Anatomical distance affects functional connectivity at rest in medicine-free obsessive-compulsive disorder.

BACKGROUND: Brain functional abnormalities at rest have been observed in obsessive-compulsive disorder (OCD). However, whether and how anatomical distance influences functional connectivity (FC) at rest is ambiguous in OCD. METHODS: Using resting-state functional magnetic resonance imaging data, we calculated the FC of each voxel in the whole-brain and divided FC into short- and long-range FCs in 40 medicine-free patients with OCD and 40 healthy controls (HCs). A support vector machine (SVM) was used to determine whether the altered short- and long-range FCs could be utilized to distinguish OCD from HCs. RESULTS: Patients had lower short-range positive FC (spFC) and long-range positive FC (lpFC) in the left precentral/postcentral gyrus (t = -5.57 and -5.43; P < 0.05, GRF corrected) and higher lpFC in the right thalamus/caudate, left thalamus, left inferior parietal lobule (IPL) and left cerebellum CrusI/VI (t = 4.59, 4.61, 4.41, and 5.93; P < 0.05, GRF corrected). Furthermore, lower spFC in the left precentral/postcentral gyrus might be used to distinguish OCD from HCs with an accuracy of 80.77%, a specificity of 81.58%, and a sensitivity of 80.00%. CONCLUSION: These findings highlight that anatomical distance has an effect on the whole-brain FC patterns at rest in OCD. Meanwhile, lower spFC in the left precentral/postcentral gyrus might be applied in distinguishing OCD from HCs.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Restoring both continence and micturition after chronic spinal cord injury by pudendal neuromodulation.

Neurogenic bladder management after spinal cord injury (SCI) is very challenging. Daily urethral catheterization is most commonly used to empty the bladder, which causes frequent infections of the lower urinary tract. This study reports a novel idea to restore both continence and micturition after SCI by an implantable pudendal nerve stimulator (PNS). The PNS was surgically implanted in four cats with complete SCI at T9-T10 spinal level and tested weekly for 13-14 weeks under awake conditions. These chronic SCI cats consistently exhibited large residual bladder volumes (average 40-50 ml) due to their inability to void efficiently, while urine leakage also occurred frequently. The PNS which consisted of stimulating the pudendal nerve at 20-30 Hz to trigger a spinal reflex bladder contraction and at the same time blocking the pudendal nerves bilaterally with 10 kHz stimulation to relax the external urethral sphincter and reduce the urethral outlet resistance successfully induced highly efficient (average 80-100%), low pressure (<50 cmH2O) voiding. The PNS at 5 Hz also promoted urine storage by inhibiting reflex bladder activity and increasing bladder capacity. At the end of 14-week chronic testing, low pressure efficient voiding induced by PNS was further confirmed under anesthesia by directly measuring voiding pressure using a bladder catheter inserted through the bladder dome. This study demonstrated the efficacy and safety of the PNS in awake chronic SCI cats, suggesting that a novel neuroprosthesis can be developed for humans to restore bladder function after SCI by stimulating and/or blocking the pudendal nerves.

Global Functional Connectivity Analysis Indicating Dysconnectivity of the Hate Circuit in Major Depressive Disorder.

BACKGROUND: Abnormalities of functional connectivity (FC) in certain brain regions are closely related to the pathophysiology of major depressive disorder (MDD). Findings are inconsistent with different presuppositions in regions of interest. Our research focused on voxel-wise brain-wide FC changes in patients with MDD in an unbiased manner. METHOD: We examined resting-state functional MRI in 23 patients with MDD and 26 healthy controls. Imaging data were analyzed by using global-brain FC (GFC) and used to explore the correlation of abnormal GFC values with clinical variables. RESULTS: Increased GFC values in the left medial superior frontal gyrus (SFGmed) and decreased GFC values in the right supplementary motor area (SMA) were observed in the patients with MDD compared with the controls. The decreased GFC values in the right SMA had a positive correlation with vitamin D and Hamilton Anxiety Scale (HAM-A) scores. CONCLUSION: Abnormal GFC in the hate circuit, particularly increased GFC in the left SFGmed and decreased GFC in the right SMA, appears to be a new sight for comprehending the pathological alterations in MDD.

3D RNA-seq: a powerful and flexible tool for rapid and accurate differential expression and alternative splicing analysis of RNA-seq data for biologists.

