bluuebunny/crossref_metadata_2025 huggingface dataset:
Time Course of Severe Fever With Thrombocytopenia Syndrome Virus and Antibodies in Patients by Long-Term Follow-Up Study, China
Authors: Hu Lifen , Kong Qinxiang , Liu Yanyan , Li Jiajia , Bian Tingting , Ma Xuejiao , Ye Ying , Li Jiabin
Published: October 2021

Objectives: The objective was to describe the changes of severe fever with thrombocytopenia syndrome virus (SFTSV) and antibody in the disease course and explore the relationship between antibody titers and patients’ prognosis.

Methods: The levels of SFTSV, virus-specific immunoglobulin M (IgM), immunoglobulin G (IgG) titers, and cytokines in 37 patients with severe fever with thrombocytopenia syndrome (SFTS) were measured dynamically by real-time PCR and ELISA during the disease course; IgG titers were followed up in 53 cases. The correlation analysis of antibody titers with individual serum cytokines was calculated using the Spearman test.

Results: The average time of SFTSV duration in individual serum was 22.45 ± 7.6 days from onset. We found SFTSV turned negative within the 10th day from the onset in two patients. SFTSV-specific IgM seroconversion occurred as early as within 3 days from the onset, increased gradually within the first 2 months, decreased gradually 3 months later, and disappeared after 6 months in all the patients. The average time of SFTSV-specific IgG antibody seroconversion was at 17 days from onset in the patients; the time was later in severe cases than in mild cases (23 ± 1.4 vs. 14.3 ± 1.0 days, p < 0.0001). IgG titers were maintained at the peak levels during the periods from 6 months to 1 year and decreased from the second year gradually. Severe cases had higher IgG levels than mild cases and also had a slower decreasing trend. During follow-up, only one lost IgG antibody 7 years later; no chronic infection and sequela were found among the 53 patients. None of the patients had SFTSV reinfection even if they were bitten by ticks again. The correlation analysis showed a positive relationship between inflammatory factors and IgG antibody levels.

Conclusion: IgM antibody has important value in early diagnosis of SFTS. A moderate inflammatory response is beneficial for production and duration of IgG antibodies.
Co-metabolic Effect of Glucose on Methane Production and Phenanthrene Removal in an Enriched Phenanthrene-Degrading Consortium Under Methanogenesis
Authors: Zhou Ziyan , Wang Yanqin , Wang Mingxia , Zhou Zhifeng
Published: October 2021

Anaerobic digestion is used to treat diverse waste classes, and polycyclic aromatic hydrocarbons (PAHs) are a class of refractory compounds that common in wastes treated using anaerobic digestion. In this study, a microbial consortium with the ability to degrade phenanthrene under methanogenesis was enriched from paddy soil to investigate the cometabolic effect of glucose on methane (CH4) production and phenanthrene (a representative PAH) degradation under methanogenic conditions. The addition of glucose enhanced the CH4 production rate (from 0.37 to 2.25mg⋅L−1⋅d−1) but had no influence on the degradation rate of phenanthrene. Moreover, glucose addition significantly decreased the microbial α-diversity (from 2.59 to 1.30) of the enriched consortium but showed no significant effect on the microbial community (R2=0.39, p=0.10), archaeal community (R2=0.48, p=0.10), or functional profile (R2=0.48, p=0.10). The relative abundance of genes involved in the degradation of aromatic compounds showed a decreasing tendency with the addition of glucose, whereas that of genes related to CH4 synthesis was not affected. Additionally, the abundance of genes related to the acetate pathway was the highest among the four types of CH4 synthesis pathways detected in the enriched consortium, which averagely accounted for 48.24% of the total CH4 synthesis pathway, indicating that the acetate pathway is dominant in this phenanthrene-degrading system during methanogenesis. Our results reveal that achieving an ideal effect is diffcult via co-metabolism in a single-stage digestion system of PAH under methanogenesis; thus, other anaerobic systems with higher PAH removal efficiency should be combined with methanogenic digestion, assembling a multistage pattern to enhance the PAH removal rate and CH4 production in anaerobic digestion.
Mutations Suppressing the Lack of Prepilin Peptidase Provide Insights Into the Maturation of the Major Pilin Protein in Cyanobacteria
Authors: Linhartová Markéta , Skotnicová Petra , Hakkila Kaisa , Tichý Martin , Komenda Josef , Knoppová Jana , Gilabert Joan F. , Guallar Victor , Tyystjärvi Taina , Sobotka Roman
Published: October 2021

Type IV pili are bacterial surface-exposed filaments that are built up by small monomers called pilin proteins. Pilins are synthesized as longer precursors (prepilins), the N-terminal signal peptide of which must be removed by the processing protease PilD. A mutant of the cyanobacterium Synechocystis sp. PCC 6803 lacking the PilD protease is not capable of photoautotrophic growth because of the impaired function of Sec translocons. Here, we isolated phototrophic suppressor strains of the original ΔpilD mutant and, by sequencing their genomes, identified secondary mutations in the SigF sigma factor, the γ subunit of RNA polymerase, the signal peptide of major pilin PilA1, and in the pilA1-pilA2 intergenic region. Characterization of suppressor strains suggests that, rather than the total prepilin level in the cell, the presence of non-glycosylated PilA1 prepilin is specifically harmful. We propose that the restricted lateral mobility of the non-glycosylated PilA1 prepilin causes its accumulation in the translocon-rich membrane domains, which attenuates the synthesis of membrane proteins.
Integrative Analyses and Verification of the Expression and Prognostic Significance for RCN1 in Glioblastoma Multiforme
Authors: Lu Weicheng , Chen Hong , Liang Bo , Ou Chaopeng , Zhang Mingwei , Yue Qiuyuan , Xie Jingdun
Published: October 2021

