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2,331,300 | Automated Left Ventricle Ischemic Scar Detection in CT Using Deep Neural Networks. | <b>Objectives:</b> The aim of this study is to develop a scar detection method for routine computed tomography angiography (CTA) imaging using deep convolutional neural networks (CNN), which relies solely on anatomical information as input and is compatible with existing clinical workflows. <b>Background:</b> Identifying cardiac patients with scar tissue is important for assisting diagnosis and guiding interventions. Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) is the gold standard for scar imaging; however, there are common instances where it is contraindicated. CTA is an alternative imaging modality that has fewer contraindications and is faster than Cardiovascular magnetic resonance imaging but is unable to reliably image scar. <b>Methods:</b> A dataset of LGE MRI (200 patients, 83 with scar) was used to train and validate a CNN to detect ischemic scar slices using segmentation masks as input to the network. MRIs were segmented to produce 3D left ventricle meshes, which were sampled at points along the short axis to extract anatomical masks, with scar labels from LGE as ground truth. The trained CNN was tested with an independent CTA dataset (25 patients, with ground truth established with paired LGE MRI). Automated segmentation was performed to provide the same input format of anatomical masks for the network. The CNN was compared against manual reading of the CTA dataset by 3 experts. <b>Results:</b> Note that 84.7% cross-validated accuracy (AUC: 0.896) for detecting scar slices in the left ventricle on the MRI data was achieved. The trained network was tested against the CTA-derived data, with no further training, where it achieved an 88.3% accuracy (AUC: 0.901). The automated pipeline outperformed the manual reading by clinicians. <b>Conclusion:</b> Automatic ischemic scar detection can be performed from a routine cardiac CTA, without any scar-specific imaging or contrast agents. This requires only a single acquisition in the cardiac cycle. In a clinical setting, with near zero additional cost, scar presence could be detected to triage images, reduce reading times, and guide clinical decision-making. |
2,331,301 | Cardiac Chamber Quantification by Echocardiography in Adults With Sickle Cell Disease: Need Attention to Eccentric Hypertrophy. | Introduction and aim Sickle cell anemia (SCA) is the most common hemoglobinopathy worldwide, and cardiovascular diseases are the most common causes of death. In these patients, cardiac remodeling begins from childhood and leads to sickle cell cardiomyopathy in the following years. Concentric hypertrophy and eccentric hypertrophy are known to predict early cardiac events. This study aims to reveal the relationship between cardiac remodeling types and survival in patients with SCA and investigate the factors that may affect left ventricular mass. Materials and methods A total of 146 patients with SCA were included in the study, and the left ventricular mass index (LVMI) and relative wall thickness (RWT) of the patients were calculated according to echocardiographic measurements, and the patients were categorized into normal, concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH) groups. Results The median age of the patients is 32 (18-72). In logistic regression analysis, hemoglobin S (HbS) and ferritin levels were independent predictors for LVMI (p = 0.01 and p < 0.001, respectively). It was observed that 56 (38.4%) of the patients had normal left ventricles, 24 (16.4%) had CR, 21 (14.4%) had CH, and 45 (30.8%) had EH. 31 (21.2%) of the patients died. When we look at the survival curves, there was a statistically significant difference between the four groups (log-rank p < 0.001). It was observed that patients with EH were the group with the lowest probability of survival. Conclusion Cardiac death is one of the most common causes of death in patients with SCA. Early detection of cardiac disorders and starting treatment may be important in reducing mortality in these patients. |
2,331,302 | Bridging the intracranial pressure gap: a smooth transition strategy for slit ventricle syndrome. | Slit ventricle syndrome (SVS) is a well-known complication of long-standing shunts. Patients develop intermittent severe headache, vomiting with other symptoms of increased intra-cranial pressure. Brain computed tomography (CT) usually reveals slit-like ventricles with nearly obstructed proximal catheters. Treatment for SVS usually involves upgrading the shunt valve pressure setting. Currently, many patients carry programmable shunts and pressure setting can be adjusted noninvasively. However, when the programmable valve pressure setting is upgraded, some patients with SVS experience worsened symptoms. This is caused by the time gap between ICP increase and real ventricular expansion (and freeing proximal catheter) after shunt upgrading. Therefore, it is important to control a patient's symptoms during the transition period. We report our experience in controlling ICP in a patient with SVS using external ventricular drainage. |
2,331,303 | Using deep learning convolutional neural networks to automatically perform cerebral aqueduct CSF flow analysis. | Since the development of phase-contrast magnetic resonance imaging (PC-MRI), quantification of cerebrospinal fluid (CSF) flow across the cerebral aqueduct has been utilized for diagnosis of conditions such as normal pressure hydrocephalus (NPH). This study aims to develop an automated method of aqueduct CSF flow analysis using convolution neural networks (CNNs), which can replace the current standard involving manual segmentation of aqueduct region of interest (ROI). Retrospective analysis was performed on 333 patients who underwent PC-MRI, totaling 353 imaging studies. Aqueduct flow measurements using manual ROI placement was performed independently by two radiologists. Two types of CNNs, MultiResUNet and UNet, were trained using ROI data from the senior radiologist, with PC-MRI studies being randomly divided into training (80%) and validation (20%) datasets. Segmentation performance was assessed using Dice similarity coefficient (DSC), and CSF flow parameters were calculated from both manual and CNN-derived ROIs. MultiResUNet, UNet and second radiologist (Rater 2) had DSCs of 0.933, 0.928, and 0.867, respectively, with p < 0.001 between CNNs and Rater 2. Comparison of CSF flow parameters showed excellent intraclass correlation coefficients (ICCs) for MultiResUNet, with lowest correlation being 0.67. For UNet, lower ICCs of -0.01 to 0.56 were observed. Only 3/353 (0.8%) studies failed to have appropriate ROIs placed by MultiResUNet, compared to 12/353 (3.4%) failed cases for UNet. In conclusion, CNNs were able to measure aqueductal CSF flow with similar performance to a senior neuroradiologist. MultiResUNet demonstrated fewer cases of segmentation failure and more consistent flow measurements compared to the widely adopted UNet. |
2,331,304 | Outcomes of the endoscopic endonasal approach for tumors in the third ventricle or invading the third ventricle. | We aimed to retrospectively analyze the surgical and clinical outcomes of the endoscopic endonasal approach (EEA) for tumors in the third ventricle or invading the third ventricle. In total, 82 patients who had undergone surgical treatment using the EEA for tumors involving the third ventricle were enrolled in this study. This cohort study comprised 46 male and 36 female patients. The median age was 37 years (range, 5-76), and the median follow-up duration was 56.5 months (range, 6-117). Seventy-six patients had craniopharyngiomas, and 6 had gangliocytomas, gangliogliomas, astrocytomas, diffuse midline gliomas and lymphomas. Gross total removal was performed in 71 (86.5%) of the 82 patients, subtotal tumor removal in 7 patients and partial removal or biopsy in 4 patients. The pituitary stalk was preserved in 20 cases. Visual function improved in 40 (81.6%) of 49 patients. Endocrine function worsened in 41 (50%) of 82 patients. Hypothalamic function improved in 16 (72.7%) of 22 cases. Postoperative obesity occurred in 3 (20.0%) of 15 children and 11 (23.9%) of 46 adult patients. The postoperative cerebrospinal fluid leakage rate was 3.6%. Postoperative meningitis occurred in 18 (21.9%) cases. Permanent diabetes insipidus was identified in 73 (89.0%) of 82 patients. Tumor recurrence was observed in 10 patients (12%). The EEA appears to be a safe and effective treatment modality for tumors in the third ventricle or involving the third ventricle. However, more cases and long-term follow-up outcomes are required to confirm the clinical efficacy of the EEA. |
2,331,305 | Management trends and outcomes of pineal germinoma in a multi-institutional Australian cohort. | Pineal germinoma is rare with high cure rates following craniospinal radiotherapy. Efforts to reduce the radiotherapy dose and field via combination with chemotherapy suggest comparable disease control and reduced neurocognitive impairments, while the efficacy of immunotherapy in pineal germinoma remains undetermined. This report aimed to review clinical outcomes in patients treated for pineal germinoma in Queensland, Australia, and assess for Programmed Death-Ligand1 (PD-L1) expression. Patients who commenced radiation and/or chemotherapy for pineal germinoma from 2005 to 2017 were retrospectively identified using Queensland Oncology Online database. Demographic, diagnostic, treatment, and outcome data was obtained from electronic medical records. PD-L1 immuno-histochemistry was performed on available specimens. Eighteen patients with long-term follow-up data were identified. Median age at diagnosis was 16.8 years (range 9-46 years). Diagnosis was made histologically in fifteen patients, and radiologically in three. All patients underwent radiotherapy (median 36 Gy (range 21-54 Gy)) with lower median dose delivered with whole ventricle irradiation (12/18patients) than craniospinal irradiation (5/18patients). Sixteen patients received chemotherapy preceding radiotherapy. All patients are alive at median 7.25 years from primary treatment completion (range 2.03-13.1 years). Relapse occurred in three patients (16.67%) following treatment response, all of whom achieved remission following high-dose chemotherapy with stem-cell support and craniospinal radiotherapy. Post-treatment functional outcomes were similarly excellent. PD-L1 expression was low (1-49% cells) or negative in 87% of tumours tested but results were confounded by specimen quality and availability. Reduced-dose radiotherapy with chemotherapy does not compromise outcome and is standard of care at this institution. Immunotherapy is unlikely to become standard treatment in the near future. |
2,331,306 | Activation of GPR40 attenuates neuroinflammation and improves neurological function via PAK4/CREB/KDM6B pathway in an experimental GMH rat model. | Germinal matrix hemorrhage (GMH) is defined by the rupture of immature blood vessels in the germinal matrix, where subsequent hemorrhage enters the subependymal zone and the cerebral lateral ventricles. The consequent blood clot has been identified as the causative factor of secondary brain injury, which triggers a series of complex parallel and sequential harmful mechanisms, including neuroinflammation. The orphan G-protein-coupled receptor 40 (GPR40), a free fatty acid (FFA) receptor 1, has been shown to exert anti-inflammatory effects when activated and improved outcomes in animal models of stroke. We aimed to investigate the anti-inflammatory effects of GPR40 and its underlying mechanisms after GMH.</AbstractText>GMH model was induced in 7-day-old rat pups by an intraparenchymal injection of bacterial collagenase. GPR40 agonist, GW9508, was administered intranasally 1 h, 25 h, and 49 h after GMH induction. CRISPR targeting GPR40, PAK4, and KDM6B were administered through intracerebroventricular injection 48 h before GMH induction. Neurologic scores, microglia polarization, and brain morphology were evaluated by negative geotaxis, right reflex, rotarod test, foot fault test, Morris water maze, immunofluorescence staining, Western blots, and nissl staining respectfully.</AbstractText>The results demonstrated that GW9508 improved neurological and morphological outcomes after GMH in the short (24 h, 48 h, 72h) and long-term (days 21-27). However, the neuroprotective effects of treatment were abolished by GW1100, a selective GPR40 antagonist. GW9508 treatment increased populations of M2 microglia and decreased M1 microglia in periventricular areas 24 h after GMH induction. GW9508 upregulated the phosphorylation of PAK4, CREB, and protein level of KDM6B, CD206, IL-10, which was also met with the downregulation of inflammatory markers IL-1β and TNF-α. The mechanism study demonstrated that the knockdown of GPR40, PAK4, and KDM6B reversed the neuroprotective effects brought on by GW9508. This evidence suggests that GPR40/PAK4/CREB/KDM6B signaling pathway in microglia plays a role in the attenuation of neuroinflammation after GMH.</AbstractText>In conclusion, the present study demonstrates that the activation of GPR40 attenuated GMH-induced neuroinflammation through the activation of the PAK4/CREB/KDM6B signaling pathway, and M2 microglia may be a major mediator of this effect. Thus, GPR40 may serve as a potential target in the reduction of the inflammatory response following GMH, thereby improving neurological outcomes in the short- and long-term.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,331,307 | Role of intra-operative squash cytology in rosette-forming glioneuronal tumor of the fourth ventricle: a case report. | Rosette-forming glioneuronal tumor (RGNT) of the 4th ventricle is a newly described WHO grade I brain tumor included in recent WHO classification of CNS tumors. It is a biphasic tumor thought to originate from pluripotent progenitor cells of subependymal plate. Intra-operative diagnosis plays an important role, as complete surgical excision is the treatment of choice. We are reporting a case of RGNT in a 19 years-old young male emphasizing the intra-operative pathological pointers and their role in accurate diagnosis for the suitable surgical intervention. |
2,331,308 | A multimodal approach to the study of children treated for posterior fossa tumor: A review of the literature and a pilot study. | The aims of the present study were: (1) to review the literature on long-lasting cognitive sequelae in children treated for Posterior Fossa Tumor and (2) to investigate anatomic functional relations in a case series of 7 children treated for PFT using magnetic resonance imaging (MRI) post-processing methods.</AbstractText>We retrospectively analyzed MRIs of children who underwent complete surgical resection of PFT and performed extensive neuropsychological evaluation. Tumor, ventricular volumes, and VPS insertion site were drawn on T1 volumetric MRI scans and normalized to a pediatric template. Children showed worse performances on tasks tapping executive functions, memory, visuo-motor precision, and expressive language.</AbstractText>Volumes of interest related to these functions showed a maximum overlap on the left vermis and the lateral ventricle enlargement, except for impaired narrative fluency -which was associated with left lateral ventricle enlargement- and narrative memory -which was related to the right vermis and the enlarged fourth ventricle.</AbstractText>Results suggest that anatomic functional relations in children treated for PFT are related to a combination of different pathophysiological factors.</AbstractText>Copyright © 2021 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,331,309 | Automatic left ventricle volume calculation with explainability through a deep learning weak-supervision methodology. | Magnetic resonance imaging is the most reliable imaging technique to assess the heart. More specifically there is great importance in the analysis of the left ventricle, as the main pathologies directly affect this region. In order to characterize the left ventricle, it is necessary to extract its volume. In this work we present a neural network architecture that is capable of directly estimating the left ventricle volume in short axis cine Magnetic Resonance Imaging in the end-diastolic frame and provide a segmentation of the region which is the basis of the volume calculation, thus offering explainability to the estimated value.</AbstractText>The network was designed to directly target the volumes to estimate, not requiring any labeled segmentation on the images. The network was based on a 3D U-net with extra layers defined in a scanning module that learned features like the circularity of the objects and the volumes to estimate in a weakly-supervised manner. The only targets defined were the left ventricle volumes and the circularity of the object detected through the estimation of the π value derived from its shape. We had access to 397 cases corresponding to 397 different subjects. We randomly selected 98 cases to use as test set.</AbstractText>The results show a good match between the real and estimated volumes in the test set, with a mean relative error of 8% and a mean absolute error of 9.12 ml with a Pearson correlation coefficient of 0.95. The derived segmentations obtained by the network achieved Dice coefficients with a mean value of 0.79.</AbstractText>The proposed method is capable of obtaining the left ventricle volume biomarker in the end-diastole and offer an explanation of how it obtains the result in the form of a segmentation mask without the need of segmentation labels to train the algorithm, making it a potentially more trustworthy method for clinicians and a way to train neural networks more easily when segmentation labels are not readily available.</AbstractText>Copyright © 2021. Published by Elsevier B.V.</CopyrightInformation> |
2,331,310 | Two-Dimensional Echocardiographic Right Ventricular Size and Systolic Function Measurements Stratified by Sex, Age, and Ethnicity: Results of the World Alliance of Societies of Echocardiography Study. | Echocardiographic assessment of right ventricular (RV) systolic function is an important component of clinical decision making. Although professional societies have worked to define normal ranges of RV size and function, their guidelines have not included the impacts of age, sex, and ethnicity on these parameters, as they have for the left ventricle. The World Alliance of Societies of Echocardiography study was designed to investigate the effects of age, sex, and ethnicity on all cardiac chambers. The aim of this study was to explore whether these differences exist for RV systolic parameters.</AbstractText>Adequate two-dimensional RV-focused views for the measurement of systolic parameters, including fractional area change and global and free wall longitudinal strain, were available in 1,913 subjects (mean age, 47 ± 17 years; 51% men). Basal and mid-RV dimensions, length, tricuspid annular peak systolic excursion, tissue Doppler S' velocity, and myocardial performance index were also measured. Subjects were grouped by age (<40, 41-65, and >65 years), with results also stratified by sex and ethnicity (Asian, black, or white) and analyzed using vendor-independent software. Differences among groups were evaluated using analysis of variance.</AbstractText>Women had smaller absolute and indexed RV areas and absolute RV dimensions and higher magnitudes of fractional area change, free wall strain, and global longitudinal strain compared to men. With respect to age, most of the statistically significant differences were noted between the <40- and >65-year age groups, with RV areas and lengths smaller in older age groups and RV functional parameters (S', fractional area change, tricuspid annular plane systolic excursion, global longitudinal strain, free wall strain, and myocardial performance index) showing minimal decreases or no changes with age. Although there were no meaningful differences in functional parameters among ethnic groups, RV size was smallest in Asians.</AbstractText>These findings suggest that although two-dimensional RV parameters are age and sex dependent, association with race is less apparent, excepting that the Asian population appears to have smaller chamber sizes compared with whites and blacks.</AbstractText>Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,331,311 | Development of health-based exposure limits for radiofrequency radiation from wireless devices using a benchmark dose approach. | Epidemiological studies and research on laboratory animals link radiofrequency radiation (RFR) with impacts on the heart, brain, and other organs. Data from the large-scale animal studies conducted by the U.S. National Toxicology Program (NTP) and the Ramazzini Institute support the need for updated health-based guidelines for general population RFR exposure.</AbstractText>The development of RFR exposure limits expressed in whole-body Specific Absorption Rate (SAR), a metric of RFR energy absorbed by biological tissues.</AbstractText>Using frequentist and Bayesian averaging modeling of non-neoplastic lesion incidence data from the NTP study, we calculated the benchmark doses (BMD) that elicited a 10% response above background (BMD10</sub>) and the lower confidence limits on the BMD at 10% extra risk (BMDL10</sub>). Incidence data for individual neoplasms and combined tumor incidence were modeled for 5% and 10% response above background.</AbstractText>Cardiomyopathy and increased risk of neoplasms in male rats were the most sensitive health outcomes following RFR exposures at 900 MHz frequency with Code Division Multiple Access (CDMA) and Global System for Mobile Communications (GSM) modulations. BMDL10</sub> for all sites cardiomyopathy in male rats following 19 weeks of exposure, calculated with Bayesian model averaging, corresponded to 0.27-0.42 W/kg whole-body SAR for CDMA and 0.20-0.29 W/kg for GSM modulation. BMDL10</sub> for right ventricle cardiomyopathy in female rats following 2 years of exposure corresponded to 2.7-5.16 W/kg whole-body SAR for CDMA and 1.91-2.18 W/kg for GSM modulation. For multi-site tumor modeling using the multistage cancer model with a 5% extra risk, BMDL5</sub> in male rats corresponded to 0.31 W/kg for CDMA and 0.21 W/kg for GSM modulation.</AbstractText>BMDL10</sub> range of 0.2-0.4 W/kg for all sites cardiomyopathy in male rats was selected as a point of departure. Applying two ten-fold safety factors for interspecies and intraspecies variability, we derived a whole-body SAR limit of 2 to 4 mW/kg, an exposure level that is 20-40-fold lower than the legally permissible level of 0.08 W/kg for whole-body SAR under the current U.S. regulations. Use of an additional ten-fold children's health safety factor points to a whole-body SAR limit of 0.2-0.4 mW/kg for young children.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,331,312 | Hyperpolarized <sup>129</sup> Xe multi-slice imaging of the human brain using a 3D gradient echo pulse sequence. | To demonstrate the possibility of performing multi-slice in-vivo human brain MRI using hyperpolarized (HP) xenon-129 (129</sup> Xe) in two different orientations and to calculate the signal-to-noise ratio (SNR).</AbstractText>Two healthy female participants were imaged during a single breath-hold of HP 129</sup> Xe using a Philips Achieva 3.0T MRI scanner (Philips, Andover, MA). Each HP 129</sup> Xe multi-slice brain image was acquired during separate HP 129</sup> Xe breath-holds using 3D gradient echo (GRE) imaging. The acquisition started 10 s after the inhalation of 1 L of HP 129</sup> Xe. Overall, four sagittal and three axial images were acquired (seven imaging sessions per participant). The SNR was calculated for each slice in both orientations.</AbstractText>The first ever HP 129</sup> Xe multi-slice images of the brain were acquired in axial and sagittal orientations. The HP 129</sup> Xe signal distribution correlated well with the gray matter distribution. The highest SNR values were close in the axial and sagittal orientations (19.46 ± 3.25 and 18.76 ± 4.94, respectively). Additionally, anatomical features, such as the ventricles, were observed in both orientations.</AbstractText>The possibility of using multi-slice HP 129</sup> Xe human brain magnetic resonance imaging was demonstrated for the first time. HP 129</sup> Xe multi-slice MRI can be implemented for brain imaging to improve current diagnostic methods.</AbstractText>© 2021 International Society for Magnetic Resonance in Medicine.</CopyrightInformation> |
