Feasibility of Two-Screw Anterior Fixation for Odontoid Fractures in a Chinese Population: A Morphometric Study Based on Computed Tomography.

Background: To evaluate the feasibility of treating odontoid fractures in the Chinese population with two cortical screws based on computed tomography (CT) scans and describe a new measurement strategy to guide screw insertion in treating these fractures. Methods: A retrospective review of cervical computed tomographic scans of 128 patients (aged 18-76 years; men, 55 [43.0%]) was performed. The minimum external transverse diameter (METD), minimum external anteroposterior diameter (MEAD), maximum screw length (MSL), and screw projection back angle (SPBA) of the odontoid process were measured on coronal and sagittal CT images. Results: The mean values of METD and MEAD were 10.0 ± 1.1 mm and 12.0 ± 1.0 mm, respectively, in men and 9.2 ± 1.0 mm and 11.0 ± 1.0 mm, respectively, in women. Both measurements were significantly higher in men (p < 0.001). In total, 87 individuals (68%) had METD > 9.0 mm that could accommodate two 3.5-mm cortical screws. The mean MSL value and SPBA range were 34.4 ± 2.9 mm and 13.5°-24.2°, respectively, with no statistically significant difference between men and women. Conclusions: The insertion of two 3.5-mm cortical screws was possible for anterior fixation of odontoid fractures in 87 patients (68%) in our study, and there was a statistically significant difference between men and women.

Radiomics features from 3D-MPRAGE imaging can differentiate temporal-plus epilepsy from temporal lobe epilepsy.

OBJECTIVE: This study aimed to differentiate temporal-plus epilepsy (TPE) from temporal lobe epilepsy (TLE) using extraction of radiomics features from three-dimensional magnetization-prepared rapid acquisition gradient echo (3D-MPRAGE) imaging data. METHODS: Data from patients with TLE or TPE who underwent epilepsy surgery between January 2019 and January 2021 were retrospectively analyzed. Thirty-three regions of interest in the affected hemisphere of each patient were defined on 3D-MPRAGE images. A total of 3531 image features were extracted from each patient. Four feature selection methods and 10 machine learning algorithms were used to build 40 differentiation models. Model performance was evaluated using receiver operating characteristic analysis. RESULTS: Eighty-two patients were included for analysis, 47 with TLE and 35 with TPE. The model combining logistic regression and the relief selection method had the best performance (area under the receiver operating characteristic curve, .779; accuracy, .875; sensitivity, .800; specificity, .929; positive predictive value, .889; negative predictive value, .867). SIGNIFICANCE: Radiomics analysis can differentiate TPE from TLE. The logistic regression classifier trained with radiomics features extracted from 3D-MPRAGE images had the highest accuracy and best performance.

Techniques of Frameless Robot-Assisted Deep Brain Stimulation and Accuracy Compared with the Frame-Based Technique.

BACKGROUND: Frameless robot-assisted deep brain stimulation (DBS) is an innovative technique for leads implantation. This study aimed to evaluate the accuracy and precision of this technique using the Sinovation SR1 robot. METHODS: 35 patients with Parkinson's disease who accepted conventional frame-based DBS surgery (n = 18) and frameless robot-assisted DBS surgery (n = 17) by the same group of neurosurgeons were analyzed. The coordinate of the tip of the intended trajectory was recorded as xi, yi, and zi. The actual position of lead implantation was recorded as xa, ya, and za. The vector error was calculated by the formula of √(xi - xa)2 + (yi - ya)2 + (zi - za)2 to evaluate the accuracy. RESULTS: The vector error was 1.52 ± 0.53 mm (range: 0.20-2.39 mm) in the robot-assisted group and was 1.77 ± 0.67 mm (0.59-2.98 mm) in the frame-based group with no significant difference between two groups (p = 0.1301). In 10.7% (n = 3) frameless robot-assisted implanted leads, the vector error was greater than 2.00 mm with a maximum offset of 2.39 mm, and in 35.5% (n = 11) frame-based implanted leads, the vector error was larger than 2.00 mm with a maximum offset of 2.98 mm. Leads were more posterior than planned trajectories in the robot-assisted group and more medial and posterior in the conventional frame-based group. CONCLUSIONS: Awake frameless robot-assisted DBS surgery was comparable to the conventional frame-based technique in the accuracy and precision for leads implantation.

Efficacy of intraoperative sedation combined with preemptive analgesia for single-level kyphoplasty under local anesthesia: A randomized clinical trial.

