Different MRI-based radiomics models for differentiating misdiagnosed or ambiguous pleomorphic adenoma and Warthin tumor of the parotid gland: a multicenter study.

Purpose: To evaluate the effectiveness of MRI-based radiomics models in distinguishing between Warthin tumors (WT) and misdiagnosed or ambiguous pleomorphic adenoma (PA). Methods: Data of patients with PA and WT from two centers were collected. MR images were used to extract radiomic features. The optimal radiomics model was found by running nine machine learning algorithms after feature reduction and selection. To create a clinical model, univariate logistic regression (LR) analysis and multivariate LR were used. The independent clinical predictors and radiomics were combined to create a nomogram. Two integrated models were constructed by the ensemble and stacking algorithms respectively based on the clinical model and the optimal radiomics model. The models' performance was evaluated using the area under the curve (AUC). Results: There were 149 patients included in all. Gender, age, and smoking of patients were independent clinical predictors. With the greatest average AUC (0.896) and accuracy (0.839) in validation groups, the LR model was the optimal radiomics model. In the average validation group, the radiomics model based on LR did not have a higher AUC (0.795) than the clinical model (AUC = 0.909). The nomogram (AUC = 0.953) outperformed the radiomics model in terms of discrimination performance. The nomogram in the average validation group had a highest AUC than the stacking model (0.914) or ensemble model (0.798). Conclusion: Misdiagnosed or ambiguous PA and WT can be non-invasively distinguished using MRI-based radiomics models. The nomogram exhibited excellent and stable diagnostic performance. In daily work, it is necessary to combine with clinical parameters for distinguishing between PA and WT.

Anti-NMDAR antibodies, the blood-brain barrier, and anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an antibody-related autoimmune encephalitis. It is characterized by the existence of antibodies against NMDAR, mainly against the GluN1 subunit, in cerebrospinal fluid (CSF). Recent research suggests that anti-NMDAR antibodies may reduce NMDAR levels in this disorder, compromising synaptic activity in the hippocampus. Although anti-NMDAR antibodies are used as diagnostic indicators, the origin of antibodies in the central nervous system (CNS) is unclear. The blood-brain barrier (BBB), which separates the brain from the peripheral circulatory system, is crucial for antibodies and immune cells to enter or exit the CNS. The findings of cytokines in this disorder support the involvement of the BBB. Here, we aim to review the function of NMDARs and the relationship between anti-NMDAR antibodies and anti-NMDAR encephalitis. We summarize the present knowledge of the composition of the BBB, especially by emphasizing the role of BBB components. Finally, we further provide a discussion on the impact of BBB dysfunction in anti-NMDAR encephalitis.

Semiquantitative magnetic resonance imaging parameters for differentiating parotid pleomorphic adenoma from Warthin tumor.

Background: Accurately distinguishing between pleomorphic adenoma (PA) and Warthin tumor (WT) is beneficial for their respective management. Preoperative magnetic resonance imaging (MRI) can provide valuable information due to its excellent soft tissue contrast. This study explored the value of semiquantitative contrast-enhanced MRI parameters in the differential diagnosis of PA and WT. Methods: Data from 106 patients, 62 with PA and 44 with WT (confirmed by histopathology) were retrospectively and consecutively analyzed. The tumor-to-spinal cord contrast ratios (TSc-CR) based on the mean, maximum, and minimum signal intensity (T1-mean TSc-CR, T1-max TSc-CR, and T1-min TSc-CR, respectively) in the early and delayed phases were calculated on contrast-enhanced T1-weighted images as semiquantitative parameters, and then compared between PA and WT. Receiver operating characteristic (ROC) curve analysis and areas under the curve (AUCs) were used to determine the performance of these parameters in the differential diagnosis of PA from WT. Results: Except T1-min TSc-CR in the early phase, all semiquantitative MRI parameters differed significantly between PA and WT (all P<0.05). T1-max TSc-CR showed higher sensitivity {70.45% [95% confidence interval (CI): 0.548-0.832]} and specificity [70.97% (95% CI: 0.581-0.818)] and had a higher AUC [0.707 (95% CI: 0.610-0.791)] in the early phase when using a cutoff value of 1.89. T1-max TSc-CR showed higher sensitivity [88.64% (95% CI: 0.754-0.962)], specificity [72.58% (95% CI: 0.598-0.831)], and AUC [0.854 (95% CI: 0.772-0.915)] in the delayed phase when using a cutoff value of 2.33. The sensitivity, specificity, and AUC were improved to 90.91% (95% CI: 0.783-0.975), 93.55% (95% CI: 0.843-0.982), and 0.960 (95% CI: 0.903-0.988), respectively, after combination of all semiquantitative parameters in the early and delayed phases. The two radiologists had excellent interobserver agreement on TSc-CRs [all interclass correlation coefficient (ICC) >0.75]. Conclusions: Semiquantitative parameters using TSc-CR are valuable in distinguishing PA from WT, and a combination of these parameters can improve the differential diagnostic efficiency.