RNA-sequencing (RNA-seq) analysis of gene expression and alternative splicing should be routine and robust but is often a bottleneck for biologists because of different and complex analysis programs and reliance on specialized bioinformatics skills. We have developed the '3D RNA-seq' App, an R shiny App and web-based pipeline for the comprehensive analysis of RNA-seq data from any organism. It represents an easy-to-use, flexible and powerful tool for analysis of both gene and transcript-level gene expression to identify differential gene/transcript expression, differential alternative splicing and differential transcript usage (3D) as well as isoform switching from RNA-seq data. 3D RNA-seq integrates state-of-the-art differential expression analysis tools and adopts best practice for RNA-seq analysis. The program is designed to be run by biologists with minimal bioinformatics experience (or by bioinformaticians) allowing lab scientists to analyse their RNA-seq data. It achieves this by operating through a user-friendly graphical interface which automates the data flow through the programs in the pipeline. The comprehensive analysis performed by 3D RNA-seq is extremely rapid and accurate, can handle complex experimental designs, allows user setting of statistical parameters, visualizes the results through graphics and tables, and generates publication quality figures such as heat-maps, expression profiles and GO enrichment plots. The utility of 3D RNA-seq is illustrated by analysis of data from a time-series of cold-treated Arabidopsis plants and from dexamethasone-treated male and female mouse cortex and hypothalamus data identifying dexamethasone-induced sex- and brain region-specific differential gene expression and alternative splicing.

Superficial peroneal neuromodulation of nonobstructive urinary retention in cats.

AIMS: To determine if superficial peroneal nerve stimulation (SPNS) can improve nonobstructive urinary retention (NOUR). METHODS: In α-chloralose anesthetized cats, NOUR was induced by repetitive application (4-16 times) of 30-minute tibial nerve stimulation (TNS: 5 Hz frequency, 0.2 ms pulse width) at 4 to 6 times threshold intensity (T) for inducing toe twitches. SPNS (1 Hz, 0.2 ms) at 2 to 4 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) during a cystometrogram (CMG) or during voiding (SPNSv) by a surgically implanted cuff electrode or by skin surface electrodes to determine if the stimulation reduced NOUR induced by prolonged TNS. RESULTS: During control CMGs, efficient (86.4% ± 5.5%) voiding occurred with a postvoid residual (PVR) volume equal to 14.9% ± 6.2% of control bladder capacity. NOUR elicited by prolonged TNS significantly (P < .05) increased bladder capacity to 168.6% ± 15.5% of control, reduced voiding efficiency to 30.4% ± 4.8%, and increased PVR to 109% ± 9.2% of control. Using the implanted cuff electrode, SPNSc and SPNSv significantly (P < .05) increased voiding efficiency to 66.7% ± 7.4% and 65.0% ± 5.9%, respectively, and reduced PVR to 52.2% ± 11.4% and 64.3% ± 11.6%, respectively. SPNSc but not SPNSv significantly (P < .05) reduced bladder capacity to 133.4% ± 15% of control. Transcutaneous SPNSv but not SPNSc also significantly (P < .05) reversed the TNS-induced NOUR responses. CONCLUSIONS: This study shows that SPNS is effective in reversing NOUR induced by prolonged TNS. Transcutaneous SPNS provides the opportunity to develop a noninvasive neuromodulation therapy for NOUR to treat more patients than current sacral neuromodulation therapy.

Novel pectin based composite hydrogel derived from grapefruit peel for enhanced Cu(II) removal.

Novel biochar/pectin/alginate hydrogel beads (BPA) derived from grapefruit peel were synthesized and used for Cu(II) removal from aqueous solution. FTIR, SEM-EDS, XRD, TGA and XPS, etc. were applied for characterization analysis. The synergistic reinforcing effect of polymer matrix and biochar fillers improved the adsorptive, mechanical and thermostabilized performance of BPA. Factors like component contents of biochar and pectin, pH, contact time, Cu(II) concentration and coexisting inorganic salts or organic ligands were systematically investigated in batch mode. The adsorption isotherms were fitted well by the Freundlich model and the experimental maximum adsorption capacity of optimized BPA-9 beads (mass ratio of pectin to alginate = 10:1) with 0.25% biochar, was ∼80.6 mg/g at pH 6. Kinetic process was well described by the pseudo-second-order model and film diffusion primarily governed the overall adsorption rate, followed by intraparticle diffusion. Thermodynamics analysis suggested spontaneous feasibility and endothermic nature of adsorption behavior. Moreover, BPA also showed better environmental adaptability in the presence of NaCl, MgCl2, CaCl2, EDTA-2Na and CA as well as good adsorption potential for other heavy metal [e.g. Pb(III)]. Crucially, the BPA beads showed good regeneration ability after five cycles. All these results indicated the potential of BPA for removing heavy metal from water.

