Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

Background

Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging.

Methods

A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity.

Results

Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores.

Conclusion

Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for assessment of neuronal damage and the prediction of clinical outcomes in acute SCI.     

The Selective Impairment of Resting-State Functional Connectivity of the Lateral Subregion of the Frontal Pole in Schizophrenia

Objective

Although extensive resting-state functional connectivity (rsFC) changes have been reported in schizophrenia, rsFC changes of the frontal pole (FP) remain unclear. The FP contains several subregions with different connection patterns; however, it is unknown whether the FP subregions are differentially affected in schizophrenia. To explore this possibility, we compared rsFC differences of the FP subregions between schizophrenia patients and healthy controls.

Method

One hundred healthy controls and 91 patients with schizophrenia underwent resting-state functional MRI with a sensitivity-encoded spiral-in (SENSE-SPIRAL) imaging sequence to reduced susceptibility-induced signal loss and distortion. The FP was subdivided into the orbital (FPo), medial (FPm), and lateral (FPl) subregions. Mean fMRI time series were extracted for each FP subregion and entered into a seed-based rsFC analysis.

Results

The FP subregions exhibited differential rsFC patterns in both healthy controls and schizophrenia patients. Direct comparison between groups revealed reduced rsFCs between the bilateral FPl and several cognitive-related regions, including the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex/precuneus, temporal cortex and inferior parietal lobule in schizophrenia. Although the FPl exhibited obvious atrophy, rsFC changes were unrelated to volumetric atrophy in the FPl, to duration of illness, and to antipsychotic medication dosage. No significant differences were observed in the rsFCs of other FP subregions.

Conclusion

These findings suggest a selective (the lateral subregion) functional disconnection of the FP subregions in schizophrenia.     

Impact of Pacemaker Lead Characteristics on Pacemaker Related Infection and Heart Perforation: A Nationwide Population-Based Cohort Study

Background

Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications.

Methods and Results

Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07–0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08–0.83; P = 0.023).

Conclusions

There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.     

Inhibition of the Inositol Kinase Itpkb Augments Calcium Signaling in Lymphocytes and Reveals a Novel Strategy to Treat Autoimmune Disease

Emerging approaches to treat immune disorders target positive regulatory kinases downstream of antigen receptors with small molecule inhibitors. Here we provide evidence for an alternative approach in which inhibition of the negative regulatory inositol kinase Itpkb in mature T lymphocytes results in enhanced intracellular calcium levels following antigen receptor activation leading to T cell death. Using Itpkb conditional knockout mice and LMW Itpkb inhibitors these studies reveal that Itpkb through its product IP4 inhibits the Orai1/Stim1 calcium channel on lymphocytes. Pharmacological inhibition or genetic deletion of Itpkb results in elevated intracellular Ca²⁺ and induction of FasL and Bim resulting in T cell apoptosis. Deletion of Itpkb or treatment with Itpkb inhibitors blocks T-cell dependent antibody responses in vivo and prevents T cell driven arthritis in rats. These data identify Itpkb as an essential mediator of T cell activation and suggest Itpkb inhibition as a novel approach to treat autoimmune disease.     

SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma

Hodgkin’s lymphoma (HL) is a lymphoid neoplasm characterized by Hodgkin’s and Reed-Sternberg (H/RS) cells, which is regulated by CD99. We previously reported that CD99 downregulation led to the transformation of murine B lymphoma cells (A20) into cells with an H/RS phenotype, while CD99 upregulation induced differentiation of classical Hodgkin’s lymphoma (cHL) cells (L428) into terminal B-cells. However, the molecular mechanism remains unclear. In this study, using fluorescence two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), we have analyzed the alteration of protein expression following CD99 upregulation in L428 cells as well as downregulation of mouse CD99 antigen-like 2 (mCD99L2) in A20 cells. Bioinformatics analysis showed that SEPTIN2 and STATHMIN, which are cytoskeleton proteins, were significantly differentially expressed, and chosen for further validation and functional analysis. Differential expression of SEPTIN2 was found in both models and was inversely correlated with CD99 expression. STATHMIN was identified in the A20 cell line model and its expression was positively correlated with that of CD99. Importantly, silencing of SEPTIN2 with siRNA substantially altered the cellular cytoskeleton in L428 cells. The downregulation of STATHMIN by siRNA promoted the differentiation of H/RS cells toward terminal B-cells. These results suggest that SEPTIN2-mediated cytoskeletal rearrangement and STATHMIN-mediated differentiation may contribute to changes in cell morphology and differentiation of H/RS cells with CD99 upregulation in HL.     