Glioblastoma multiform is a lethal primary brain tumor derived from astrocytic, with a poor prognosis in adults. Reticulocalbin-1 (RCN1) is a calcium-binding protein, dysregulation of which contributes to tumorigenesis and progression in various cancers. The present study aimed to identify the impact of RCN1 on the outcomes of patients with Glioblastoma multiforme (GBM). The study applied two public databases to require RNA sequencing data of Glioblastoma multiform samples with clinical data for the construction of a training set and a validation set, respectively. We used bioinformatic analyses to determine that RCN1 could be an independent factor for the overall survival of Glioblastoma multiform patients. In the training set, the study constructed a predictive prognostic model based on the combination of RCN1 with various clinical parameters for overall survival at 0.5-, 1.0-, and 1.5-years, as well as developed a nomogram, which was further validated by validation set. Pathways analyses indicated that RCN1 was involved in KEAS and MYC pathways and apoptosis. In vitro experiments indicated that RCN1 promoted cell invasion of Glioblastoma multiform cells. These results illustrated the prognostic role of RCN1 for overall survival in Glioblastoma multiform patients, indicated the promotion of RCN1 in cell invasion, and suggested the probability of RCN1 as a potential targeted molecule for treatment in Glioblastoma multiform.
Uncovering Disease Mechanisms in a Novel Mouse Model Expressing Humanized APOEε4 and Trem2*R47H
Authors: Kotredes Kevin P. , Oblak Adrian , Pandey Ravi S. , Lin Peter Bor-Chian , Garceau Dylan , Williams Harriet , Uyar Asli , O’Rourke Rita , O’Rourke Sarah , Ingraham Cynthia , Bednarczyk Daria , Belanger Melisa , Cope Zackary , Foley Kate E. , Logsdon Benjamin A. , Mangravite Lara M. , Sukoff Rizzo Stacey J. , Territo Paul R. , Carter Gregory W. , Sasner Michael , Lamb Bruce T. , Howell Gareth R.
Published: October 2021

Late-onset Alzheimer’s disease (AD; LOAD) is the most common human neurodegenerative disease, however, the availability and efficacy of disease-modifying interventions is severely lacking. Despite exceptional efforts to understand disease progression via legacy amyloidogenic transgene mouse models, focus on disease translation with innovative mouse strains that better model the complexity of human AD is required to accelerate the development of future treatment modalities. LOAD within the human population is a polygenic and environmentally influenced disease with many risk factors acting in concert to produce disease processes parallel to those often muted by the early and aggressive aggregate formation in popular mouse strains. In addition to extracellular deposits of amyloid plaques and inclusions of the microtubule-associated protein tau, AD is also defined by synaptic/neuronal loss, vascular deficits, and neuroinflammation. These underlying processes need to be better defined, how the disease progresses with age, and compared to human-relevant outcomes. To create more translatable mouse models, MODEL-AD (Model Organism Development and Evaluation for Late-onset AD) groups are identifying and integrating disease-relevant, humanized gene sequences from public databases beginning with APOEε4 and Trem2*R47H, two of the most powerful risk factors present in human LOAD populations. Mice expressing endogenous, humanized APOEε4 and Trem2*R47H gene sequences were extensively aged and assayed using a multi-disciplined phenotyping approach associated with and relative to human AD pathology. Robust analytical pipelines measured behavioral, transcriptomic, metabolic, and neuropathological phenotypes in cross-sectional cohorts for progression of disease hallmarks at all life stages. In vivo PET/MRI neuroimaging revealed regional alterations in glycolytic metabolism and vascular perfusion. Transcriptional profiling by RNA-Seq of brain hemispheres identified sex and age as the main sources of variation between genotypes including age-specific enrichment of AD-related processes. Similarly, age was the strongest determinant of behavioral change. In the absence of mouse amyloid plaque formation, many of the hallmarks of AD were not observed in this strain. However, as a sensitized baseline model with many additional alleles and environmental modifications already appended, the dataset from this initial MODEL-AD strain serves an important role in establishing the individual effects and interaction between two strong genetic risk factors for LOAD in a mouse host.
Troponin Elevation on Admission Along With Dynamic Changes and Their Association With Hemorrhagic Transformation After Thrombolysis
Authors: Cheng Zicheng , Zhan Zhenxiang , Huang Xiaoyan , Xia Lingfan , Xu Tong , Han Zhao
Published: October 2021

Background: Hemorrhagic transformation (HT) is a common complication of intravenous thrombolysis with alteplase. Cardiac troponin has been found to be associated with poor prognosis and cognitive impairment in acute ischemic stroke. But studies on the relationship between troponin and HT after thrombolysis are scarce.

Methods: This study retrospectively analyzed thrombolytic patients from June 2015 to June 2021 in the Second Affiliated Hospital of Wenzhou Medical University. Cardiac troponin I were measured on admission and on following days to determine the presence of elevation and dynamic changes. HT within 24–36 h after treatment was identified by cranial computed tomography (CT). Besides, a score on the modified Rankin Scale (mRS) > 2 at discharge was defined as unfavorable outcome. Univariate analysis was used to explore the factors related to the troponin elevation on admission and troponin dynamic changes. Multivariate logistic regression model was used to investigated the association between troponin elevation on admission, troponin dynamic changes and HT after thrombolysis, respectively.

