bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the Colonization of Environmental Microbes in the Fish Gut: A Case Study of Wild Fish Populations in the Yangtze River
Authors: Yang Haile , Wu Jinming , Du Hao , Zhang Hui , Li Junyi , Wei Qiwei
Published: February 2022

In aquatic animals, gut microbial communities shift with host development and living environments. Understanding the mechanism by which the environment impacts the gut microbial communities of aquatic animals is crucial for assessing and managing aquatic ecosystem health. Here, we proposed a simplified framework for the colonization and dynamics of gut microbial communities. Then, to quantify the colonization of environmental microbes in the wild fish gut, the current study used 16S rRNA gene amplicon sequencing to obtain the structure of the water environmental microbial community and the gut microbial community in 10 wild fish populations (Leiocassis crassilabris, Leiocassis longirostris, Pelteobagrus vachelli, Silurus asotus, Siniperca chuatsi, Coilia brachygnathus, Aristichthys nobilis, Hypophthalmichthys molitrix, Coreius heterodon, and Xenocypris argentea) from the Wuhan section of the Yangtze River, and the relationship of these microbial communities was analyzed. The results identified that in most individuals, approximately 80% of gut microbes [at the operational taxonomic unit (OTU) level] were shared with the water environmental microbial community (except for individuals of Siniperca chuatsi and Coilia brachygnathus, approximately 74%). In approximately 80% of individuals, more than 95% of microbial species (OTUs) in the gut were transient. For fish species, more than 99% of microbial species (OTUs) that were introduced into the gut were transient. Nearly 79% of OTUs and 89% of species of water environmental microbes could be introduced into the fish gut. Driven by the introduction of transient microbes, fishes with similar feeding habits had similar gut microbial communities. The results indicated that for adult wild fishes, most gut microbiota were transient from the environmental microbiota that were related to fish feeding habits. We therefore encourage future research to focus on environmental microbiota monitoring and management to promote the better conservation of aquatic animals. It was important to note that, because of various influence factors, interspecific differences and individual variations on gut microbial community characteristics, the quantification of gut microbes in the current work was approximate rather than accurate. We hope that more comparable research could be conducted to outline the quantitative characteristics of the relationship between gut microbial community and aquatic environment microbial community as soon as possible.
Isolation of a Highly Thermostable Bile Salt Hydrolase With Broad Substrate Specificity From Lactobacillus paragasseri
Authors: Kusada Hiroyuki , Arita Masanori , Tohno Masanori , Tamaki Hideyuki
Published: February 2022

Bile salt hydrolase (BSH) enzymes produced by intestinal Lactobacillus species have been recognized as major targets for probiotic studies owing to their weight-loss and cholesterol-lowering effects. In this study, we isolated a highly thermostable BSH with broad substrate specificity, designed as LapBSH (BSH from a probiotic bacterium, Lactobacillus paragasseri JCM 5343T). The recombinant LapBSH protein clearly hydrolyzed 12 different substrates, including primary/secondary, major/minor, and taurine/glycine-conjugated bile salts in mammalian digestive tracts. Intriguingly, LapBSH further displayed a highly thermostable ability among all characterized BSH enzymes. Indeed, this enzyme retained above 80% of its optimum BSH activity even after 6 h of incubation at 50–90°C. LapBSH also exerted a functionally stable activity and maintained above 85% of its original activity after pre-heating at 85°C for 2 h. Therefore, LapBSH is a very unique probiotic enzyme with broad substrate specificity and high thermostability. The strain itself, JCM 5343T, was also found to exhibit high heat-resistance ability and could form colonies even after exposure to 85°C for 2 h. As thermostable enzyme/bacterium offers industrial and biotechnological advantages in terms of its productivity and stability improvements, both thermostable LapBSH and thermotolerant L. paragasseri JCM 5343T could be promising candidates for future probiotic research.
A Comprehensive Analysis of the Lysine Acetylome in the Aquatic Animals Pathogenic Bacterium Vibrio mimicus
Authors: Wang Junlin , Pang Huanying , Yin Linlin , Zeng Fuyuan , Wang Na , Hoare Rowena , Monaghan Sean J. , Li Wanxin , Jian Jichang
Published: February 2022

Protein lysine acetylation is an evolutionarily conserved post-translational modification (PTM), which is dynamic and reversible, playing a crucial regulatory role in almost every aspect of metabolism, of both eukaryotes and prokaryotes. Several global lysine acetylome studies have been carried out in various bacteria, but thus far, there have been no reports of lysine acetylation for the commercially important aquatic animal pathogen Vibrio mimicus. In the present study, we used anti-Ac-K antibody beads to highly sensitive immune-affinity purification and combined high-resolution LC-MS/MS to perform the first global lysine acetylome analysis in V. mimicus, leading to the identification of 1,097 lysine-acetylated sites on 582 proteins, and more than half (58.4%) of the acetylated proteins had only one site. The analysis of acetylated modified peptide motifs revealed six significantly enriched motifs, namely, KacL, KacR, L(-2) KacL, LKacK, L(-7) EKac, and IEKac. In addition, bioinformatic assessments state clearly that acetylated proteins have a hand in many important biological processes in V. mimicus, such as purine metabolism, ribosome, pyruvate metabolism, glycolysis/gluconeogenesis, the TCA cycle, and so on. Moreover, 13 acetylated proteins were related to the virulence of V. mimicus. To sum up, this is a comprehensive analysis whole situation protein lysine acetylome in V. mimicus and provides an important foundation for in-depth study of the biological function of lysine acetylation in V. mimicus.
Bacillus toyonensis SAU-19 and SAU-20 Isolated From Ageratina adenophora Alleviates the Intestinal Structure and Integrity Damage Associated With Gut Dysbiosis in Mice Fed High Fat Diet
Authors: Okyere Samuel Kumi , Wen Juan , Cui Yujing , Xie Lei , Gao Pei , Zhang Ming , Wang Jianchen , Wang Shu , Ran Yinan , Ren Zhihua , Hu Yanchun
Published: February 2022