Pathological α-synuclein accumulation, CSF metabolites changes and brain microstructures in cynomolgus monkeys treated with 6-hydroxydopamine.

The lack of evidence indicating the accumulation of phosphorylated α-synuclein (P-α-syn), a neuropathological hallmark of Parkinson disease (PD), limits the application of 6-OHDA animal models. In cynomolgus monkeys received unilateral 6-hydroxydopamine (6-OHDA) injection, we identified nigrostriatal dysfunction related behavioral defects, such as the increase of PD score, decrease of locomotor activities, and exhibition of typical rotations. We found the dopaminergic neurons were significantly reduced and had fragmented morphology in substantia nigra (SN). Furthermore, insoluble P-α-syn aggregates were observed. The P-α-syn aggregates were extracellular distributed and had typical morphology of inclusion. Immunofluorescence staining showed that the P-α-syn colocalized with ubiquitin (Ub) and p62. We also found there were more actived astrocytes and microglial in SN and striatum, reflecting neuroinflammations increase in nigrostriatal pathway. At last, to determine the long-term consequence of dopamine (DA) neuron loss induced by 6-OHDA injection, the changes of cerebrospinal fluid (CSF) neurotransmitters over time as well as the brain microstructure alternations were examined. The dopamine-related metabolites were decreased after 6-OHDA injection reflecting dopaminergic neuron loss. The levels of γ-aminobutyric acid (GABA) and acetylcholine (Ach) showed an increasing trend but not significant. By diffusion tensor Magnetic Resonance Imaging (MRI) image scans, the fractional anisotropy (FA) value in the ipsilateral SN and caudate was found to reduce, which indicated neural fiber injury. Therefore, these results suggested that α-syn pathology might participate in process of 6-OHDA injuring DA neurons, and may expand the application of 6-OHDA monkeys on investigations into the pathogenesis of PD.

Development and Validation of an MRI-based Radiomics Nomogram for Assessing Deep Myometrial Invasion in Early Stage Endometrial Adenocarcinoma.

RATIONALE AND OBJECTIVES: To establish a radiomics nomogram for detecting deep myometrial invasion (DMI) in early stage endometrioid adenocarcinoma (EAC). MATERIALS AND METHODS: A total of 266 patients with stage I EAC were divided into training (n = 185) and test groups (n = 81). Logistic regression were used to identify clinical predictors. Radiomics features were extracted and selected from multiparameter MR images. The important clinical factors and radiomics features were integrated into a nomogram. A receiver operating characteristic curve was used to evaluate the nomogram. Two radiologists evaluated MR images with or without the help of the nomogram to detect DMI. The clinical benefit of using the nomogram was evaluated by decision curve analysis (DCA) and by calculating net reclassification index (NRI) and integrated discrimination index (IDI). RESULTS: Age and CA125 were independent clinical predictors. The area under the curves of the clinical parameters, radiomics signature and nomogram in evaluating DMI were 0.744, 0.869 and 0.883, respectively. The accuracies of the two radiologists increased from 79.0% and 80.2% to 90.1% and 92.5% when they used the nomogram. The NRI of the two radiologists were 0.262 and 0.318, and the IDI were 0.322 and 0.405. According to DCA, the nomogram showed a higher net benefit than the radiomics signature or unaided radiologists. Cross-validation showed the outcome of radiomics analysis may not be influenced by changes in field strength. CONCLUSION: The radiomics nomogram based on radiomics features and clinical factors can help radiologists evaluate DMI and improve their accuracy in predicting DMI in early stage EAC.