BACKGROUND: Kyphoplasty is widely used for Osteoporotic Vertebral Compression Fracture (OVCF) under general or local anesthesia, more attention was paid to its post-operative efficacy. Patients' pain and discomfort control strategies during surgery have not been taken seriously. OBJECTIVE: This study aimed at assessing the efficacy of preoperative preemptive analgesia combined with intraoperative sedation for pain and tension relief in OVCF patients undergoing kyphoplasty under local anesthesia. METHODS: We enrolled 128 patients with single-level OVCF who underwent kyphoplasty in our hospital from July 2013 to July 2016. The patients were randomly allocated into three groups: conventional group (i.e., local anesthesia with 0.5% lidocaine (1); n = 42), preemptive group (i.e, (1) + oral 200 mg Celecoxib on the night before surgery with intravenous 40 mg parecoxib sodium an hour before surgery (2); n = 43), and combined group (i.e., (1) + (2) + continuous intravenous 0.5 µg/kg/h dexmedetomidine intraoperatively; n = 43). Hemodynamic variations (heart rate, blood pressure, pulse oxygen saturation (SpO2)), Pain Visual Analogue Score (VAS), Ramsay score, and adverse events were recorded during perioperative period. RESULTS: Blood pressure and heart rate were more stable with significantly smaller values in the combined group than in the conventional and preemptive groups both intra- and postoperatively. In contrast, SpO2 showed no significant difference among the groups throughout the perioperative period. Intraoperative VAS scores revealed significant differences among the groups with the combined group having the smallest values followed by the preemptive group. Similarly, intraoperative Ramsay scores reflected significantly more favorable effects of sedation in the combined than in conventional group. Both VAS and Ramsay scores showed no significant differences among the groups postoperatively, and no differences in complication incidences were noted among the groups as well. CONCLUSIONS: For kyphoplasty under local anesthesia for single-level OVCF, intraoperative sedation combined with preemptive analgesia worked better in mitigating pain and tension intraoperatively and in preventing hemodynamic changes intra- and post-operatively, as compared to local anesthesia alone or additional preemptive analgesia.

Direct Targeting of the Anterior Nucleus of the Thalamus via 3 T Quantitative Susceptibility Mapping.

Objective: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a potentially effective, minimally invasive, and reversible method for treating epilepsy. The goal of this study was to explore whether 3 T quantitative susceptibility mapping (QSM) could delineate the ANT from surrounding structures, which is important for the direct targeting of DBS surgery. Methods: We obtained 3 T QSM, T1-weighted (T1w), and T2-weighted (T2w) images from 11 patients with Parkinson's disease or dystonia who received subthalamic nucleus (STN) or globus pallidus interna (GPi) DBS surgery in our center. The ANT and its surrounding white matter structures on QSM were compared with available atlases. The contrast-to-noise ratios (CNRs) of ANT relative to the external medullary lamina (eml) were compared across the three imaging modalities. Additionally, the morphology and location of the ANT were depicted in the anterior commissure (AC)-posterior commissure (PC)-based system. Results: ANT can be clearly distinguished from the surrounding white matter laminas and appeared hyperintense on QSM. The CNRs of the ANT-eml on QSM, T1w, and T2w images were 10.20 ± 4.23, 1.71 ± 1.03, and 1.35 ± 0.70, respectively. One-way analysis of variance (ANOVA) indicated significant differences in CNRs among QSM, T1w, and T2w imaging modalities [F(2) = 85.28, p < 0.0001]. In addition, both the morphology and location of the ANT were highly variable between patients in the AC-PC-based system. Conclusion: The potential utility of QSM for the visualization of ANTs in clinical imaging is promising and may be suitable for targeting the ANT for DBS to treat epilepsy.

Localization of the Epileptogenic Zone by Multimodal Neuroimaging and High-Frequency Oscillation.

Accurate localization of the epileptogenic zone (EZ) is a key factor to obtain good surgical outcome for refractory epilepsy patients. However, no technique, so far, can precisely locate the EZ, and there are barely any reports on the combined application of multiple technologies to improve the localization accuracy of the EZ. In this study, we aimed to explore the use of a multimodal method combining PET-MRI, fluid and white matter suppression (FLAWS)-a novel MRI sequence, and high-frequency oscillation (HFO) automated analysis to delineate EZ. We retrospectively collected 15 patients with refractory epilepsy who underwent surgery and used the above three methods to detect abnormal brain areas of all patients. We compared the PET-MRI, FLAWS, and HFO results with traditional methods to evaluate their diagnostic value. The sensitivities, specificities of locating the EZ, and marking extent removed versus not removed [RatioChann(ev)] of each method were compared with surgical outcome. We also tested the possibility of using different combinations to locate the EZ. The marked areas in every patient established using each method were also compared to determine the correlations among the three methods. The results showed that PET-MRI, FLAWS, and HFOs can provide more information about potential epileptic areas than traditional methods. When detecting the EZs, the sensitivities of PET-MRI, FLAWS, and HFOs were 68.75, 53.85, and 87.50%, and the specificities were 80.00, 33.33, and 100.00%. The RatioChann(ev) of HFO-marked contacts was significantly higher in patients with good outcome than those with poor outcome (p< 0.05). When intracranial electrodes covered all the abnormal areas indicated by neuroimaging with the overlapping EZs being completely removed referred to HFO analysis, patients could reach seizure-free (p < 0.01). The periphery of the lesion marked by neuroimaging may be epileptic, but not every lesion contributes to seizures. Therefore, approaches in multimodality can detect EZ more accurately, and HFO analysis may help in defining real epileptic areas that may be missed in the neuroimaging results. The implantation of intracranial electrodes guided by non-invasive PET-MRI and FLAWS findings as well as HFO analysis would be an optimized multimodal approach for locating EZ.