This study was performed to identify potential probiotic endophytes from Ageratina adenophora and evaluate their ameliorating effects on gut injury and integrity damage associated with microbiota dysbiosis in mice fed high fat diet. Using morphological and biochemical tests, and 16S rRNA gene sequencing technique, two bacteria endophytes were identified as strains of Bacillus toyonensis and were named Bacillus toyonensis SAU-19 (GenBank No. MW287198) and Bacillus toyonensis SAU-20 (GenBank No. MW287199). Sixty (60) mice were divided into five groups, group 1 was the negative control fed normal diet (NS), group 2 was fed High fat diet (HF), Group 3 was fed High fat diet + 106Lactobacillus rhamnosus (LGG), group 4 was fed High fat + 106Bacillus toyonensis SAU-19 and group 5 fed High fat diet + 106Bacillus toyonensis SAU-20. After 35 days, histological and immunohistochemistry examination were performed in the ileum tissues. Furthermore, DAO and antioxidants activities were measured in serum, mRNA expressions of tight junction proteins (occludin and ZO-1) and inflammation related cytokines (IL-1β, TFN-α, IL-2, IL-4, and IL-10) in the ileum tissues as well as sIgA levels and total bacteria (Escherichia coli, Salmonella, Staphylococcus, and Lactobacillus) in the small intestine and cecum content. The results showed an increase in the DAO activity, oxidative stress parameter (MDA), pro-inflammation cytokines (IL-1β, TFN-α, IL-2), reduce immunity (sIgA), and destroyed intestinal structure and integrity (reduce tight junction proteins) in the high fat diet group and this was associated with destruction of the gut microbiota composition (increasing pathogenic bacteria; E. coli, Salmonella, Staphylococcus and reducing beneficial bacteria, Lactobacillus spp.) in mice (P < 0.05). However, the administration of Bacillus toyonensis SAU-19 and SAU-20 reverted these effects. Our findings indicated that, Bacillus toyonensis SAU-19 and SAU-20 isolated from A. adenophora could prevent the excess weight gain from high fat diet feeding, improved antioxidant status and alleviated the intestine integrity damage as well as reduce the population of enteric bacteria such as E. coli, Salmonella, and S. aureus and increasing the population of beneficial bacteria such as Lactobacillus in the gut of mice fed high fat diet, therefore, can serve as a potential probiotics in humans and animals.
Recent Advances in the Siderophore Biology of Shewanella
Authors: Liu Lulu , Wang Wei , Wu Shihua , Gao Haichun
Published: February 2022

Despite the abundance of iron in nature, iron acquisition is a challenge for life in general because the element mostly exists in the extremely insoluble ferric (Fe3+) form in oxic environments. To overcome this, microbes have evolved multiple iron uptake strategies, a common one of which is through the secretion of siderophores, which are iron-chelating metabolites generated endogenously. Siderophore-mediated iron transport, a standby when default iron transport routes are abolished under iron rich conditions, is essential under iron starvation conditions. While there has been a wealth of knowledge about the molecular basis of siderophore synthesis, uptake and regulation in model bacteria, we still know surprisingly little about siderophore biology in diverse environmental microbes. Shewanella represent a group of γ-proteobacteria capable of respiring a variety of organic and inorganic substrates, including iron ores. This respiratory process relies on a large number of iron proteins, c-type cytochromes in particular. Thus, iron plays an essential and special role in physiology of Shewanella. In addition, these bacteria use a single siderophore biosynthetic system to produce an array of macrocyclic dihydroxamate siderophores, some of which show particular biological activities. In this review, we first outline current understanding of siderophore synthesis, uptake and regulation in model bacteria, and subsequently discuss the siderophore biology in Shewanella.
Epidemiology and Prevalence of Oral Candidiasis in HIV Patients From Chad in the Post-HAART Era
Authors: Taverne-Ghadwal Liliane , Kuhns Martin , Buhl Timo , Schulze Marco H. , Mbaitolum Weina Joseph , Kersch Lydia , Weig Michael , Bader Oliver , Groß Uwe
Published: February 2022

Oral candidiasis remains a common problem in HIV-infected individuals, especially in sub-Saharan Africa. Here, we performed the first study in Chad on the prevalence of oral yeasts carriage and oral candidiasis in HIV-positive subjects from southern Chad and analyzed the influence of HAART, CD4+ T-cell numbers, and antimycotics in 589 patients. These patients were recruited from a specialized medical center for HIV patients in Sarh and from a rural medical health dispensary in the vicinity, including a total of 384 HIV-positive and 205 HIV-negative individuals. Yeasts obtained from oral specimen were identified by MALDI-TOF MS and their antifungal susceptibility profiles determined. The overall prevalence of yeast colonization and symptomatic oral candidiasis in HIV-infected patients was 25.1%. The prevalence of oral candidiasis was higher in untreated than in HAART-treated HIV-positive patients (16% vs. 2%; p < 0.01). Oral candidiasis was furthermore associated with high fungal burdens of Candida albicans and a CD4+ T-cell number <200/μl. A shift toward non-albicans Candida species was observed under nucleoside-based HAART therapy. Azole antifungal drug resistance was only observed for the intrinsically resistant species Candida krusei and Candida glabrata. Prevalence of oral candidiasis in the studied area was very low. The species distribution was similar to other countries around the world, with C. albicans being dominant. Candida dubliniensis was not isolated. Nucleoside-based HAART therapy significantly reduced oral colonization as well as occurrence of oral candidiasis caused by C. albicans and led to a species shift toward non-albicans species. Antifungal resistance was not yet a concern in Chad.
Urinary Proteomics Analysis of Active Vitiligo Patients: Biomarkers for Steroid Treatment Efficacy Prediction and Monitoring
Authors: Qian Yue-Tong , Liu Xiao-Yan , Sun Hai-Dan , Xu Ji-Yu , Sun Jia-Meng , Liu Wei , Chen Tian , Liu Jia-Wei , Tan Yan , Sun Wei , Ma Dong-Lai
Published: February 2022