Dynamics of heavy metals during the development and decomposition of leaves of Avicennia marina and Kandelia obovata in a subtropical mangrove swamp.

In mangrove wetlands, leaves make up a high proportion of the plant biomass and can accumulate heavy metals from contaminated sediment. Despite this, it is still unclear how heavy metal concentrations in leaves change as they develop and how metals in senescence leaves are recycled back into the mangrove ecosystems during decomposition. The present study aims to investigate the dynamics of six heavy metals (Cu, Zn, Cr, Ni, Cd, and Pb) in leaves of two common mangrove plants, Avicennia marina and Kandelia obovata, at different stages of development (young, mature, and senescent) and leaf litter decomposition (from 0 to 20 weeks). Based on litterbag experiments in a subtropical mangrove swamp, both plant species showed similar trends in alternations of the six heavy metals during leaf development, that was, decreased in Cu and Zn but increased in Pb, while Cr, Ni, and Cd remained steady. All heavy metals in litter gradually increased in concentration during decomposition. By the end of the 20-weeks decomposition, the concentrations of Cu, Zn, and Cd in decayed leaves were comparable to those in sediment, with Cu, Zn, and Cd at approximately 18, 75, and 0.2 mg·kg-1, respectively, while Cr (66 mg·kg-1), Ni (65 mg·kg-1), and Pb (55 mg·kg-1) were lower than those in sediment, indicating that metals were not retained in litter but recycled back to the sediment. Tannins in mangrove leaf litter might chelate heavy metals, affecting their migration and transformation of heavy metals in estuarine mangrove wetlands. The findings of our study provide insight into the interactions between toxic heavy metals and mangrove plant species during leaf development, representing the first example of how most metals would be retained in leaf litter during decomposition, thereby reducing their release to estuarine and marine ecosystems.

Different multiparametric MRI-based radiomics models for differentiating stage IA endometrial cancer from benign endometrial lesions: A multicenter study.

Purpose: The aim of this study was to evaluate the value of different multiparametric MRI-based radiomics models in differentiating stage IA endometrial cancer (EC) from benign endometrial lesions. Methods: The data of patients with endometrial lesions from two centers were collected. The radiomics features were extracted from T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, and late contrast-enhanced T1-weighted imaging (LCE-T1WI). After data dimension reduction and feature selection, nine machine learning algorithms were conducted to determine which was the optimal radiomics model for differential diagnosis. The univariate analyses and logistic regression (LR) were performed to reduce valueless clinical parameters and to develop the clinical model. A nomogram using the radscores combined with clinical parameters was developed. Two integrated models were obtained respectively by the ensemble strategy and stacking algorithm based on the clinical model and optimal radiomics model. The area under the curve (AUC), clinical decisive curve (CDC), net reclassification index (NRI), and integrated discrimination index (IDI) were used to evaluate the performance and clinical benefits of the models. Results: A total of 371 patients were incorporated. The LR model was the optimal radiomics model with the highest average AUC (0.854) and accuracy (0.802) in the internal and external validation groups (AUC = 0.910 and 0.798, respectively), and outperformed the clinical model (AUC = 0.739 and 0.592, respectively) or the radiologist (AUC = 0.768 and 0.628, respectively). The nomogram (AUC = 0.917 and 0.802, respectively) achieved better discrimination performance than the optimal radiomics model in two validation groups. The stacking model (AUC = 0.915) and ensemble model (AUC = 0.918) had a similar performance compared with the nomogram in the internal validation group, whereas the AUCs of the stacking model (AUC = 0.792) and ensemble model (AUC = 0.794) were lower than those of the nomogram and radiomics model in the external validation group. According to the CDC, NRI, and IDI, the optimal radiomics model, nomogram, stacking model, and ensemble model achieved good net benefits. Conclusions: Multiparametric MRI-based radiomics models can non-invasively differentiate stage IA EC from benign endometrial lesions, and LR is the best machine learning algorithm. The nomogram presents excellent and stable diagnostic efficiency.