2,331,313 | Fractalkine signaling regulates oligodendroglial cell genesis from SVZ precursor cells. | Neural and oligodendrocyte precursor cells (NPCs and OPCs) in the subventricular zone (SVZ) of the brain contribute to oligodendrogenesis throughout life, in part due to direct regulation by chemokines. The role of the chemokine fractalkine is well established in microglia; however, the effect of fractalkine on SVZ precursor cells is unknown. We show that murine SVZ NPCs and OPCs express the fractalkine receptor (CX3CR1) and bind fractalkine. Exogenous fractalkine directly enhances OPC and oligodendrocyte genesis from SVZ NPCs in vitro. Infusion of fractalkine into the lateral ventricle of adult NPC lineage-tracing mice leads to increased newborn OPC and oligodendrocyte formation in vivo. We also show that OPCs secrete fractalkine and that inhibition of endogenous fractalkine signaling reduces oligodendrocyte formation in vitro. Finally, we show that fractalkine signaling regulates oligodendrogenesis in cerebellar slices ex vivo. In summary, we demonstrate a novel role for fractalkine signaling in regulating oligodendrocyte genesis from postnatal CNS precursor cells. |
2,331,314 | Spatiotemporal Mapping of Early Volume Loss in the Mouse Brain after Cranial Irradiation. | Sequelae after pediatric cranial radiotherapy (CRT) result in long-term changes in brain structure. While past evidence indicates regional differences in brain volume change, it remains unclear how these manifest in the time course of change after CRT. In this study, we spatiotemporally characterized volume losses induced by cranial irradiation in a mouse model, with a dense sampling of measurements over the first week postirradiation. Wild-type mice received whole-brain irradiation (7 Gy) or sham irradiation (0 Gy) at 16 days of age. In vivo magnetic resonance imaging was performed at one time point before, and 2-4 time points postirradiation in each mouse, with a particular focus on sampling during the first week after cranial irradiation. Volume changes across the brain were measured, and the degree and timing of volume loss were quantified across structures from a predefined atlas. Volume measurements across the brain after cranial irradiation revealed a ∼2-day delay in which volume is not significantly altered, after which time volume change proceeds over the course of four days. Volume losses were 3% larger and emerged 40% slower in white matter than in gray matter. Large volume loss was also observed in the ventricles. Differences in the timing and magnitude of volume change between gray and white matter after cranial irradiation were observed. These results suggest differences in the mechanism and/or kinetics underlying the associated radio-response, which may have implications in development. |
2,331,315 | Central µ-Opioid Receptor Antagonism Blocks Glucoprivic LH Pulse Suppression and Gluconeogenesis/Feeding in Female Rats. | Energetic status often affects reproductive function, glucose homeostasis, and feeding in mammals. Malnutrition suppresses pulsatile release of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) and increases gluconeogenesis and feeding. The present study aims to examine whether β-endorphin-μ-opioid receptor (MOR) signaling mediates the suppression of pulsatile GnRH/LH release and an increase in gluconeogenesis/feeding induced by malnutrition. Ovariectomized female rats treated with a negative feedback level of estradiol-17β (OVX + low E2) receiving 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, intravenously (iv) were used as a malnutrition model. An administration of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective MOR antagonist, into the third ventricle blocked the suppression of the LH pulse and increase in gluconeogenesis/feeding induced by iv 2DG administration. Histological analysis revealed that arcuate Kiss1 (kisspeptin gene)-expressing cells and preoptic Gnrh1 (GnRH gene)-expressing cells co-expressed little Oprm1 (MOR gene), while around 10% of arcuate Slc17a6 (glutamatergic marker gene)-expressing cells co-expressed Oprm1. Further, the CTOP treatment decreased the number of fos-positive cells in the paraventricular nucleus (PVN) in OVX + low E2 rats treated with iv 2DG but failed to affect the number of arcuate fos-expressing Slc17a6-positive cells. Taken together, these results suggest that the central β-endorphin-MOR signaling mediates the suppression of pulsatile LH release and that the β-endorphin may indirectly suppress the arcuate kisspeptin neurons, a master regulator for GnRH/LH pulses during malnutrition. Furthermore, the current study suggests that central β-endorphin-MOR signaling is also involved in gluconeogenesis and an increase in food intake by directly or indirectly acting on the PVN neurons during malnutrition in female rats. |
2,331,316 | Impaired generation of mature neurons due to extended expression of Tlx by repressing Sox2 transcriptional activity. | As a master regulator of the dynamic process of adult neurogenesis, timely expression and regulation of the orphan nuclear receptor Tailless (Tlx) is essential. However, there is no study yet to directly investigate the essential role of precise spatiotemporal expressed Tlx. Here, we generated a conditional gain of Tlx expression transgenic mouse model, which allowed the extended Tlx expression in neural stem cells (NSCs) and their progeny by mating with a TlxCreER<sup>T2</sup> mouse line. We demonstrate that extended expression of Tlx induced the impaired generation of mature neurons in adult subventricular zone and subgranular zone. Furthermore, we elucidated for the first time that this mutation decreased the endogenous expression of Sox2 by directly binding to its promoter. Restoration experiments further confirmed that Sox2 partially rescued these neuron maturation defects. Together, these findings not only highlight the importance of shutting-off Tlx on time in controlling NSC behavior, but also provide insights for further understanding adult neurogenesis and developing treatment strategies for neurological disorders. |
2,331,317 | Quantitative roles of ion channel dynamics on ventricular action potential. | Mathematical models for the action potential (AP) generation of the electrically excitable cells including the heart are involved different mechanisms including the voltage-dependent currents with nonlinear time- and voltage-gating properties. From the shape of the AP waveforms to the duration of the refractory periods or heart rhythms are greatly affected by the functions describing the features or the quantities of these ion channels. In this work, a mathematical measure to analyze the regional contributions of voltage-gated channels is defined by dividing the AP into phases, epochs, and intervals of interest. The contribution of each time-dependent current for the newly defined cardiomyocyte model is successfully calculated and it is found that the contribution of dominant ion channels changes substantially not only for each phase but also for different regions of the cardiac AP. Besides, the defined method can also be applied in all Hodgkin-Huxley types of electrically excitable cell models to be able to understand the underlying dynamics better. |
2,331,318 | Adult Hippocampal Neurogenesis and Alzheimer's Disease: Novel Application of Mesenchymal Stem Cells and their Role in Hippocampal Neurogenesis. | The neurogenesis can occur in two regions of the adult mammalian brain throughout the lifespan: the subgranular zone of the hippocampal dentate gyrus, and the subventricular zone of the lateral ventricle. The proliferation and maturation of neural progenitor cells are tightly regulated through intrinsic and extrinsic factors. The integration of maturated cells into the circuitry of the adult hippocampus emphasizes the importance of adult hippocampal neurogenesis in learning and memory. There is a large body of evidence demonstrating that alteration in the neurogenesis process in the adult hippocampus results in an early event in the course of Alzheimer's disease (AD). In AD condition, the number and maturation of neurons declines progressively in the hippocampus. Innovative therapies are required to modulate brain homeostasis. Mesenchymal stem cells (MSCs) hold an immense potential to regulate the neurogenesis process, and are currently tested in some brain-related disorders, such as AD. Therefore, the aim of this review is to discuss the use of MSCs to regulate endogenous adult neurogenesis and their significant impact on future strategies for the treatment of AD. |
2,331,319 | Glioblastoma Proximity to the Lateral Ventricle Alters Neurogenic Cell Populations of the Subventricular Zone. | Despite current strategies combining surgery, radiation, and chemotherapy, glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Tumor location plays a key role in the prognosis of patients, with GBM tumors located in close proximity to the lateral ventricles (LVs) resulting in worse survival expectancy and higher incidence of distal recurrence. Though the reason for worse prognosis in these patients remains unknown, it may be due to proximity to the subventricular zone (SVZ) neurogenic niche contained within the lateral wall of the LVs. We present a novel rodent model to analyze the bidirectional signaling between GBM tumors and cells contained within the SVZ. Patient-derived GBM cells expressing GFP and luciferase were engrafted at locations proximal, intermediate, and distal to the LVs in immunosuppressed mice. Mice were either sacrificed after 4 weeks for immunohistochemical analysis of the tumor and SVZ or maintained for survival analysis. Analysis of the GFP+ tumor bulk revealed that GBM tumors proximal to the LV show increased levels of proliferation and tumor growth than LV-distal counterparts and is accompanied by decreased median survival. Conversely, numbers of innate proliferative cells, neural stem cells (NSCs), migratory cells and progenitors contained within the SVZ are decreased as a result of GBM proximity to the LV. These results indicate that our rodent model is able to accurately recapitulate several of the clinical aspects of LV-associated GBM, including increased tumor growth and decreased median survival. Additionally, we have found the neurogenic and cell division process of the SVZ in these adult mice is negatively influenced according to the presence and proximity of the tumor mass. This model will be invaluable for further investigation into the bidirectional signaling between GBM and the neurogenic cell populations of the SVZ. |
2,331,320 | Evaluation of Posterior Fossa Biometric Measurements on Fetal MRI in the Evaluation of Dandy-Walker Continuum. | Dandy-Walker malformation, vermian hypoplasia, and Blake pouch remnant represent a continuum of anomalies and are common reasons for referral for fetal MR imaging. This study aimed to determine biometric measurements that quantitatively delineate these 3 posterior fossa phenotypes.</AbstractText>Our single-center institutional review board approved a retrospective analysis of all fetal MRIs for posterior fossa malformations, including Dandy-Walker malformation, vermian hypoplasia, and Blake pouch remnant. Measurements included the anterior-to-posterior pons, craniocaudal and anterior-to-posterior vermis, lateral ventricle size, and tegmentovermian and posterior fossa angles. Measurements were compared with normal biometry and also between each subgroup.</AbstractText>Thirty-three fetuses met the criteria and were included in the study. Seven were designated as having Dandy-Walker malformation; 16, vermian hypoplasia; and 10, Blake pouch remnant. No significant group interactions with adjusted mean gestational age for tegmentovermian and posterior fossa angles were observed. The tegmentovermian angle was significantly higher in Dandy-Walker malformation (109.5° [SD, 20.2°]) compared with vermian hypoplasia (52.13° [SD, 18.8°]) and Blake pouch remnant (32.1° [SD, 17.9°]), regardless of gestational age. Lateral ventricle sizes were significantly higher in Dandy-Walker malformation at a mean of ≥23.1 weeks' gestational age compared with vermian hypoplasia and Blake pouch remnant. The anterior-to-posterior and craniocaudal vermes were significantly smaller in Dandy-Walker malformation compared with vermian hypoplasia and Blake pouch remnant at mean of ≥23.1 weeks' gestational age.</AbstractText>Dandy-Walker malformation can be described in relation to vermian hypoplasia and Blake pouch remnant by an increased tegmentovermian angle; however, other potential qualifying biometric measurements are more helpful at ≥23.1 weeks' gestational age. Because they fall along the same spectrum of abnormalities, the difficulty in distinguishing these entities from one another makes precise morphologic and biometric descriptions important.</AbstractText>© 2021 by American Journal of Neuroradiology.</CopyrightInformation> |
2,331,321 | The implications of hypothalamic abnormalities for schizophrenia. | Until a few years ago, the hypothalamus was believed to play only a marginal role in schizophrenia pathophysiology. However, recent findings show that this rather small brain region involved in many pathways found disrupted-in schizophrenia. Gross anatomic abnormalities (volume changes of the third ventricle, the hypothalamus, and its individual nuclei) as well as alterations at the cellular level (circumscribed loss of neurons) can be observed. Further, increased or decreased expression of hypothalamic peptides such as oxytocin, vasopressin, several factors involved in the regulation of appetite and satiety, endogenous opiates, products of schizophrenia susceptibility genes as well as of enzymes involved in neurotransmitter and neuropeptide metabolism have been reported in schizophrenia and/or animal models of the disease. Remarkably, although profound disturbances of the hypothalamus-pituitary-adrenal axis, hypothalamus-pituitary-thyroid axis, and the hypothalamus-pituitary-gonadal axis are typical signs of schizophrenia, there is currently no evidence for alterations in the expression of hypothalamic-releasing and inhibiting factors that control these hormonal axes. Finally, the implications of hypothalamus for disease-related disturbances of the sleep-wakefulness cycle and neuroimmune dysfunctions in schizophrenia are outlined. |
2,331,322 | Using models to advance medicine: mathematical modeling of post-myocardial infarction left ventricular remodeling. | The heart is an organ with limited capacity for regeneration and repair. The irreversible cell death and corresponding diminished ability of the heart to repair after myocardial infarction (MI), is a leading cause of morbidity and mortality worldwide. In this paper, a new mathematical model is presented to study the left ventricular (LV) remodeling and associated events after MI. The model accurately describes and predicts the interactions among heart cells and the immune system post-MI in the absence of medical interventions. The resulting system of nonlinear ordinary differential equations is studied both analytically and numerically in order to demonstrate the functionality and performance of the new model. To the best of our knowledge, this model is the only one of its kind to consider and correctly apply all of the known factors in diseased heart LV modeling. This model has the potential to provide researchers with a predictive computational tool to better understand the MI pathology and develop various cell-based treatment options, with benefits of lowering the cost and reducing the development time. |
2,331,323 | [Influence of monosodium glutamate consumption by albino rats during pregnancy and lactation on their offspring]. | The consequences of dietary intake of significant amounts of monosodium glutamate (MSG) are the excess body weight; structural and functional disorders of the central nervous system, liver, kidneys. We have not found information about the influence of excessive using of the MSG by a woman during pregnancy and lactation on the fetus and infants. <b>The aim</b> of the study was the experimental evaluation of the MSG consumption consequences during pregnancy and lactation to the offspring health. <b>Material and methods</b>. The offspring of 3-month old pregnant female white Wistar rats, who received 1% MSG solution (200 mg per kg of body weight per day) ad libitum as the source of liquid during the pregnancy and lactation, have been studied (MSG group). The control group included offspring of pregnant female rats that received water as the source of liquid. In 25-day-old offspring histological examination and morphometry of the nucleo-nucleolar apparatus of neurons in the neocortex of the proper parietal lobe, cardiomyocytes of the subendocardial zones of the left and right ventricles have been performed. Gravimetry have been also carried out (body weight and weight of brain, heart, liver, kidney, thymus and spleen); mitotic activity of anterior corneal epithelium has been evaluated, the state of erythrocyte membranes have been analyzed by the method of acid erythrograms; behavioral tests "Open field", "The elevated plus-maze test", "Hanging on a horizontal wire" have been performed. <b>Results</b>. MSG consumption during pregnancy and lactation led to an increase of brain (by 19.1%) and kidneys (by 7.8%) relative masses; masses of thymus and spleen were decreased. Significant decrease of locomotor activity and increase of time of hanging in "horizontal wire test" were registered. A histological study showed an increase in the number of nucleoli in the neurons of the V layer of the neocortex of the proper parietal lobe (control - 1.56±0.09; MSG group - 1.81±0.07, р=0.03); decrease of the nucleolar parameters of cardiomyocytes; increase of mitotic activity of anterior corneal epithelium (control - 4.021±0.612‰; MSG group - 6.985±0.889‰, р=0.019). A decrease of the resistance of erythrocyte membranes to acid hemolysis was also registered. <b>Conclusion</b>. The results obtained indicate the effect of oral consumption of MSG food additive during pregnancy and lactation on the organism of the offspring. |
2,331,324 | Expression of type one cannabinoid receptor in different subpopulation of kisspeptin neurons and kisspeptin afferents to GnRH neurons in female mice. | The endocannabinoids have been shown to target the afferents of hypothalamic neurons via cannabinoid 1 receptor (CB1) and thereby to influence their excitability at various physiological and/or pathological processes. Kisspeptin (KP) neurons form afferents of multiple neuroendocrine cells and influence their activity via signaling through a variation of co-expressed classical neurotransmitters and neuropeptides. The differential potency of endocannabinoids to influence the release of classical transmitters or neuropeptides, and the ovarian cycle-dependent functioning of the endocannabinoid signaling in the gonadotropin-releasing hormone (GnRH) neurons initiated us to study whether (a) the different subpopulations of KP neurons express CB1 mRNAs, (b) the expression is influenced by estrogen, and (c) CB1-immunoreactivity is present in the KP afferents to GnRH neurons. The aim of the study was to investigate the site- and cell-specific expression of CB1 in female mice using multiple labeling in situ hybridization and immunofluorescent histochemical techniques. The results support that CB1 mRNAs are expressed by both the GABAergic and glutamatergic subpopulations of KP neurons, the receptor protein is detectable in two-thirds of the KP afferents to GnRH neurons, and the expression of CB1 mRNA shows an estrogen-dependency. The applied estrogen-treatment, known to induce proestrus, reduced the level of CB1 transcripts in the rostral periventricular area of the third ventricle and arcuate nucleus, and differently influenced its co-localization with vesicular GABA transporter or vesicular glutamate transporter-2 in KP neurons. This indicates a gonadal cycle-dependent role of endocannabinoid signaling in the neuronal circuits involving KP neurons. |
2,331,325 | Reverse Takotsubo Cardiomyopathy in the Setting of Acute Asthma Exacerbation. | Takotsubo cardiomyopathy (TTC) is a reversible form of myocardial injury characterized by transient systolic and diastolic dysfunction secondary to regional left ventricle (LV) wall motion abnormalities. We present a case of a rare variant of TTC, termed reverse TTC (rTTC), involving basal hypokinesis with apical hyperkinesis accounting for less than 5% of identified cases of TTC. Our patient is a 49-year-old Hispanic female who presented for evaluation of dyspnea. She was diagnosed with acute asthma exacerbation. The patient admitted to more frequent use of her albuterol rescue inhaler. Over the course of her hospitalization the patient had elevation of Troponin I and underwent an echocardiogram and coronary angiogram, which revealed the diagnosis of rTTC in the setting of inhaled beta agonist overuse for acute asthma exacerbation. Our case highlights the importance of adequately managing asthma to prevent exacerbation and overuse of inhaled sympathomimetic agents in an effort to decrease the incidence of TTC in the asthmatic population. |
2,331,326 | Conductance artery stiffness impairs atrio-ventriculo-arterial coupling before manifestation of arterial hypertension or left ventricular hypertrophic remodelling. | As part of normal ageing, conductance arteries lose their cushion function, left ventricle (LV) filling and also left atrial emptying are impaired. The relation between conductance artery stiffness and LV diastolic function is normally explained by arterial hypertension and LV hypertrophy as needed intermediaries. We examined whether age-related aortic stiffening may influence LV diastolic function in normal healthy subjects. Aortic distensibility and pulse wave velocity (PWV) were related to LV emptying and filling parameters and left atrial emptying parameters as determined by magnetic resonance imaging in 36 healthy young (< 35 years) and 16 healthy middle-aged and elderly (> 35 years) with normal arterial blood pressure and myocardial mass. In the overall cohort, total aorta PWV correlated to a decrease in LV peak-emptying volume (r = 0.43), LV peak-filling (r = 0.47), passive atrial emptying volume (r = 0.66), and an increase in active atrial emptying volume (r = 0.47) (all p < 0.001). PWV was correlated to passive atrial emptying volume even if only the > 35-year-old were considered (r = 0.53; p < 0.001). Total peripheral resistance demonstrated similar correlations as PWV, but in a regression analysis only the total aorta PWV was related to left atrial (LA) passive emptying volume. Via impaired ventriculo-arterial coupling, the increased aortic PWV seen with normal ageing hence affects atrio-ventricular coupling, before increased aortic PWV is associated with significantly increased arterial blood pressure or LV hypertrophic remodelling. Our findings reinforce the existence of atrio-ventriculo-arterial coupling and suggest aortic distensibility should be considered an early therapeutic target to avoid diastolic dysfunction of the LV. |