Vitiligo is a common acquired skin disorder caused by immune-mediated destruction of epidermal melanocytes. Systemic glucocorticoids (GCs) have been used to prevent the progression of active vitiligo, with 8.2–56.2% of patients insensitive to this therapy. Currently, there is a lack of biomarkers that can accurately predict and evaluate treatment responses. The goal of this study was to identify candidate urinary protein biomarkers to predict the efficacy of GCs treatment in active vitiligo patients and monitor the disease. Fifty-eight non-segmental vitiligo patients were enrolled, and 116 urine samples were collected before and after GCs treatment. Patients were classified into a treatment-effective group (n= 42) and a treatment-resistant group (n= 16). Each group was divided equally into age- and sex-matched experimental and validation groups, and proteomic analyses were performed. Differentially expressed proteins were identified, and Ingenuity Pathway Analysis was conducted for the functional annotation of these proteins. Receiver operating characteristic curves were used to evaluate the diagnostic value. A total of 245 and 341 differentially expressed proteins between the treatment-resistant and treatment-effective groups were found before and after GCs treatment, respectively. Bioinformatic analysis revealed that the urinary proteome reflected the efficacy of GCs in active vitiligo patients. Eighty and fifty-four candidate biomarkers for treatment response prediction and treatment response evaluation were validated, respectively. By ELISA analysis, retinol binding protein-1 and torsin 1A interacting protein 1 were validated to have the potential to predict the efficacy of GCs with AUC value of 1 and 0.875, respectively. Retinol binding protein-1, torsin 1A interacting protein 1 and protein disulfide-isomerase A4 were validated to have the potential to reflect positive treatment effect to GCs treatment in active vitiligo with AUC value of 0.861, 1 and 0.868, respectively. This report is the first to identify urine biomarkers for GCs treatment efficacy prediction in vitiligo patients. These findings might contribute to the application of GCs in treating active vitiligo patients.
Retinal Microvascular Density Was Associated With the Clinical Progression of Parkinson’s Disease
Authors: Xu Bei , Wang Xin , Guo Jifeng , Xu Huizhuo , Tang Beisha , Jiao Bin , Shen Lu
Published: February 2022

Background

Retinal microvascular density has been studied in neurodegenerative diseases, whereas patients with Parkinson’s disease (PD) at different clinical stages have been rarely investigated. The present study aimed to evaluate the microvascular variations in superficial retinal capillary plexus (SCP) in patients with PD on different Hoehn-Yahr (H-Y) stages by optical coherence tomography angiography (OCTA), as well as determine their relationships with clinical parameters.

Methods

In total, 115 patients with PD and 67 healthy controls (HCs) were recruited. The PD group was divided into three groups based on the H-Y stage. The OCTA examination was performed in all participants, and the macular vessel density (m-VD), peripapillary vessel density (p-VD), and foveal avascular zone (FAZ) area were measured.

Results

The m-VD in all regions, p-VD in center [6.1 (4.8, 6.95) mm–1 in healthy eyes vs. 5.1 (3.7, 6.4) mm–1 in patients], nasal inner (NI) [18.5 (17.8, 19.3) mm–1 in healthy eyes vs. 17.9 (17.1, 18.7) mm–1 in patients], temporal outer (TO) [19.6 (18.9, 20.2) mm–1 in healthy eyes vs. 19.3 (18.5, 19.7) mm–1 in patients] regions and FAZ area [0.36 (0.32, 0.39) mm2 in healthy eyes vs. 0.29 (0.26, 0.33) mm2 in patients] noticeably decreased in PD groups compared with HC (p < 0.05). Moreover, the FAZ area was suggested to decline significantly in patients with PD with H-Y I stage (p < 0.05), while it was more serious in the H-Y III stage in patients. Furthermore, we found that m-VD exhibited a significant negative correlation with age, disease duration, UPDRS scores, NMSS scores, and H-Y stage.

Conclusion

OCTA has the potential to non-invasively detect the microvascular changes in patients with PD with different clinical stages in vivo, and it may be a valuable tool to monitor the PD progression.
Identification of Genetic Networks Reveals Complex Associations and Risk Trajectory Linking Mild Cognitive Impairment to Alzheimer’s Disease
Authors: Strafella Claudia , Caputo Valerio , Termine Andrea , Fabrizio Carlo , Calvino Giulia , Megalizzi Domenica , Ruffo Paola , Toppi Elisa , Banaj Nerisa , Bassi Andrea , Bossù Paola , Caltagirone Carlo , Spalletta Gianfranco , Giardina Emiliano , Cascella Raffaella
Published: February 2022

