Effects of individual metabolic brain network changes co-affected by T2DM and aging on the probabilities of T2DM: protective and risk factors.

Neuroimaging markers for risk and protective factors related to type 2 diabetes mellitus are critical for clinical prevention and intervention. In this work, the individual metabolic brain networks were constructed with Jensen-Shannon divergence for 4 groups (elderly type 2 diabetes mellitus and healthy controls, and middle-aged type 2 diabetes mellitus and healthy controls). Regional network properties were used to identify hub regions. Rich-club, feeder, and local connections were subsequently obtained, intergroup differences in connections and correlations between them and age (or fasting plasma glucose) were analyzed. Multinomial logistic regression was performed to explore effects of network changes on the probability of type 2 diabetes mellitus. The elderly had increased rich-club and feeder connections, and decreased local connection than the middle-aged among type 2 diabetes mellitus; type 2 diabetes mellitus had decreased rich-club and feeder connections than healthy controls. Protective factors including glucose metabolism in triangle part of inferior frontal gyrus, metabolic connectivity between triangle of the inferior frontal gyrus and anterior cingulate cortex, degree centrality of putamen, and risk factors including metabolic connectivities between triangle of the inferior frontal gyrus and Heschl's gyri were identified for the probability of type 2 diabetes mellitus. Metabolic interactions among critical brain regions increased in type 2 diabetes mellitus with aging. Individual metabolic network changes co-affected by type 2 diabetes mellitus and aging were identified as protective and risk factors for the likelihood of type 2 diabetes mellitus, providing guiding evidence for clinical interventions.

Human-Guided Functional Connectivity Network Estimation for Chronic Tinnitus Identification: A Modularity View.

The functional connectivity network (FCN) has been used to achieve several remarkable advancements in the diagnosis of neuro-degenerative disorders. Therefore, it is imperative to accurately estimate biologically meaningful FCNs. Several efforts have been dedicated to this purpose by encoding biological priors. However, owing to the high complexity of the human brain, the estimation of an 'ideal' FCN remains an open problem. To the best of our knowledge, almost all existing studies lack the integration of domain expert knowledge, which limits their performance. In this study, we focused on incorporating domain expert knowledge into the FCN estimation from a modularity perspective. To achieve this, we presented a human-guided modular representation (MR) FCN estimation framework. Specifically, we designed an adversarial low-rank constraint to describe the module structure of FCNs under the guidance of domain expert knowledge (i.e., a predefined participant index). The chronic tinnitus (TIN) identification task based on the estimated FCNs was conducted to examine the proposed MR methods. Remarkably, MR significantly outperformed the baseline and state-of-the-art(SOTA) methods, achieving an accuracy of 92.11%. Moreover, post-hoc analysis revealed that the FCNs estimated by the proposed MR could highlight more biologically meaningful connections, which is beneficial for exploring the underlying mechanisms of TIN and diagnosing early TIN.

Excitotoxicity Induced by Realgar in the Rat Hippocampus: the Involvement of Learning Memory Injury, Dysfunction of Glutamate Metabolism and NMDA Receptors.