Brain structural abnormalities as potential markers for detecting individuals with ultra-high risk for psychosis: A systematic review and meta-analysis.

OBJECTIVE: This study aims to determine whether structural alterations can be used as neuroimaging markers to detect individuals with ultra-high risk (UHR) for psychosis for the diagnosis of schizophrenia and improvement of treatment outcomes. METHODS: Embase and Pubmed databases were searched for related studies in July 2018. The search was performed without restriction on time and regions or languages. A total of 188 articles on voxel-based morphometry (VBM) and 96 articles on cortical thickness were obtained, and another 6 articles were included after the reference lists were checked. Our researchers assessed and extracted the data in accordance with the PRISMA guideline. The data were processed with a seed-based mapping method. RESULTS: Fourteen VBM and nine cortical thickness studies were finally included in our study. In individuals with UHR, the gray matter volumes in the bilateral median cingulate (Z = 1.034), the right fusiform gyrus (Z = 1.051), the left superior temporal gyrus (Z = 1.048), and the right thalamus (Z = 1.039) increased relative to those of healthy controls. By contrast, the gray matter volumes in the right gyrus rectus (Z = -2.109), the right superior frontal gyrus (Z = -2.321), and the left superior frontal gyrus (Z = -2.228) decreased. The robustness of these findings was verified through Jackknife sensitivity analysis, and heterogeneity across studies was low. Typically, cortical thickness alterations were not detected in individuals with UHR. CONCLUSIONS: Structural abnormalities of the thalamocortical circuit may underpin the neurophysiology of psychosis and mark the vulnerability of transition to psychosis in UHR subjects.

Functional asymmetry of thalamocortical networks in subjects at ultra-high risk for psychosis and first-episode schizophrenia.

Disrupted functional asymmetry has been implicated in schizophrenia. However, it remains unknown whether disrupted functional asymmetry originates from intra-hemispheric and/or inter-hemispheric functional connectivity (FC) in the patients, and whether it starts at very early stage of psychosis. Seventy-six patients with first-episode, drug-naive schizophrenia, 74 subjects at ultra-high risk for psychosis (UHR), and 71 healthy controls underwent resting-state functional magnetic resonance imaging. The 'Parameter of asymmetry' (PAS) metric was calculated and support vector machine (SVM) classification analysis was applied to analyze the data. Compared with healthy controls, patients exhibited decreased PAS in the left thalamus/pallidum, right hippocampus/parahippocampus, right inferior frontal gyrus/insula, right thalamus, and left inferior parietal lobule, and increased PAS in the left calcarine, right superior occipital gyrus/middle occipital gyrus, and right precentral gyrus/postcentral gyrus. By contrast, UHR subjects showed decreased PAS in the left thalamus relative to healthy controls. A negative correlation was observed between decreased PAS in the right hippocampus/parahippocampus and Brief Visuospatial Memory Test-Revised (BVMT-R) scores in the patients (r = -0.364, p = 0.002). Moreover, the PAS values in the left thalamus could discriminate the patients/UHR subjects from the controls with acceptable sensitivities (68.42%/81.08%). First-episode patients and UHR subjects shared decreased PAS in the left thalamus. This observed pattern of functional asymmetry highlights the involvement of the thalamus in the pathophysiology of psychosis and may also be applied as a very early marker for psychosis.

Isotryptophan from Antarctic Bacillus amyloliquefaciens Pc3: purification, identification, characterization, and antifungal activity.

Strain Pc3 was isolated from Antarctic seawater and identified as Bacillus amyloliquefaciens. A compound with antifungal activity was purified from the fermentation supernatant of B. amyloliquefaciens Pc3. Its structure was determined to be (S)-2-amino-3-(1H-indol-2-yl) propanoic acid, named as isotryptophan, based on detailed analysis of its nuclear magnetic resonance (NMR) and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS). Isotryptophan exhibited good thermal stability and antifungal activity against several plant-pathogenic fungi with low minimum inhibitory concentrations. Therefore, the characterisation of isotryptophan from the Antarctic B. amyloliquefaciens Pc3 will facilitate its potential application in the control of plant-pathogenic fungal infection.

Abnormal causal connectivity by structural deficits in first-episode, drug-naive schizophrenia at rest.

Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.