Amnestic mild cognitive impairment (aMCI) and sporadic Alzheimer’s disease (AD) are multifactorial conditions resulting from a complex crosstalk among multiple molecular and biological processes. The present study investigates the association of variants localized in genes and miRNAs with aMCI and AD, which may represent susceptibility, prognostic biomarkers or multi-target treatment options for such conditions. We included 371 patients (217 aMCI and 154 AD) and 503 healthy controls, which were genotyped for a panel of 120 single nucleotide polymorphisms (SNPs) and, subsequently, analyzed by statistical, bioinformatics and machine-learning approaches. As a result, 21 SNPs were associated with aMCI and 13 SNPs with sporadic AD. Interestingly, a set of variants shared between aMCI and AD displayed slightly higher Odd Ratios in AD with respect to aMCI, highlighting a specific risk trajectory linking aMCI to AD. Some of the associated genes and miRNAs were shown to interact within the signaling pathways of APP (Amyloid Precursor Protein), ACE2 (Angiotensin Converting Enzyme 2), miR-155 and PPARG (Peroxisome Proliferator Activated Receptor Gamma), which are known to contribute to neuroinflammation and neurodegeneration. Overall, results of this study increase insights concerning the genetic factors contributing to the neuroinflammatory and neurodegenerative mechanisms underlying aMCI and sporadic AD. They have to be exploited to develop personalized approaches based on the individual genetic make-up and multi-target treatments.
D1 Receptor Mediated Dopaminergic Neurotransmission Facilitates Remote Memory of Contextual Fear Conditioning
Authors: Saito Nae , Itakura Makoto , Sasaoka Toshikuni
Published: February 2022

Dopaminergic neurotransmission via dopamine D1 receptors (D1Rs) is considered to play an important role not only in reward-based learning but also in aversive learning. The contextual and auditory cued fear conditioning tests involve the processing of classical fear conditioning and evaluates aversive learning memory. It is possible to evaluate aversive learning memory in two different types of neural transmission circuits. In addition, when evaluating the role of dopaminergic neurotransmission via D1R, to avoid the effects in D1R-mediated neural circuitry alterations during development, it is important to examine using mice who D1R expression in the mature stage is suppressed. Herein, we investigated the role of dopaminergic neurotransmission via D1Rs in aversive memory formation in contextual and auditory cued fear conditioning tests using D1R knockdown (KD) mice, in which the expression of D1Rs could be conditionally and reversibly controlled with doxycycline (Dox) treatment. For aversive memory, we examined memory formation using recent memory 1 day after conditioning, and remote memory 4 weeks after conditioning. Furthermore, immunostaining of the brain tissues of D1RKD mice was performed after aversive footshock stimulation to investigate the distribution of activated c-Fos, an immediate-early gene, in the hippocampus (CA1, CA3, dentate gyrus), striatum, amygdala, and prefrontal cortex during aversive memory formation. After aversive footshock stimulation, immunoblotting was performed using hippocampal, striatal, and amygdalar samples from D1RKD mice to investigate the increase in the amount of c-Fos and phosphorylated SNAP-25 at Ser187 residue. When D1R expression was suppressed using Dox, behavioral experiments revealed impaired contextual fear learning in remote aversion memory following footshock stimulation. Furthermore, expression analysis showed a slight increase in the post-stimulation amount of c-Fos in the hippocampus and striatum, and a significant increase in the amount of phosphorylated SNAP-25 in the hippocampus, striatum, and prefrontal cortex before and after stimulation. These findings indicate that deficiency in D1R-mediated dopaminergic neurotransmission is an important factor in impairing contextual fear memory formation for remote memory.
The Spino-Parabrachial Pathway for Itch
Authors: Piyush Shah Devanshi , Barik Arnab
Published: February 2022

Itch-induced scratching is an evolutionarily conserved behavioral response that protects organisms from potential parasites/irritants in their immediate vicinity. How the exposure to a pruritogen is translated to the perception of itch and how that perception drives scratching directed towards the site of exposure remains poorly understood. In this review, we focus on the recent findings that shed light on the neural pathways in the brain that underlie itch-induced scratching. We compare the molecularly defined itch pathways with the known pain circuits as they have anatomical and functional overlap. We review the roles played by the neurons in the spinoparabrachial pathway—comprising of the neurons in the spinal cord and the parabrachial nucleus (PBN), which acts as a hub for transmitting itch information across the brain. Lastly, we deliberate on scratching as a behavioral measure of the intensity of itch and its implication in unraveling the underlying supraspinal mechanisms. In summary, we provide a resource on the recent advances and discuss a path forward on our understanding of the neural circuits for itch.
Brainstem Associated Somatosensory Evoked Potentials and Response to Vagus Nerve Stimulation: An Investigation of the Vagus Afferent Network
Authors: Suresh Hrishikesh , Mithani Karim , Brar Karanbir , Yan Han , Strantzas Samuel , Vandenberk Mike , Sharma Roy , Yau Ivanna , Go Christina , Pang Elizabeth , Kerr Elizabeth , Ochi Ayako , Otsubo Hiroshi , Jain Puneet , Donner Elizabeth , Snead O. Carter , Ibrahim George M.
Published: February 2022