Results: Troponin levels on admission were measured in 377 patients, and follow-up assay was performed in 292 patients (77.5%). 39 patients (10.3%) had troponin elevation on admission, and 66 patients (22.6%) had troponin dynamic changes comprising rising and falling pattern. The pre-existing heart disease, renal insufficiency and higher stroke severity are related to both troponin elevation on admission and the subsequent troponin dynamic changes. After adjusting the potential confounding factors, logistic regression model showed that patients with troponin elevation on admission had insignificant trend to develop HT (OR 2.23, 95%CI 0.96–5.21, p = 0.063), while patients with troponin dynamic changes had significantly higher risk of HT (OR 2.27, 95%CI 1.06–4.85, p = 0.034). Compared to the troponin elevation, a statistically stronger association was present between rising troponin dynamic changes and unfavorable outcome (OR 2.20, 95%CI 1.05–4.60, p = 0.037).

Conclusion: Troponin dynamic changes are associated with HT after thrombolysis. Serial measurements are quite necessary in thrombolytic patients with risk factors associated with troponin dynamic changes (e.g., advanced age, pre-existing heart disease, higher NIHSS score, and troponin elevation on admission).
Niwaki Instead of Random Forests: Targeted Serial Sectioning Scanning Electron Microscopy With Reimaging Capabilities for Exploring Central Nervous System Cell Biology and Pathology
Authors: Schifferer Martina , Snaidero Nicolas , Djannatian Minou , Kerschensteiner Martin , Misgeld Thomas
Published: October 2021

Ultrastructural analysis of discrete neurobiological structures by volume scanning electron microscopy (SEM) often constitutes a “needle-in-the-haystack” problem and therefore relies on sophisticated search strategies. The appropriate SEM approach for a given relocation task not only depends on the desired final image quality but also on the complexity and required accuracy of the screening process. Block-face SEM techniques like Focused Ion Beam or serial block-face SEM are “one-shot” imaging runs by nature and, thus, require precise relocation prior to acquisition. In contrast, “multi-shot” approaches conserve the sectioned tissue through the collection of serial sections onto solid support and allow reimaging. These tissue libraries generated by Array Tomography or Automated Tape Collecting Ultramicrotomy can be screened at low resolution to target high resolution SEM. This is particularly useful if a structure of interest is rare or has been predetermined by correlated light microscopy, which can assign molecular, dynamic and functional information to an ultrastructure. As such approaches require bridging mm to nm scales, they rely on tissue trimming at different stages of sample processing. Relocation is facilitated by endogenous or exogenous landmarks that are visible by several imaging modalities, combined with appropriate registration strategies that allow overlaying images of various sources. Here, we discuss the opportunities of using multi-shot serial sectioning SEM approaches, as well as suitable trimming and registration techniques, to slim down the high-resolution imaging volume to the actual structure of interest and hence facilitate ambitious targeted volume SEM projects.
The Expression Patterns of Cytochrome Oxidase and Immediate-Early Genes Show Absence of Ocular Dominance Columns in the Striate Cortex of Squirrel Monkeys Following Monocular Inactivation
Authors: Li Shuiyu , Yao Songping , Zhou Qiuying , Takahata Toru
Published: October 2021

Because at least some squirrel monkeys lack ocular dominance columns (ODCs) in the striate cortex (V1) that are detectable by cytochrome oxidase (CO) histochemistry, the functional importance of ODCs on stereoscopic 3-D vision has been questioned. However, conventional CO histochemistry or trans-synaptic tracer study has limited capacity to reveal cortical functional architecture, whereas the expression of immediate-early genes (IEGs), c-FOS and ZIF268, is more directly responsive to neuronal activity of cortical neurons to demonstrate ocular dominance (OD)-related domains in V1 following monocular inactivation. Thus, we wondered whether IEG expression would reveal ODCs in the squirrel monkey V1. In this study, we first examined CO histochemistry in V1 of five squirrel monkeys that were subjected to monocular enucleation or tetrodotoxin (TTX) treatment to address whether there is substantial cross-individual variation as reported previously. Then, we examined the IEG expression of the same V1 tissue to address whether OD-related domains are revealed. As a result, staining patterns of CO histochemistry were relatively homogeneous throughout layer 4 of V1. IEG expression was also moderate and homogeneous throughout layer 4 of V1 in all cases. On the other hand, the IEG expression was patchy in accordance with CO blobs outside layer 4, particularly in infragranular layers, although they may not directly represent OD clusters. Squirrel monkeys remain an exceptional species among anthropoid primates with regard to OD organization, and thus are potentially good subjects to study the development and function of ODCs.
Neuronal NMNAT2 Overexpression Does Not Achieve Significant Neuroprotection in Experimental Autoimmune Encephalomyelitis/Optic Neuritis
Authors: Liu Pingting , Huang Haoliang , Fang Fang , Liu Liang , Li Liang , Feng Xue , Chen Wei , Dalal Roopa , Sun Yang , Hu Yang
Published: October 2021

