus was determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The expression of nuclear factor-ΚB p65 (NF-ΚB p65) was determined by Western Blot. The contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA).</AbstractText>Compared with Sham group, the expression of miR-181b in hippocampus of CLP group was significantly decreased at 6 hours after CLP (2-ΔΔCT</sup>: 0.70±0.12 vs. 0.98±0.06, P < 0.05), and the expressions of NF-ΚB p65, IL-1β and TNF-α were significantly increased [NF-ΚB p65/Histone H3: 0.30±0.03 vs. 0.07±0.01, IL-1β (ng/L): 120.39±8.02 vs. 50.55±11.12, TNF-α (ng/L): 59.48±4.60 vs. 40.31±3.96, all P < 0.05], this trend was continued till 24 hours, and these results indicated that there was obvious inflammation in hippocampus of sepsis rats. There was no statistical difference in the expression of miR-181b, NF-ΚB p65, IL-1β or TNF-α in hippocampus between NS+CLP group and CLP group, which indicated that injection of NS into the rat lateral ventricle, had not aggravated the damage degree of hippocampus. Compared with CLP group, the expression of miR-181b in hippocampus of Ag+CLP group was significantly increased at 6 hours after CLP (2-ΔΔCT</sup>: 1.87±0.25 vs. 0.70±0.12, P < 0.05), and the expressions of NF-ΚB p65, IL-1β and TNF-α were significantly lowered [NF-ΚB p65/Histone H3: 0.16±0.03 vs. 0.30±0.03, IL-1β (ng/L): 73.76±8.17 vs. 120.39±8.02, TNF-α (ng/L): 49.52±4.77 vs. 59.48±4.60, all P < 0.05]. There was no statistical difference in the expression of miR-181b in hippocampus between An+CLP group and CLP group (2-ΔΔCT</sup>: 0.80±0.08 vs. 0.70±0.12 at 6 hours, 0.48±0.03 vs. 0.46±0.05 at 12 hours, 0.61±0.09 vs. 0.63±0.07 at 24 hours, all P > 0.05), but the expressions of NF-ΚB p65, IL-1β and TNF-α in hippocampus at 6 hours after CLP of An+CLP group were significantly higher than those of CLP group [NF-ΚB p65/Histone H3: 0.44±0.02 vs. 0.30±0.03, IL-1β (ng/L): 134.21±5.78 vs. 120.39±8.02, TNF-α (ng/L): 67.62±5.86 vs. 59.48±4.60, all P < 0.05], this trend was continued till 24 hours after CLP. The above results showed that overexpression of miR-181b might attenuate the inflammation of hippocampus through down-regulation of NF-ΚB, IL-1β and TNF-α.</AbstractText>The expression of hippocampal miR-181b was significantly decreased in septic rats. Up-regulation of miR-181b could inhibit the activation of NF-ΚB signal pathway and the release of the inflammatory cytokine IL-1β and TNF-α stimulated by sepsis, and alleviate the inflammatory reaction and hippocampus injury in rat with sepsis.</AbstractText> |
2,328,695 | Diurnal, Seasonal, and Monthly Variations in Ventricular Arrhythmias in Patients With Implantable Cardioverter-Defibrillators. | The aim of this study was to assess the variations in ventricular arrhythmia (VA) occurrence according to seasons, months of the year, days of the week, and the time of day in a large implantable cardioverter-defibrillator patient population.</AbstractText>Limited data exist on how VA occurrence varies as a function of time.</AbstractText>Data from 6 prospective studies were pooled to assess VA frequency over time. All adjudicated episodes of VAs ≤500 ms were included. VA distribution as a function of hour, day, month, and season were assessed through the construction of 4 negative binomial models. The models included a random patient effect and offset for days spent in each time period.</AbstractText>Among 3,969 patients, 7,126.8 cumulative device-years with an average follow-up duration of 1.8 ± 1.4 years/patient were analyzed. VA occurrence was higher in the spring than the summer (0.86% vs. 0.70%; p = 0.009) but not significantly different from the fall (0.74%; p = 0.069) or winter (0.84%; p = 0.732). The estimated probability of occurrence of at least 1 VA episode in each 1-h block during the hours of 8 am to 10 pm over 365 days (0.10% to 0.12%) was higher (estimated 35% to 63% higher) than the referent period of midnight to 1 am (0.07%). No significant variations in VA occurrence were observed according to weekday and individual months of the year.</AbstractText>Significantly higher VA occurrence in the spring and during the hours of 8 am to 10 pm were observed. Additional studies are needed to further understand the reasons for these observations, which may involve variations in temperature or differences in catecholamine triggers.</AbstractText>Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,696 | First trimester supratentorial and infratentorial abnormalities in fetuses with open spina bifida. | To examine whether supratentorial, infratentorial, and calvarial manifestations of open spina bifida (OSB) occur in the first-trimester.</AbstractText>Supratentorial (midbrain curvature, thalamic height), infratentorial (fourth ventricle diameter, brain-stem diameter [BSD], ratio of BSD to BSD-occipital bone diameter [BSOB]), and calvarial (frontomaxillary facial [FMF] angle) parameters were measured in stored midsagittal facial images at 110-136 weeks of 500 normal and 10 open spina-bifida fetuses by 3 blinded examiners.