2,331,327 | Corrigendum: Possible roles for the hominoid-specific DSCR4 gene in human cells [Genes Genet. Syst. (2021) 96, p. 1-11]. | Legends to Figures 4 and 5 (p. 7) should be exchanged. Below are the correct legends to Figure 4 and Figure 5. Fig. 4. Interconnection of DSCR4 overexpression-mediated perturbed pathways. KEGG analysis of DSCR4 overexpression-mediated DEGs shows enrichment for the tightly interconnected pathways of the coagulation cascade and the complement cascade (highlighted in red) and further confirm the connection of these cascades with cell adhesion, migration and proliferation (red circle). Fig. 5. Expression profile of DSCR4 across human cell lines and tissues. According to Roadmap Epigenomics Project data, DSCR4 and DSCR8, which share a bidirectional promoter, are highly expressed only in K562 cells, a type of leukemia cell. Analysis of transcriptome data provided by Prescott et al. (2015) showed that DSCR4 and DSCR8 also display high expression in human and chimpanzee neural crest cells, which are critical migratory cells involved in facial morphogenesis in the embryo. (1) Data from Prescott et al. (2015). (2) Samples also include esophagus, lung, spleen and fetal large intestine. (3) Samples also include brain germinal matrix, hippocampus, fetal small intestine, stomach, left ventricle, small intestine, sigmoid colon, HEPG2 cells and HMEC cells. The PDF file for DOI: https://doi.org/10.1266/ggs.20-00012 has been replaced with the corrected version as of June 17, 2021. |
2,331,328 | Associations between physical activity, sedentary behaviour and left ventricular structure and function from the Echocardiographic Study of Latinos (ECHO-SOL). | The cross-sectional association between accelerometer-measured physical activity (PA), sedentary behaviour (SB) and cardiac structure and function is less well described. This study's primary aim was to compare echocardiographic measures of cardiac structure and function with accelerometer measured PA and SB.</AbstractText>Participants included 1206 self-identified Hispanic/Latino men and women, age 45-74 years, from the Echocardiographic Study of Latinos. Standard echocardiographic measures included M-mode, two-dimensional, spectral, tissue Doppler and myocardial strain. Participants wore an Actical accelerometer at the hip for 1 week.</AbstractText>The mean±SE age for the cohort was 56±0.4 years, 57% were women. Average moderate to vigorous PA (MVPA) was 21±1.1 min/day, light PA was 217±4.2 min/day and SB was 737±8.1 min/day. Both higher levels of light PA and MVPA (min/day) were associated with lower left ventricular (LV) mass index (LVMI)/end-diastolic volume and a lower E/e' ratio. Higher levels of MVPA (min/day) were associated with better right ventricular systolic function. Higher levels of SB were associated with increased LVMI. In a multivariable linear regression model adjusted for demographics and cardiovascular disease modifiable factors, every 10 additional min/day of light PA was associated with a 0.03 mL/m2</sup> increase in left atrial volume index (LAVI) (p<0.01) and a 0.004 cm increase in tricuspid annular plane systolic excursion (p<0.01); every 10 additional min/day of MVPA was associated with a 0.18 mL/m2</sup> increase in LAVI (p<0.01) and a 0.24% improvement in global circumferential strain (p<0.01).</AbstractText>Our findings highlight the potential positive association between the MVPA and light PA on cardiac structure and function.</AbstractText>© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation> |
2,331,329 | Single-cell analysis of the ventricular-subventricular zone reveals signatures of dorsal and ventral adult neurogenesis. | The ventricular-subventricular zone (V-SVZ), on the walls of the lateral ventricles, harbors the largest neurogenic niche in the adult mouse brain. Previous work has shown that neural stem/progenitor cells (NSPCs) in different locations within the V-SVZ produce different subtypes of new neurons for the olfactory bulb. The molecular signatures that underlie this regional heterogeneity remain largely unknown. Here, we present a single-cell RNA-sequencing dataset of the adult mouse V-SVZ revealing two populations of NSPCs that reside in largely non-overlapping domains in either the dorsal or ventral V-SVZ. These regional differences in gene expression were further validated using a single-nucleus RNA-sequencing reference dataset of regionally microdissected domains of the V-SVZ and by immunocytochemistry and RNAscope localization. We also identify two subpopulations of young neurons that have gene expression profiles consistent with a dorsal or ventral origin. Interestingly, a subset of genes are dynamically expressed, but maintained, in the ventral or dorsal lineages. The study provides novel markers and territories to understand the region-specific regulation of adult neurogenesis.<CopyrightInformation>© 2021, Cebrian-Silla et al.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Cebrian-Silla</LastName><ForeName>Arantxa</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0003-4623-7655</Identifier><AffiliationInfo><Affiliation>Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Nascimento</LastName><ForeName>Marcos Assis</ForeName><Initials>MA</Initials><Identifier Source="ORCID">0000-0002-9830-9801</Identifier><AffiliationInfo><Affiliation>Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Redmond</LastName><ForeName>Stephanie A</ForeName><Initials>SA</Initials><Identifier Source="ORCID">0000-0002-5580-6269</Identifier><AffiliationInfo><Affiliation>Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Mansky</LastName><ForeName>Benjamin</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0001-8652-0928</Identifier><AffiliationInfo><Affiliation>Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>David</ForeName><Initials>D</Initials><Identifier Source="ORCID">0000-0002-9030-3667</Identifier><AffiliationInfo><Affiliation>Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Medical Scientist Training Program, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Obernier</LastName><ForeName>Kirsten</ForeName><Initials>K</Initials><Identifier Source="ORCID">0000-0002-4025-1299</Identifier><AffiliationInfo><Affiliation>Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Romero Rodriguez</LastName><ForeName>Ricardo</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gonzalez-Granero</LastName><ForeName>Susana</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0003-1531-550X</Identifier><AffiliationInfo><Affiliation>Laboratorio de Neurobiología Comparada, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València - Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Paterna, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>García-Verdugo</LastName><ForeName>Jose Manuel</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Laboratorio de Neurobiología Comparada, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València - Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Paterna, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lim</LastName><ForeName>Daniel A</ForeName><Initials>DA</Initials><Identifier Source="ORCID">0000-0001-7221-3425</Identifier><AffiliationInfo><Affiliation>Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Álvarez-Buylla</LastName><ForeName>Arturo</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0003-4426-8925</Identifier><AffiliationInfo><Affiliation>Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>GEO</DataBankName><AccessionNumberList><AccessionNumber>GSE165555</AccessionNumber></AccessionNumberList></DataBank></DataBankList><GrantList CompleteYN="Y"><Grant><GrantID>F32 NS103221</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS028478</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 GM007618</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K99 NS121273</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS113910</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>I01 BX000252</GrantID><Acronym>BX</Acronym><Agency>BLRD VA</Agency><Country>United States</Country></Grant><Grant><GrantID>R37 HD032116</GrantID><Acronym>HD</Acronym><Agency>NICHD NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>F31 NS106868</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS091544</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS112357</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>07</Month><Day>14</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Elife</MedlineTA><NlmUniqueID>101579614</NlmUniqueID><ISSNLinking>2050-084X</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020547" MajorTopicYN="N">Lateral Ventricles</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D042282" MajorTopicYN="N">Microdissection</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058953" MajorTopicYN="N">Neural Stem Cells</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055495" MajorTopicYN="N">Neurogenesis</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059010" MajorTopicYN="N">Single-Cell Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059467" MajorTopicYN="N">Transcriptome</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList><OtherAbstract Type="plain-language-summary" Language="eng">Nerve cells, or neurons, are the central building blocks of brain circuits. Their damage, death or loss of function leads to cognitive decline. Neural stem/progenitor cells (NSPCs) first appear during embryo development, generating most of the neurons found in the nervous system. However, the adult brain retains a small subpopulation of NSPCs, which in some species are an important source of new neurons throughout life. In the adult mouse brain the largest population of NSPCs, known as B cells, is found in an area called the ventricular-subventricular zone (V-SVZ). These V-SVZ B cells have properties of specialized support cells known as astrocytes, but they can also divide and generate intermediate ‘progenitor cells’ called C cells. These, in turn, divide to generate large numbers of young ‘A cells’ neurons that undertake a long and complex migration from V-SVZ to the olfactory bulb, the first relay in the central nervous system for the processing of smells. Depending on their location in the V-SVZ, B cells can generate different kinds of neurons, leading to at least ten subtypes of neurons. Why this is the case is still poorly understood. To examine this question, Cebrián-Silla, Nascimento, Redmond, Mansky et al. determined which genes were expressed in B, C and A cells from different parts of the V-SVZ. While cells within each of these populations had different expression patterns, those that originated in the same V-SVZ locations shared a set of genes, many of which associated with regional specification in the developing brain. Some, however, were intriguingly linked to hormonal regulation. Salient differences between B cells depended on whether the cells originated closer to the top (‘dorsal’ position) or to the bottom of the brain (‘ventral’ position). This information was used to stain slices of mouse brains for the RNA and proteins produced by these genes in different regions. These experiments revealed dorsal and ventral territories containing B cells with distinct ‘gene expression’. This study highlights the heterogeneity of NSPCs, revealing key molecular differences among B cells in dorsal and ventral areas of the V-SVZ and reinforcing the concept that the location of NSPCs determines the types of neuron they generate. Furthermore, the birth of specific types of neurons from B cells that are so strictly localized highlights the importance of neuronal migration to ensure that young neurons with specific properties reach their appropriate destination in the olfactory bulb. The work by Cebrián-Silla, Nascimento, Redmond, Mansky et al. has identified sets of genes that are differentially expressed in dorsal and ventral regions which may contribute to regional regulation. Furthering the understanding of how adult NSPCs differ according to their location will help determine how various neuron types emerge in the adult brain. |
2,331,330 | The evaluation of right ventricle dyssynchrony by speckle tracking echocardiography in systemic sclerosis patients. | Systemic sclerosis (SSc) is associated with right ventricle (RV) remodeling and dysfunction. The primary aim of this study was to evaluate RV dyssynchrony (RV-Dys) in SSc patients using two-dimensional speckle tracking echocardiography (2D-STE).</AbstractText>Fifty-five SSc patients with functional class I-II and 45 healthy controls were consecutively included and underwent 2D-STE. RV-Dys was defined as the standard deviation of time to peak strain of mid and basal segments of RV free wall and interventricular septum. SSc group was further classified according to the presence of pulmonary arterial hypertension (PAH). Patients with tricuspid regurgitant velocity >2.8 m/s with additional echocardiographic PAH signs were defined as SSc PAH (+).</AbstractText>SSc patients had lower RV longitudinal strain (RV-LS) (-17.6 ± 4.6% vs. -20.8 ± 2.8%, p < 0.001) and greater RV-Dys (49.9 ± 25.4 ms vs 24.3 ± 11.8 ms, p = 0.006) than controls despite no significant difference in conventional echocardiographic variables regarding RV function. Although SSc PAH(+) patients had lower RV-LS and higher RV-Dys than SSc PAH(-) patients, the differences were not statistically significant. The only independent predictor of RV-Dys was RV-LS (β:-0.324 [-3.89- -0.45]; p = 0.014).</AbstractText>SSc patients had not only reduced RV-LS but also impaired RV synchronicity even as conventional echocardiographic variables were preserved.</AbstractText>© 2021 Wiley Periodicals LLC.</CopyrightInformation> |
2,331,331 | Neuroanatomical changes seen in MRI in patients with cerebral metastasized breast cancer after radiotherapy. | To quantify neuroanatomical changes using magnetic resonance imaging (MRI) in patients with cerebral metastasized breast cancer after brain radiotherapy (RT).</AbstractText>Fifteen patients with breast cancer with brain metastases who underwent whole brain RT (WBR), radiosurgery (RS), and/or hypofractionated stereotactic treatment (STX) were examined at four time points (TPs). A total of 48 MRIs were available: prior to RT (TP1), 5-8 months after RT (TP2), 9-11 months after RT (TP3), and >20 months after RT (TP4). Using automatic segmentation, 25 subcortical structures were analyzed. Patients were split into three groups: STX (receiving STX and RS), RS (receiving RS only), and WBR (receiving WBR at least once). After testing for a normal distribution for all values using the Kolmogorov-Smirnov test, a two-sided paired t</i> test was used to analyze volumetric changes. For those values that were not normally distributed, the nonparametric Mann-Whitney test was employed.</AbstractText>The left cerebellum white matter (p</i> = 0.028), the right pallidum (p</i> = 0.038), and the left thalamus (p</i> = 0.039) significantly increased at TP2 compared to TP1. The third ventricle increased at all TPs (p</i> = 0.034-0.046). The left choroid plexus increased at TP3 (p</i> = 0.037) compared to TP1. The left lateral ventricle increased at TP3 (p</i> = 0.012) and TP4 (p</i> = 0.027). Total gray matter showed a trend of volume decline in STX and WBR groups.</AbstractText>These findings indicate that alterations in the volume of subcortical structures may act as a sensitive parameter when evaluating neuroanatomical changes and brain atrophy due to radiotherapy. Differences observed for patients who received STX and WBR, but not those treated with RS, need to be validated further.</AbstractText> |
2,331,332 | Injectable Anesthesia With Medetomidine, Ketamine, and Butorphanol in Captive Humboldt Penguins (<i>Spheniscus humboldti</i>). | The effects of an injectable anesthesia with 0.05 mg/kg medetomidine, 5 mg/kg ketamine, and 0.5 mg/kg butorphanol administered together intramuscularly were evaluated in 22 captive Humboldt penguins (<i>Spheniscus humboldti</i>, 10 male and 12 female), with a mean age of 8.5 ± 8.23 years. The birds fasted for18-24 hours prior to the procedure. Induction was followed by 4 distinct progressive responses of the birds to the anesthetic effect, including onset of initial effects at 2.0 ± 1.7 minutes (x̄ ± SD), sternal recumbency with the head still elevated at 2.2 ± 1.6 minutes, lowering and placing the beak tip to the ground at 3.6 ± 3.4 minutes, and lateral positioning of the neck and head at 4.2 ± 3.4 minutes. A general state of sedation, muscle relaxation, and analgesia were noted 10.0 ± 2.8 minutes postinjection. However, according to an established scoring system for the assessment of anesthetic depth in avian patients, a surgical plane of anesthesia was not achieved. Muscle relaxation determined by the same scoring system lasted for 31.4 ± 17.1 minutes. The penguins' mean respiratory rate did not demonstrate significant change and spontaneous ventilation was present throughout the procedure. Relative peripheral arterial oxygen saturation decreased significantly from 92.83 ± 5.77% at 10 minutes to 90.91 ± 5.77% at 40 minutes following induction. The birds' heart rate also decreased significantly from 112.55 ± 23.97 beats/min at 10 minutes to 101.65 ± 25.42 beats/min at 40 minutes. The measured cloacal temperatures were maintained within normal range despite ambient temperatures of up to 28.3°C (82.9°F). Reversal of medetomidine with 0.25 mg/kg atipamezole was conducted after 45.1 ± 7.3 minutes. Recovery was smooth but of variable duration with patients being able or willing to stand steadily in an upright position after 50.1 ± 34.6 minutes. One penguin died during recovery from a ruptured left ventricle and consecutive pericardial tamponade, but no predisposing factors were identified. The anesthetic protocol proved to be effective for noninvasive and minor painful procedures (eg, diagnostic imaging, blood collection). Disadvantages to the administration of the combined anesthetic agents in the penguins included a short period of muscle relaxation and smooth but potentially prolonged recovery. The safety of the anesthetic protocol described for Humboldt penguins in this report has to be evaluated critically against the the death of 1 penguin during recovery. |
2,331,333 | [The research progress on assessment methods of right heart function]. | 随着对血流动力学认识的深入，右心功能评估逐渐得到重视，右心功能评价的方法也趋于多样化。本文就目前常用的右心功能评价方法，特别是各种无创右心功能评价方法及其各自优缺点进行对比。. |
2,331,334 | An Infundibular Unidentified Object (IUO): a new pituitary stalk marker? | Measurement of the pituitary stalk (PS) diameter does not always solve the issue of minimal PS thickening. A previously undescribed image is found at the infundibular level on high resolution thin section T2W MRI in a large number of normal individuals. We speculate that this image-whose exact origin is still unknown-may serve as a marker of the normal infundibulum.</AbstractText>In the last 6 months, 350 consecutive adult patients suspected of sellar pathology or controlled after medical or surgical treatment prospectively underwent a pituitary MRI including a sagittal T2W high resolution sequence. One hundred twelwe patients presenting a pituitary mass with suprasellar extension or those whose PS was not entirely visible were excluded.</AbstractText>A short focal annular T2 hypointense thickening of the wall of the infundibular recess of the third ventricle, more pronounced anteriorly was found in 151/238 patients. Additionally, a more or less tiny ventral extension was demonstrated on sagittal T2W sequence in 105/151 patients. These images were not identified on T1W or on T1W gadolinium enhanced sequences. The ring-like infundibular thickening and/or its ventral extension were not identified in 87/238 patients; in 43/87 of these patients the PS was found severely stretched mainly in case of primary or secondary empty sella. If patients with empty sella were excluded, our finding was observed in 194/238 cases, i.e. in 82%.</AbstractText>A detailed appearance of the PS on T2W MRI is described for the first time. A previously unreported T2W hypointense annular focal image prolonged by a tiny spicular or nodular ventral bud is found at the lower part of the infundibulum in a majority of normal patients, but not if the PS is stretched such as in empty sella. This image has to be recognized as a normal anatomical landmark. The possible origin of this image is discussed but not totally elucidated. An ongoing research will demonstrate or not if this image may serve as a marker to improve the early diagnosis of PS lesions.</AbstractText>© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</CopyrightInformation> |
2,331,335 | THAN: task-driven hierarchical attention network for the diagnosis of mild cognitive impairment and Alzheimer's disease. | To assist doctors to diagnose mild cognitive impairment (MCI) and Alzheimer's disease (AD) early and accurately, convolutional neural networks based on structural magnetic resonance imaging (sMRI) images have been developed and shown excellent performance. However, they are still limited in their capacity in extracting discriminative features because of large sMRI image volumes yet small lesion regions and the small number of sMRI images.</AbstractText>We proposed a task-driven hierarchical attention network (THAN) taking advantage of the merits of patch-based and attention-based convolutional neural networks for MCI and AD diagnosis. THAN consists of an information sub-network and a hierarchical attention sub-network. In the information sub-network, an information map extractor, a patch-assistant module, and a mutual-boosting loss function are designed to generate a task-driven information map, which automatically highlights disease-related regions and their importance for final classification. In the hierarchical attention sub-network, a visual attention module and a semantic attention module are devised based on the information map to extract discriminative features for disease diagnosis.</AbstractText>Extensive experiments were conducted for four classification tasks: MCI versus (vs.</i>) normal controls (NC), AD vs.</i> NC, AD vs.</i> MCI, and AD vs.</i> MCI vs.</i> NC. Results demonstrated that THAN attained the accuracy of 81.6% for MCI vs.</i> NC, 93.5% for AD vs.</i> NC, 80.8% for AD vs.</i> MCI, and 62.9% for AD vs.</i> MCI vs.</i> NC. It outperformed advanced attention-based and patch-based methods. Moreover, information maps generated by the information sub-network could highlight the potential biomarkers of MCI and AD, such as the hippocampus and ventricles. Furthermore, when the visual and semantic attention modules were combined, the performance of the four tasks was highly improved.</AbstractText>The information sub-network can automatically highlight the disease-related regions. The hierarchical attention sub-network can extract discriminative visual and semantic features. Through the two sub-networks, THAN fully exploits the visual and semantic features of disease-related regions and meanwhile considers global features of sMRI images, which finally facilitate the diagnosis of MCI and AD.</AbstractText>2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.</CopyrightInformation> |