Fluid and White Matter Suppression Imaging and Voxel-Based Morphometric Analysis in Conventional Magnetic Resonance Imaging-Negative Epilepsy.

Purpose: Delineation of subtle lesions in magnetic resonance imaging (MRI)-negative patients is of great importance in preoperative epilepsy evaluation. The aim of our study was to explore the diagnostic value of the novel fluid and white matter suppression (FLAWS) sequence in comparison with a voxel-based MRI postprocessing morphometric analysis program (MAP) in a consecutive cohort of non-lesional patients. Methods: Surgical candidates with a negative finding on an official neuroradiology report were enrolled. High-resolution FLAWS image and MAP maps generated based on high-resolution three-dimensional (3D) T1 image were visually inspected for each patient. The findings of FLAWS or MAP-positive (FLAWS/MAP+) regions were compared with the surgical resection cavity in correlation with surgical outcome and pathology. Results: Forty-five patients were enrolled; the pathological examination revealed focal cortical dysplasia (FCD) in 32 patients and other findings in 13 patients. The positive rate, sensitivity, and specificity were 48.9%, 0.43, and 0.87, respectively, for FLAWS and 64.4%, 0.57, and 0.8, respectively, for MAP. Concordance between surgical resection and FLAWS+ or MAP+ regions was significantly associated with a seizure-free outcome (FLAWS: p = 0.002; MAP: p = 0.0003). A positive finding in FLAWS and MAP together with abnormalities in the same gyrus (FLAWS-MAP gyral+) was detected in 31.1% of patients. FLAWS+ only and MAP+ only were found in 7 (15.5%) and 14 (31.1%) patients, respectively. Conclusions: FLAWS showed a promising value for identifying subtle epileptogenic lesions and can be used as a complement to current MAP in patients with MRI-negative epilepsy.

Voxel-based morphometric MRI post-processing and PET/MRI co-registration reveal subtle abnormalities in cingulate epilepsy.

OBJECTIVE: Diagnostic challenges exist in the presurgical evaluation of patients with magnetic resonance imaging (MRI) negative cingulate epilepsy (CE) because of the heterogeneity in clinical semiology and lack of localizing findings on scalp electroencephalographic (EEG) recordings. We aimed to examine the neuroimaging characteristics in a consecutive cohort of patients with MRI-negative CE with a focus on two image post-processing methods, including the MRI post-processing morphometric analysis program (MAP) and 18F-fluorodeoxyglucose-positron emission tomography-MRI (PET/MRI) co-registration. METHODS: Included in this retrospective study were patients with MRI-negative CE who met the following criteria: negative on preoperative MRI, invasive EEG (iEEG) confirmed cingulate gyrus-onset seizures, surgical resection of the cingulate gyrus with/without adjacent cortex, and seizure-free for more than 12 months. MAP and PET/MRI co-registration were performed and investigated by comparison to ictal intracranial EEG findings. Other characteristics obtained from scalp EEG, magnetoencephalography (MEG), iEEG, and pathological study were also reported. RESULTS: Ten patients were included, of which eight were diagnosed with anterior CE, one with middle CE, and one with posterior CE. The semiology included fear, embarrassment, vocalization, ictal pouting, asymmetric tonic posture, hypermotor, and automatism. Scalp EEG revealed unilateral or bilateral frontal-temporal onset. MEG localized the dipoles correctly in one patient (1/10). MAP detected subtle abnormalities in regions concordant with iEEG onset in seven patients (7/10) while PET/MRI co-registration revealed focal concordant hypometabolism in five patients (5/10). Combining MAP with PET/MRI co-registration improved the detection rate to 90 % in this cohort. The pathology was focal cortical dysplasia (FCD), including FCD type IIA in three, type IIB in three, and type I in four. CONCLUSION: MAP and PET/MRI co-registration show promising results in identifying subtle FCD abnormalities in CE with negative results on conventional MRI, which can be otherwise challenging. More importantly, a combination of MRI post-processing and PET/MRI co-registration can greatly improve the identification of epileptic abnormalities, which can be used as surgical target. MAP and PET/MRI co-registration should be incorporated into the routine presurgical evaluation.