Enhanced Resting-State Functional Connectivity With Decreased Amplitude of Low-Frequency Fluctuations of the Salience Network in Mindfulness Novices.

Mindfulness and accordant interventions are often used as complementary treatments to psychological or psychosomatic problems. This has also been gradually integrated into daily lives for the promotion of psychological well-being in non-clinical populations. The experience of mindful acceptance in a non-judgmental way brought about the state, which was less interfered by a negative effect. Mindfulness practice often begins with focused attention (FA) meditation restricted to an inner experience. We postulate that the brain areas related to an interoceptive function would demonstrate an intrinsic functional change after mindfulness training for the mindful novices along with paying more attention to internal processes. To further explore the influence of mindfulness on the organization of the brain regions, both functional connectivity (FC) in the voxel and the region of interest (ROI) level were calculated. In the current study, 32 healthy volunteers, without any meditation experiences, were enrolled and randomly assigned to a mindfulness-based stress reduction group (MBSR) or control group (CON). Participants in the MBSR group completed 8 weeks of mindfulness-based stress reduction (MBSR) and rated their mindfulness skills before and after MBSR. All subjects were evaluated via resting-state functional MRI (rs-fMRI) in both baselines and after 8 weeks. They also completed a self-report measure of their state and trait anxiety as well as a positive and negative affect. Pre- and post-MBSR assessments revealed a decreased amplitude of low-frequency fluctuations (ALFF) in the right anterior cingulate gyrus (ACC.R), left anterior and posterior insula (aIC.L, pIC.L), as well as left superior medial frontal gyrus (SFGmed.L) in MBSR practitioners. Strengthened FC between right anterior cingulate cortex (ACC.R) and aIC.R was observed. The mean ALFF values of those regions were inversely and positively linked to newly acquired mindful abilities. Along with a decreased negative affect score, our results suggest that the brain regions related to attention and interoceptive function were involved at the beginning of mindfulness. This study provides new clues in elucidating the time of evaluating the brain mechanisms of mindfulness novices.

Longitudinal brain atlases of early developing cynomolgus macaques from birth to 48 months of age.

Longitudinal brain imaging atlases with densely sampled time-points and ancillary anatomical information are of fundamental importance in studying early developmental characteristics of human and non-human primate brains during infancy, which feature extremely dynamic imaging appearance, brain shape and size. However, for non-human primates, which are highly valuable animal models for understanding human brains, the existing brain atlases are mainly developed based on adults or adolescents, denoting a notable lack of temporally densely-sampled atlases covering the dynamic early brain development. To fill this critical gap, in this paper, we construct a comprehensive set of longitudinal brain atlases and associated tissue probability maps (gray matter, white matter, and cerebrospinal fluid) with totally 12 time-points from birth to 4 years of age (i.e., 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 months of age) based on 175 longitudinal structural MRI scans from 39 typically-developing cynomolgus macaques, by leveraging state-of-the-art computational techniques tailored for early developing brains. Furthermore, to facilitate region-based analysis using our atlases, we also provide two popular hierarchy parcellations, i.e., cortical hierarchy maps (6 levels) and subcortical hierarchy maps (6 levels), on our longitudinal macaque brain atlases. These early developing atlases, which have the densest time-points during infancy (to the best of our knowledge), will greatly facilitate the studies of macaque brain development.

Diagnostic Accuracy of MRI for Detecting Cervical Invasion in Patients with Endometrial Carcinoma: A Meta-Analysis.