2,331,336 | Diagnostic accuracy of cardiac magnetic resonance tissue tracking technology for differentiating between acute and chronic myocardial infarction. | This study aimed to explore the diagnostic accuracy of cardiac magnetic resonance tissue tracking (CMR-TT) technology in the quantitative evaluation of left myocardial infarction for differentiating between acute and chronic myocardial infarction.</AbstractText>A total of 104 human subjects were enrolled in this prospective study. Among them, 64 healthy subjects and 40 patients with left ventricular myocardial infarction and 7 days and 6 months' follow-up CMR studies, including steady-state free precession (SSFP) sequence and late gadolinium enhancement MR imaging, were enrolled. The strain parameters of the infarcted myocardium, its corresponding remote segments, and global right ventricular strain were analyzed using tissue tracking technology, and CMR-TT 3D strain parameters in radial, circumferential, and longitudinal directions were obtained. Receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy of the CMR-TT strain parameters for discriminating between acute and chronic myocardial infarction.</AbstractText>Peak radial strain (RS) of infarcted myocardium increased from 12.99±7.28 to 18.57±6.66 at 6 months (P<0.001), whereas peak circumferential strain (CS) increased from -8.82±4.71 to -12.78±3.55 (P<0.001). CS yielded the best areas under the ROC curve (AUC) of 0.751 in showing differentiation between acute and chronic myocardial infarction of all the strain parameters obtained. The highest significant differences between acute myocardial infarction and normal myocardium, both in the left and right ventricles, were also found in the RS (P<0.001) and CS (P<0.001).</AbstractText>RS and CS obtained by CMR-TT have high sensitivity and specificity in the differential diagnosis of acute versus chronic myocardial infarction, and their use is thus worth popularizing in clinical application.</AbstractText>2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.</CopyrightInformation> |
2,331,337 | Effectiveness of fetal ultrasound diagnostics in cardiac malformations and association with polyhydramnios and oligohydramnios. | Examine the effectiveness of prenatal ultrasound diagnostics in the detection of cardiovascular malformations, and their association with polyhydramnios and oligohydramnios.</AbstractText>We examined the fetal ultrasonography and postnatal clinical/fetopathological data of 372 newborns/fetuses over a 7-year period in a tertiary centre. Fetal echocardiography was performed in cases of suspected US findings between 18-32 weeks. During the ultrasound the amniotic fluid amount was measured and the amniotic fluid index (AFI) or largest amniotic fluid pocket was determined.</AbstractText>Prenatal ultrasonographic results and postnatal/fetopathological diagnosis were fully congruent in 236/372 cases (63.4%), and in 66/372 cases of cardiovascular anomalies (17.7%) the discovery was partial, while in 70/372 cases no fetal cardiovascular anomalies were diagnosed during pregnancy (18.8%) (false negative). Cardiovascular malformations were isolated in 255 cases, in 172 of which (67.5%) the results of prenatal ultrasonography and postnatal diagnostics were fully congruent. In 43 cases (16.9%) the prenatal discovery was partial, and in 40 cases (15.7%) there was no prenatal recognition of the malformation. Cardiovascular abnormalities were found as a part of multiple malformations in 76 cases. In 41 fetuses the cardiovascular malformation was associated with chromosomal abnormalities. Cardiovascular malformations were significantly associated with polyhydramnios. Although in some of the cardiovascular malformations the association rate with polyhydramnios was high (AVSD, double outlet right ventricle, tetralogy of Fallot), we found a moderate association rate (19.7%). The association with oligohydramnios was 8.57%.</AbstractText>Echocardiography plays an important role in the prenatal diagnostics. In cases of polyhydramnios and oligohydramnios, fetal echocardiography should be performed.</AbstractText>2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.</CopyrightInformation> |
2,331,338 | Microbiota Modulates Cardiac Transcriptional Responses to Intermittent Hypoxia and Hypercapnia. | The microbiota plays a critical role in regulating organismal health and response to environmental stresses. Intermittent hypoxia and hypercapnia, a condition that represents the main hallmark of obstructive sleep apnea in humans, is known to induce significant alterations in the gut microbiome and metabolism, and promotes the progression of atherosclerosis in mouse models. To further understand the role of the microbiome in the cardiovascular response to intermittent hypoxia and hypercapnia, we developed a new rodent cage system that allows exposure of mice to controlled levels of O<sub>2</sub> and CO<sub>2</sub> under gnotobiotic conditions. Using this experimental setup, we determined the impact of the microbiome on the transcriptional response to intermittent hypoxia and hypercapnia in the left ventricle of the mouse heart. We identified significant changes in gene expression in both conventionally reared and germ-free mice. Following intermittent hypoxia and hypercapnia exposure, we detected 192 significant changes in conventionally reared mice (96 upregulated and 96 downregulated) and 161 significant changes (70 upregulated and 91 downregulated) in germ-free mice. Only 19 of these differentially expressed transcripts (∼10%) were common to conventionally reared and germ-free mice. Such distinct transcriptional responses imply that the host microbiota plays an important role in regulating the host transcriptional response to intermittent hypoxia and hypercapnia in the mouse heart. |
2,331,339 | A Case Report of Adult-Onset Alexander Disease with a Tumor-Like Lesion in the Lateral Ventricle. | Adult-onset Alexander disease (AOAD) is an autosomal dominant progressive astrogliopathy caused by pathogenic variants in glial fibrillary acidic protein (<i>GFAP</i>). Individuals with this disorder often present with a typical neuroradiologic pattern, including frontal white matter abnormality with contrast enhancement, atrophy and signal intensity changes of the medulla oblongata and upper cervical cord on MRI. Focal lesions are rarely seen in AOAD, which causes concern for primary malignancies. This study aimed to present the case of a 37-year-old male patient initially diagnosed with an astrocytoma in the lateral ventricle that was later identified as GFAP mutation-confirmed AOAD. <i>GFAP</i> sequencing revealed a heterogeneous missense mutation point c.236G>A. Hence, AOAD should be considered in patients with tumor-like lesion brain lesion in association with atrophy of medulla oblongata and upper cervical spinal cord, and frontal white matter abnormality with contrast enhancement. |
2,331,340 | Pediatric Hydrocephalus and the Primary Care Provider. | Hydrocephalus is a pathologic condition that results in the disruption of normal cerebrospinal fluid flow dynamics often characterized by an increase in intracranial pressure resulting in an abnormal dilation of the ventricles. The goal of this article was to provide the necessary background information to understand the pathophysiology related to hydrocephalus, recognize the presenting signs and symptoms of hydrocephalus, identify when to initiate a workup with further studies, and understand the management of pediatric patients with a new and preexisting diagnosis of hydrocephalus. |
2,331,341 | The feasibility and efficacy of short-term visual-motor training in pediatric posterior fossa tumor survivors. | Pediatric posterior fossa tumor (PFT) survivors experience a range of cognitive and motor impairments that require timely rehabilitation of these functions. In Russia, rehabilitation services are only just beginning to be formed; therefore, it is necessary to test rehabilitation protocols for children surviving cancer.</AbstractText>To evaluate the efficacy of short-term cognitive and motor training (CMT) aimed on visual-motor integration in PFT survivors using training devices.</AbstractText>"Single center" quasi randomized controlled experiment.</AbstractText>Outpatients of the Russkoe Pole Rehabilitation Center.</AbstractText>The 63 children cancer survivors between the ages of 6 and 17 years.</AbstractText>The baseline level of cognitive and motor functions was assessed in all participants. Then the sample of patients split into two subgroups of equal sex, age, and diagnosis. The intervention subgroup received six sessions of CMT for two weeks, and the other subgroup underwent 'empty' two weeks with no intervention. Reassessment of motor and cognitive functions was conducted in all participants. Then the subgroups changed: the first subgroup underwent 'empty' two weeks, and the second subgroup completed the CMT, and further reassessment was provided.</AbstractText>The primary results demonstrate an increase in gross and fine motor skills, motor coordination, visual-motor integration, and visual processing after CMT. Secondary results show that the age at onset is an important factor in the subsequent decline in cognitive, motor functions, and eye movements. Children with medulloblastoma perform worse on motor tests than children with astrocytoma. A tumor in the IV ventricle is the most harmful, and a tumor in the cerebellar hemispheres is the least harmful to a child's cognitive and motor development.</AbstractText>This study shows the effectiveness of a short-term CMT program for children who survived PFT. The study also found that cognitive, motor, and visual-motor functions are affected by the tumor's localization, malignancy, and the child's age at onset.</AbstractText>Short-term rehabilitation methods can be useful in pediatric oncological practice. Reconstruction of cognitive functions can occur during the training of more "simple" functions, such as hand-eye integration. The study makes a significant contribution to the methods of short-term rehabilitation in children who survived cancer.</AbstractText> |
2,331,342 | Toxicity of polymer-modified CuS nanoclusters on zebrafish embryo development. | Despite the vast amount of research on the toxicity of copper-based nanoparticles, the toxicity of CuS nanoparticles is still largely unknown. Due to the application of CuS-based nanomaterials in biomedical engineering, it is necessary to study their potential toxicity and biological effects. In this study, we evaluated the toxicity of polymer-modified CuS nanoclusters (PATA3-C4@CuS) on embryo development through exposing zebrafish embryos to 1, 2.5, 5, 7.5, and 10 mg/L PATA3-C4@CuS at 0.75-h post-fertilization. The morphological results demonstrated that PATA3-C4@CuS at concentrations greater than 1 mg/L PATA3-C4@CuS induced abnormal phenotypes including smaller heads and eyes, pericardial edema, and epiboly retardation and it increased mortality, lowered the hatching rate, and inhibited swim bladder inflation. In situ hybridization and quantitative reverse transcription polymerase chain reaction showed that PATA3-C4@CuS could alter the expression patterns of tbxta, dlx3, and cstlb and increase the expression levels of wnt5 and wnt11, which suggested that PATA3-C4@CuS disrupts cell migration by increasing the levels of wnt5 and wnt11 during gastrulation. It was also discovered that PATA3-C4@CuS exposure caused a slow heart rate and smaller ventricles in zebrafish larvae. Immunofluorescence and behavioral analyses showed that PATA3-C4@CuS could damage the ventral projection of the primary motor neurons CaP, which was in accordance with the reduction in locomotion ability. Together, our data demonstrated that functional PATA3-C4@CuS could disrupt cell migration during gastrulation, affect cardiac development and function, and decrease locomotive activity. |
2,331,343 | [Analysis of genetic variant in a fetus featuring pontocerebellar hypoplasia type 6]. | To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles.</AbstractText>The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.</AbstractText>Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4).</AbstractText>The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.</AbstractText> |
2,331,344 | [New variants in FLNA gene cause periventricular nodular heterotopia and epileptic seizure in three cases]. | To explore the genetic bases of 3 patients with periventricular nodular heterotopia and epileptic seizure.</AbstractText>The clinical data of three patients presenting with periventricular nodular ectopic with epileptic seizure were analyzed. Whole exome sequencing (WES) was performed on the patients, and Sanger sequencing was used to validate the suspected variants.</AbstractText>In three female patients, head MRI showed nodular gray matter ectopic in the bilateral ventricle. WES identified the heterozygous c.2720del T(p.Leu907Argfs*39) variant of FLNA gene in case 1 and her mother (case 2), and heterozygous c.1387_1390del GTGC(p.Val463Profs*34) of FLNA gene in case 3. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC (p.Val463Profs*34) variants of FLNA gene were predicted to be pathogenic (PVS1+PM2+PP1) and likely pathogenic(PVS1+PM2), respectively.</AbstractText>The c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC(p.Val463Profs*34) variants of FLNA gene may be the genetic cause of the three patients.</AbstractText> |
2,331,345 | Cortical and Subcortical Anatomy of the Orbitofrontal Cortex: A White Matter Microfiberdissection Study and Case Series. | The literature on white matter anatomy underlying the human orbitofrontal cortex (OFC) is scarce in spite of its relevance for glioma surgery.</AbstractText>To describe the anatomy of the OFC and of the underlying white matter fiber anatomy, with a particular focus on the surgical structures relevant for a safe and efficient orbitofrontal glioma resection. Based on anatomical and radiological data, the secondary objective was to describe the growth pattern of OFC gliomas.</AbstractText>The study was performed on 10 brain specimens prepared according to Klingler's protocol and dissected using the fiber microdissection technique modified according to U.T., under the microscope at high magnification.</AbstractText>A detailed stratigraphy of the OFC was performed, from the cortex up to the frontal horn of the lateral ventricle. The interposed neural structures are described together with relevant neighboring topographic areas and nuclei. Combining anatomical and radiological data, it appears that the anatomical boundaries delimiting and guiding the macroscopical growth of OFC gliomas are as follows: the corpus callosum superiorly, the external capsule laterally, the basal forebrain and lentiform nucleus posteriorly, and the gyrus rectus medially. Thus, OFC gliomas seem to grow ventriculopetally, avoiding the laterally located neocortex.</AbstractText>The findings in our study supplement available anatomical knowledge of the OFC, providing reliable landmarks for a precise topographical diagnosis of OFC lesions and for perioperative orientation. The relationships between deep anatomic structures and glioma formations described in this study are relevant for surgery in this highly interconnected area.</AbstractText>© Congress of Neurological Surgeons 2021.</CopyrightInformation> |
2,331,346 | Effect of atrial artificial electrical stimulation on depolarization and repolarization and hemodynamics of the heart ventricle in rainbow trout Oncorhynchus mykiss.<Pagination><StartPage>1329</StartPage><EndPage>1339</EndPage><MedlinePgn>1329-1339</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s10695-021-00983-0</ELocationID><Abstract><AbstractText>The spatial-temporal organization of the activation, repolarization and hemodynamics of the heart ventricle in rainbow trout, Oncorhynchus mykiss, adapted to a temperature of 5-7 °C, were studied from the normal sinus rhythm (21.6 ± 4.9 bpm) to the highest possible heart rhythm (HR) (60 bpm), during which deterioration of the contractile activity of the myocardium occurred. Regardless of the HR, the main pattern of excitation of the heart ventricle was the movement of the depolarization wave from the dorsal areas of the base in the base-apical and ventral directions with the capture of the entire thickness of the walls, with a slight difference in the time of activation of the subendocardium compared to the subepicardium. The increase in HR above the sinus rhythm caused significant shortening of local repolarization durations in all areas and layers (endocardial, intramural and subepicardial) of the heart ventricle. Changes in local durations of repolarization led to an increase in the heterogeneity of repolarization of the ventricular myocardium; as a result, a deterioration of its contractility was observed. In relation to the sinus rhythm, the maximal systolic pressure in the heart ventricle decreased, the diastolic and end-diastolic pressure increased, and the maximum rates of pressure rise and fall decreased. In rainbow trout adapted to a temperature of 5-7 °C at sinus rhythm, the pumping function of the heart was probably within the upper limit of the physiological norm, and a further increase in the heart rate led to a decline in myocardial contractility.</AbstractText><CopyrightInformation>© 2021. The Author(s), under exclusive licence to Springer Nature B.V.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kibler</LastName><ForeName>Natalya A</ForeName><Initials>NA</Initials><Identifier Source="ORCID">0000-0002-9775-7717</Identifier><AffiliationInfo><Affiliation>Institute of Physiology, Federal Research Centre Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya str., Syktyvkar, 167982, Komi Republic, Russia. natanadya@mail.ru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nuzhny</LastName><ForeName>Vladimir P</ForeName><Initials>VP</Initials><AffiliationInfo><Affiliation>Institute of Physiology, Federal Research Centre Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya str., Syktyvkar, 167982, Komi Republic, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kharin</LastName><ForeName>Sergey N</ForeName><Initials>SN</Initials><AffiliationInfo><Affiliation>Institute of Physiology, Federal Research Centre Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya str., Syktyvkar, 167982, Komi Republic, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shmakov</LastName><ForeName>Dmitry N</ForeName><Initials>DN</Initials><AffiliationInfo><Affiliation>Institute of Physiology, Federal Research Centre Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya str., Syktyvkar, 167982, Komi Republic, Russia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>07</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Fish Physiol Biochem</MedlineTA><NlmUniqueID>100955049</NlmUniqueID><ISSNLinking>0920-1742</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016275" MajorTopicYN="Y">Atrial Function</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004558" MajorTopicYN="N">Electric Stimulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006325" MajorTopicYN="N">Heart Atria</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006439" MajorTopicYN="N">Hemodynamics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009200" MajorTopicYN="N">Myocardial Contraction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017686" MajorTopicYN="N">Oncorhynchus mykiss</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016276" MajorTopicYN="Y">Ventricular Function</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Activation-recovery interval</Keyword><Keyword MajorTopicYN="N">Atrial pacing</Keyword><Keyword MajorTopicYN="N">Fish</Keyword><Keyword MajorTopicYN="N">Heart</Keyword><Keyword MajorTopicYN="N">Oncorhynchus mykiss</Keyword><Keyword MajorTopicYN="N">Pumping function</Keyword><Keyword MajorTopicYN="N">Rainbow trout</Keyword><Keyword MajorTopicYN="N">Ventricle</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>1</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>6</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>7</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>8</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>7</Month><Day>9</Day><Hour>12</Hour><Minute>23</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34241764</ArticleId><ArticleId IdType="doi">10.1007/s10695-021-00983-0</ArticleId><ArticleId IdType="pii">10.1007/s10695-021-00983-0</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Abramochkin DV, Vornanen M (2015) Seasonal acclimatization of the cardiac potassium currents (IK<sub>1</sub> and IKr) in an arctic marine teleost, the navaga cod (Eleginusnavaga). 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Regardless of the HR, the main pattern of excitation of the heart ventricle was the movement of the depolarization wave from the dorsal areas of the base in the base-apical and ventral directions with the capture of the entire thickness of the walls, with a slight difference in the time of activation of the subendocardium compared to the subepicardium. The increase in HR above the sinus rhythm caused significant shortening of local repolarization durations in all areas and layers (endocardial, intramural and subepicardial) of the heart ventricle. Changes in local durations of repolarization led to an increase in the heterogeneity of repolarization of the ventricular myocardium; as a result, a deterioration of its contractility was observed. In relation to the sinus rhythm, the maximal systolic pressure in the heart ventricle decreased, the diastolic and end-diastolic pressure increased, and the maximum rates of pressure rise and fall decreased. In rainbow trout adapted to a temperature of 5-7 °C at sinus rhythm, the pumping function of the heart was probably within the upper limit of the physiological norm, and a further increase in the heart rate led to a decline in myocardial contractility.<CopyrightInformation>© 2021. The Author(s), under exclusive licence to Springer Nature B.V.