Direct visualization of deep brain stimulation targets in patients with Parkinson's disease via 3-T quantitative susceptibility mapping.

BACKGROUND: The direct visualization of brain nuclei on magnetic resonance (MR) images is important for target localization during deep brain stimulation (DBS) in patients with Parkinson's disease (PD). We demonstrated the superiority of 3-T high-resolution submillimeter voxel size quantitative susceptibility mapping (QSM) for delineating the subthalamic nucleus (STN) and the globus pallidus internus (GPi). METHODS: Preoperative 3-T QSM and T2 weighted (T2w) images were obtained from ten patients with PD. Qualitative visualization scores were analyzed by two neurosurgeons on both images using a 4-point and 5-point scale, respectively. Images were also compared with regard to contrast-to-noise ratios (CNRs) and edge detection power for the STN and GPi. The Wilcoxon rank-sum test and the signed-rank test were used to compare measurements between the two images. RESULTS: Visualization scores for the STN and GPi, the mean CNR of the STN relative to the zona incerta (ZI) and the substantia nigra, and the mean CNR of the GPi relative to the internal capsule (IC) and the globus pallidum externum, were significantly higher on QSM images than on T2w images (P < 0.01). The edge detection powers of the STN-ZI and GPi-IC on QSM were significantly larger (by 2.6- and 3.8-fold, respectively) than those on T2w images (P < 0.01). QSM detected asymmetry of the STN in two patients. CONCLUSIONS: QSM images provided improved delineation ability for the STN and GPi when compared to T2w images. Our findings are important for patients with PD who undergo DBS surgery, particularly those with asymmetric bilateral nuclei.

The value of magnetoencephalography for stereo-EEG-guided radiofrequency thermocoagulation in MRI-negative epilepsy.

OBJECTIVE: Magnetoencephalography (MEG) is valuable for guiding resective surgery in patients with epilepsy. However, its value for minimally invasive treatment is still unknown. This study aims to evaluate the value of MEG for stereo-electroencephalogram (EEG)-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in magnetic resonance imaging (MRI)-negative epilepsies. METHODS: An observational cohort study was performed and 19 MRI-negative patients who underwent SEEG-guided RF-TC in our epilepsy center were included. In addition, 16 MRI-positive patients were included as a reference group. Semiology, electrophysiology, and imaging information were collected. To evaluate the value of locating the MEG cluster, the proportion of the RF-TC contacts located in the MEG cluster out of all contacts used to perform RF-TC in each patient was calculated. All patients underwent the standard SEEG-guided RF-TC procedure and were followed up after the treatment. RESULTS: Nineteen MRI-negative patients were divided into two groups based on the existence of MEG clusters; 10 patients with MEG clusters were in group I and nine patients without any MEG cluster were in group II. No significant difference was observed in terms of age, sex, type of seizures, or number of SEEG electrodes implanted. The median of the proportion of contacts in the MEG cluster was 77.0 % (IQR 57.7-100.0 %). The follow-up results showed that the probability of being seizure-free at one year after RFTC in MRI-negative patients with an MEG cluster was 30.0 % (95 % CI 11.6-77.3 %), significantly (p = 0.014) higher than that in patients without an MEG cluster; there was no significant difference when compared with MRI-positive patients. CONCLUSION: This is the first study to evaluate the value of MEG in SEEG-guided RF-TC in MRI-negative epilepsies. MEG is a useful supplement for patients with MRI-negative epilepsy. MEG can be applied in minimally invasive treatment. MEG clusters can help identify better candidates and provide a valuable target for SEEG-guided RF-TC, which leads to better outcomes.

Long-term outcome of unilateral deep brain stimulation of the subthalamic nucleus for a patient with drug-resistant focal myoclonic seizure.

It remains an unsolved problem in the treatment of patients with refractory focal epilepsy originating from the motor cortex since resection surgery can result in significant morbidity. Neurostimulation has emerged as an effective method for treating patients who are not suitable for conventional surgical procedures due to its relative safety, reversibility, and lower risk of complications. The subthalamic nucleus (STN) has been shown to be a potential target for treating refractory motor seizures. Here, we report a favorable outcome of unilateral deep brain stimulation (DBS) of the STN for a patient with drug-resistant focal myoclonic seizures during a 5-year follow-up period.