Despite decades of clinical usage, selection of patients with drug resistant epilepsy who are most likely to benefit from vagus nerve stimulation (VNS) remains a challenge. The mechanism of action of VNS is dependent upon afferent brainstem circuitry, which comprises a critical component of the Vagus Afferent Network (VagAN). To evaluate the association between brainstem afferent circuitry and seizure response, we retrospectively collected intraoperative data from sub-cortical recordings of somatosensory evoked potentials (SSEP) in 7 children with focal drug resistant epilepsy who had failed epilepsy surgery and subsequently underwent VNS. Using multivariate linear regression, we demonstrate a robust negative association between SSEP amplitude (p< 0.01), and seizure reduction. There was no association between SSEP latency and seizure outcomes. Our findings provide novel insights into the mechanism of VNS and inform our understanding of the importance of brainstem afferent circuitry within the VagAN for seizure responsiveness following VNS.
Case Report: Yellow Fever Vaccine-Associated Neurotropic Disease and Associated MRI, EEG, and CSF Findings
Authors: Cohen Michelle , Nguyen Madeline , Nix Chad D. , Case Brendan , Nickerson Joshua P. , Bernard Jacqueline , Durrant Julia , Safarpour Delaram , Tucker Tarvez , Vagnerova Kamila , Messer William B.
Published: February 2022

Yellow fever vaccine-associated neurotropic disease (YEL-AND) is a rare and serious complication following vaccination with the 17D live attenuated yellow fever vaccine. Cases of YEL-AND have presented as acute inflammatory demyelinating polyneuropathy, acute disseminated encephalomyelitis, and meningoencephalitis. To date, intracranial imaging of the progression and resolution of this disease has been minimally depicted in the literature. We present the case of a 67-year-old woman who developed YEL-AND following vaccination. Her diagnosis was complicated by imaging findings consistent with variant Creutzfeldt Jakob Disease. Her clinical history and the progression of her intracranial imaging is discussed in this case report.
Natural Plant Compounds: Does Caffeine, Dipotassium Glycyrrhizinate, Curcumin, and Euphol Play Roles as Antitumoral Compounds in Glioblastoma Cell Lines?
Authors: Bonafé Gabriel Alves , Boschiero Matheus Negri , Sodré André Rodrigues , Ziegler Jussara Vaz , Rocha Thalita , Ortega Manoela Marques
Published: February 2022

Many plant-derived compounds are shown to be promising antitumor therapeutic agents by enhancing apoptosis-related pathways and cell cycle impairment in tumor cells, including glioblastoma (GBM) cell lines. We aimed to review four natural plant compounds effective in GBM cell lines as caffeine, dipotassium glycyrrhizinate (DPG), curcumin, and euphol. Furthermore, antitumoral effect of these plant compounds on GBM cell lines through microRNAs (miRs) modulation was investigated. However, only DPG and curcumin were found as effective on miR modulation. Caffeine arrests GBM cell cycle in G0/G1 phase by cyclin-dependent kinases (CDK) complex inhibition and by decreasingBCL-2and increasingFOXO1expression levels causing greater apoptotic activity. Caffeine can also directly inhibit IP3R3, p38 phosphorylation, and rho-associated protein kinase (ROCK), decreasing cell invasion and migration capacity or indirectly by inhibiting the tissue inhibitor metalloproteinase-1 (TIMP-1) and integrins β1 and β3, leading to lower matrix metalloproteinases, MMP-2 and MMP-9. DPG presents antitumoral effect in GBM cells related to nuclear factor kappa B (NF-κB) pathway suppression byIRAK2andTRAF6-mediating miR-16 and miR-146a, respectively. More recently, it was observed that DPG upregulated miR-4443 and miR-3620, responsible for post-transcriptional inhibition of the NF-κB pathway byCD209andTNCmodulation, respectively leading to lower MMP-9 and migration capacity. Curcumin is able to increase miR-223-3p, miR-133a-3p, miR-181a-5p, miR-34a-5p, miR-30c-5p, and miR-1290 expression leading to serine or threonine kinase (AKT) pathway impairment and also it decreases miR-27a-5p, miR-221-3p, miR-21-5p, miR-125b-5p, and miR-151-3p expression causing p53-BCL2 pathway inhibition and consequently, cellular apoptosis. Interestingly, lower expression of miR-27a by curcumin action enhanced the C/EBP homologous protein(CHOP) expression, leading to paraptosis. Curcumin can inhibit miR-21 expression and consequently activate apoptosis through caspase 3 and death receptor (DR) 4 and 5 activation. Autophagy is controlled by the LC-3 protein that interacts with Atg family for the LC3-II formation and autophagy activation. Euphol can enhance LC3-II levels directly in GBM cells or inhibits tumor invasion and migration through PDK1 modulation.
Electrical Properties of Lumbar Paraspinal Muscles in Young Adults With and Without Chronic Low Back Pain Based on Electrical Impedance Myography: A Cross-Sectional Study
Authors: Wang Hongjiang , Zheng Jiaxuan , Yu Qiuhua , Fan Ziyan , Lo Wai Leung Ambrose , Li Le , Wang Chuhuai
Published: February 2022

Background

Lumbar paraspinal muscle (LPM) is important in spinal stabilization in patients with chronic low back pain (CLBP). However, the electrical properties of LPM in patients with CLBP remain unclear. Electrical impedance myography (EIM) is a novel and non-invasive technique that provides a simple quantitative evaluation of electrical properties of the LPM.

Purpose

This study aimed to apply EIM to assess the electrical properties of the LPM between patients with CLBP and healthy control (HC).

Methods

Thirty participants (15 CLBP participants; 15 healthy controls) were enrolled in the study. Participants in the CLBP group were asked to complete the visual analog scale (VAS), Oswestry Disability Index (ODI), and Roland–Morris Disability Questionnaire (RDQ) to assess the pain intensity and disability in daily life. Independent sample t-tests were adopted to analyze the basic characteristics between the two groups. At 5, 50, 100, and 200 kHz current frequencies, the electrical properties were measured on each side of the LPM. The EIM parameters of resistance (R), reactance (X), phase angle (PA), and Z value were analyzed by one-way analysis of variance (ANOVA), with age as covariate. Spearman's rank correlation coefficient analysis was applied to explore the relationships between the questionnaires and the EIM parameters.