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kibler</LastName><ForeName>Natalya A</ForeName><Initials>NA</Initials><Identifier Source="ORCID">0000-0002-9775-7717</Identifier><AffiliationInfo><Affiliation>Institute of Physiology, Federal Research Centre Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya str., Syktyvkar, 167982, Komi Republic, Russia. natanadya@mail.ru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nuzhny</LastName><ForeName>Vladimir P</ForeName><Initials>VP</Initials><AffiliationInfo><Affiliation>Institute of Physiology, Federal Research Centre Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya str., Syktyvkar, 167982, Komi Republic, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kharin</LastName><ForeName>Sergey N</ForeName><Initials>SN</Initials><AffiliationInfo><Affiliation>Institute of Physiology, Federal Research Centre Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya str., Syktyvkar, 167982, Komi Republic, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shmakov</LastName><ForeName>Dmitry N</ForeName><Initials>DN</Initials><AffiliationInfo><Affiliation>Institute of Physiology, Federal Research Centre Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya str., Syktyvkar, 167982, Komi Republic, Russia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>07</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Fish Physiol Biochem</MedlineTA><NlmUniqueID>100955049</NlmUniqueID><ISSNLinking>0920-1742</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016275" MajorTopicYN="Y">Atrial Function</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004558" MajorTopicYN="N">Electric Stimulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006325" MajorTopicYN="N">Heart Atria</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006439" MajorTopicYN="N">Hemodynamics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009200" MajorTopicYN="N">Myocardial Contraction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017686" MajorTopicYN="N">Oncorhynchus mykiss</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016276" MajorTopicYN="Y">Ventricular Function</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Activation-recovery interval</Keyword><Keyword MajorTopicYN="N">Atrial pacing</Keyword><Keyword MajorTopicYN="N">Fish</Keyword><Keyword MajorTopicYN="N">Heart</Keyword><Keyword MajorTopicYN="N">Oncorhynchus mykiss</Keyword><Keyword MajorTopicYN="N">Pumping function</Keyword><Keyword MajorTopicYN="N">Rainbow trout</Keyword><Keyword MajorTopicYN="N">Ventricle</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>1</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>6</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>7</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>8</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>7</Month><Day>9</Day><Hour>12</Hour><Minute>23</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34241764</ArticleId><ArticleId IdType="doi">10.1007/s10695-021-00983-0</ArticleId><ArticleId IdType="pii">10.1007/s10695-021-00983-0</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Abramochkin DV, Vornanen M (2015) Seasonal acclimatization of the cardiac potassium currents (IK<sub>1</sub> and IKr) in an arctic marine teleost, the navaga cod (Eleginusnavaga). J Comp Physiol B 185:883–890. https://doi.org/10.1007/s00360-015-0925-5</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00360-015-0925-5</ArticleId><ArticleId IdType="pubmed">26253844</ArticleId></ArticleIdList></Reference><Reference><Citation>Azarov YaE, Kibler NA, Vaykshnorayte MA, Tsvetkova AS, Kharin SN, Vityazev VA, Shmakov DN (2013) Effect of heart electric stimulation on repolarization of ventricular myocardium of fish and amphibians. Zh Evol Biohim Fiziol 49:165–174. https://doi.org/10.1134/S0022093013020059</Citation><ArticleIdList><ArticleId IdType="doi">10.1134/S0022093013020059</ArticleId></ArticleIdList></Reference><Reference><Citation>Badr A, El-Sayed MF, Vornanen M (2016) Effects of seasonal acclimatization on temperature dependence of cardiac excitability in the roach, Rutilus rutilus. J Exp Biol 219:1495–1504. https://doi.org/10.1242/jeb.138347</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/jeb.138347</ArticleId><ArticleId IdType="pubmed">26994185</ArticleId></ArticleIdList></Reference><Reference><Citation>Bigdai EV, Samoilov VO (2004) Heterogeneity of olfactory transduction mechanisms in the Rana Temporaria frog. Zh Evol Biohim Fiziol 40:112–117. https://doi.org/10.1023/B:JOEY.0000033804.79865.4a</Citation></Reference><Reference><Citation>Casselman MT, Anttila К, Farrell AP (2012) Using maximum heart rate as a rapid screening tool to determine optimum temperature for aerobic scope in Pacific salmon Oncorhynchus spp. J Fish Biol 80:З58-377. https://doi.org/10.1111/j.1095-8649.2011.03182.x</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1095-8649.2011.03182.x</ArticleId></ArticleIdList></Reference><Reference><Citation>Coyne MD, Kim KC, Cameron JS, Gwathmey JK (2000) Effects of temperature and calcium availability on ventricular myocardium from rainbow trout. 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J Gen Physiol 112:665–678. https://doi.org/10.1085/jgp.112.6.665</Citation><ArticleIdList><ArticleId IdType="doi">10.1085/jgp.112.6.665</ArticleId><ArticleId IdType="pubmed">9834139</ArticleId><ArticleId IdType="pmc">2229447</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">34240664</PMID><DateRevised><Year>2022</Year><Month>04</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1360-046X</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year><Month>Jul</Month><Day>09</Day></PubDate></JournalIssue><Title>British journal of neurosurgery</Title><ISOAbbreviation>Br J Neurosurg</ISOAbbreviation></Journal><ArticleTitle>Postoperative hydrocephalus is a high-risk lethal factor for patients with low-grade optic pathway glioma.</ArticleTitle><Pagination><StartPage>1</StartPage><EndPage>7</EndPage><MedlinePgn>1-7</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/02688697.2021.1947971</ELocationID><Abstract><AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">To explore the prognostic factors of patients with low-grade optic pathway glioma (OPG) and the optimal treatment to reduce the incidence of postoperative hydrocephalus.<AbstractText Label="PATIENTS AND METHODS" NlmCategory="METHODS">This single-center study retrospectively analyzed data from 66 patients with OPGs who underwent surgery. The patients were followed, and overall survival (OS) and progression-free survival (PFS) were determined. The effects of different treatments on the hydrocephalus of patients were compared.<AbstractText Label="RESULTS" NlmCategory="RESULTS">Postoperative hydrocephalus was identified as a factor to increase the risk of mortality by 1.99-fold (<i>p</i> = .028). And, 5-year survival rate was significantly lower among patients with postoperative hydrocephalus (<i>p</i> = .027). The main factors leading to preoperative hydrocephalus in patients are large tumor volume and invasion into the third ventricle. Gross total resections (GTR) could reduce the risk of long-term hydrocephalus (<i>p</i> = .046). Age younger than 4 years (<i>p</i> = .046) and tumor invasion range/classification (<i>p</i> = .029) are the main factors to reduce the five-year survival rate. Postoperative radiotherapy (RT) and chemotherapy (CT) had no significant effects on OS. Extraventricular drainage (EVD) was not associated with perioperative infection (<i>p</i> = .798 > .05) and bleeding (<i>p</i> = .09 > .05). Compared with 2 stage surgery (external ventricular drainage or ventriculoperitoneal shunt (VPS) was first placed, followed by tumor resection), 1 stage surgery (direct resection of tumor) had no complication increase.<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Postoperative hydrocephalus is mostly obstructive hydrocephalus, and it is an important factor that reduces the OS of patients with low-grade OPGs. Surgery to remove the tumor to the greatest extent improves cerebrospinal fluid circulation is effective at reducing the incidence postoperative hydrocephalus. For patients whose ventricles are still dilated after surgery, in addition to considering poor ventricular compliance, they need to be aware of the persistence and progression of hydrocephalus. |
2,331,347 | Pathological Change and Whole Transcriptome Alternation Caused by ePTFE Implantation in Myocardium. | Expanded polytetrafluoroethylene (ePTFE) is commonly used in cardiovascular surgery, but usually causes postoperation complications. Although great efforts have been done to relieve these complications or to understand their mechanism, there are no applicable strategies available and no understanding mechanisms, especially in the myocardium. Here, ePTFE membranes are implanted into the right ventricular outflow tract of rabbits, and the implant-related myocardium is dissected and analyzed by histology and transcriptome sequencing. ePTFE implantation causes myocardium inflammation and fibrosis. There are 1867 differently expressed mRNAs (DEmRNAs, 1107 upregulated and 760 downregulated) and 246 differently expressed lncRNAs (DElncRNAs, 110 upregulated and 136 downregulated) identified. Bioinformatic analysis indicates that the upregulated DEmRNAs and DElncRNAs are mainly involved in inflammatory, immune responses, and extracellular matrix remodeling, while the downregulated DEmRNAs and DElncRNAs are predominantly functioned in the metabolism and cardiac remodeling. Analysis of coexpression and regulatory relationship of DEmRNAs and DElncRNAs reveals that most DElncRNAs are <i>trans</i>-regulated on the relevant DEmRNAs. In conclusion, ePTFE implantation causes severe myocardial tissue damages and alters the transcriptome profiles of the myocardium. Such novel data may provide a landscape of mechanisms underlying the adverse reactions caused by ePTFE implantation and uncover new therapeutic targets for inhibiting the ePTFE-related complications. |
2,331,348 | Resveratrol Prevents Right Ventricle Dysfunction, Calcium Mishandling, and Energetic Failure via SIRT3 Stimulation in Pulmonary Arterial Hypertension. | Pulmonary arterial hypertension (PAH) is characterized by pulmonary vessel remodeling; however, its severity and impact on survival depend on right ventricular (RV) failure. Resveratrol (RES), a polyphenol found in red wine, exhibits cardioprotective effects on RV dysfunction in PAH. However, most literature has focused on RES protective effect on lung vasculature; recent finding indicates that RES has a cardioprotective effect independent of pulmonary arterial pressure on RV dysfunction, although the underlying mechanism in RV has not been determined. Therefore, this study is aimed at evaluating sirtuin-3 (SIRT3) modulation by RES in RV using a monocrotaline- (MC-) induced PAH rat model. Myocyte function was evaluated by confocal microscopy as cell contractility, calcium signaling, and mitochondrial membrane potential (ΔΨ<i>m</i>); cell energetics was assessed by high-resolution respirometry, and western blot and immunoprecipitation evaluated posttranslational modifications. PAH significantly affects mitochondrial function in RV; PAH is prone to mitochondrial permeability transition pore (mPTP) opening, thus decreasing the mitochondrial membrane potential. The compromised cellular energetics affects cardiomyocyte function by decreasing sarco-endoplasmic reticulum Ca<sup>2+</sup>-ATPase (SERCA) activity and delaying myofilament unbinding, disrupting cell relaxation. RES partially protects mitochondrial integrity by deacetylating cyclophilin-D, a critical component of the mPTP, increasing SIRT3 expression and activity and preventing mPTP opening. The preserved energetic capability rescues cell relaxation by maintaining SERCA activity. Avoiding Ca<sup>2+</sup> transient and cell contractility mismatch by preserving mitochondrial function describes, for the first time, impairment in excitation-contraction-energetics coupling in RV failure. These results highlight the importance of mitochondrial energetics and mPTP in PAH. |
2,331,349 | Prenatal diagnosis of the Dandy-Walker malformation associated with partial trisomy 12p and distal 15q deletion. | Dandy-Walker malformation (DWM) is characterized by complete or partial agenesis of the cerebellar vermis, cyatic dilatation of the forth ventricle, and enlarged posterior fossa. However, the mechanism is still not completely understood up to now. In this study, we reported a rare case that a foetus with DWM showed partial trisomy 12p and distal 15q deletion. Karyotype analysis and chromosomal microarray analysis (CMA) were not always concordant with each other, and it is suggested that they should be performed for prenatal genetic diagnosis together. DWM is a rare central nervous system malformation, reported in 1/25-30,000 live births, characterized by complete or partial agenesis of the cerebellar vermis, cyatic dilatation of the forth ventricle, and enlarged posterior fossa (Kumar <i>et al.</i> 2001; Klein <i>et al.</i> 2003; Agrawal <i>et al.</i> 2016). The neurological development of children with DWM may range from normal to severely retarded, and cause variable clinical feature. Although several efforts have been made to explore its pathogenesis, however, it is still not completely understood. During the past decade, some genetic loci, microdeletion or duplication have been reported to be associated with DWM, such as 9p trisomy, partial deletions of the long arm of chromosome 13, genes <i>ZIC1</i> and <i>ZIC4</i> (von Kaisenberg <i>et al.</i> 2000; McCormack <i>et al.</i> 2003; Grinberg <i>et al.</i> 2004). In the present study, we describe a prenatal diagnosis case that a foetus with DWM on ultrasound scanning accepted genetic testing, and it revealed a microduplication of 12p13.33p11.1 and microdeletion of 15q11.2 in 750K single nucleotide polymorphism (SNP) array, while it showed 46,XX,der(8)(8pter→8q24::12p10→12qter),i(12)(p10) in karyotyping. |
2,331,350 | Craniopharyngiomas primarily affecting the hypothalamus. | The concept of craniopharyngiomas (CPs) primarily affecting the hypothalamus, or "hypothalamic CPs" (Hy-CPs), refers, in a restrictive sense, to the subgroup of CPs originally developing within the neural tissue of the infundibulum and tuber cinereum, the components of the third ventricle floor. This subgroup, also known as infundibulo-tuberal CPs, largely occupies the third ventricle and comprises up to 40% of this pathological entity. The small subgroup of strictly intraventricular CPs (5%), lesions wholly developed within the third ventricle above an anatomically intact third ventricle floor, can also be included within the Hy-CP category. The remaining types of sellar and/or suprasellar CPs may compress or invade the hypothalamic region during their growth but will not be considered in this review. Hy-CPs predominantly affect adults, causing a wide range of symptoms derived from hypothalamic dysfunction, such as adiposogenital dystrophy (Babinski-Fröhlich's syndrome), diabetes insipidus (DI), abnormal diurnal somnolence, and a complex set of cognitive (dementia-like, Korsakoff-like), emotional (rage, apathy, depression), and behavioral (autism-like, psychotic-like) disturbances. Accordingly, Hy-CPs represent a neurobiological model of psychiatric disorders caused by a lesion restricted to the hypothalamus. The vast majority (90%) of squamous-papillary CPs belong to the Hy-CP category. Pathologically, most Hy-CPs present extensive and strong adhesions to the surrounding hypothalamus, usually formed of a thick band of gliotic tissue encircling the central portion of the tumor ("ring-like" attachment) or its entire boundary ("circumferential" attachment). CPs with these severe adhesion types associate high surgical risk, with morbidity and mortality rates three times higher than those for sellar/suprasellar CPs. Consequently, radical surgical removal of Hy-CPs cannot be generally recommended. Rather, Hy-CPs should be accurately classified according to an individualized surgery-risk stratification scheme considering patient age, CP topography, presence of hypothalamic symptoms, tumor size, and, most importantly, the CP-hypothalamus adhesion pattern. |
2,331,351 | Association of immune cell subsets with cardiac mechanics in the Multi-Ethnic Study of Atherosclerosis. | BackgroundImmunomodulatory therapy may help prevent heart failure (HF). Data on immune cells and myocardial remodeling in older adults with cardiovascular risk factors are limited.MethodsIn the Multi-Ethnic Study of Atherosclerosis cohort, 869 adults had 19 peripheral immune cell subsets measured and underwent cardiac MRI during the baseline exam, of which 321 had assessment of left ventricular global circumferential strain (LV-GCS). We used linear regression with adjustment for demographics, cardiovascular risk factors, and cytomegalovirus serostatus to evaluate the cross-sectional association of immune cell subsets with left ventricular mass index (LVMI) and LV-GCS.ResultsThe average age of the cohort was 61.6 ± 10.0 years and 53% were women. Higher proportions of γ/δ T cells were associated with lower absolute (worse) LV-GCS (-0.105% [95% CI -0.164%, -0.046%] per 1 SD higher proportion of γ/δ T cells, P = 0.0006). This association remained significant after Bonferroni's correction. Higher proportions of classical monocytes were associated with worse absolute LV-GCS (-0.04% [95% CI -0.07%, 0.00%] per 1 SD higher proportion of classical monocytes, P = 0.04). This did not meet significance after Bonferroni's correction. There were no other significant associations with LV-GCS or LVMI.ConclusionPathways associated with γ/δ T cells may be potential targets for immunomodulatory therapy targeted at HF prevention in populations at risk.FundingContracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and grant R01 HL98077 from the National Heart, Lung, and Blood Institute/NIH and grants KL2TR001424, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences/NIH. |
2,331,352 | Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes. | On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes.</AbstractText>In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method.</AbstractText>A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006).</AbstractText>Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.</AbstractText>© 2021 Wiley Periodicals LLC.</CopyrightInformation> |
2,331,353 | A Rare Case of Third Ventricular Glioblastoma. | Glioblastoma, also known as glioblastoma multiforme, is an aggressive type of cancer that is made up of abnormal astrocytic cells, but also contain a mixture of different cell types (including blood vessels) and areas of necrosis. It is often seen in the brain and spinal cord, but glioblastomas are rarely found in the third ventricle. In this case, it was diagnosed in a 22-year-old male patient and we intended to draw attention to its atypical localization and surgical access to this third ventricle glioblastoma.<CopyrightInformation>© Copyright Istanbul Medeniyet University Faculty of Medicine.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gacic</LastName><ForeName>Asmira</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0001-6501-6538</Identifier><AffiliationInfo><Affiliation>University of Zenica, Faculty of Medicine, Department of Anatomy, Bosnia and Herzegovina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beculic</LastName><ForeName>Hakija</ForeName><Initials>H</Initials><Identifier Source="ORCID">0000-0002-6904-2490</Identifier><AffiliationInfo><Affiliation>Cantonal Hospital Zenica, Department of Neurosurgery, University of Zenica, Faculty of Medicine, Department of Anatomy, Bosnia and Herzegovina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Skomorac</LastName><ForeName>Rasim</ForeName><Initials>R</Initials><Identifier Source="ORCID">0000-0002-7085-5720</Identifier><AffiliationInfo><Affiliation>Cantonal Hospital Zenica, Department of Neurosurgery, Bosnia and Herzegovina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Efendic</LastName><ForeName>Alma</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0002-8834-2034</Identifier><AffiliationInfo><Affiliation>Cantonal Hospital Zenica, Department of Radiology, Bosnia and Herzegovina.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>06</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>Turkey</Country><MedlineTA>Medeni Med J</MedlineTA><NlmUniqueID>101676811</NlmUniqueID><ISSNLinking>2149-4606</ISSNLinking></MedlineJournalInfo><OtherAbstract Type="Publisher" Language="tur">Glioblastoma multiforme olarak da bilinen glioblastoma, anormal astrositik hücrelerden oluşan agresif bir kanser türüdür, ancak aynı zamanda farklı hücre tipleri (kan damarları dahil) ve nekroz alanlarının bir karışımını da içerir. Sıklıkla beyinde ve omurilikte görülür, ancak glioblastomların nadiren bulunduğu yer üçüncü ventriküldür. Bu vakada 22 yaşında bir erkek hastaya teşhis koyuldu ve üçüncü ventrikül glioblastoma için atipik lokalizasyona ve cerrahi girişime dikkat çekmeyi amaçladık. |
2,331,354 | Correlation Between 2D Strain and Classic Echocardiographic Indices in the Diagnosis of Right Ventricular Dysfunction in COPD. | This study aims to define which of the right ventricular myocardial deformation indices best correlates with the classic echocardiographic measurements and indices of right ventricular (RV) dysfunction in patients with stable chronic obstructive pulmonary disease (COPD).</AbstractText>Ninety-one patients with stable COPD underwent clinical evaluation, spirometry, a 6-minute walk test, and echocardiographic examination. Patients were divided into two groups: "with RV dysfunction" (≥1 classic parameter) and "without RV dysfunction". We used speckle tracking to estimate myocardial deformation. For all analyses, results were considered significant if p < 0.05.</AbstractText>The mean age across all participants was 65 ± 9 years, with 53% (48/91) being male. Patients in the group with RV dysfunction were able to walk shorter distances and had higher estimated right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP). The RV free wall longitudinal strain (RVFWLS) was the only deformation indices that showed a significant correlation with all classic measurements and indices in the diagnosis of RV dysfunction (Wald test, 10.24; p < 0.01; odds ratio, 1.61). In the ROC curve analysis, the absolute value <20% was the lowest cut-off point of this index for detection of RV dysfunction (AUC = 0.93, S: 95.8%, and E: 88%).</AbstractText>In COPD patients, RVFWLS is the myocardial deformation index that best correlates with classic echocardiographic parameters for the diagnosis of RV dysfunction using <20% as a cut-off point.</AbstractText>© 2021 Masson Silva et al.</CopyrightInformation> |
2,331,355 | The regulatory roles of motile cilia in CSF circulation and hydrocephalus. | Cerebrospinal fluid (CSF) is an ultra-filtrated colorless brain fluid that circulates within brain spaces like the ventricular cavities, subarachnoid space, and the spine. Its continuous flow serves many primary functions, including nourishment, brain protection, and waste removal.</AbstractText>The abnormal accumulation of CSF in brain cavities triggers severe hydrocephalus. Accumulating evidence had indicated that synchronized beats of motile cilia (cilia from multiciliated cells or the ependymal lining in brain ventricles) provide forceful pressure to generate and restrain CSF flow and maintain overall CSF circulation within brain spaces. In humans, the disorders caused by defective primary and/or motile cilia are generally referred to as ciliopathies. The key role of CSF circulation in brain development and its functioning has not been fully elucidated.</AbstractText>In this review, we briefly discuss the underlying role of motile cilia in CSF circulation and hydrocephalus. We have reviewed cilia and ciliated cells in the brain and the existing evidence for the regulatory role of functional cilia in CSF circulation in the brain. We further discuss the findings obtained for defective cilia and their potential involvement in hydrocephalus. Furthermore, this review will reinforce the idea of motile cilia as master regulators of CSF movements, brain development, and neuronal diseases.</AbstractText> |
2,331,356 | Genomics of human congenital hydrocephalus. | Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of pathological cerebrospinal fluid (CSF) accumulation and, therefore, treated largely by neurosurgical CSF diversion. The persistence of ventriculomegaly and poor neurodevelopmental outcomes in some post-surgical patients highlights our limited knowledge of disease mechanisms. Recent whole-exome sequencing (WES) studies have shown that rare, damaging de novo and inherited mutations with large effect contribute to ~ 25% of sporadic CH. Interestingly, multiple CH genes are key regulators of neural stem cell growth and differentiation and converge in human transcriptional networks and cell types pertinent to fetal neurogliogenesis. These data implicate genetic disruption of early brain development as the primary pathomechanism in a substantial minority of patients with sporadic CH, shedding new light on human brain development and the pathogenesis of hydrocephalus. These data further suggest WES as a clinical tool with potential to re-classify CH according to a molecular nomenclature of increased precision and utility for genetic counseling, outcome prognostication, and treatment stratification. |