The Effect of Intraoperative Vertebral Anesthesia on Osteoporotic Fractures Treated With Percutaneous Kyphoplasty: A Prospective Cohort Study.

STUDY DESIGN: A prospective randomized cohort study. OBJECTIVE: The objective of this study was to investigate the effect of intraoperative vertebral anesthesia on osteoporotic vertebral compression fractures (OVCFs) when treated with percutaneous kyphoplasty (PKP). SUMMARY OF BACKGROUND DATA: Only a few studies have evaluated the intraoperative pain reducing strategies during PKP. MATERIALS AND METHODS: A total of 64 patients with OVCFs were enrolled in the study. All of the patients were randomized into 2 groups: the traditional local anesthesia group (from the skin to the periosteum, group A) and the experimental group (from the skin to a vertebral body, group B). Visual Analogue Scale (VAS) score was used to evaluate the degree of pain at six time points, that is, VAS before surgery, VAS during balloon dilation, VAS during bone cement injection, VAS soon after surgery, and VAS 12 hours and 24 hours after surgery. In addition, we noted the patients' willingness to undergo reoperation if necessary, and the variations in surgical complications between the 2 groups. RESULTS: There was no significant difference in VAS score before surgery between the 2 groups (t=1.694, P=0.095). The VAS scores during balloon dilatation, bone cement injection and soon after surgery were significantly different between the 2 groups (t=4.405, P=0.000; t=2.481, P=0.016; t=2.992, P=0.004, respectively). The willingness to undergo reoperation was significantly different between 2 groups (χ=6.020, P=0.049), whereas the complications showed no significant difference (χ=0.000, P=0.754). CONCLUSIONS: Traditional local anesthesia combined with vertebral anesthesia was effective in alleviating perioperative pain during PKP. No serious complication was noted during the operation. LEVEL OF EVIDENCE: Level I.

[Effects of perioperative transcutaneous electrical acupoint stimulation on postoperative analgesia in patients undergoing shoulder arthroscopic surgery].

OBJECTIVE: To observe and evaluate the effects of transcutaneous electrical acupoint stimulation (TEAS) at different time points on postoperative analgesia in perioperative period in patients undergoing shoulder arthroscopic surgery, and to explore the optimal time to use TEAS for shoulder arthroscopic surgery. METHODS: A total of 120 patients undergoing unilateral shoulder arthroscopy under general anesthesia, graded withⅠtoⅡaccording to ASA criteria were randomly divided into 3 groups, 40 patients in each one. The patients in the group A were treated with preoperative TEAS at sham acupoints combined with postoperative TEAS at Hegu (LI 4) and Neiguan (PC 6); the patients in the group B were treated with preoperative TEAS at Hegu (LI 4) and Neiguan (PC 6) combined with postoperative TEAS at sham acupoints; the patients in the group C were treated with TEAS at sham acupoints before and after operation. The parameters of TEAS were dilatational wave, 2 Hz/100 Hz in frequency, 30 min. When the resting-state visual analogue scale (VAS) of incision was more than 3 points, the patient-controlled intravenous analgesia (PCIA) pump of sufentanil was administered to maintain the VAS no more than 3 points. The time point when PCIA pump was firstly used, the used dose of sufentanil and effective pressing number of PCIA pump within 24 hours after surgery were recorded. Intraoperative anesthetic doses were recorded in the three groups. The resting-state and task-state VAS were evaluated at 0, 6, 12, 24 hours after surgery; the patient's satisfaction rate and adverse effects were recorded. RESULTS: The time when PCIA pump was firstly used in the group A and the group B was significantly longer than that in the group C, and the used dose of sufentanil and effective pressing number of PCIA pump within 24 hours after surgery in the group A and group B were significantly less than those in the group C (all P<0.05); the incidence of postoperative nausea-vomiting and sore throat was reduced (all P<0.05). The time when PCIA pump was firstly used in the group A was significantly longer than that in the group B, and the used dose of sufentanil and effective pressing number of PCIA pump within 24 hours after surgery in the group A were significantly less than those in the group B (all P<0.05); no significant difference of the incidence of postoperative nausea-vomiting and sore throat was observed between the group A and group B (both P>0.05). There were no statistically significant difference in VAS score at different postoperative time points and postoperative analgesia satisfaction rate between the two groups (all P>0.05). CONCLUSION: Perioperative TEAS could improve the postoperative analgesia in patients undergoing arthroscopic shoulder surgery, delay the time when PCIA pump is firstly used, reduce the dosage of postoperative analgesics and adverse events. Compared before surgery, postoperative TEAS has better analgesia.