Objectives: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in the preoperative assessment of cervical invasion and to analyse the influence of different imaging protocols in patients with endometrial carcinoma. Methods: An extensive search of articles about MRI for assessing cervical invasion in patients with endometrial carcinoma was performed on PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials from January 2000 to July 2020. Two reviewers independently evaluated the methodological quality of each study by using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Diagnostic accuracy results and additional useful information were extracted. The pooled estimation data was obtained by statistical analysis. Results: A total of 42 eligible studies were included in the meta-analysis. Significant evidence of heterogeneity was found for detecting cervical invasion (I2 = 74.1%, P = 0.00 for sensitivity and I2 = 56.2%, P = 0.00 for specificity). The pooled sensitivity and specificity of MRI were 0.58 and 0.95 respectively. The use of higher field strength (3.0 T) demonstrated higher pooled sensitivity (0.74). Using diffusion weighted imaging (DWI) alone presented higher pooled sensitivity (0.86) than using other sequences. The studies that used dynamic contrast-enhanced MRI (DCE-MRI) alone showed higher sensitivity (0.80) and specificity (0.96) than those that used T2-weighted imaging (T2WI) alone. Conclusions: MRI shows high specificity for detecting cervical infiltration in endometrial carcinoma. Using DWI or a 3.0-T device may improve the pooled sensitivity. DCE-MRI demonstrates higher pooled sensitivity and specificity than T2WI.

The value of clinical parameters combined with magnetic resonance imaging (MRI) features for preoperatively distinguishing different subtypes of uterine sarcomas: An observational study (STROBE compliant).

To investigate clinical parameters combined with magnetic resonance imaging (MRI) features including apparent diffusion coefficient (ADC) values in preoperative identification of different subtypes of uterine sarcomas including uterine leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and carcinosarcoma (CS).Data from 71 patients with uterine sarcoma confirmed by surgery and pathology were collected. The clinical characteristics, conventional MRI features, mean ADC values, minimum ADC values, and lesion-muscle ADC ratio (rADC) values were compared with different subtypes of uterine sarcomas.Age, clinical manifestation, tumor location, shape, and T1-weighted image (T1WI) signals were significantly different between CS and LMS or ESS (all P < .01). The presence of band sign was significantly higher in ESS than in LMS or CS (both P < .001). The cystic change or necrosis and enhancement could help to differentiate LMS from ESS or CS (both P < .02). Significant differences were observed in T2-weighted image (T2WI) signals of the solid components of LMS compared with CS (P < .001). There was a significant difference between ESS and CS in the rADC values (P = .004).Clinical parameters combined with MRI features could help narrowing preoperative diagnostic possibilities in distinguishing subtypes of uterine sarcomas. These findings may be beneficial in helping guide operative decisions.

The Diagnostic Value of MRI for Preoperative Staging in Patients with Endometrial Cancer: A Meta-Analysis.

OBJECTIVES: To assess the diagnostic accuracy of magnetic resonance imaging (MRI) for detecting myometrial invasion, cervical invasion, and lymph node metastases in endometrial cancer. MATERIALS AND METHODS: A systematic literature search was performed in PubMed, Embase, Cochrane Library, Web of Science, and Clinical trials. The methodological quality of each study was assessed by using the standard Quality Assessment of Diagnostic Accuracy Studies-2. Statistical analysis included evaluating publication bias, assessing threshold effect, exploring heterogeneity, pooling data, meta-regression, forest plot, and summary receiver-operating characteristics curves construction. RESULTS: Fourteen studies could be analyzed. For detecting deep myometrial invasion, the pooled sensitivity and specificity were 0.79 and 0.81 respectively, and patients younger than 60 years old demonstrated higher sensitivity (0.84) and specificity (0.90). The diagnostic accuracy is highest by jointly using T2-weighted image, dynamic contrast-enhanced MRI, and diffusion weighted imaging to detect the deep myometrial invasion. There were low sensitivity and high specificity for the diagnosis of cervical invasion (0.53, 0.95), cervical stromal invasion (0.50, 0.95), pelvic or/and para-aortic lymph node metastases (0.59, 0.95), and pelvic lymph node metastases (0.65, 0.95). CONCLUSION: MRI has good diagnostic performance for assessing myometrial invasion in patients with endometrial cancer, especially in patients younger than 60 years old. Dynamic contrast-enhanced MRI and diffusion weighted imaging can help improve sensitivity and specificity for detecting myometrial invasion. MRI shows high specificity for detecting cervical invasion and lymph node metastases in endometrial cancer.