2,331,357 | Novel CLTC variants cause new brain and kidney phenotypes. | Heterozygous variants in CLTC, which encode the clathrin heavy chain protein, cause neurodevelopmental delay of varying severity, and often accompanied by dysmorphic features, seizures, hypotonia, and ataxia. To date, 28 affected individuals with CLTC variants have been reported, although their phenotypes have not been fully elucidated. Here, we report three novel de novo CLTC (NM_001288653.1) variants in three individuals with previously unreported clinical symptoms: c.3662_3664del:p.(Leu1221del) in individual 1, c.2878T>C:p.(Trp960Arg) in individual 2, and c.2430+1G>T:p.(Glu769_Lys810del) in individual 3. Consistent with previous reports, individuals with missense or small in-frame variants were more severely affected. Unreported symptoms included a brain defect (cystic lesions along the lateral ventricles of the brain in individuals 1 and 3), kidney findings (high-echogenic kidneys in individual 1 and agenesis of the left kidney and right vesicoureteral reflux in individual 3), respiratory abnormality (recurrent pneumonia in individual 1), and abnormal hematological findings (anemia in individual 1 and pancytopenia in individual 3). Of note, individual 1 even exhibited prenatal abnormality (fetal growth restriction, cystic brain lesions, high-echogenic kidneys, and a heart defect), suggesting that CLTC variants should be considered when abnormal prenatal findings in multiple organs are detected. |
2,331,358 | An automatic multi-tissue human fetal brain segmentation benchmark using the Fetal Tissue Annotation Dataset. | It is critical to quantitatively analyse the developing human fetal brain in order to fully understand neurodevelopment in both normal fetuses and those with congenital disorders. To facilitate this analysis, automatic multi-tissue fetal brain segmentation algorithms are needed, which in turn requires open datasets of segmented fetal brains. Here we introduce a publicly available dataset of 50 manually segmented pathological and non-pathological fetal magnetic resonance brain volume reconstructions across a range of gestational ages (20 to 33 weeks) into 7 different tissue categories (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, deep grey matter, brainstem/spinal cord). In addition, we quantitatively evaluate the accuracy of several automatic multi-tissue segmentation algorithms of the developing human fetal brain. Four research groups participated, submitting a total of 10 algorithms, demonstrating the benefits the dataset for the development of automatic algorithms. |
2,331,359 | Rosette-Forming Glioneural tumor of the fourth ventricle: A case report and literature review. | Rosette-forming glioneural tumors (RGNTs) are rare. Here, we report a case of RGNT of the fourth ventricle in an 18-year-old female. The patient presented with a 4-month history of headache and dizziness. Neurological examination showed papilledema, impaired tandem gait, and right-sided dysmetria. Radiological images showed a posterior fossa lesion in the fourth ventricle with hydrocephalus. An emergent ventriculostomy was performed followed by gross total surgical resection of the lesion. Histopathological examination confirmed the diagnosis of RGNT. The patient developed posterior fossa syndrome postoperatively which improved on follow-up. Although rare, RGNT should be considered in the differential diagnoses of posterior fossa lesions in young patients. Given its benign course, surgical resection remains the treatment of choice. |
2,331,360 | The median preoptic nucleus: A major regulator of fluid, temperature, sleep, and cardiovascular homeostasis. | Located in the midline lamina terminalis of the anterior wall of the third ventricle, the median preoptic nucleus is a thin elongated nucleus stretching around the rostral border of the anterior commissure. Its neuronal elements, composed of various types of excitatory glutamatergic and inhibitory GABAergic neurons, receive afferent neural signals from (1) neighboring subfornical organ and organum vasculosum of the lamina terminalis related to plasma osmolality and hormone concentrations, e.g., angiotensin II; (2) from peripheral sensors such as arterial baroreceptors and cutaneous thermosensors. Different sets of these MnPO glutamatergic and GABAergic neurons relay output signals to hypothalamic, midbrain, and medullary regions that drive homeostatic effector responses. Included in the effector responses are (1) thirst, antidiuretic hormone secretion and renal sodium excretion that subserve osmoregulation and body fluid homeostasis; (2) vasoconstriction or dilatation of skin blood vessels, and shivering and brown adipose tissue thermogenesis for core temperature homeostasis; (3) inhibition of hypothalamic and midbrain nuclei that stimulate wakefulness and arousal, thereby promoting both REM and non-REM sleep; and (4) activation of sympathetic pathways that drive vasoconstriction and heart rate to maintain arterial pressure and the perfusion of vital organs. The small size of MnPO belies its massive homeostatic significance. |
2,331,361 | Neurogenesis in the adult hypothalamus: A distinct form of structural plasticity involved in metabolic and circadian regulation, with potential relevance for human pathophysiology. | The adult brain harbors specific niches where stem cells undergo substantial plasticity and, in some regions, generate new neurons throughout life. This phenomenon is well known in the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampus and has recently also been described in the hypothalamus of several rodent and primate species. After a brief overview of preclinical studies illustrating the pathophysiologic significance of hypothalamic neurogenesis in the control of energy metabolism, reproduction, thermoregulation, sleep, and aging, we review current literature on the neurogenic niche of the human hypothalamus. A comparison of the organization of the niche between humans and rodents highlights some common features, but also substantial differences, e.g., in the distribution and extent of the hypothalamic neural stem cells. Exploring the full dynamics of hypothalamic neurogenesis in humans raises a formidable challenge however, given among others, inherent technical limitations. We close with discussing possible functional role(s) of the human hypothalamic niche, and how gaining more insights into this form of plasticity could be relevant for a better understanding of pathologies associated with disturbed hypothalamic function. |
2,331,362 | Tanycytes in the infundibular nucleus and median eminence and their role in the blood-brain barrier. | The blood-brain barrier is generally attributed to endothelial cells. However, in circumventricular organs, such as the median eminence, tanycytes take over the barrier function. These ependymoglial cells form the wall of the third ventricle and send long extensions into the parenchyma to contact blood vessels and hypothalamic neurons. The shape and location of tanycytes put them in an ideal position to connect the periphery with central nervous compartments. In line with this, tanycytes control the transport of hormones and key metabolites in and out of the hypothalamus. They function as sensors of peripheral homeostasis for central regulatory networks. This chapter discusses current evidence that tanycytes play a key role in regulating glucose balance, food intake, endocrine axes, seasonal changes, reproductive function, and aging. The understanding of how tanycytes perform these diverse tasks is only just beginning to emerge and will probably lead to a more differentiated view of how the brain and the periphery interact. |
2,331,363 | Arcuate nucleus, median eminence, and hypophysial pars tuberalis. | The arcuate nucleus (ARC) is located in the mediobasal hypothalamus and forms a morphological and functional entity with the median eminence (ME), the ARC-ME. The ARC comprises several distinct types of neurons controlling prolactin release, food intake, and metabolism as well as reproduction and onset of puberty. The ME lacks a blood-brain barrier and provides an entry for peripheral signals (nutrients, leptin, ghrelin). ARC neurons are adjacent to the wall of the third ventricle. This facilitates the exchange of signals from and to the cerebrospinal fluid. The ventricular wall is composed of tanycytes that serve different functions. Axons of ARC neurons contribute to the tuberoinfundibular tract terminating in the ME on the hypophysial portal vessels (HPV) and establish one of the neurohumoral links between the hypothalamus and the pituitary. ARC neurons are reciprocally connected with several other hypothalamic nuclei, the brainstem, and reward pathways. The hypophysial pars tuberalis (PT) is attached to the ME and the HPV. The PT, an important interface of the neuroendocrine system, is mandatory for the control of seasonal functions. This contribution provides an update of our knowledge about the ARC-ME complex and the PT which, inter alia, is needed to understand the pathophysiology of metabolic diseases and reproduction. |
2,331,364 | Lamina terminalis fenestration: An important neurosurgical corridor. | Cerebrospinal fluid (CSF) disorders are challenging conditions in neurosurgical practice. The majority of CSF is contained in the basal cisterns of the brain, which are subarachnoid compartments that communicate with each other, and contribute to the circulation of CSF. Yaşargil et al. (1976) was the first to provide the systematic classification and naming of the basal cisterns. The lamina terminalis (LT) starts from the gyrus rectus and descends to the lateral aspect of the optic chiasm. It is a thick arachnoidal membrane delineating the anterior wall of the third ventricle that borders the LT cistern. With the introduction of the operating microscope and the progressive development of modern neurosurgery, the arachnoid and basal cisterns have been used as surgical corridors in order to reach deep areas of the brain and to release CSF for brain relaxation. In this way, the LT is used as a surgical corridor for the treatment of several conditions such as obstructive hydrocephalus and diencephalic tumors. In this chapter, we will describe the anatomy of the LT, possible conditions treated by opening the LT, the different surgical approaches to opening the LT, along with their advantages and disadvantages. |
2,331,365 | Fetal Echocardiography in Predicting Postnatal Outcome in Borderline Left Ventricle. |  Prenatal prediction of postnatal univentricular versus biventricular circulation in patients with borderline left ventricle (bLV) remains challenging. This study investigated prenatal fetal echocardiographic parameters and postnatal outcome of patients with a prenatally diagnosed bLV.</AbstractText> We report a retrospective study of bLV patients at four prenatal centers with a follow-up of one year. BLV was defined as z-scores of the left ventricle (LV) between -2 and -4. Single-ventricle palliation (SVP), biventricular repair (BVR), and no surgical or catheter-based intervention served as the dependent outcome. Prenatal ultrasound parameters were used as independent variables. Cut-off values from receiver operating characteristic curves (ROC) were determined for significant discrimination between outcomes.</AbstractText> A total of 54 patients were diagnosed with bLV from 2010 to 2018. All were live births. Out of the entire cohort, 8 (15 %) received SVP, 34 (63 %) BVR, and 12 (22 %) no intervention. There was no significant difference with regard to genetic or extracardiac anomalies. There were significantly more patients with endocardial fibroelastosis (EFE) in the SVP group compared to the BVR group (80 % vs. 10 %), (p < 0.001). Apex-forming LV (100 % vs. 70 %) and lack of retrograde arch flow (20 % vs. 80 %) were associated with no intervention (p < 0.001). With respect to BVR vs. SVP, the LV sphericity index provided the highest specificity (91.7 %) using a cutoff value of ≤ 0.5.</AbstractText> The majority of bLV patients maintained biventricular circulation. EFE, retrograde arch flow, and LV sphericity can be helpful parameters for counseling parents and further prospective studies can be developed.</AbstractText>Thieme. All rights reserved.</CopyrightInformation> |
2,331,366 | Changes in the expression of cardiac genes responsive to thyroid hormones in the chickens with cold-induced pulmonary hypertension. | Cold stress is an environmental cause of pulmonary hypertension syndrome (PHS) in broiler chickens. This factor could increase the rate of metabolic activity via thyroid hormones (T3 and T4). To evaluate the effect of these hormones on the heart, the plasma concentration of T3, T4, and the gene expression of their receptors (THRα and THRβ) and many contractile proteins (ACTC1, MHCα, MHCβ, RYR2, SERCA2, THRα, THRβ, and troponin I) were measured in the right ventricle in 2 periods of age (21 and 35 d). Plasma T3 concentration was significantly higher in the PHS group of chickens than in the control one at 21 and 35 d while plasma T4 did not change. The relative expression of MHCα, RYR2, SERCA2, and THRα genes in the right ventricle tissues was only higher in PHS group of broilers than control group at 21 d (P < 0.05) whereas the expression of ACTC1, MHCβ, and troponin I did not differ at 2 periods of age. The positive correlations between MHCα, RYR2, SERCA2, and T3, THRα were confirmed. The expression of THRβ gene was only higher in PHS group of broilers than control at 35 d (P < 0.05). The data determined that cold stress could increase thyroid hormones and the gene expression of their receptor (THRα) in the pick of chicken growth (21 d) that they themselves elevates the expression of many genes related to contractile elements (MHCα, RYR2, and SERCA2), leading to adaptive right ventricle hypertrophy. |
2,331,367 | Uridine diphosphate-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase deletion in mice leads to lethal intracerebral hemorrhage during embryonic development. | Among the enzymes of the biosynthesis of sialoglycoconjugates, uridine diphosphate-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), catalyzing the first essential step of the sialic acid (Sia) de novo biosynthesis, and cytidine monophosphate (CMP)-Sia synthase (CMAS), activating Sia to CMP-Sia, are particularly important. The knockout of either of these enzymes in mice is embryonically lethal. While the lethality of Cmas-/- mice has been attributed to a maternal complement attack against asialo fetal placental cells, the cause of lethality in Gne-deficient embryos has remained elusive. Here, we advanced the significance of sialylation for embryonic development through detailed histological analyses of Gne-/- embryos and placentae. We found that Gne-/- embryonic and extraembryonic tissues are hyposialylated rather than being completely deficient of sialoglycans, which holds true for Cmas-/- embryos. Residual sialylation of Gne-/- cells can be explained by scavenging free Sia from sialylated maternal serum glycoconjugates via the lysosomal salvage pathway. The placental architecture of Gne-/- mice was unaffected, but severe hemorrhages in the neuroepithelium with extensive bleeding into the cephalic ventricles were present at E12.5 in the mutants. At E13.5, the vast majority of Gne-/- embryos were asystolic. This phenotype persisted when Gne-/- mice were backcrossed to a complement component 3-deficient background, confirming distinct pathomechanisms of Cmas-/- and Gne-/- mice. We conclude that the low level of sialylation observed in Gne-/- mice is sufficient both for immune homeostasis at the fetal-maternal interface and for embryonic development until E12.5. However, formation of the neural microvasculature is the first critical process, depending on a higher degree of sialylation during development of the embryo proper. |
2,331,368 | Right Ventricular Dysfunction and Its Association With Mortality in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome. | To assess whether right ventricular dilation or systolic impairment is associated with mortality and/or disease severity in invasively ventilated patients with coronavirus disease 2019 acute respiratory distress syndrome.</AbstractText>Retrospective cohort study.</AbstractText>Single-center U.K. ICU.</AbstractText>Patients with coronavirus disease 2019 acute respiratory distress syndrome undergoing invasive mechanical ventilation that received a transthoracic echocardiogram between March and December 2020.</AbstractText>None.</AbstractText>Right ventricular dilation was defined as right ventricular:left ventricular end-diastolic area greater than 0.6, right ventricular systolic impairment as fractional area change less than 35%, or tricuspid annular plane systolic excursion less than 17 mm. One hundred seventy-two patients were included, 59 years old (interquartile range, 49-67), with mostly moderate acute respiratory distress syndrome (n = 101; 59%). Ninety-day mortality was 41% (n = 70): 49% in patients with right ventricular dilation, 53% in right ventricular systolic impairment, and 72% in right ventricular dilation with systolic impairment. The right ventricular dilation with systolic impairment phenotype was independently associated with mortality (odds ratio, 3.11 [95% CI, 1.15-7.60]), but either disease state alone was not. Right ventricular fractional area change correlated with Pao2:Fio2 ratio, Paco2, chest radiograph opacification, and dynamic compliance, whereas right ventricular:left ventricle end-diastolic area correlated negatively with urine output.</AbstractText>Right ventricular systolic impairment correlated with pulmonary pathophysiology, whereas right ventricular dilation correlated with renal dysfunction. Right ventricular dilation with systolic impairment was the only right ventricular phenotype that was independently associated with mortality.</AbstractText>Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.</CopyrightInformation> |
2,331,369 | Endoscopic treatment of intracranial cysts in infants: personal experience and review of literature. | A wide variety of intracranial cysts is known to occur in infants. If symptomatic, they require treatment; the ideal surgical treatment and indications of surgery are yet a matter of discussion. Traditional treatment is either by cystoperitoneal shunting, or microsurgical fenestration. Endoscopic treatment is an alternative procedure that avoids the invasiveness of open craniotomy and the complications caused by shunting.</AbstractText>This article reviews the endoscopic treatment of intracranial cysts in infants. The author presents personal experience by reviewing the results of endoscopic treatment in different subgroups among his series of pediatric patients extending over 20 years.</AbstractText>Different types of intracranial cysts in infants were discussed and the role of endoscopy in the management of these patients was reviewed. The author also presented the results of endoscopic treatment of a personal series including 87 infants with intracranial cysts operated by the endoscopic procedure.</AbstractText>It has been recommended to use the endoscopic procedure in the treatment of intracranial cysts in infants, because it is effective, simple, minimally invasive, and associated with low morbidity and mortality rates. However, an important prerequisite is the presence of an area of contiguity with the subarachnoid cisterns and/or the ventricular system.</AbstractText>© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</CopyrightInformation> |
2,331,370 | Long-Term Effect of a Vaccine Targeting Endothelin-1 Receptor Type A in Pulmonary Arterial Hypertension. | <b>Background:</b> Previously, we invented a therapeutic vaccine targeting the endothelin-A receptor (termed ETRQβ-002). ETRQβ-002 successfully prevented the remodeling of pulmonary arterioles (PAs) and right ventricle (RV) without significant immune-mediated damage in experimental pulmonary arterial hypertension (PAH) mice models. <b>Objective:</b> Here, we aim to further evaluate the long-term effects of ETRQβ-002. <b>Methods:</b> PAH mice model was induced by a combination of subcutaneous injection with Sugen5416 and chronic hypoxic conditions (10% O<sub>2</sub>). PAH mice were immunized with ETRQβ-002 at different time points, and the experiment lasted for 21 weeks. Hemodynamic, histological, and biochemical analyses were conducted to evaluate the long-term effects of ETRQβ-002. <b>Results:</b> We demonstrated that the titer of the specific antibody against ETR-002 could be maintained chronically after periodic booster immunization in PAH mice. Long-term reduction of right ventricular systolic pressure and amelioration of PA remodeling by ETRQβ-002 were confirmed. Moreover, we found that ETRQβ-002 also exerted antiproliferation, anti-inflammation, and antifibrosis effects in PA remodeling. Besides, ETRQβ-002 durably limited pathological RV hypertrophy and fibrosis. Finally, no immune-mediated damage was observed in hepatic or renal function or by pathology in liver and kidney during the long-term administration of ETRQβ-002. <b>Conclusion:</b> Our findings indicate that ETRQβ-002 provides long-term therapeutic effects in Sugen/hypoxia-induced PAH animals and offers a promising clinical prospect for PAH treatment. |
2,331,371 | Cerebellar metastasis of a Liposarcoma: Case report and literature review. | Liposarcoma (LPS) is a rare type of tumor; they come from the adipose tissue. It is the most common type of soft-tissue sarcoma. Every type of LPS has morphological features, immunophenotypic, and molecular pathogenesis characteristics of their own. In this case, we are going to report a cerebellar metastatic disease from a well-differentiated liposarcoma (WDL) with pleomorphic component, not found in our literature research.</AbstractText>A 72-year-old woman with progressive pain and inflammation in the left knee with functional limitation when climbing stairs. MRI shows a tumor in the vastus medialis of the left thigh. Pathology result was pleomorphic and WDL, Stage III and negative for MDM2 and CDK4. Extension study was carried out, finding nodular lesion in the right cerebellar hemisphere with mass effect and partial obliteration of the fourth ventricle, suspicious of distant disease.</AbstractText>Cerebellar metastasis of LPS is uncommon; there are only a few cases reports with the literature reviews describing orbital or skull base metastases, but not in the cerebellum. Our case allows us to remember that neurological symptoms, no matter how subtle, in patients diagnosed with LPS, a secondary affectation of the central nervous system must be ruled out, even though it is a rare location. The findings of distant disease in LPSs, allow planning oncological treatment options and targeted radiotherapeutic.</AbstractText>Copyright: © 2021 Surgical Neurology International.</CopyrightInformation> |