Optic neuritis, inflammation, and demyelination of the optic nerve (ON), is one of the most common clinical manifestations of multiple sclerosis; affected patients suffer persistent visual symptoms due to ON degeneration and secondary retinal ganglion cell (RGC) death. The mouse experimental autoimmune encephalomyelitis (EAE) model replicates optic neuritis and significant RGC soma and axon loss. Nicotinamide mononucleotide adenylyltransferases (NMNATs) are NAD+-synthetic enzymes that have been shown to be essential for axon integrity, activation of which significantly delays axonal Wallerian degeneration. NMNAT2, which is enriched in axons, has been proposed as a promising therapeutic target for axon injury-induced neurodegeneration. We therefore investigated whether activation of NMNAT2 can be used as a gene therapy strategy for neuroprotection in EAE/optic neuritis. To avoid the confounding effects in inflammatory cells, which play important roles in EAE initiation and progression, we used an RGC-specific promoter to drive the expression of the long half-life NMNAT2 mutant in mouse RGCs in vivo. However, optical coherence tomography in vivo retina imaging did not reveal significant protection of the ganglion cell complex, and visual function assays, pattern electroretinography, and optokinetic response also showed no improvement in mice with NMNAT2 overexpression. Postmortem histological analysis of retina wholemounts and semithin sections of ON confirmed the in vivo results: NMNAT2 activation in RGCs does not provide significant neuroprotection of RGCs in EAE/optic neuritis. Our studies suggest that a different degenerative mechanism than Wallerian degeneration is involved in autoimmune inflammatory axonopathy and that NMNAT2 may not be a major contributor to this mechanism.
The Effect of the APOE-ε4 Allele on the Cholinergic Circuitry for Subjects With Different Levels of Cognitive Impairment
Authors: Lai Ying-Liang Larry , Chen Kuan , Lee Tzu-Wei , Tso Chao-Wei , Lin Hui-Hsien , Kuo Li-Wei , Chen Cheng-Yu , Liu Hua-Shan
Published: October 2021

Background: Cholinergic deficiency has been suggested to associate with the abnormal accumulation of Aβ and tau for patients with Alzheimer's disease (AD). However, no studies have investigated the effect of APOE-ε4 and group differences in modulating the cholinergic basal forebrain–amygdala network for subjects with different levels of cognitive impairment. We evaluated the effect of APOE-ε4 on the cholinergic structural association and the neurocognitive performance for subjects with different levels of cognitive impairment.

Methods: We used the structural brain magnetic resonance imaging scans from the Alzheimer's Disease Neuroimaging Initiative dataset. The study included cognitively normal (CN, n = 167) subjects and subjects with significant memory concern (SMC, n = 96), early mild cognitive impairment (EMCI, n = 146), late cognitive impairment (LMCI, n = 138), and AD (n = 121). Subjects were further categorized according to the APOE-ε4 allele carrier status. The main effects of APOE-ε4 and group difference on the brain volumetric measurements were assessed. Regression analyses were conducted to evaluate the associations among cholinergic structural changes, APOE-ε4 status, and cognitive performance.

Results: We found that APOE-ε4 carriers in the disease group showed higher brain atrophy than non-carriers in the cholinergic pathway, while there is no difference between carriers and non-carriers in the CN group. APOE-ε4 allele carriers in the disease groups also exhibited a stronger cholinergic structural correlation than non-carriers did, while there is no difference between the carriers and non-carriers in the CN subjects. Disease subjects exhibited a stronger structural correlation in the cholinergic pathway than CN subjects did. Moreover, APOE-ε4 allele carriers in the disease group exhibited a stronger correlation between the volumetric changes and cognitive performance than non-carriers did, while there is no difference between carriers and non-carriers in CN subjects. Disease subjects exhibited a stronger correlation between the volumetric changes and cognitive performance than CN subjects did.

Conclusion: Our results confirmed the effect of APOE-ε4 on and group differences in the associations with the cholinergic structural changes that may reflect impaired brain function underlying neurocognitive degeneration in AD.
Amide Proton Transfer-Weighted MRI Might Help Distinguish Amnestic Mild Cognitive Impairment From a Normal Elderly Population
Authors: Guo Zixuan , Jiang Yanchun , Qin Xiaoyan , Mu Ronghua , Meng Zhuoni , Zhuang Zeyu , Liu Fuzhen , Zhu Xiqi
Published: October 2021

Objectives: To evaluate whether 3D amide proton transfer weighted (APTw) imaging based on magnetization transfer analysis can be used as a novel imaging marker to distinguish amnestic mild cognitive impairment (aMCI) patients from the normal elderly population by measuring changes in APTw signal intensity in the hippocampus and amygdala.

Materials and Methods: Seventy patients with aMCI and 74 age- and sex-matched healthy volunteers were recruited for routine MRI and APT imaging examinations. Magnetic transfer ratio asymmetry (MTRasym) of the amide protons (at 3.5 ppm), or APTw values, were measured in the bilateral hippocampus and amygdala on three consecutive cross-sectional APT images and were compared between the aMCI and control groups. The independent sample t-test was used to evaluate the difference in APTw values of the bilateral hippocampus and amygdala between the aMCI and control groups. Receiver operator characteristic analysis was used to assess the diagnostic performance of the APTw. The paired t-test was used to assess the difference in APTw values between the left and right hippocampus and amygdala, in both the aMCI and control groups.