Determining the Quantitative Threshold of High-Frequency Oscillation Distribution to Delineate the Epileptogenic Zone by Automated Detection.

Objective: We proposed an improved automated high frequency oscillations (HFOs) detector that could not only be applied to various intracranial electrodes, but also automatically remove false HFOs caused by high-pass filtering. We proposed a continuous resection ratio of high order HFO channels and compared this ratio with each patient's post-surgical outcome, to determine the quantitative threshold of HFO distribution to delineate the epileptogenic zone (EZ). Methods: We enrolled a total of 43 patients diagnosed with refractory epilepsy. The patients were used to optimize the parameters for SEEG electrodes, to test the algorithm for identifying false HFOs, and to calculate the continuous resection ratio of high order HFO channels. The ratio can be used to determine a quantitative threshold to locate the epileptogenic zone. Results: Following optimization, the sensitivity, and specificity of our detector were 66.84 and 73.20% (ripples) and 69.76 and 66.13% (fast ripples, FRs), respectively. The sensitivity and specificity of our algorithm for removing false HFOs were 76.82 and 94.54% (ripples) and 72.55 and 94.87% (FRs), respectively. The median of the continuous resection ratio of high order HFO channels in patients with good surgical outcomes, was significantly higher than in patients with poor outcome, for both ripples and FRs (P < 0.05 ripples and P < 0.001 FRs). Conclusions: Our automated detector has the advantage of not only applying to various intracranial electrodes but also removing false HFOs. Based on the continuous resection ratio of high order HFO channels, we can set the quantitative threshold for locating epileptogenic zones.

GADD45ß-I attenuates oxidative stress and apoptosis via Sirt3-mediated inhibition of ER stress in osteoarthritis chondrocytes.

Osteoarthritis (OA) is one of the most characterized joint diseases associated with chondrocyte apoptosis. JNK plays an important role in apoptosis in many pathological conditions, but systemic inhibition of JNK was shown to result in detrimental side effects. MAPK kinase 7 (MKK7) is a direct upstream kinase that regulates JNK and has been shown to activate JNK specifically under toxic conditions. In this study, we investigated the effect of GADD45ß-I, a cell-permeable inhibitor targeted for MKK7, on IL-1ß-induced cytotoxicity in rat chondrocytes. The results showed that IL-1ß exposure resulted in toxicity in a dose-dependent manner, which was nullified by endoplasmic reticulum (ER) stress inhibitors. GADD45ß-I significantly preserved cell survival, inhibited oxidative injury and reduced apoptosis after IL-1ß treatment. ER stress in chondrocytes was attenuated by GADD45ß-I, as evidenced by reduced levels of GRP78 and CHOP, as well as decreased caspase-12 cleavage. In addition, GADD45ß-I increased the enzymatic activities of mitochondrial antioxidant enzymes, including IDH2, GSH-Px and SOD2. GADD45ß-I significantly upregulated the expression of Sirt3 and attenuated IL-1ß-induced acetylation of SOD2. Furthermore, GADD45ß-I-induced inhibition of ER stress and protection in chondrocytes were partially reversed by knockdown of Sirt3. In conclusion, our data indicated that GADD45ß-I protected chondrocytes against IL-1ß through Sirt3-mediated inhibition of ER stress. Targeting MKK7 might be an ideal therapeutic strategy for reducing chondrocyte apoptosis in OA.

Gray-matter-specific MR imaging improves the detection of epileptogenic zones in focal cortical dysplasia: A new sequence called fluid and white matter suppression (FLAWS).