2,331,372 | Infratentorial abscess secondary to dermal sinus associated with dermoid cyst in children: Review of the literature and report of a rare case. | Dermal sinus is usually located at either end of neural tube but most commonly lumbosacral. When occipital, it extends caudally and is mostly localized in the midline position or in the cavity of the fourth ventricle. It could communicate with the skin through a fistula with potential risk of deeper abscesses. Posterior fossa abscess secondary to dermal sinus associated with intracranial dermal cyst is an uncommon pathology.</AbstractText>A 24-month-old girl was admitted to our institution with a cutaneous fistula in the midline of the occipital region. Brain imaging showed an infratentorial intradiploic cyst with peripheral enhancement to contrast medium. The mass showed hyperintensity on T1-weighted sequences, with the lower signal on T2-weighted images. A suboccipital craniotomy was performed with evacuation of the abscess and excision of the capsule. Contextually a 3 cm whitish and encapsulated cystic mass with hair component was extracted. Histology confirmed the diagnosis of abscess associated with dermal cyst and dermal sinus. The patient condition improved and 15 days after excision, was discharged. The postoperative MRI showed total removal of the lesion. A 36-month follow-up highlighted no evidence of recurrence.</AbstractText>Posterior fossa dermoid cyst should be considered in all children with a cutaneous fistula. Early neurosurgical treatment of these benign tumors should be performed to prevent the development of severe intracranial infection. Best results are associated with early diagnosis and complete removal of the abscess. The present work further reviews the few similar cases that have been reported in the literature confirming the need for future research.</AbstractText>Copyright: © 2021 Surgical Neurology International.</CopyrightInformation> |
2,331,373 | Endoscopic resection of a low-grade ependymoma of the pineal region. | Full endoscopic resection of solid brain tumors represents a challenge for neurosurgeons. This can be achieved with modern technology and advanced surgical tools.</AbstractText>A 23-years-old male was referred to our unit with raised intracranial pressure. Head computed tomography and magnetic resonance imaging (MRI) revealed obstructive hydrocephalus and a third ventricle lesion. Endoscopic third ventriculostomy and biopsy were performed, a left frontal external ventricular drain was left in place. A second-look surgery for endoscopic removal was planned. Decision to proceed with an endoscopic removal was supported by the following characteristics found during the first surgery: tumor exophytic, soft texture, scarce vascularity, and low-grade appearance. A rescue strategy for microscopic resection via transcallosal approach was decided. A straight trajectory to the tumor was planned with navigation. A further anterior left frontal burr-hole was performed, and the ventricular system was entered via the left frontal horn. Resection was carried out alternating laser for hemostasis and cutting, endoscopic ultrasonic aspirator, and endoscopic forceps for piecemeal resection. Laser hemostasis and cutting (1 Watt power at tip, continuous wave mode) were useful at the ventricular wall-tumor interface. Relevant landmarks guided the approach and the resection (foramen of Monro, mammillary bodies, aqueduct, pineal and suprapineal recess, and posterior commissure). The surgery was carried uneventfully. Histopathology confirmed a lowgrade ependymoma. Post-operative MRI showed residual tumor within the lower aqueduct. At 3 years follow-up, residual tumor is stable.</AbstractText>In selected cases, endoscopic resection for third ventricular tumors is feasible and safe, and represents a valid alternative to microsurgical approaches.</AbstractText>Copyright: © 2021 Surgical Neurology International.</CopyrightInformation> |
2,331,374 | A rare giant mixed germ cell tumor of the pineal region with immature elements: Case report and review of the literature. | The diagnosis and management of mixed intracranial germ cell tumors may be complicated by the diversity present within this tumor category. Mixed germ cell tumors demonstrate variable natural histories which may be altered by the inclusion of even the most minute immature histological components. We report the case of an 18-year-old male who presented with a 3-month history of progressive headache and nausea leading to lethargy. Imaging revealed a giant pineal region mass extending superiorly from the roof of the fourth ventricle into the lateral ventricle, with resultant obstructive hydrocephalus. No spinal lesions were noted. Following gross total resection, the patient experienced marked improvement. Pathologic analysis identified an uncommon tumor composition: mature teratoma (96%), immature teratoma (2%), and germinoma (2%). Guided by the immature component, chemotherapy and radiation were added post-operatively to provide this patient with the greatest chance of long-term survival. Intracranial pathology, including germ cell tumors, should be included in the differential for any young patient presenting with new and progressive headache and nausea. This case emphasizes the benefit of a multimodal approach to mixed germ cell tumors of the pineal region and the importance of careful pathologic review of all submitted material. |
2,331,375 | Adult Hippocampal Neurogenesis and Affective Disorders: New Neurons for Psychic Well-Being. | A paradigm shift in neuroscience was the discovery that new neurons are constantly produced in the adult mammalian brain of several species, including Homo sapiens. These new-born cells are formed in some main neurogenic niches, including the subventricular zone (SVZ) at the margin of the lateral ventricle and subgranular zone (SGZ) in the hippocampal dentate gyrus (DG). In the DG, neuroblasts derive from SGZ progenitors and migrate to the hippocampal granular layer becoming adult granule cells, which are integrated into functional adult circuits. It has been confirmed that adult hippocampal neurogenesis (AHN) is a long-lasting phenomenon in the human brain. The functions of hippocampal new-born cells are not fully established. Experimental studies suggest that they have unique electrophysiological properties, including hyperexcitability, which enable them to regulate adult granule cells. Their specific function depends on the anatomical hippocampal location along the hippocampal dorsal-ventral axis. Dorsal hippocampus plays a more defined role on spatial learning and contextual information, while the ventral hippocampus is more related to emotional behavior, stress resilience and social interaction. Several reports suggest a role for AHN in pattern separation, cognitive flexibility, forgetting and reversal learning. It has been proposed that deficits in AHN might impair normal DG function, including pattern separation and cognitive flexibility, which could play a role on the etiology of affective disorders, such as depression, anxiety and post-traumatic stress disorder (PTSD). In this paper, we review recent scientific evidence suggesting that impairment of AHN may underlie the pathophysiology of affective disorders even in humans and that neurogenesis-inspired therapies may be a promising approach to reduce symptoms of affective disorders in humans. |
2,331,376 | 3×Tg-AD Mice Overexpressing Phospholipid Transfer Protein Improves Cognition Through Decreasing Amyloid-β Production and Tau Hyperphosphorylation. | Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer's disease (AD); however, the exact effect and mechanism remain unknown.</AbstractText>To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice.</AbstractText>AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain.</AbstractText>3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-β42 (Aβ42) and Aβ40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3β (GSK3β) inactivation via upregulating GSK3β (pSer9).</AbstractText>These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aβ production and tau phosphorylation, which is related to GSK3β inactivation.</AbstractText> |
2,331,377 | Persistent fibrosis and decreased cardiac function following cardiac injury in the Ctenopharyngodon idella (grass carp). | Following the discovery of heart regeneration in zebrafish, several more species within the Cyprinidae family have been found to have the same capability, suggesting heart regeneration may be conserved within this family. Although gonad regeneration has been observed in grass carp (Ctenopharyngodon idella), one of the largest cyprinid fish, the species' response to cardiac injury has not been characterized. Surprisingly, we found cardiomyocytes do not repopulate the injured region following cryoinjury to the ventricle, instead exhibiting unresolved fibrosis and decreased cardiac function that persists for the 8-week duration of this study. Additionally, fibroblasts are likely depleted following injury, a phenomenon not previously described in any cardiac model. The data collected in this study indicate that heart regeneration is unlikely in grass carp (C. idella). It is possible that not all members of the Cyprinidae family possesses regenerative capability observed in zebrafish. Further study of these phenomenon may reveal the underlying differences between regeneration versus unresolved fibrosis in heart disease. |
2,331,378 | Factors Associated with Prolonged Impairment of Consciousness in Adult Patients Admitted for Seizures: A Comprehensive Single-center Study. | Seizures are common neurological emergencies that occasionally cause prolonged impairment of consciousness. The aim of this retrospective single-center study is to clarify factors associated with prolonged impairment of consciousness for admitted adult patients investigating patient backgrounds, blood tests, electroencephalographic patterns, and MRI findings. The patients who were admitted to the hospital due to epileptic seizures were classified into two groups: (1) early recovery group, in which patients recovered their consciousness within 6 hr, and (2) delayed recovery group, in which patients showed impairment of consciousness more than 6 hr. Factors associated with prolonged impairment of consciousness were compared between these groups. In this study, 42 cases (33 patients), with a mean age of 67.8 years, were included. Fifteen cases (13 patients) and 27 cases (20 patients) were classified into the early and delayed recovery groups, respectively. The populations of older patients and patients from a nursing home were significantly higher in the delayed recovery group. With regard to radiological analyses, a high grade of periventricular hyperintensity (PVH), high Evans index score, and enlarged bilateral atrial widths were significantly associated with prolonged impairment of consciousness. Multivariable analyses showed that a high grade of PVH was significantly associated with delayed recovery of consciousness independent of age and status epilepticus. In conclusion, we proposed that diffuse white matter degeneration around the lateral ventricles contributes to prolonged impairment of consciousness. |
2,331,379 | The association of reduced left ventricular strains with increased extracellular volume and their collective impact on clinical outcomes. | Myocardial fibrosis and left ventricular (LV) longitudinal strain are independently associated with adverse clinical outcomes. However, the relationship between tissue properties and strain indices as well as their collective impact on outcomes are yet to be fully elucidated. We aim to investigate the relationship between LV global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) with extracellular volume (ECV) and their collective impact.</AbstractText>Consecutive patients referred for clinical cardiovascular magnetic resonance (CMR) due to cardiomyopathy were prospectively enrolled. All patients underwent CMR with T1 mapping. ECV was calculated incorporating native and post-contrast T1 as well as hematocrit. LV GLS, GCS, and GRS were assessed by feature tracking. Hazard ratios and Kaplan-Meier curves were produced to assess the association between strains and T1 mapping indices with a composite outcome of all-cause mortality and hospitalized heart failure.</AbstractText>The study consisted of 259 patients with mixed referring diagnoses of non-ischemic/ischemic cardiomyopathy and 21 normal controls. Decreased GLS, GCS and GRS were associated with increased ECV, increased native T1, and reduced post-contrast T1 in a dose dependent manner when T1 or ECV was in the abnormal range. After a mean follow-up of 31 ± 23 months, 41 events occurred including 37 heart failure admissions and 4 deaths. Kaplan-Meier plots demonstrated that reduced strains were associated with reduced event-free survival predominantly in patients with increased ECV (≥ 28.3%). The worst outcome was among those with both reduced strains and increased ECV. In the multivariable models, increased ECV, reduced post-contrast T1 and reduced strains in all 3 directions remained predictors of outcome risk, respectively.</AbstractText>Our findings highlight the intrinsic link between altered CMR tissue properties and impaired myocardial mechanical performance and additionally demonstrate improved risk stratification by characterizing tissue property among patients with reduced strain.</AbstractText> |
2,331,380 | Effect of Intraoperative Computed Tomography on Ventriculoperitoneal Shunt Survival. | In patients with hydrocephalus who undergo ventriculoperitoneal shunt placement, the ventricular catheter tip position is one of the most important prognostic factors influencing shunt survival. The aim of this study was to present our findings of ventriculoperitoneal shunt placement performed with intraoperative computed tomography (CT) and to evaluate the effect of intraoperative CT-based image guidance on optimal catheter positioning and overall shunt survival.</AbstractText>Of the study enrolled 345 patients with hydrocephalus who underwent ventriculoperitoneal shunt placement for the first time between 2008 and 2018. Ventricular catheters were inserted freehand via the Kocher point into the lateral ventricle in all patients. In 163 patients, intraoperative CT was performed to confirm the tip position. In this group of patients, if the tip position was nonoptimal, the catheter was ejected and reinserted during the surgery. In the remaining 182 patients, the tip position was assessed with routine postoperative CT. The effect of performing intraoperative CT on catheter tip positioning and shunt failure was investigated.</AbstractText>Nonoptimal tip position was significantly correlated with shunt dysfunction even when excluding nonobstructive causes (P < 0.001). In the intraoperative CT group, 11 ventricular catheters (6.7%) were intraoperatively repositioned. The repositioning significantly improved the optimal tip position rate from 54% to 58.3% (P = 0.007). Intraoperative CT usage also showed direct correlation with shunt survival (P = 0.006).</AbstractText>Intraoperative CT is an effective tool for increasing the rate of optimal tip positioning and thereby overall shunt survival.</AbstractText>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,331,381 | MicroRNA-16-5p/BTG2 axis affects neurological function, autophagy and apoptosis of hippocampal neurons in Alzheimer's disease. | Studies have focused on the functions of microRNAs (miRNAs) in Alzheimer's disease (AD), but not much on miR-16-5p. Hence, this study intends to unearth the mechanism of AD, mainly focusing on miR-16-5p/B-cell translocation gene 2 (BTG2) axis.</AbstractText>APPswe/PS1dE9 mice were injected with depleted BTG2 and/or restored miR-16-5p vectors into the third ventricle to explore their roles in neurological function, neuronal damage, autophagy and apoptosis in AD mice. In vitro cultured hippocampal neurons were transfected with depleted BTG2 and/or restored miR-16-5p vector to interpret their functions in neuronal viability and apoptosis. MiR-16-5p and BTG2 expression in hippocampal tissues and neurons were detected.</AbstractText>Lower miR-16-5p and higher BTG2 expression levels were found in hippocampal tissues and neurons. MiR-16-5p up-regulation or BTG2 down-regulation improved neurological function and neuronal damage and inhibited neuronal autophagy and apoptosis in AD mice. Restored miR-16-5p or depleted BTG2 restrained neuronal viability and apoptosis in vitro.</AbstractText>Our study reveals that restored miR-16-5p or depleted BTG2 protects neurological function and suppresses neuronal autophagy and apoptosis in AD mice, which renews a novel guide toward AD treatments from the perspective of miR-16-5p/BTG2 axis.</AbstractText>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,331,382 | Bushen-Huatan-Yizhi formula reduces spatial learning and memory challenges through inhibition of the GSK-3β/CREB pathway in AD-like model rats. | There is an increase in cases of Alzheimer's disease (AD) stemming from a globally ageing population demographic. Although substantial research efforts were performed for the scope of prophylaxis and therapeutic measure development against AD, based on its pathogenesis, most were unsuccessful. Bushen-Huatan-Yizhi formula (BSHTYZ) is extensively implemented to manage dementia. However, few studies have been carried out to understand how BSHTYZ enhances recovery of spatial learning and memory and how it modulates relevant molecular interplays in order to achieve this.</AbstractText>To investigate neuroprotective function, ameliorating learning/memory capacity of BSHTYZ via GSK-3β / CREB signaling pathway in rat AD models influenced through Aβ1-42</sub>.</AbstractText>A total of 60 male SD rats (3 months old) were randomized into six groups and treated with 2.6 μg/μl Aβ1-42</sub> (5 μl) into the lateral ventricle, though the control group (Con) was administered an equivalent volume of vehicle. Consequently, the rat cohorts were administered either BSHTYZ or donepezil hydrochloride or normal saline, by intragastric administration, for four weeks. Spatial learning / memory were detected through the Morris water maze, and possible mechanisms detected by histomorphological examination and Western blot in the rat AD models induced by Aβ1-42</sub>.</AbstractText>Spatial learning/memory issues were monitored after Aβ1-42</sub> infusion in rats. Simultaneously, neuron loss in cornuammonis1 (CA1) / dentate gyrus (DG) within hippocampus region were identified, together with enhanced black granule staining within the hippocampus and hyperphosphorylated tau within Ser202 and Ser396 sites. It was also elucidated that Aβ1-42</sub> had the capacity to up-regulate glycogen synthase kinase-3β (GSK-3β) and down-regulate cAMP response element binding protein (CREB). BSHTYZ was found to reverse such molecular interplays.</AbstractText>The study suggested BSHTYZ could possibly provide neuroprotective role against learning / memory impairment, which provided a potential therapeutic tool delaying the progression of AD molecular interplays that includes the GSK-3β / CREB signaling pathway.</AbstractText>Copyright © 2021. Published by Elsevier GmbH.</CopyrightInformation> |
2,331,383 | Neuroendoscopic surgery in neonates - indication and results over a 10-year practice. | Neuroendoscopic procedures for treatment of term and preterm newborn infants, such as endoscopic lavage for posthemorrhagic hydrocephalus, are gaining popularity despite sparse data. This single-institution report compiles all neuroendoscopic surgical procedures performed in neonates during a 10-year period.</AbstractText>Charts and electronic records were reviewed of all consecutive newborns who underwent a neuroendoscopic procedure before reaching a postmenstrual age of 44 weeks between 09/2010 and 09/2020. Available documentation was reviewed regarding the performed neuroendoscopic procedure, course of disease, complications, and all re-operations throughout the first year of life.</AbstractText>During the 10-year study period, 116 infants (median gestational age at birth: 29 1</sup>/7 weeks) underwent a total of 153 neuroendoscopic procedures (median postmenstrual age at surgery: 35 0</sup>/7 weeks). The most common indication at the time of the neuroendoscopic procedures (n = 153) was intraventricular hemorrhage (IVH, n = 119), intraventricular infection (n = 15), congenital malformation (n = 8), isolated 4th ventricle (n = 7), multiloculated hydrocephalus (n = 3), and tumor (n = 1). Thirty-eight of 116 children (32.8%) underwent 43 operative revisions after 153 neuroendoscopic procedure (28.1%). Observed complications requiring surgical revision were secondary infection (n = 11), CSF fistula (n = 9), shunt dysfunction (n = 8), failure of ETV (n = 6), among others. 72 children (62%) of 116 children required permanent CSF diversion via a shunt. The respective shunt rates per diagnosis were 47 of 80 (58.8%) for previously untreated IVH, 11 of 13 (84.6%) for intraventricular infection. Shunt survival rate for the first year of life was 74% for the whole cohort.</AbstractText>The experience with this large cohort of neonates demonstrates the feasibility of neuroendoscopic technique for the treatment of posthemorrhagic or postinfectious hydrocephalus. Rate and type of complications after neuroendoscopic procedures were within the expected range. Assessing the potential long-term benefits of neuroendoscopic techniques has to await results of ongoing studies.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,331,384 | Identification of key molecular biomarkers involved in reactive and neurodegenerative processes present in inherited congenital hydrocephalus. | Periventricular extracellular oedema, myelin damage, inflammation, and glial reactions are common neuropathological events that occur in the brain in congenital hydrocephalus. The periventricular white matter is the most affected region. The present study aimed to identify altered molecular and cellular biomarkers in the neocortex that can function as potential therapeutic targets to both treat and evaluate recovery from these neurodegenerative conditions. The hyh mouse model of hereditary hydrocephalus was used for this purpose.</AbstractText>The hyh mouse model of hereditary hydrocephalus (hydrocephalus with hop gait) and control littermates without hydrocephalus were used in the present work. In tissue sections, the ionic content was investigated using energy dispersive X-ray spectroscopy scanning electron microscopy (EDS-SEM). For the lipid analysis, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) was performed in frozen sections. The expression of proteins in the cerebral white matter was analysed by mass spectrometry. The oligodendrocyte progenitor cells (OPCs) were studied with immunofluorescence in cerebral sections and whole-mount preparations of the ventricle walls.</AbstractText>High sodium and chloride concentrations were found indicating oedema conditions in both the periventricular white matter and extending towards the grey matter. Lipid analysis revealed lower levels of two phosphatidylinositol molecular species in the grey matter, indicating that neural functions were altered in the hydrocephalic mice. In addition, the expression of proteins in the cerebral white matter revealed evident deregulation of the processes of oligodendrocyte differentiation and myelination. Because of the changes in oligodendrocyte differentiation in the white matter, OPCs were also studied. In hydrocephalic mice, OPCs were found to be reactive, overexpressing the NG2 antigen but not giving rise to an increase in mature oligodendrocytes. The higher levels of the NG2 antigen, diacylglycerophosphoserine and possibly transthyretin in the cerebrum of hydrocephalic hyh mice could indicate cell reactions that may have been triggered by inflammation, neurocytotoxic conditions, and ischaemia.</AbstractText>Our results identify possible biomarkers of hydrocephalus in the cerebral grey and white matter. In the white matter, OPCs could be reacting to acquire a neuroprotective role or as a delay in the oligodendrocyte maturation.</AbstractText> |