</AbstractText>OSB fetuses displayed a larger midbrain curvature (93.26 ± 6.97 versus 97.79 ± 10.04, p</i> < .05), decreased FMF angle (84.10 ± 5.44 versus 78.46 ± 5.82, p</i> < .001), smaller fourth ventricle diameter (0.25 ± 0.04 mm versus 0.18 ± 0.05 mm, p</i> < .001), smaller BSD (0.29 ± 0.04 mm versus 0.23 ± 0.04 mm; p</i> < .001), and increased BSD to BSOB ratio (0.64 ± 0.71 versus 0.73 ± 0.93, p</i> < .03) than normal controls, respectively. Thalamic height was not significantly altered. Detection rates of OSB were highest for fourth ventricle diameter and FMF angle (60% and 40%, respectively, at 95% specificity). BSD, BSD to BSOB ratio, midbrain curvature yielded sensitivities of 30% with 95% specificity. Two-dimensional discrimination for pairs of measures combining fourth ventricle diameter with FMF angle increased sensitivity to 90% with specificity of 90.7%.</AbstractText>Our findings suggest that supratentorial, infratentorial, and calvarial changes consistent with the Chiari-II malformation are already established in first-trimester fetuses with OSB.</AbstractText> |
2,328,697 | Ocular Dyskinesia and Hemifacial Spasm Secondary to Fourth Ventricular Tumor: Report of 4 Cases and Review of the Literature. | In clinical pediatric neurosurgery practice, fourth ventricle and cerebellar tumors are not rare. However, reports of secondary refractory hemifacial spasm are very rare. No report is currently available on the treatment of hemifacial spasm secondary to fourth ventricle and cerebellar tumors in China. Zamponi et al. [Childs Nerv Syst 2011 Jun;27(6):1001-5] reported that these lesions can occur in neonates and infants, and surgical resection is effective. |
2,328,698 | A case of recurrent epilepsy-associated rosette-forming glioneuronal tumor with anaplastic transformation in the absence of therapy. | Rosette-forming glioneuronal tumor (RGNT) most commonly occurs adjacent to the fourth ventricle and therefore rarely presents with epilepsy. Recent reports describe RGNT occurrence in other anatomical locations with considerable morphologic and genetic overlap with the epilepsy-associated dysembryoplastic neuroepithelial tumor (DNET). Examples of RGNT or DNET with anaplastic change are rare, and typically occur in the setting of radiation treatment. We present the case of a 5-year-old girl with seizures, who underwent near total resection of a cystic temporal lobe lesion. Pathology showed morphologic and immunohistochemical features of RGNT, albeit with focally overlapping DNET-like patterns. Resections of residual or recurrent tumor were performed 1 year and 5 years after the initial resection, but no adjuvant radiation or chemotherapy was given. Ten years after the initial resection, surveillance imaging identified new and enhancing nodules, leading to another gross total resection. This specimen showed areas similar to the original tumor, but also high-grade foci with oligodendroglial morphology, increased cellularity, palisading necrosis, microvascular proliferation, and up to 13 mitotic figures per 10 high power fields. Ancillary studies the status by sequencing showed wild-type of the isocitrate dehydrogenase 1 (IDH1), IDH2, and human histone 3.3 (H3F3A) genes, and BRAF studies were negative for mutation or rearrangement. Fluorescence in situ hybridization (FISH) showed codeletion of 1p and 19q limited to the high-grade regions. By immunohistochemistry there was loss of nuclear alpha-thalassemia mental retardation syndrome, X-linked (ATRX) expression only in the high-grade region. Next-generation sequencing showed an fibroblast growth factor receptor receptor 1 (FGFR1) kinase domain internal tandem duplication in three resection specimens. ATRX mutation in the high-grade tumor was confirmed by sequencing which showed a frameshift mutation (p.R1427fs), while the apparent 1p/19q-codeletion by FISH was due to loss of chromosome arm 1p and only partial loss of 19q. Exceptional features of this case include the temporal lobe location, 1p/19q loss by FISH without true whole-arm codeletion, and anaplastic transformation associated with ATRX mutation without radiation or chemotherapy. |
2,328,699 | EGFR Signaling Termination via Numb Trafficking in Ependymal Progenitors Controls Postnatal Neurogenic Niche Differentiation. | Specialized microenvironments, called niches, control adult stem cell proliferation and differentiation. The brain lateral ventricular (LV) neurogenic niche is generated from distinct postnatal radial glial progenitors (pRGPs), giving rise to adult neural stem cells (NSCs) and niche ependymal cells (ECs). Cellular-intrinsic programs govern stem versus supporting cell maturation during adult niche assembly, but how they are differentially initiated within a similar microenvironment remains unknown. Using chemical approaches, we discovered that EGFR signaling powerfully inhibits EC differentiation by suppressing multiciliogenesis. We found that EC pRGPs actively terminated EGF activation through receptor redistribution away from CSF-contacting apical domains and that randomized EGFR membrane targeting blocked EC differentiation. Mechanistically, we uncovered spatiotemporal interactions between EGFR and endocytic adaptor protein Numb. Ca<sup>2+</sup>-dependent basolateral targeting of Numb is necessary and sufficient for proper EGFR redistribution. These results reveal a previously unknown cellular mechanism for neighboring progenitors to differentially engage environmental signals, initiating adult stem cell niche assembly. |
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