Results: The APTw values of the bilateral hippocampus and amygdala in the aMCI group were significantly higher than those in the control group (left hippocampus 1.01 vs. 0.77% p < 0.001; right hippocampus 1.02 vs. 0.74%, p < 0.001; left amygdala 0.98 vs. 0.70% p < 0.001; right amygdala 0.94 vs. 0.71%, p < 0.001). The APTw values of the left amygdala had the largest AUC (0.875) at diagnosis of aMCI. There was no significant difference in APTw values between the left and right hippocampus and amygdala, in either group. (aMCI group left hippocampus 1.01 vs. right hippocampus 1.02%, p = 0.652; healthy control group left hippocampus 0.77 vs. right hippocampus 0.74%, p = 0.314; aMCI group left amygdala 0.98 vs. right amygdala 0.94%, p = 0.171; healthy control group left amygdala 0.70 vs. right amygdala 0.71%, p = 0.726).

Conclusion: APTw can be used as a new imaging marker to distinguish aMCI patients from the normal elderly population by indirectly reflecting the changes in protein content in the hippocampus and amygdala.
Contributions of Sex Chromosomes and Gonadal Hormones to the Male Bias in a Maternal Antibody-Induced Model of Autism Spectrum Disorder
Authors: Gata-Garcia Adriana , Porat Amit , Brimberg Lior , Volpe Bruce T. , Huerta Patricio T. , Diamond Betty
Published: October 2021

Autism Spectrum Disorder (ASD) is a group of neurodevelopmental conditions that is four times more commonly diagnosed in males than females. While susceptibility genes located in the sex chromosomes have been identified in ASD, it is unclear whether they are sufficient to explain the male bias or whether gonadal hormones also play a key role. We evaluated the sex chromosomal and hormonal influences on the male bias in a murine model of ASD, in which mice are exposed in utero to a maternal antibody reactive to contactin-associated protein-like 2 (Caspr2), which was originally cloned from a mother of a child with ASD (termed C6 mice henceforth). In this model, only male mice are affected. We used the four-core-genotypes (FCG) model in which the Sry gene is deleted from the Y chromosome (Y−) and inserted into autosome 3 (TgSry). Thus, by combining the C6 and FCG models, we were able to differentiate the contributions of sex chromosomes and gonadal hormones to the development of fetal brain and adult behavioral phenotypes. We show that the presence of the Y chromosome, or lack of two X chromosomes, irrespective of gonadal sex, increased the susceptibility to C6-induced phenotypes including the abnormal growth of the developing fetal cerebral cortex, as well as a behavioral pattern of decreased open-field exploration in adult mice. Our results indicate that sex chromosomes are the main determinant of the male bias in the maternal C6-induced model of ASD. The less dominant hormonal effect may be due to modulation by sex chromosome genes of factors involved in gonadal hormone pathways in the brain.
Measurement and Analysis of Human Infant Crawling for Rehabilitation: A Narrative Review
Authors: Xiong Qi L. , Wu Xiao Y. , Liu Yuan , Zhang Cong X. , Hou Wen S.
Published: October 2021

When a child shows signs of potential motor developmental disorders, early diagnosis of central nervous system (CNS) impairment is beneficial. Known as the first CNS-controlled mobility for most of infants, mobility during crawling usually has been used in clinical assessments to identify motor development disorders. The current clinical scales of motor development during crawling stage are relatively subjective. Objective and quantitative measures of infant crawling afford the possibilities to identify those infants who might benefit from early intervention, as well as the evaluation of intervention progress. Thus, increasing researchers have explored objective measurements of infant crawling in typical and atypical developing infants. However, there is a lack of comprehensive review on infant-crawling measurement and analysis toward bridging the gap between research crawling analysis and potential clinical applications. In this narrative review, we provide a practical overview of the most relevant measurements in human infant crawling, including acquisition techniques, data processing methods, features extraction, and the potential value in objective assessment of motor function in infancy; meanwhile, the possibilities to develop crawling training as early intervention to promote the locomotor function for infants with locomotor delays are also discussed.
Disruption in Surface-Based Functional Connectivity in the Right Posterior Hippocampal CA3 Subfield: A Probable Neural Basis of Visuospatial Working Memory Impairment in Patients With Right Temporal Lobe Epilepsy
Authors: Lv Zongxia , Chen Zirong , Ye Wei , Pang Xiaomin , Nie Liluo , Chang Weiwei , Long Qijia , Zheng Jinou
Published: October 2021

Visuospatial working memory (VSWM) impairment is common in patients with right temporal lobe epilepsy (rTLE). The posterior hippocampus is critical for spatial memory, but the contributions of the different subfields to VSWM deficits remain unclear. Forty-six rTLE patients and 42 healthy controls (HCs) were recruited. Resting-state fMRI (rsfMRI) and structural MRI scans were administered, followed by a VSWM_Nback test. The right posterior hippocampus was automatically segmented, and the surface-based functional connectivity (SBFC) of the subiculum (Sub), CA1, CA3, dentate gyrus (DG), hippocampal tail, and right entorhinal cortex (EC) were compared between groups. Correlation analysis was performed between the altered SBFC and VSWM_Nback scores for rTLE patients. The results showed that rTLE patients underperformed in the VSWM_Nback test, with longer mean reaction time of accurate response (ACCmeanRT) in 0back and 2back condition, lower hit rate (HR) and higher false alarm rate (FAR) in 2back condition. Compared with HCs, the rCA3 in the rTLE group exhibited decreased SBFC with inferior parietal cortex (IPC), temporal lateral cortex (TLC), and posterior visual cortex (PVC) in the right hemisphere as well as the bilateral dorsolateral prefrontal cortex (DLPFC). The SBFC of the rEC and right anterior cingulate cortex (rACC) increased in the rTLE group. Within the rTLE group, the decreased SBFC of the rCA3-rIPC and rCA3-rLTC were correlated with worse VSWM performance. Therefore, the decreased SBFC of the rCA3-rIPC and rCA3-rLTC might be the critical aberrant FC pattern reflecting VSWM impairment in rTLE patients. The mechanism might involve functional disruption between the core subsystem and the medial temporal subsystem of the default mode network (DMN).
Increased Systemic Immune-Inflammation Index Is Associated With Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage Patients
Authors: Chen Liuwei , Pandey Sajan , Shen Rui , Xu Yi , Zhang Quanbin
Published: October 2021

Background:Systemic immune-inflammation index (SII) is a novel biomarker that reflects the state of a patient's inflammatory and immune status. This study aimed to determine the clinical significance of SII as a predictor of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (SAH).