Objectives: To evaluate the diagnostic value and characteristic features of FCD epileptogenic zones using a novel sequence called fluid and white matter suppression (FLAWS). Materials and methods: Thirty-nine patients with pathologically confirmed FCD and good surgery outcomes (class I or II, according to the Engel Epilepsy Surgery Outcome Scale) were retrospectively included in the study. All the patients underwent a preoperative whole-brain MRI examination that included conventional sequences (T2WI, T1WI, two-dimensional (2D) axial, coronal fluid-attenuated inversion recovery [FLAIR]) and FLAWS. An additional 3D-FLAIR MRI sequence was performed in 17 patients. To evaluate the sensitivity and specificity of FLAWS and investigate the cause of false-positives, 36 healthy volunteers were recruited as normal controls. Two radiologists evaluated all the image data. The detection rates of the FCD epileptogenic zone on different sequences were compared based on five criteria: abnormal cortical morphology (thickening, thinning, or abnormally deep sulcus); abnormal cortical signal intensity; blurred gray-white matter junction; abnormal signal intensity of the subcortical white matter, and the transmantle sign. The sensitivity and specificity of FLAWS for detecting the FCD lesions were calculated with the reviewers blinded to all the clinical information, i.e. to the patient identity and the location of the resected regions. To explore how many features were sufficient for the diagnosis of the epileptogenic zones, the frequency of each criterion in the resected regions and their combinations were assessed on FLAWS, according to the results of the assessment when the reviewers were aware of the location of the resected regions. Based on the findings of the 17 patients with an additional 3D-FLAIR scan when the reviewers were aware of the location of the resected regions, quantitative analysis of the regions of interest was used to compare the tissue contrast among 2D-axial FLAIR, 3D-FLAIR, and the FLAWS sequence. Visualization score analysis was used to evaluate the visualization of the five features on conventional, 3D-FLAIR, and FLAWS images. Finally, to explore the reason for false-positive results, a further evaluation of the whole brain FLAWS images was conducted for all the subjects. Results: The sensitivity and specificity for detecting the FCD lesions on the FLAWS sequence were 71.9% and 71.1%, respectively. When the reviewers were blinded to the location of the resected regions, the detection rate of the FLAWS sequence was significantly higher than that of the conventional sequences (P = 0.00). In the 17 patients who underwent an additional 3D FLAIR scan, no statistically significant difference was found between the FLAWS and the 3D-FLAIR (P = 0.25). All the patients had at least two imaging features, one of which was "the blurred junction of the gray-white matter." The transmantle sign, which is widely believed to be a specific feature of FCD type II, could also be observed in type I on the FLAWS sequence. The relative tissue contrast of FLAWS was higher than that of the 2D-FLAIR with respect to lesion/white matter (WM), deep gray matter (GM)/WM, and cortex/WM (P = 0.00 for all three measures) and higher than that of the 3D-FLAIR with respect to the lesion/WM (P = 0.01). The visualization score analysis showed that the visualization of FLAWS was more enhanced than that of the conventional and 3D-FLAIR images with respect to the blurred junction (P = 0.00 for both comparisons) and the abnormal signal intensity of the subcortical white matter (P = 0.01 for both comparisons). The thin-threadlike signal and individual FCD features outside the epileptogenic regions were considered the primary cause of the false-positive results of FLAWS. Conclusions: FLAWS can help in the detection of FCD epileptogenic zones. It is recommended that epileptogenic zone on FLAWS be diagnosed based on a combination of two features, one of which should be the "blurred junction of the gray-white matter" in types I and II. In type III, the combination of "the blurred junction of the gray-white matter" with "abnormal signal intensity of subcortical white matter" is recommended.

Quantitative volume-based morphometry in focal cortical dysplasia: A pilot study for lesion localization at the individual level.

PURPOSE: Surgical resection is the most effective treatment for focal cortical dysplasia (FCD). However, many patients with FCD have unremarkable or even negative findings on conventional magnetic resonance imaging (MRI). In this study, we explored the brain volume abnormalities of FCD patients at the individual level using an experimental volume-based morphometry algorithm and further estimated whether the volume abnormalities can help in the detection of FCD lesions. MATERIALS AND METHODS: Sixteen patients with histologically-proven FCD lesions were retrospectively studied. Among them, eight patients had no visible abnormalities on routine MRI, three had abnormalities which partly matched the location of the surgical resection regions, and two did not match. For each patient, cerebral high-resolution T1-weighted magnetization-prepared rapid acquisition with gradient echo (MPRAGE) images were segmented into 45 structures, according to a brain anatomy template, and the volume of each structure was compared with an age- and gender-matched normal population at the individual level, based on a MorphoBox prototype. A Receiver Operating Characteristics (ROC) curve was used to evaluate the performance of the prototype in patients. To find the most appropriate threshold value for localizing the epileptogenic zones, deviations from the normative ranges of each resulting volume estimate were assessed by z-scores. RESULTS: Volume abnormalities including atrophic and hypertrophic volumes could be found in all the patients. Epileptogenic zones were found in brain structures with an abnormal volume in 87.5% (14/16) of patients. In 71.4% of patients (10/14), these zones were fully located in regions with an atrophic volume. This suggests that FCD lesions are more likely to be in regions with an atrophic volume than in those with a hypertrophic volume. When the best cut-off z-score value was -3.0, the sensitivity, specificity, and ROC area under the curve of the volume estimates were 93.9%, 79.6%, and 0.89, respectively. CONCLUSION: Volume abnormalities can assist in the diagnosis of epileptogenic zones at the individual level in FCD patients with negative or positive findings on conventional MR images. Atrophic regions are more likely than hypertrophic ones to represent epileptogenic zones. Volume-based morphometry based on a MorphoBox prototype has potential to assist a careful scrutiny by radiologists with target in atrophic regions in patients who are initially deemed to be MR-negative, further trying to increase the detection rate of FCD.