2,331,385 | Activation of CRF<sub>1</sub> receptors expressed in brainstem autonomic nuclei stimulates colonic enteric neurons and secreto-motor function in male rats. | Hypothalamic corticotropin-releasing factor (CRF) receptor 1 (CRF1</sub> ) plays a role in acute stress-related stimulation of colonic motor function. Less is known on CRF1</sub> signaling in the brainstem.</AbstractText>We investigate CRF1</sub> expression in the brainstem and the colonic response to 4th</sup> ventricle (4V) injection of CRF and urocortin (Ucn) 2 (3 µg/rat) in chronically cannulated male rats.</AbstractText>Transcripts of CRF1</sub> wild-type 1a and splice variants 1c, 1e, 1f, 1o along with three novel variants 1a-2 (desK-110 in exon 5), 1p (-exon 7), and 1q (exon 5 extension) were identified in the pons and medulla. The area postrema, nucleus tractus solitarius, dorsal motor nucleus of the vagus, locus coeruleus, and Barrington's nucleus isolated by laser capture microdissection expressed 1a, 1a-2, and 1p but not 1q. Compared to 4V vehicle, 4V CRF induced fecal pellet output (FPO) and diarrhea that were blocked by the CRF antagonist, astressin-B. CRF2</sub> agonist, Ucn2 had no effect on basal or CRF-induced FPO. CRF actions were correlated with the induction of c-Fos immunoreactivity in myenteric neurons of the proximal and distal colon (pC, dC) and submucosal neurons of dC. c-Fos immunoreactivity occurred in 39% and 37% of myenteric cholinergic and 7% and 58% of nitrergic neurons in the pC and dC, respectively.</AbstractText><AbstractText Label="CONCLUSIONS & INFERENCES">CRF1a</sub> and its splice variants are expressed in brainstem nuclei, and activation of CRF1</sub> signaling at the level of the brainstem stimulates colonic secretory-motor function through activation of colonic enteric neurons.</AbstractText>© 2021 John Wiley & Sons Ltd.</CopyrightInformation> |
2,331,386 | Longitudinal Reference Values for Cerebral Ventricular Size in Preterm Infants Born at 23-27 Weeks of Gestation. | To establish longitudinal reference values for cerebral ventricular size in the most vulnerable patients at risk for intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilatation (PHVD).</AbstractText>This retrospective study included neurologically healthy preterm neonates born at 230/7</sup>-266/7</sup> weeks of gestational age between September 2011 and April 2019. Patients were treated at 2 Austrian tertiary centers, Medical University of Vienna and Medical University of Innsbruck. All available cerebral ultrasound scans until 30 weeks corrected age were analyzed. Ventricular measurements included ventricular index, anterior horn width (AHW), and thalamo-occipital distance (TOD) and longitudinal percentiles were created.</AbstractText>The study cohort consisted of 244 preterm neonates, with a median gestational age of 253/7</sup> weeks (IQR, 244/7</sup>-260/7</sup> weeks) and a median birth weight of 735 g (IQR, 644-849 g). A total of 993 ultrasound scans were available for analysis, resulting in >1800 measurements of ventricular index, AHW, and TOD. Special attention was given to the 97th percentile as well as 2 mm and 4 mm above the 97th percentile, which are used internationally as cutoffs for intervention in the presence of PHVD.</AbstractText>We present percentile charts based on a cohort of extremely premature infants including neonates born at the border of viability suited to follow-up the most vulnerable patients at risk for IVH and PHVD. Furthermore, we provide an extensive literature research and comparison of all available reference values, focusing on ventricular index, AHW, and TOD.</AbstractText>Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,331,387 | Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase 1, dose-escalation trial. | Malignant glioma is the most common and lethal primary brain tumour, with dismal survival rates and no effective treatment. We examined the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells (NSCs), in patients with newly diagnosed high-grade glioma.</AbstractText>This was a first-in-human, open-label, phase 1, dose-escalation trial done to determine the maximal tolerated dose of NSC-CRAd-S-pk7, following a 3 + 3 design. Patients with newly diagnosed, histologically confirmed, high-grade gliomas (WHO grade III or IV) were recruited. After neurosurgical resection, NSC-CRAd-S-pk7 was injected into the walls of the resection cavity. The first patient cohort received a dose starting at 6·25 × 1010</sup> viral particles administered by 5·00 × 107</sup> NSCs, the second cohort a dose of 1·25 × 1011</sup> viral particles administered by 1·00 × 108</sup> NSCs, and the third cohort a dose of 1·875 × 1011</sup> viral particles administered by 1·50 × 108</sup> NSCs. No further dose escalation was planned. Within 10-14 days, treatment with temozolomide and radiotherapy was initiated. Primary endpoints were safety and toxicity profile and the maximum tolerated dose for a future phase 2 trial. All analyses were done in all patients who were included in the trial and received the study treatment and were not excluded from the study. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT03072134.</AbstractText>Between April 24, 2017, and Nov 13, 2019, 12 patients with newly diagnosed, malignant gliomas were recruited and included in the safety analysis. Histopathological evaluation identified 11 (92%) of 12 patients with glioblastoma and one (8%) of 12 patients with anaplastic astrocytoma. The median follow-up was 18 months (IQR 14-22). One patient receiving 1·50 × 108</sup> NSCs loading 1·875 × 1011</sup> viral particles developed viral meningitis (grade 3) due to the inadvertent injection of NSC-CRAd-S-pk7 into the lateral ventricle. Otherwise, treatment was safe as no formal dose-limiting toxicity was reached, so 1·50 × 108</sup> NSCs loading 1·875 × 1011</sup> viral particles was recommended as a phase 2 trial dose. There were no treatment-related deaths. The median progression-free survival was 9·1 months (95% CI 8·5-not reached) and median overall survival was 18·4 months (15·7-not reached).</AbstractText>NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S-pk7 in a phase 2/3 clinical trial.</AbstractText>US National Institutes of Health.</AbstractText>Copyright © 2021 Elsevier Ltd. All rights reserved.</CopyrightInformation> |
2,331,388 | Effect of Tongfu Xingshen capsule on the endogenous neural stem cells of experimental rats with intracerebral hemorrhage. | Intracerebral hemorrhage (ICH) can stimulate neural regeneration, promoting tissue repair and recovery of nerve function. Tongfu Xingshen capsule (TXC) is a Chinese medicinal formula used to treat ICH and has been shown to protect brain tissue and improve nerve function in clinical studies. However, the effect of TXC on endogenous neural stem cells (NSCs) remains elusive. To explore the mechanisms underlying TXC action, a rat model of ICH was established. The effects of TXC on the proliferation and differentiation of NSCs were assessed in the subventricular zone (SVZ). TXC significantly improved nerve function defects, decreased brain water content and restored blood‑brain barrier integrity. Additionally, BrdU labeling showed that both high and low doses of TXC significantly increased the proportion of actively cycling NSCs positive for Nestin and glial fibrillary acidic protein, but did not affect the proliferation rates of NeuN‑positive neurons. Finally, TXC also upregulated the mRNA levels of brain‑derived neurotrophic factor and its receptor, TrκB, in affected brain tissues. Taken together, TXC accelerated neural repair and functional recovery after brain injury by potentially enhancing the proliferation and differentiation of endogenous NSCs into astroglial cells in the SVZ area. |
2,331,389 | A Case of Sellar/Suprasellar Neurocysticercosis Mimicking a Craniopharyngioma. | Neurocysticercosis (NCC) commonly presents with seizures in developing countries such as Nepal. It may also present with raised intracranial pressure due to obstructive hydrocephalus when cyst is located in the fourth ventricle or foramen of Monro. There are four main stages of NCC (1) Vesicular, (2) Colloidal vesicular, (3) Granular nodular, and (4) Nodular calcified. The colloidal vesicular stages can cause arachnoiditis and thus can cause hydrocephalus whereas obstructive hydrocephalus is usually caused by racemose type of NCC. This case was a suprasellar cyst mimicking craniopharyngioma, supported with clinical history of poor visual acuity, endocrine abnormality, suggested radiological findings by computed tomography scan, and magnetic resonance imaging. Suprasellar NCC was confirmed only by intraoperative findings and histopathology report. |
2,331,390 | Endoscopic Third Ventriculostomy in the Fourth Ventricle Outlet Obstruction Associated with Chiari Malformation Type I and Syringomyelia: Case Report. | Hydrocephalus by the fourth ventricle outlet obstruction (FVOO) associated with a Chiari malformation type I and syringomyelia is a well-known entity but a rare situation in clinical practice. Although suboccipital craniectomy with the opening of the obstruction membrane appears to be the most physiological approach, by restoring the original pathway of cerebrospinal fluid flow, the endoscopic third ventriculostomy (ETV) represents an important minimally invasive alternative. We report the case of an adult patient with tetra ventricular hydrocephalus by FVOO associated with Chiari malformation and syringomyelia. The ETV alone completely resolved all symptoms, as well as neuroimaging abnormalities on the control magnetic resonance imaging. The ETV is a minimally invasive option for the treatment of hydrocephalus in patients with obstruction at the exit of the fourth ventricle, even in cases associated with Chiari malformation and syringomyelia. |
2,331,391 | The Dilemma of Multifocality in Insular Tumors: Multicentricity versus Metastasis. | Multifocality and metastasis from insular glioma are extremely rare. Pathological insights and elaboration of the clinical course of this condition will contribute to their better understanding.</AbstractText>Among 123 consecutively operated insular gliomas, 5 patients (4.2%) presented with a multifocal tumor. The clinico-radiological, histo-molecular, and treatment outcomes were noted and compared with the unifocal insular glioma cohort.</AbstractText>Among the five patients, all were males and involved the right insular lobe. Three patients presented with synchronous tumors, while two patients developed metachronous multifocal tumors. The histology of the insular tumor was Grade I glioma in 1, Grade II astrocytoma with p53 mutation in 2, and anaplastic astrocytoma and glioblastoma in one patient each. Histological confirmation of the second lesion was performed in two patients, showing the same histology of the insular tumor. Interconnection between the tumors was apparent through cerebrospinal fluid pathways in four patients, while no such connection could be established in one patient. Barring the patient of Grade I glioma, the rest of the patients died within months of the diagnosis.</AbstractText>Multifocal insular glioma is rare and probably represents a biologically more aggressive tumor. Insular glioma that touches the ventricle appears a common denominator for multifocality. True multicentricity is rare. The prognosis in insular glioma with multifocality is poor in non-Grade I gliomas.</AbstractText>Copyright: © 2021 Asian Journal of Neurosurgery.</CopyrightInformation> |
2,331,392 | Assessment of Left Ventricular Diastolic Function in Young Adults with Nonalcoholic Fatty Liver Disease. | There is strong evidence that, in addition to increasing the risk of cirrhosis as well as hepatocellular carcinoma, nonalcoholic liver disease represents an independent risk factor for different diseases including cardiovascular and chronic kidney disease and also type 2 diabetes.</AbstractText>to assess whether nonalcoholic fatty liver disease is associated with diastolic dysfunction of the left ventricle, independent of other classic risk factors.</AbstractText>we included 79 patients aged 15-45, diagnosed with non-alcoholic liver disease, and a group of 80 healthy people in the same age group. We assessed left ventricular diastolic function using Doppler pulsed wave transmitral flow and Tissue Doppler Imaging methods.</AbstractText>there were lower velocities of E and e' wave, a decrease in E/A ratio and an increase in E/e' ratio in the group of patients with hepatic steatosis and in those with associated diabetes compared to the control group, but not the same was observed when comparing patients with steatosis alone vs. hepatic steatosis and associated diabetes mellitus.</AbstractText>nonalcoholic steatosis is linked to echocardiographic features of early diastolic dysfunction that are present in patients suffering from diabetes.</AbstractText>Copyright © 2014, Medical University Publishing House Craiova.</CopyrightInformation> |
2,331,393 | Vascular cell-specific roles of mineralocorticoid receptors in pulmonary hypertension. | Abnormalities that characterize pulmonary arterial hypertension include impairment in the structure and function of pulmonary vascular endothelial and smooth muscle cells. Aldosterone levels are elevated in human pulmonary arterial hypertension and in experimental pulmonary hypertension, while inhibition of the aldosterone-binding mineralocorticoid receptor attenuates pulmonary hypertension in multiple animal models. We explored the role of mineralocorticoid receptor in endothelial and smooth muscle cells in using cell-specific mineralocorticoid receptor knockout mice exposed to sugen/hypoxia-induced pulmonary hypertension. Treatment with the mineralocorticoid receptor inhibitor spironolactone significantly reduced right ventricular systolic pressure. However, this is not reproduced by selective mineralocorticoid receptor deletion in smooth muscle cells or endothelial cells. Similarly, spironolactone attenuated the increase in right ventricular cardiomyocyte area independent of vascular mineralocorticoid receptor with no effect on right ventricular weight or interstitial fibrosis. Right ventricular perivascular fibrosis was significantly decreased by spironolactone and this was reproduced by specific deletion of mineralocorticoid receptor from endothelial cells. Endothelial cell-mineralocorticoid receptor deletion attenuated the sugen/hypoxia-induced increase in the leukocyte-adhesion molecule, E-selectin, and collagen IIIA1 in the right ventricle. Spironolactone also significantly reduced pulmonary arteriolar muscularization, independent of endothelial cell-mineralocorticoid receptor or smooth muscle cell-mineralocorticoid receptor. Finally, the degree of pulmonary perivascular inflammation was attenuated by mineralocorticoid receptor antagonism and was fully reproduced by smooth muscle cell-specific mineralocorticoid receptor deletion. These studies demonstrate that in the sugen/hypoxia pulmonary hypertension model, systemic-mineralocorticoid receptor blockade significantly attenuates the disease and that mineralocorticoid receptor has cell-specific effects, with endothelial cell-mineralocorticoid receptor contributing to right ventricular perivascular fibrosis and smooth muscle cell-mineralocorticoid receptor participating in pulmonary vascular inflammation. As mineralocorticoid receptor antagonists are being investigated to treat pulmonary arterial hypertension, these findings support novel mechanisms and potential mineralocorticoid receptor targets that mediate therapeutic benefits in patients. |
2,331,394 | ROCK Inhibition as Potential Target for Treatment of Pulmonary Hypertension. | Pulmonary hypertension (PH) is a cardiovascular disease caused by extensive vascular remodeling in the lungs, which ultimately leads to death in consequence of right ventricle (RV) failure. While current drugs for PH therapy address the sustained vasoconstriction, no agent effectively targets vascular cell proliferation and tissue inflammation. Rho-associated protein kinases (ROCKs) emerged in the last few decades as promising targets for PH therapy, since ROCK inhibitors demonstrated significant anti-remodeling and anti-inflammatory effects. In this review, current aspects of ROCK inhibition therapy are discussed in relation to the treatment of PH and RV dysfunction, from cell biology to preclinical and clinical studies. |
2,331,395 | Fetal Gene Reactivation in Pulmonary Arterial Hypertension: GOOD, BAD, or BOTH? | Pulmonary arterial hypertension is a debilitating chronic disorder marked by the progressive obliteration of the pre-capillary arterioles. This imposes a pressure overload on the right ventricle (RV) pushing the latter to undergo structural and mechanical adaptations that inexorably culminate in RV failure and death. Thanks to the advances in molecular biology, it has been proposed that some aspects of the RV and pulmonary vascular remodeling processes are orchestrated by a subversion of developmental regulatory mechanisms with an upregulation of a suite of genes responsible for the embryo's early growth and normally repressed in adults. In this review, we present relevant background regarding the close relationship between overactivation of fetal genes and cardiopulmonary remodeling, exploring whether the reawakening of developmental factors plays a causative role or constitutes a protective mechanism in the setting of PAH. |
2,331,396 | Neurosonological Findings Related to Non-Motor Features of Parkinson's Disease: A Systematic Review. | Non-motor symptoms (NMS) in Parkinson's disease (PD), including neuropsychiatric or dysautonomic complaints, fatigue, or pain, are frequent and have a high impact on the patient's quality of life. They are often poorly recognized and inadequately treated. In the recent years, the growing awareness of NMS has favored the development of techniques that complement the clinician's diagnosis. This review provides an overview of the most important ultrasonographic findings related to the presence of various NMS. Literature research was conducted in PubMed, Scopus, and Web of Science from inception until January 2021, retrieving 23 prospective observational studies evaluating transcranial and cervical ultrasound in depression, dementia, dysautonomic symptoms, psychosis, and restless leg syndrome. Overall, the eligible articles showed good or fair quality according to the QUADAS-2 assessment. Brainstem raphe hypoechogenicity was related to the presence of depression in PD and also in depressed patients without PD, as well as to overactive bladder. Substantia nigra hyperechogenicity was frequent in patients with visual hallucinations, and larger intracranial ventricles correlated with dementia. Evaluation of the vagus nerve showed contradictory findings. The results of this systematic review demonstrated that transcranial ultrasound can be a useful complementary tool in the evaluation of NMS in PD. |
2,331,397 | Echocardiography in Pulmonary Arterial Hypertension: Is It Time to Reconsider Its Prognostic Utility? | Pulmonary arterial hypertension (PAH) is characterized by an insult in the pulmonary vasculature, with subsequent right ventricular (RV) adaptation to the increased afterload that ultimately leads to RV failure. The awareness of the importance of RV function in PAH has increased considerably because right heart failure is the predominant cause of death in PAH patients. Given its wide availability and reduced cost, echocardiography is of paramount importance in the evaluation of the right heart in PAH. Several echocardiographic parameters have been shown to have prognostic implications in PAH; however, the role of echocardiography in the risk assessment of the PAH patient is limited under the current guidelines. This review discusses the echocardiographic evaluation of the RV in PAH and during therapy, and its prognostic implications, as well as the potential significant role of repeated echocardiographic assessment in the follow-up of patients with PAH. |
2,331,398 | Life and Death of Immature Neurons in the Juvenile and Adult Primate Amygdala. | In recent years, a large population of immature neurons has been documented in the paralaminar nucleus of the primate amygdala. A substantial fraction of these immature neurons differentiate into mature neurons during postnatal development or following selective lesion of the hippocampus. Notwithstanding a growing number of studies on the origin and fate of these immature neurons, fundamental questions about the life and death of these neurons remain. Here, we briefly summarize what is currently known about the immature neurons present in the primate ventral amygdala during development and in adulthood, as well as following selective hippocampal lesions. We provide evidence confirming that the distribution of immature neurons extends to the anterior portions of the entorhinal cortex and layer II of the perirhinal cortex. We also provide novel arguments derived from stereological estimates of the number of mature and immature neurons, which support the view that the migration of immature neurons from the lateral ventricle accompanies neuronal maturation in the primate amygdala at all ages. Finally, we propose and discuss the hypothesis that increased migration and maturation of neurons in the amygdala following hippocampal dysfunction may be linked to behavioral alterations associated with certain neurodevelopmental disorders. |
2,331,399 | Right Ventricle Remodeling Metabolic Signature in Experimental Pulmonary Hypertension Models of Chronic Hypoxia and Monocrotaline Exposure. | Over time and despite optimal medical management of patients with pulmonary hypertension (PH), the right ventricle (RV) function deteriorates from an adaptive to maladaptive phenotype, leading to RV failure (RVF). Although RV function is well recognized as a prognostic factor of PH, no predictive factor of RVF episodes has been elucidated so far. We hypothesized that determining RV metabolic alterations could help to understand the mechanism link to the deterioration of RV function as well as help to identify new biomarkers of RV failure.</AbstractText>In the current study, we aimed to characterize the metabolic reprogramming associated with the RV remodeling phenotype during experimental PH induced by chronic-hypoxia-(CH) exposure or monocrotaline-(MCT) exposure in rats. Three weeks after PH initiation, we hemodynamically characterized PH (echocardiography and RV catheterization), and then we used an untargeted metabolomics approach based on liquid chromatography coupled to high-resolution mass spectrometry to analyze RV and LV tissues in addition to plasma samples from MCT-PH and CH-PH rat models.</AbstractText>CH exposure induced adaptive RV phenotype as opposed to MCT exposure which induced maladaptive RV phenotype. We found that predominant alterations of arginine, pyrimidine, purine, and tryptophan metabolic pathways were detected on the heart (LV+RV) and plasma samples regardless of the PH model. Acetylspermidine, putrescine, guanidinoacetate RV biopsy levels, and cytosine, deoxycytidine, deoxyuridine, and plasmatic thymidine levels were correlated to RV function in the CH-PH model. It was less likely correlated in the MCT model. These pathways are well described to regulate cell proliferation, cell hypertrophy, and cardioprotection. These findings open novel research perspectives to find biomarkers for early detection of RV failure in PH.</AbstractText> |
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