Methods:Retrospective data were collected from aneurysmal SAH patients who had been admitted to our hospital between January 2015 and October 2019. Both univariate and multivariate analyses were performed to investigate whether SII was an independent predictor of DCI. In addition, the receiver operating characteristic (ROC) curve and area under the curve (AUC) were also evaluated.

Results:There were 333 patients with aneurysmal SAH included in this study. Multivariate logistic analysis revealed that a modified Fisher grade 3 and 4 score [odds ratio (OR) = 7.851, 95% confidence interval (CI): 2.312–26.661,P= 0.001] and elevated SII (OR = 1.001, 95% CI: 1.001–1.002,P< 0.001) were independent risk factors for DCI. ROC curves showed that SII could predict DCI with an AUC of 0.860 (95% CI: 0.818–0.896,P< 0.001). The optimal cut-off value for SII to predict DCI was 1,424, and an SII ≥ 1,424 could predict DCI with a sensitivity of 93.1% and a specificity of 68.1%. Patients with higher SII value on admission tended to have higher incidence of acute hydrocephalus and DCI, greater modified Fisher and Hunt-Hess scales, and poorer outcomes.

Conclusions:SII is an independent predictor of DCI in patients with aneurysmal SAH. The SII system can be implemented in a routine clinical setting to help clinicians diagnose patients with high risk of DCI.
A Single Low Dose of Dexmedetomidine Efficiently Attenuates Esketamine-Induced Overactive Behaviors and Neuronal Hyperactivities in Mice
Authors: Chu Qinjun , Zhu Kuicheng , Bai Yafan , Shang Huijie , Zhang Dongqing , Zhao Mingming , Zheng Ping , Jin Xiaogao
Published: October 2021

Introduction: Esketamine (Esk) (S(+)-ketamine) is now used as an alternative to its racemic mixture, i. e., ketamine in anesthesia. Esk demonstrated more powerful potency and rapid recovery in anesthesia and less psychotomimetic side effects comparing with ketamine, but Esk could still induce psychological side effects in patients. This study was to investigate whether dexmedetomidine (Dex) can attenuate the Esk-induced neuronal hyperactivities in Kunming mice.

Methods: Dexmedetomidine 0.25, 0.5, and 1 mg/kg accompanied with Esk 50 mg/kg were administrated on Kunming mice to assess the anesthesia quality for 1 h. The indicators, such as time to action, duration of agitation, duration of ataxia, duration of loss pedal withdrawal reaction (PWR), duration of catalepsy, duration of righting reflex (RR) loss, duration of sedation, were recorded for 1 h after intraperitoneal administration. The c-Fos expression in the brain was detected by immunohistochemistry and Western Blot after 1 h of administration. Considering the length of recovery time for more than 1 h in Dex and Dex with Esk groups, other mice were repeatedly used to evaluate recovery time from the administration to emerge from anesthesia.

Results: Dexmedetomidine dose-dependently increased recovery time when administrated with Esk or alone. Dex combined with Esk efficiently attenuated the duration of agitation, ataxia, and catalepsy. Dex synergically improved the anesthesia of Esk by increasing the duration of sedation, loss of RR, and loss of PWR. Esk induced the high expression of c-Fos in the cerebral cortex, hippocampus, thalamus, amygdala, hypothalamus, and cerebellum 1 h after administration. Western Blot results indicated that Dex at doses of 0.25, 0.5, and 1 mg/kg could significantly alleviate the Esk-induced c-Fos expression in the mice brain.

Conclusion: Dexmedetomidine ranged from 0.25 to 1 mg/kg could improve the anesthesia quality and decreased the neuronal hyperactivities and the overactive behaviors when combined with Esk. However, Dex dose-dependently increased the recovery time from anesthesia. It demonstrated that a small dose of Dex 0.25 mg/kg could be sufficient to attenuate Esk-induced psychotomimetic side effects without extension of recovery time in Kunming mice.
A Method to Experimentally Estimate the Conductivity of Chronic Stroke Lesions: A Tool to Individualize Transcranial Electric Stimulation
Authors: van der Cruijsen Joris , Piastra Maria Carla , Selles Ruud W. , Oostendorp Thom F.
Published: October 2021