Repairing a bone defect with a three-dimensional cellular construct composed of a multi-layered cell sheet on electrospun mesh.

In addition to providing maneuverability, electrospun nanofibrous meshes can make excellent supports for constructing flexible cell sheets to regulate cell behavior by nanofiber features. With the target of bone regeneration, herein composite nanofibers with two different fiber arrangements (nestlike, random) were electrospun from a blend solution containing poly(l-lactide) (PLLA) and gelatin (1:1 in weight ratio). Unlike the non-woven morphology in a random nanofibrous mesh, PLLA/gelatin composite nanofibers in the nestlike nanofibrous mesh displayed both non-woven and parallel morphologies. Both kinds of nanofibrous mesh were ∼50 µm thick as-prepared, and shrank to ∼30 µm after seeding with bone mesenchymal stromal cells (BMSCs). After 7 days of in vitro culture, cell sheets could form on both meshes (CSM) and on the culture plate. It was found that application of nanofibrous mesh promoted the osteogenic differentiation of BMSC sheets compared with the control. The nestlike mesh displayed slight superiority over the random mesh in enhancing osteogenic differentiation, but their different fiber arrangements did not cause much difference in cell proliferation. Three-dimensional multi-layered CSM constructs were built by stacking four mono-layered CSMs together. The CSM constructs (based on a nestlike or random nanofibrous mesh) were incubated in vitro for 3 days before being implanted into rat cranial defects. In comparison with the control group, there was significant formation of new calcified bone in both CSM construct-filled groups at 12 weeks' post-operation. The nestlike group showed slightly better bone healing (based on both qualitative and quantitative analysis) than the random group, while showing insignificant differences. We showed that the concept of using a three-dimensional multi-layered CSM construct in enhancing bone regeneration was feasible. Future studies should take more nanofiber features (e.g. bioactive components) into account to further enhance osteogenesis.

Evaluation of changes in lumbar neuroforaminal dimensions in symptomatic young adults using positional MRI.

PURPOSE: To investigate the changes of lumbar neural foramina size during dynamic motion using positional MRI. METHODS: Two hundred and fifty neural foramina from 50 patients were analyzed. Lumbar foraminal height, width, and area parameters from L1 to S1 were evaluated for changes in extension, neutral, and flexion positions on T2 parasagittal positional MRI images, and were correlated to lumbar angular motion. One-way analysis of variance (ANOVA) and post hoc analysis were used to examine the differences between levels and positions. RESULTS: Compared to the neutral position, almost all lumbar foraminal parameters (height, width at inferior level, and area) increased in flexion and decreased in extension at all levels, except for L5-S1 foraminal width at superior and middle levels. The foraminal height and area in all lumbar segments except L5-S1 increased as the lumbar angular motion changed from extension to flexion in <40° group. The foraminal width increased significantly at L3-4 and L4-5 among all groups. CONCLUSION: Lumbar foraminal dimensions increased in flexion compared to neutral and extension positions. Lumbar angular motion contributed to the changes of foraminal height and area at most of the segments, while it affected foraminal width only at L3-4 and L4-5. This information can be useful in the understanding of patient symptoms and the correlation with the imaging studies with dynamic foraminal stenosis. Furthermore, data from our study may help with patient positioning for foraminal injections or endoscopic surgery.

Effective Bone Regeneration Using Thermosensitive Poly(N-Isopropylacrylamide) Grafted Gelatin as Injectable Carrier for Bone Mesenchymal Stem Cells.

In this study, thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) was grafted onto gelatin via atom transfer radical polymerization (ATRP). The chemical structure of PNIPAAm-grafted gelatin (Gel-PNIPAAm) was confirmed by XPS, ATR-IR, and (1)H NMR characterizations. Gel-PNIPAAm aqueous solution exhibited sol-to-gel transformation at physiological temperature, and was studied as injectable hydrogel for bone defect regeneration in a cranial model. The hydrogel was biocompatible and demonstrated the ability to enhance bone regeneration in comparison with the untreated group (control). With the incorporation of rat bone mesenchymal stem cells (BMSCs) into the hydrogel, the bone regeneration rate was further significantly enhanced. As indicated by micro-CT, histological (H&E and Masson) and immunohistochemical (osteocalcin and osteopontin) staining, newly formed woven bone tissue was clearly detected at 12 weeks postimplantation in the hydrogel/BMSCs treated group, showing indistinguishable boundary with surrounding host bone tissues. The results suggested that the thermosensitive Gel-PNIPAAm hydrogel was an excellent injectable delivery vehicle of BMSCs for in vivo bone defect regeneration.