Widespread Albedo Decreasing and Induced Melting of Himalayan Snow and Ice in the Early 21st Century

Background

The widely distributed glaciers in the greater Himalayan region have generally experienced rapid shrinkage since the 1850s. As invaluable sources of water and because of their scarcity, these glaciers are extremely important. Beginning in the twenty-first century, new methods have been applied to measure the mass budget of these glaciers. Investigations have shown that the albedo is an important parameter that affects the melting of Himalayan glaciers.

Methodology/Principal Findings

The surface albedo based on the Moderate Resolution Imaging Spectroradiometer (MODIS) data over the Hindu Kush, Karakoram and Himalaya (HKH) glaciers is surveyed in this study for the period 2000–2011. The general albedo trend shows that the glaciers have been darkening since 2000. The most rapid decrease in the surface albedo has occurred in the glacial area above 6000 m, which implies that melting will likely extend to snow accumulation areas. The mass-loss equivalent (MLE) of the HKH glacial area caused by surface shortwave radiation absorption is estimated to be 10.4 Gt yr^-1, which may contribute to 1.2% of the global sea level rise on annual average (2003–2009).

Conclusions/Significance

This work probably presents a first scene depicting the albedo variations over the whole HKH glacial area during the period 2000–2011. Most rapidly decreasing in albedo has been detected in the highest area, which deserves to be especially concerned.     

Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers

The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30) received exposure to AIE (5g/kg, i.g.) or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR) test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.     

Vascular Complications of Intercavernous Sinuses during Transsphenoidal Surgery: An Anatomical Analysis Based on Autopsy and Magnetic Resonance Venography

Purpose

Vascular complications induced by intercavernous sinus injury during dural opening in the transsphenoidal surgery may contribute to incomplete tumour resections. Preoperative neuro-imaging is of crucial importance in planning surgical approach. The aim of this study is to correlate the microanatomy of intercavernous sinuses with its contrast-enhanced magnetic resonance venography (CE-MRV).

Methods

Eighteen human adult cadavers and 24 patients were examined based on autopsy and CE-MRV. Through dissection of the cadavers and CE-MRV, the location, shape, number, diameter and type of intercavernous sinuses were measured and compared.

Results

Different intercavernous sinuses were identified by their location and shape in all the cadavers and CE-MRV. Compared to the cadavers, CE-MRV revealed 37% of the anterior intercavernous sinus, 48% of the inferior intercavernous sinus, 30% of the posterior intercavernous sinus, 30% of the dorsum sellae sinus and 100% of the basilar sinus. The smaller intercavernous sinuses were not seen in the neuro-images. According to the presence of the anterior and inferior intercavernous sinus, four types of the intercavernous sinuses were identified in cadavers and CE-MRV, and the corresponding operative space in the transsphenoidal surgical approach was implemented.

Conclusion

The morphology and classification of the cavernous sinus can be identified by CE-MRV, especially for the larger vessels, which cause bleeding more easily. Therefore, CE-MRV provides a reliable measure for individualized preoperative planning during transsphenoidal surgery.     

A Multiple Antigenic Peptide Mimicking Peptidoglycan Induced T Cell Responses to Protect Mice from Systemic Infection with Staphylococcus aureus

Due to the enormous capacity of Staphylococcus aureus to acquire antibiotic resistance, it becomes imperative to develop vaccines for decreasing the risk of its life-threatening infections. Peptidoglycan (PGN) is a conserved and major component of S. aureus cell wall. However, it has not been used as a vaccine candidate since it is a thymus-independent antigen. In this study, we synthesized a multiple antigenic peptide, named MAP27, which comprised four copies of a peptide that mimics the epitope of PGN. After immunization with MAP27 five times and boosting with heat-inactivated bacterium one time, anti-MAP27 serum bound directly to S. aureus or PGN. Immunization with MAP27 decreased the bacterial burden in organs of BALB/c mice and significantly prolonged their survival time after S. aureus lethal-challenge. The percentage of IFN-γ⁺CD3⁺ T cells and IL-17⁺CD4⁺ T cells in spleen, as well as the levels of IFN-γ, IL-17A/F and CCL3 in spleen and lung, significantly increased in the MAP27-immunized mice after infection. Moreover, in vitro incubation of heat-inactivated S. aureus with splenocytes isolated from MAP27-immunized mice stimulated the production of IFN-γ and IL-17A/F. Our findings demonstrated that MAP27, as a thymus-dependent antigen, is efficient at eliciting T cell-mediated responses to protect mice from S. aureus infection. This study sheds light on a possible strategy to design vaccines against S. aureus.