Alterations of Regional Homogeneity and Functional Connectivity Following Short-Term Mindfulness Meditation in Healthy Volunteers.

Mindfulness is described as the non-judgmental awareness of experiences in the present moment. The sustained practice of mindfulness may also have beneficial effects on an individual's well-being. For instance, mindfulness meditation is an effective approach for improving emotion regulation. Specifically, the early stage of mindfulness meditation training enhances emotional monitoring systems related to attention regulation and executive function. Reduced activity in the default mode network (DMN) would probably be observed corresponding to the attenuated mind wandering. In the present study, we hypothesized that alterations in functional activity in the frontal-parietal cortex and DMN may be induced by short-term mindfulness meditation. In this study, before and after 8 weeks of weekly Mindfulness-Based Stress Reduction (MBSR) training, healthy participants were evaluated using a mindfulness questionnaire and an affect schedule, as well as via resting-state functional magnetic resonance imaging. Sixteen right-handed non-meditators were enrolled. Another 16 demographically matched healthy adults without any meditation experience were recruited as controls. Pre- and post-MBSR assessments were compared. Increased regional homogeneity in the right superior parietal lobule and left postcentral gyrus (PoCG), as well as altered functional connectivity in PoCG-related networks, were observed post-MBSR. The mindfulness questionnaire scores also improved and negative affect was significantly decreased after MBSR. Together with reduced involvement of the posterior brain, our results suggest a tendency toward stronger involvement of the parietal cortex in mindfulness beginners. This study provides novel evidence regarding the optimization of emotional processing with short-term mindfulness meditation.

Transplantation of human ESC-derived mesenchymal stem cell spheroids ameliorates spontaneous osteoarthritis in rhesus macaques.

It has been demonstrated that mesenchymal stem cells (MSCs) differentiated from human embryonic stem cells (hESCs), name EMSCs, can treat a variety of autoimmune and inflammatory diseases, with similar efficacies to those achieved with MSCs derived from somatic tissues such as bone marrow (BMSCs). The chance increases even higher for EMSCs, than somatic tissue derived MSCs​, to become a cell drug as the former can be produced in large scale from an unlimited hESC line with easier quality control and less biosafety concern. We have further demonstrated that both human ESCs and EMSCs, after aggregation to form spheroids, can tolerate hypoxic and ambient conditions (AC) for over 4 and 10 days, respectively, without loss of their viability and alteration of their functions. Based on these advantages, we decided to test whether EMSC spheroids, made in large quantity and delivered through a long-term distance at AC, can treat osteoarthritis spontaneously developed in rhesus macaques (M. mulatta) monkeys as well as the allogenic MSCs. Methods: Xenogeneic AC-transported EMSC spheroids or allogenic BMSCs were injected into the articular cavity of both knees of the monkeys at 3 animals per group. Another two macaques were injected the same way with saline as controls. Results: Both EMSCs and BMSCs groups showed significant amelioration indicated by the reduction of swelling joint size and amplification of keen flare angle post-treatment, compared to the control group. Examinations via X-ray and MRI also indicated the decrease of inflammation and osteophyma, and recovery of the synovium and cartilage in both treated groups. No sign of allergy or graft versus host disease was observed in the animals. Conclusion: Our results demonstrate that human EMSC spheroids can prevent the osteoarthtitis progression and ameliorate osteoarthritis in the rhesus macaques as well as allogenic BMSCs, and this study shall help advance the clinical application of EMSCs.