Results

The R and Z values of bilateral LPM in the CLBP group were significantly larger than those in the HC group; the PA decreased and the X did not change at these four tested current frequencies. At 5 kHz, Z and R on the right side were non-significantly different between patients and HCs. Correlation analysis showed that at 50 kHz, ODI and RDQ scores correlated negatively with the R of the bilateral LPM (r = 0.523, r = 0.581, respectively; p < 0.05). RDQ scores correlated positively with the PA of the right LPM (r = 0.521, p < 0.05).

Conclusion

The electrical properties of the bilateral LPM differed between CLBP participants and healthy individuals, regardless of the different frequencies used. These altered electrical properties of the LPM in the patients with CLBP correlated to some extent with disability in daily life.
Adverse Events and Complications in Continuous Intra-arterial Nimodipine Infusion Therapy After Aneurysmal Subarachnoid Hemorrhage
Authors: Kapapa Thomas , König Ralph , Mayer Benjamin , Braun Michael , Schmitz Bernd , Müller Silwia , Schick Julia , Wirtz Christian Rainer , Pala Andrej
Published: February 2022

Objective

To determine the frequency and severity of complications associated with the continuous intra-arterial infusion of nimodipine (CIANI) as a new treatment of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH).

Methods

Patients from two centers (n = 718) treated for SAH between 2008 and 2016 were included. Demographic and SAH-related parameters were evaluated, and also the frequency of adverse events (AEs) and complications including their severity (mild, moderate, and severe). Clinical outcome was analyzed using Glasgow Outcome Scale (GOS). The unfavorable outcome was defined as GOS 1 to 3, and favorable outcome as GOS 4 to 5. The Short-Form 36 (SF-36) health-related quality-of-life (QoL) questionnaire served as a QoL measurement.

Results

Of 718 patients, 65 (9%) were treated by CIANI and had a higher clinical or imaging grade of bleeding severity. Clinical deterioration while on treatment happened more often in patients who were treated with CIANI than in others. In patients with CIANI, 67% had AEs and/or complications during the treatment. Nimodipine-associated hypotension was seen in 8% (mild). Catheter-associated thrombus occurred in 9% (moderate). New intracerebral hemorrhage was found in 14% (moderate). A total of 6% treated by CIANI died during the treatment period (severe). More than one-third (39%) of patients of CIANI reached at least moderate disability, and 23% showed good recovery. Patients who received CIANI showed reduced QoL, but differences in mental and general health, and also pain were minimal.

Conclusion

Patients who received CIANI had higher rates of AEs and complications. However, this does not exclude the possibility that the use of CIANI might be helpful in patients with severe and therapy-refractory CV and DCI. Controlled and randomized studies would be helpful to clarify this question but they are methodologically and ethically challenging.
Epilepsy Genetics and Precision Medicine in Adults: A New Landscape for Developmental and Epileptic Encephalopathies
Authors: Beltrán-Corbellini Álvaro , Aledo-Serrano Ángel , Møller Rikke S. , Pérez-Palma Eduardo , García-Morales Irene , Toledano Rafael , Gil-Nagel Antonio
Published: February 2022

This review aims to provide an updated perspective of epilepsy genetics and precision medicine in adult patients, with special focus on developmental and epileptic encephalopathies (DEEs), covering relevant and controversial issues, such as defining candidates for genetic testing, which genetic tests to request and how to interpret them. A literature review was conducted, including findings in the discussion and recommendations. DEEs are wide and phenotypically heterogeneous electroclinical syndromes. They generally have a pediatric presentation, but patients frequently reach adulthood still undiagnosed. Identifying the etiology is essential, because there lies the key for precision medicine. Phenotypes modify according to age, and although deep phenotyping has allowed to outline certain entities, genotype-phenotype correlations are still poor, commonly leading to long-lasting diagnostic odysseys and ineffective therapies. Recent adult series show that the target patients to be identified for genetic testing are those with epilepsy and different risk factors. The clinician should take active part in the assessment of the pathogenicity of the variants detected, especially concerning variants of uncertain significance. An accurate diagnosis implies precision medicine, meaning genetic counseling, prognosis, possible future therapies, and a reduction of iatrogeny. Up to date, there are a few tens of gene mutations with additional concrete treatments, including those with restrictive/substitutive therapies, those with therapies modifying signaling pathways, and channelopathies, that are worth to be assessed in adults. Further research is needed regarding phenotyping of adult syndromes, early diagnosis, and the development of targeted therapies.
Structural and Functional Asymmetry in Precentral and Postcentral Gyrus in Patients With Unilateral Chronic Shoulder Pain
Authors: Wei Xiaoya , Shi Guangxia , Tu Jianfeng , Zhou Hang , Duan Yanshan , Lee Chin Kai , Wang Xu , Liu Cunzhi
Published: February 2022

Objective

The purpose of this study was to explore the structural and functional asymmetry of precentral and postcentral gyrus in patients with unilateral chronic shoulder pain (CSP) utilizing MRI.

Patients and Methods

We collected structural and resting-state functional MRI (rs-fMRI) data in 22 left-sided, 15 patients with right-sided CSP, and 24 healthy controls (HCs). Here, we performed the structural asymmetry and seed-based functional connectivity (FC) analyses. We extracted regional cortical thickness and surface area measurements from T1-weighted MRI images, using asymmetry indexes (AIs) to assess asymmetries. We used Data Processing and Analysis for Brain Imaging software for seed-based FC analysis and selected unilateral-precentral and postcentral as the regions of interest. Then, we performed group comparisons of the neuroimaging metrics, and also explored the relationships between brain asymmetry and clinical variables.