The inconsistent response to transcranial electric stimulation in the stroke population is attributed to, among other factors, unknown effects of stroke lesion conductivity on stimulation strength at the targeted brain areas. Volume conduction models are promising tools to determine optimal stimulation settings. However, stroke lesion conductivity is often not considered in these models as a source of inter-subject variability. The goal of this study is to propose a method that combines MRI, EEG, and transcranial stimulation to estimate the conductivity of cortical stroke lesions experimentally. In this simulation study, lesion conductivity was estimated from scalp potentials during transcranial electric stimulation in 12 chronic stroke patients. To do so, first, we determined the stimulation configuration where scalp potentials are maximally affected by the lesion. Then, we calculated scalp potentials in a model with a fixed lesion conductivity and a model with a randomly assigned conductivity. To estimate the lesion conductivity, we minimized the error between the two models by varying the conductivity in the second model. Finally, to reflect realistic experimental conditions, we test the effect rotation of measurement electrode orientation and the effect of the number of electrodes used. We found that the algorithm converged to the correct lesion conductivity value when noise on the electrode positions was absent for all lesions. Conductivity estimation error was below 5% with realistic electrode coregistration errors of 0.1° for lesions larger than 50 ml. Higher lesion conductivities and lesion volumes were associated with smaller estimation errors. In conclusion, this method can experimentally estimate stroke lesion conductivity, improving the accuracy of volume conductor models of stroke patients and potentially leading to more effective transcranial electric stimulation configurations for this population.
Response of the Cerebral Cortex to Resistance and Non-resistance Exercise Under Different Trajectories: A Functional Near-Infrared Spectroscopy Study
Authors: Shi Ping , Li Anan , Yu Hongliu
Published: October 2021

Background: At present, the effects of upper limb movement are generally evaluated from the level of motor performance. The purpose of this study is to evaluate the response of the cerebral cortex to different upper limb movement patterns from the perspective of neurophysiology.

Method: Thirty healthy adults (12 females, 18 males, mean age 23.9 ± 0.9 years) took resistance and non-resistance exercises under four trajectories (T1: left and right straight-line movement; T2: front and back straight-line movement; T3: clockwise and anticlockwise drawing circle movement; and T4: clockwise and anticlockwise character ⁕ movement). Each movement included a set of periodic motions composed of a 30-s task and a 30-s rest. Functional near-infrared spectroscopy (fNIRS) was used to measure cerebral blood flow dynamics. Primary somatosensory cortex (S1), supplementary motor area (SMA), pre-motor area (PMA), primary motor cortex (M1), and dorsolateral prefrontal cortex (DLPFC) were chosen as regions of interests (ROIs). Activation maps and symmetric heat maps were applied to assess the response of the cerebral cortex to different motion patterns.

Result: The activation of the brain cortex was significantly increased during resistance movement for each participant. Specifically, S1, SMA, PMA, and M1 had higher participation during both non-resistance movement and resistance movement. Compared to non-resistance movement, the resistance movement caused an obvious response in the cerebral cortex. The task state and the resting state were distinguished more obviously in the resistance movement. Four trajectories can be distinguished under non-resistance movement.

Conclusion: This study confirmed that the response of the cerebral motor cortex to different motion patterns was different from that of the neurophysiological level. It may provide a reference for the evaluation of resistance training effects in the future.
Oxytocin as an Anti-obesity Treatment
Authors: Niu JingJing , Tong Jenny , Blevins James E.
Published: October 2021

Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality. However, current weight loss therapies are often associated with psychiatric or cardiovascular side effects or poor tolerability that limit their long-term use. The hypothalamic neuropeptide, oxytocin (OT), mediates a wide range of physiologic actions, which include reproductive behavior, formation of prosocial behaviors and control of body weight. We and others have shown that OT circumvents leptin resistance and elicits weight loss in diet-induced obese rodents and non-human primates by reducing both food intake and increasing energy expenditure (EE). Chronic intranasal OT also elicits promising effects on weight loss in obese humans. This review evaluates the potential use of OT as a therapeutic strategy to treat obesity in rodents, non-human primates, and humans, and identifies potential mechanisms that mediate this effect.
Gut and Brain: Investigating Physiological and Pathological Interactions Between Microbiota and Brain to Gain New Therapeutic Avenues for Brain Diseases
Authors: Deidda Gabriele , Biazzo Manuele
Published: October 2021

Brain physiological functions or pathological dysfunctions do surely depend on the activity of both neuronal and non-neuronal populations. Nevertheless, over the last decades, compelling and fast accumulating evidence showed that the brain is not alone. Indeed, the so-called “gut brain,” composed of the microbial populations living in the gut, forms a symbiotic superorganism weighing as the human brain and strongly communicating with the latterviathe gut–brain axis. The gut brain does exert a control on brain (dys)functions and it will eventually become a promising valuable therapeutic target for a number of brain pathologies. In the present review, we will first describe the role of gut microbiota in normal brain physiology from neurodevelopment till adulthood, and thereafter we will discuss evidence from the literature showing how gut microbiota alterations are a signature in a number of brain pathologies ranging from neurodevelopmental to neurodegenerative disorders, and how pre/probiotic supplement interventions aimed to correct the altered dysbiosis in pathological conditions may represent a valuable future therapeutic strategy.
Retinal Oxygen Metabolism and Haemodynamics in Patients With Multiple Sclerosis and History of Optic Neuritis
Authors: Kallab Martin , Hommer Nikolaus , Schlatter Andreas , Bsteh Gabriel , Altmann Patrick , Popa-Cherecheanu Alina , Pfister Martin , Werkmeister René M. , Schmidl Doreen , Schmetterer Leopold , Garhöfer Gerhard
Published: October 2021