Increased Functional Connectivity Between Medulla and Inferior Parietal Cortex in Medication-Free Major Depressive Disorder.

Emerging evidence has documented the abnormalities of primary brain functions in major depressive disorder (MDD). The brainstem has shown to play an important role in regulating basic functions of the human brain, but little is known about its role in MDD, especially the roles of its subregions. To uncover this, the present study adopted resting-state functional magnetic resonance imaging with fine-grained brainstem atlas in 23 medication-free MDD patients and 34 matched healthy controls (HC). The analysis revealed significantly increased functional connectivity of the medulla, one of the brainstem subregions, with the inferior parietal cortex (IPC) in MDD patients. A positive correlation was further identified between the increased medulla-IPC functional connectivity and Hamilton anxiety scores. Functional characterization of the medulla and IPC using a meta-analysis revealed that both regions primarily participated in action execution and inhibition. Our findings suggest that increased medulla-IPC functional connectivity may be related to over-activity or abnormal control of negative emotions in MDD, which provides a new insight for the neurobiology of MDD.

Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys.

Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT.

The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats.

Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using (131)iodine ((131)I) and hyperthyroidism using levothyroxine (LT4). Serum free thyroxine (FT4) and triiodothyronine (FT3) significantly decreased in the hypothyroid of rats with single injections of (131)I (5mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline-vehicle administered rats. LT4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT4 (15µg/kg) caused a greater than 10-fold increase in serum FT4 and FT3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15mg/kg) diminished serum FT4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels.

Why psychosis is frequently associated with Parkinson's disease?

Psychosis is a common non-motor symptom of Parkinson's disease whose pathogenesis remains poorly understood. Parkinson's disease in conjunction with psychosis has been shown to induce injury to extracorticospinal tracts as well as within some cortical areas. In this study, Parkinson's disease patients with psychosis who did not receive antipsychotic treatment and those without psychosis underwent diffusion tensor imaging. Results revealed that in Parkinson's disease patients with psychosis, damage to the left frontal lobe, bilateral occipital lobe, left cingulated gyrus, and left hippocampal white-matter fibers were greater than damage to the substantia nigra or the globus pallidus. Damage to white-matter fibers in the right frontal lobe and right cingulate gyrus were also more severe than in the globus pallidus, but not the substantia nigra. Damage to frontal lobe and cingulate gyrus white-matter fibers was more apparent than that to occipital or hippocampal fiber damage. Compared with Parkinson's disease patients without psychosis, those with psychosis had significantly lower fractional anisotropy ratios of left frontal lobe, bilateral occipital lobe, left cingu-lated gyrus, and left hippocampus to ipsilateral substantia nigra or globus pallidus, indicating more severe damage to white-matter fibers. These results suggest that psychosis associated with Par-kinson's disease is probably associated with an imbalance in the ratio of white-matter fibers be-tween brain regions associated with psychiatric symptoms (frontal lobe, occipital lobe, cingulate gyrus, and hippocampus) and those associated with the motor symptoms of Parkinson's disease (the substantia nigra and globus pallidus). The relatively greater damage to white-matter fibers in psychiatric symptom-related brain regions than in extracorticospinal tracts might explain why chosis often occurs in Parkinson's disease patients.

[Application of diffusion tensor imaging and 1H-magnetic resonance spectroscopy in diagnosis of traumatic brain injury].

Mild traumatic brain injury (mTBI) is a common type of brain disorders among young adults. The dysfunction of the brain is often exacerbated due to diffuse axonal injury (DAI) which based on the injury of white matter fibers and axons. Since mild and moderate brain injury or DAI are diffuse and subtle, conventional CT and MRI are difficult to make a positive diagnosis. Recent clinical study indicated that functional magnetic resonance imaging has a high detection rate in the diagnosis of acute mild and moderate brain injury, especially the diffusion tensor imaging (DTI) and 1H-magnetic resonance spectroscopy (1H-MRS). This paper has reviewed the principles and characteristics of DTI and 1H-MRS, and recent research in the clinical and animal experiments on brain injury.