Realgar is a type of mineral drug containing arsenic. The nervous system toxicity of realgar has received extensive attention. However, the underlying mechanisms of realgar-induced neurotoxicity have not been clearly elucidated. To explore the mechanisms that contribute to realgar-induced neurotoxicity, weanling rats were exposed to realgar (0, 0.3, 0.9, 2.7 g/kg) for 6 weeks, and cognitive ability was tested using the Morris water maze (MWM) test and object recognition task (ORT). The levels of arsenic in the blood and hippocampus were monitored. The ultrastructures of hippocampal neurons were observed. The levels of glutamate (Glu) and glutamine (Gln) in the hippocampus and hippocampal CA1 region; the activities of glutamine synthetase (GS) and phosphate-activated glutaminase (PAG); the mRNA and protein expression of glutamate transporter 1 (GLT-1), glutamate/aspartate transporter (GLAST), and N-methyl-D-aspartate (NMDA) receptors; and the level of intracellular Ca(2+) were also investigated. The results indicate that the rats developed deficiencies in cognitive ability after a 6-week exposure to realgar. The arsenic contained in realgar and the arsenic metabolites passed through the blood-brain barrier (BBB) and accumulated in the hippocampus, which resulted in the excessive accumulation of Glu in the extracellular space. The excessive accumulation of Glu in the extracellular space induced excitotoxicity, which was shown by enhanced GS and PAG activities, inhibition of GLT-1 mRNA and protein expression, alterations in NMDA receptor mRNA and protein expression, disturbance of intracellular Ca(2+) homeostasis, and ultrastructural changes in hippocampal neurons. In conclusion, the findings from our study indicate that exposure to realgar induces excitotoxicity and that the mechanism by which this occurs may be associated with disturbances in Glu metabolism and transportation and alterations in NMDA receptor expression.

[Prenatal diagnosis of fetal urinary abnormalities and microdeletion on chromosome 1q21.1].

OBJECTIVE: To investigate genetic etiology of fetal urinary abnormalities with array-based comparative genomic hycridization(array-CGH). METHODS: Thirty-two fetuses with variable urinary abnormalities but normal karyotyping by conventional cytogenetic technique were selected. DNA from the fetuses and their parents samples were prepared and hybridization with Affymetrix cytogenetic 2.7M arrays by follwing the manufacture's standard protocol. The data were analyzed by special CHAS software packages. RESULTS: By using array-CGH detection, genomic imbalanced copy number variations (CNVs) were identified in night fetuses(28%), four out of night CNVs were inherited from parental samples; two were indicated to be benign variants(6%) in the database; and the other three CNVs (9%) were all de novo adjacent microdeletions and microduplication mapping on to common chromosome 1q21.1 region, within which was genitourinaty system function associated gene PDZK1. CONCLUSION: The incidence of genomic unbalanced variations in fetuses with congenital urinary malformations is approximately 28%, including about 9% pathogenic variations. Copy number variations (CNVs) of chromosome 1q21.1 region are associated with congenital urinary malformations which may be due to haploinsufficiency or overexpression of PDZK1 gene.

[Effect of subchronic realgar exposure on Glu and Gln in infant rat brain].

OBJECTIVE: To study the effect of realgar on Glu and Gln on rat brain tissues. METHODS: Forty-eight Wistar rats were divided into 4 groups randomly:control group,low dosage group, moderate dosage group and high dosage group. The treatment groups were treated with realgar by gastric perfusion at a dosage of 0.3 g/kg, 0.9 g/kg, 2.7 g/kg and the control group ones were orally given the same volume of 0.5% sodium carboxymethylcellulose (CMC-Na) for 6 weeks. The contents of inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in brain tissues were measured by hydride generation-atomic absorption (HG-AAS) method. The contents of amino acid neurotransmitters in brain tissues of rats were determined by means of high performance liquid chromatography with precolumn derivatization. RESULTS: The levels of MMA and DMA in brain increased as the dosage of realgar increased, while the second methylation index declined. Compared with control group,the levels of Glu was significantly decreased in realgar treated group (P < 0.05); Gln also tended to decrease and that of low dosage group was obviously decreased compared with controls. CONCLUSION: Realgar exposure can cause accumulation of MMA and DMA,declination of second methylation index and the reduction of Glu and Gln in brain tissue.

Lactococcus garvieae endocarditis with initial presentation of acute cerebral infarction in a healthy immunocompetent man.

Lactococcus garvieae is considered a rare, opportunistic pathogen with low virulence in human infection. There are only scattered case reports of L. garvieae-related infection in humans in the past 20 years. The majority of them were reported to be infective endocarditis. We present a case study of a 41-year-old man with infective endocarditis caused by L. garvieae which is the first reported case with initial presentation as acute cerebral infarction.