Vascular changes and alterations of oxygen metabolism are suggested to be implicated in multiple sclerosis (MS) pathogenesis and progression. Recently developed in vivo retinal fundus imaging technologies provide now an opportunity to non-invasively assess metabolic changes in the neural retina. This study was performed to assess retinal oxygen metabolism, peripapillary capillary density (CD), large vessel density (LVD), retinal nerve fiber layer thickness (RNFLT) and ganglion cell inner plexiform layer thickness (GCIPLT) in patients with diagnosed relapsing multiple sclerosis (RMS) and history of unilateral optic neuritis (ON). 16 RMS patients and 18 healthy controls (HC) were included in this study. Retinal oxygen extraction was modeled using O2 saturations and Doppler optical coherence tomography (DOCT) derived retinal blood flow (RBF) data. CD and LVD were assessed using optical coherence tomography (OCT) angiography. RNFLT and GCIPLT were measured using structural OCT. Measurements were performed in eyes with (MS+ON) and without (MS-ON) history for ON in RMS patients and in one eye in HC. Total oxygen extraction was lowest in MS+ON (1.8 ± 0.2 μl O2/min), higher in MS-ON (2.1 ± 0.5 μl O2/min, p = 0.019 vs. MS+ON) and highest in HC eyes (2.3 ± 0.6 μl O2/min, p = 0.002 vs. MS, ANOVA p = 0.031). RBF was lower in MS+ON (33.2 ± 6.0 μl/min) compared to MS-ON (38.3 ± 4.6 μl/min, p = 0.005 vs. MS+ON) and HC eyes (37.2 ± 4.7 μl/min, p = 0.014 vs. MS+ON, ANOVA p = 0.010). CD, LVD, RNFLT and GCIPL were significantly lower in MS+ON eyes. The present data suggest that structural alterations in the retina of RMS patients are accompanied by changes in oxygen metabolism, which are more pronounced in MS+ON than in MS-ON eyes. Whether these alterations promote MS onset and progression or occur as consequence of disease warrants further investigation.

Clinical Trial Registration:ClinicalTrials.gov registry, NCT03401879.
Screening for Psychiatric Comorbidities and Psychotherapeutic Assessment in Inpatient Epilepsy Care: Preliminary Results of an Implementation Study
Authors: Michaelis Rosa , Schlömer Sabine , Lindemann Anja , Behrens Vanessa , Grönheit Wenke , Pertz Milena , Rammé Stephanie , Seidel Sabine , Wehner Tim , Wellmer Jörg , Schlegel Uwe , Popkirov Stoyan
Published: October 2021

Background:Anxiety and depression remain underdiagnosed in routine clinical practice in up to two thirds of epilepsy patients despite significant impact on medical and psychosocial outcome. Barriers to adequate mental health care for epilepsy and/or psychogenic non-epileptic seizures (PNES) include a lack of integrated mental health specialists and standardized procedures. This naturalistic study outlines the procedures and outcome of a recently established psychotherapeutic service.

Methods:Routine screening included the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E, cut-off value > 13) and Generalized Anxiety Disorder scale (GAD-7, cut-off value > 5). Positively (above cut-off in at least one questionnaire) screened patients were seen for a standardized interview for mental health disorders and the development of a personalized treatment plan. PNES patients were seen irrespective of their screening score. Resources were provided to support self-help and access to psychotherapy. Patients were contacted 1 month after discharge to evaluate adherence to therapeutic recommendations.

Results:120 patients were screened. Overall, 56 of 77 positively screened patients (77%) were found to have a psychiatric diagnosis through standardized interview. More epilepsy patients with an anxiety disorder had previously been undiagnosed compared to those with a depressive episode (63% vs. 30%); 24 epilepsy patients (62%) with a psychiatric comorbidity and 10 PNES patients (59%) were not receiving any mental health care. At follow-up, 16/17 (94%) epilepsy patients and 7/7 PNES patients without prior psychiatric treatment were adhering to therapeutic recommendations.

Conclusion:Integrating mental health specialists and establishing standardized screening and follow-up procedures improve adherence to mental health care recommendations in epilepsy and PNES patients.
Serotonergic Psychedelics in Neural Plasticity
Authors: Lukasiewicz Kacper , Baker Jacob J. , Zuo Yi , Lu Ju
Published: October 2021

Psychedelics, compounds that can induce dramatic changes in conscious experience, have been used by humans for centuries. Recent studies have shown that certain psychedelics can induce neural plasticity by promoting neurite growth and synapse formation. In this review, we focus on the role of classical serotonergic psychedelics in neural plasticity and discuss its implication for their therapeutic potentials.
Interest of Coffee Melanoidins as Sustainable Healthier Food Ingredients
Authors: Iriondo-DeHond Amaia , Rodríguez Casas Alejandra , del Castillo Maria Dolores
Published: October 2021

Coffee melanoidins are generated by the Maillard reaction during the thermal processes occurring in the journey of coffee from the plant to the cup (during drying and roasting). Melanoidins, the brown pigments formed as the end products of this reaction, have been reported in cascara, silverskin, spent coffee grounds, and coffee brew. The latter is one of the main natural sources of melanoidins of the daily diet worldwide. However, their presence in coffee by-products has been recently described. These complex macromolecules possess multiple health-promoting properties, such as antioxidant, anti-inflammatory, dietary fiber effect, and prebiotic capacity, which make them very interesting from a nutritional point of view. In addition, they have a great impact on the sensory profile of foods and their acceptance by the consumers. The present study is a descriptive, narrative, mini-review about the nature, structure, digestibility, properties (sensory, nutritional, and health-promoting), safety and regulatory status of melanoidins from the coffee brew and its by-products with a special emphasis on the latter.