Results

We found significant differences in surface area AIs of the precentral among three groups, the AI values were negatively correlated with the visual analog scale score and positively correlated with Constant–Murley scores (CMS) in the left-sided CSP group. Further, FC of left postcentral with cingulate gyrus and left paracentral lobule showed significant group differences; FC of right postcentral with left caudate, left paracentral, and left postcentral were different among groups; FC of right precentral with the cingulate gyrus, precuneus, and left paracentral revealed significant group differences. Besides, there was a positive correlation between right precentral-cingulate gyrus FC and CMS in the right-sided CSP group.

Conclusion

Surface area and FC patterns asymmetry exist in precentral and postcentral gyrus in patients with unilateral CSP. Asymmetry trend is associated with pain severity and shoulder joint function impairment. Brain structural and functional asymmetry may be an important indicator for understanding the potential mechanism of chronic pain.
Color Doppler Ultrasonography for the Evaluation of Subclavian Artery Stenosis
Authors: Zhang Jie , Wang Lijuan , Chen Ying , Wang Sibo , Xing Yingqi , Cui Li
Published: February 2022

Background

It is of great significance to evaluate symptomatic subclavian artery (SA) stenosis by color Doppler ultrasonography. More than 50% SA stenosis may induce symptoms. Currently, there is a paucity of published literature and lack of practitioner consensus for how ultrasonic findings should be interpreted in patients with SA stenosis.

Objective

The study aimed to prospectively evaluate SA stenosis using color Doppler ultrasonography, with digital subtraction angiography as a reference. Moreover, we aimed to determine the optimal thresholds to predict SA stenosis (≥50%).

Methods

A total of 423 SAs from 234 patients with normal or stenotic lumen were enrolled. The peak systolic velocity (PSV) and acceleration time at the stenotic and distal segments of the SA, peak reversed velocity of the vertebral artery, and waveforms of the stenotic SA, distal SA, and vertebral artery were recorded. The ratios of stenotic PSV to distal PSV (PSVr) and distal AT to stenotic AT were also calculated. The optimal cutoff values were determined using receiver operating characteristic analysis.

Results

All ultrasonic parameters were significantly correlated with the degree of SA stenosis, whereas PSV (r = 0.624, P < 0.001), PSVr (r = 0.654, P < 0.001) and VA waveform change (r = 0.631, P < 0.001) had the strongest correlation with SA stenosis. The optimal cutoff values were as follows: PSV ≥ 230 cm/s and PSVr ≥ 2.2 to predict ≥ 50% stenosis, and PSV ≥ 340 cm/s and PSVr ≥ 3.0 to predict ≥ 70% stenosis.

Conclusions

Symptomatic patients with the ultrasonic parameters of PSV ≥ 230 cm/s and PSVr ≥ 2.2 need to be considered for further verification by computed tomographic angiography or magnetic resonance angiography, or by digital subtraction angiography with a view to percutaneous transluminal angioplasty/stent implantation in the same session. The recommended graded cutoff values can help in long-term management of patients with SA stenosis.
Convolutional Neural Networks Enable Robust Automatic Segmentation of the Rat Hippocampus in MRI After Traumatic Brain Injury
Authors: De Feo Riccardo , Hämäläinen Elina , Manninen Eppu , Immonen Riikka , Valverde Juan Miguel , Ndode-Ekane Xavier Ekolle , Gröhn Olli , Pitkänen Asla , Tohka Jussi
Published: February 2022

Registration-based methods are commonly used in the automatic segmentation of magnetic resonance (MR) brain images. However, these methods are not robust to the presence of gross pathologies that can alter the brain anatomy and affect the alignment of the atlas image with the target image. In this work, we develop a robust algorithm, MU-Net-R, for automatic segmentation of the normal and injured rat hippocampus based on an ensemble of U-net-like Convolutional Neural Networks (CNNs). MU-Net-R was trained on manually segmented MR images of sham-operated rats and rats with traumatic brain injury (TBI) by lateral fluid percussion. The performance of MU-Net-R was quantitatively compared with methods based on single and multi-atlas registration using MR images from two large preclinical cohorts. Automatic segmentations using MU-Net-R and multi-atlas registration were of excellent quality, achieving cross-validated Dice scores above 0.90 despite the presence of brain lesions, atrophy, and ventricular enlargement. In contrast, the performance of single-atlas segmentation was unsatisfactory (cross-validated Dice scores below 0.85). Interestingly, the registration-based methods were better at segmenting the contralateral than the ipsilateral hippocampus, whereas MU-Net-R segmented the contralateral and ipsilateral hippocampus equally well. We assessed the progression of hippocampal damage after TBI by using our automatic segmentation tool. Our data show that the presence of TBI, time after TBI, and whether the hippocampus was ipsilateral or contralateral to the injury were the parameters that explained hippocampal volume.
Vestibulo-Ocular Reflex Is Modulated by Noisy Galvanic Vestibular Stimulation
Authors: Matsugi Akiyoshi , Shiozaki Tomoyuki , Tanaka Hiroaki
Published: February 2022

We investigated whether noisy galvanic vestibular stimulation (nGVS) modulates the vestibulo-ocular reflex (VOR) and whether this effect is correlated with the effect of nGVS on body sway. Thirty healthy young adults participated. The video head impulse test (vHIT) was used to estimate the ratio of eye motion velocity/head motion velocity to VOR-gain. The gain 60 ms after the start of head motion (VOR-gain-60 ms) and regression slope (RS) (i.e., gain in eye and head motion; VOR-gain-RS) were calculated. The total path length of the foot center of pressure (COP-TL) during upright standing was calculated to estimate body sway. Noisy Galvanic Vestibular Stimulation at 0.2, 0.6, 1.2 mA, or sham stimulation (direct current: 0 mA) was delivered to the bilateral mastoid process in random order during vHIT and COP measurements. Application of nGVS at 0.2 mA significantly reduced VOR-gain-RS, while application of nGVS at 0.6 mA significantly increased COP-TL. Vestibulo-ocular reflex-gain-60 ms differed significantly between 0.2 and 1.2 mA. There was no significant correlation between COP-TL and VOR-related parameters. These findings suggest that nGVS at 0.2 mA inhibits the VOR, while nGVS at 0.6 mA increases body sway during upright standing, although there may be no relationship between the respective effects in healthy individuals.
Assessing the Reliability of Template-Based Clustering for Tractography in Healthy Human Adults
Authors: Kai Jason , Khan Ali R.
Published: February 2022

Tractography is a non-invasive technique to investigate the brain’s structural pathways (also referred to as tracts) that connect different brain regions. A commonly used approach for identifying tracts is with template-based clustering, where unsupervised clustering is first performed on a template in order to label corresponding tracts in unseen data. However, the reliability of this approach has not been extensively studied. Here, an investigation into template-based clustering reliability was performed, assessing the output from two datasets: Human Connectome Project (HCP) and MyConnectome project. The effect of intersubject variability on template-based clustering reliability was investigated, as well as the reliability of both deep and superficial white matter tracts. Identified tracts were evaluated by assessing Euclidean distances from a dataset-specific tract average centroid, the volumetric overlap across corresponding tracts, and along-tract agreement of quantitative values. Further, two template-based techniques were employed to evaluate the reliability of different clustering approaches. Reliability assessment can increase the confidence of a tract identifying technique in future applications to study pathways of interest. The two different template-based approaches exhibited similar reliability for identifying both deep white matter tracts and the superficial white matter.
Altered Brain Functional Asymmetry in Patients With Major Depressive Disorder Related to Gastrointestinal Symptoms
Authors: Fu Xiaoya , Ding Yudan , Chen Jindong , Liu Feng , Li Huabing , Zhao Jingping , Guo Wenbin
Published: February 2022

Objective

Disrupted brain functional asymmetry has been reported in major depressive disorder (MDD). The comorbidity may be a crucial factor to this functional asymmetry. It is quite common that gastrointestinal (GI) symptoms are comorbid with MDD, but limited evidence focuses on the effect of GI comorbidity on the neuropathology of MDD from a functional lateralization perspective.

Methods

Resting-state functional magnetic resonance imaging was obtained in 28 healthy controls (HCs), 35 MDD patients with GI symptoms (GI-MDD patients), and 17 patients with MDD without GI symptoms (nGI-MDD patients). The parameter of asymmetry (PAS) was used to analyze the imaging data and evaluate the changes of functional asymmetry.

Results

The GI-MDD patients showed increased PAS scores in the left inferior frontal gyrus (IFG) and superior medial prefrontal cortex (MPFC) and decreased PAS scores in the right postcentral gyrus in comparison with nGI-MDD patients. The PAS scores of the left IFG and left superior MPFC were correlated with the severity of GI problems and could be applied to distinguish GI-MDD patients from nGI-MDD patients with an accuracy, a sensitivity, and a specificity of 92.31, 100, and 76.47%, respectively. Furthermore, GI-MDD and nGI-MDD patients both displayed increased PAS scores in the PCC/precuneus.

Conclusions

This study revealed the influence of concomitant GI symptoms on functional asymmetry in MDD patients. Increased PAS scores of the left IFG and superior MPFC might represent an unbalanced regulation of brain over GI function and had the potential to be regarded as distinctive features related to functional GI symptoms in MDD.
On the Dynamics of Spatial Updating
Authors: Blouin Jean , Pialasse Jean-Philippe , Mouchnino Laurence , Simoneau Martin
Published: February 2022

Most of our knowledge on the human neural bases of spatial updating comes from functional magnetic resonance imaging (fMRI) studies in which recumbent participants moved in virtual environments. As a result, little is known about the dynamic of spatial updating during real body motion. Here, we exploited the high temporal resolution of electroencephalography (EEG) to investigate the dynamics of cortical activation in a spatial updating task where participants had to remember their initial orientation while they were passively rotated about their vertical axis in the dark. After the rotations, the participants pointed toward their initial orientation. We contrasted the EEG signals with those recorded in a control condition in which participants had no cognitive task to perform during body rotations. We found that the amplitude of the P1N1 complex of the rotation-evoked potential (RotEPs) (recorded over the vertex) was significantly greater in the Updating task. The analyses of the cortical current in the source space revealed that the main significant task-related cortical activities started during the N1P2 interval (136–303 ms after rotation onset). They were essentially localized in the temporal and frontal (supplementary motor complex, dorsolateral prefrontal cortex, anterior prefrontal cortex) regions. During this time-window, the right superior posterior parietal cortex (PPC) also showed significant task-related activities. The increased activation of the PPC became bilateral over the P2N2 component (303–470 ms after rotation onset). In this late interval, the cuneus and precuneus started to show significant task-related activities. Together, the present results are consistent with the general scheme that the first task-related cortical activities during spatial updating are related to the encoding of spatial goals and to the storing of spatial information in working memory. These activities would precede those involved in higher order processes also relevant for updating body orientation during rotations linked to the egocentric and visual representations of the environment.