Oxiracetam alleviates anti-inflammatory activity and ameliorates cognitive impairment in the early phase of traumatic brain injury.

BACKGROUND: We aimed to investigate the effects of oxiracetam on cognitive impairment in the early phase of traumatic brain injury (TBI), for which no specific treatment is currently available. METHODS: The in vitro study used a cell injury controller to damage SH-SY5Y cells and evaluate the effect of oxiracetam at a dosage of 100 nM. The in vivo study used a stereotaxic impactor to induce a TBI model in C57BL/6 J mice and analyzed immunohistochemical changes and cognitive function after an intraperitoneal injection of oxiracetam (30 mg/kg/day) for 5 days. The number of mice used in this study was 60. They were divided into three groups (sham, TBI, and TBI with oxiracetam treatment) (20 mice in each group). RESULTS: The in vitro study showed that oxiracetam treatment resulted in increased superoxide dismutase (SOD)1 and SOD2 mRNA expression. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and interleukin (IL)-1 ß were decreased after oxiracetam treatment, along with decreases in intracellular reactive oxygen species production and apoptotic effects. TBI mice treated with oxiracetam exhibited the loss of fewer cortical damaged lesions, less brain edema, and fewer Fluoro-Jade B (FJB)-positive and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-positive cells compared to those without oxiracetam treatment. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and IL-1ß were decreased significantly after oxiracetam treatment. These inflammation-related markers, which colocalized with Iba-1-positive or GFAP-positive cells after TBI, were also decreased after oxiracetam treatment. TBI mice treated with oxiracetam had a smaller decrease in preference and more latency time than those not treated with oxiracetam, suggesting the amelioration of impaired cognitive impairment. CONCLUSIONS: Oxiracetam may be helpful in restoring cognitive impairment by ameliorating neuroinflammation in the early phase of TBI.

Regulatory Mechanism between Ferritin and Mitochondrial Reactive Oxygen Species in Spinal Ligament-Derived Cells from Ossification of Posterior Longitudinal Ligament Patient.

Primary spinal ligament-derived cells (SLDCs) from cervical herniated nucleus pulposus tissue (control, Ctrl) and ossification of the posterior longitudinal ligament (OPLL) tissue of surgical patients were analyzed for pathogenesis elucidation. Here, we found that decreased levels of ferritin and increased levels of alkaline phosphatase (ALP), a bone formation marker, provoked osteogenesis in SLDCs in OPLL. SLDCs from the Ctrl and OPLL groups satisfied the definition of mesenchymal stem/stromal cells. RNA sequencing revealed that oxidative phosphorylation and the citric acid cycle pathway were upregulated in the OPLL group. SLDCs in the OPLL group showed increased mitochondrial mass, increased mitochondrial reactive oxygen species (ROS) production, decreased levels of ROS scavengers including ferritin. ROS and ferritin levels were upregulated and downregulated in a time-dependent manner, and both types of molecules repressed ALP. Osteogenesis was mitigated by apoferritin addition. We propose that enhancing ferritin levels might alleviate osteogenesis in OPLL.

Human embryonic stem cell-derived cerebral organoids for treatment of mild traumatic brain injury in a mouse model.

OBJECTIVE: There are no effective treatments for relieving neuronal dysfunction after mild traumatic brain injury (TBI). Here, we evaluated therapeutic efficacy of human embryonic stem cell-derived cerebral organoids (hCOs) in a mild TBI model, in terms of repair of damaged cortical regions, neurogenesis, and improved cognitive function. METHODS: Male C57BL/6 J mice were randomly divided into sham-operated, mild TBI, and mild TBI with hCO groups. hCOs cultured at 8 weeks were used for transplantation. Mice were sacrificed at 7 and 14 days after transplantation followed by immunofluorescence staining, cytokine profile microarray, and novel object recognition test. RESULTS: 8W-hCOs transplantation significantly reduced neuronal cell death, recovered microvessel density, and promoted neurogenesis in the ipsilateral subventricular zone and dentate gyrus of hippocampus after mild TBI. In addition, increased angiogenesis into the engrafted hCOs was observed. Microarray results of hCOs revealed neuronal differentiation potential and higher expression of early brain development proteins associated with neurogenesis, angiogenesis and extracellular matrix remodeling. Ultimately, 8W-hCO transplantation resulted in reconstruction of damaged cortex and improvement in cognitive function after mild TBI. CONCLUSION: hCO transplantation may be feasible for treating mild TBI-related neuronal dysfunction via reconstruction of damaged cortex and neurogenesis in the hippocampus.

Single LED, Single PD-Based Adaptive Bayesian Tracking Method.

Recently, with the growing interest in indoor location-based services, visible light positioning (VLP) systems have been extensively studied owing to their advantages of low cost, high energy efficiency, and no electromagnetic interference. However, due to structural limitations which lead to the requirement of multiple signal sources, it has been challenging to apply VLP in real-world scenarios. In this study, we propose a single LED, single PD-based tracking system that solves these problems by applying a new Bayesian method that can effectively reduce the computational burden of particle filters. The method of evaluating particle reliability developed in this work adjusts the number of particles on the fly. Using the absolute position of the single LED source, the long-term cumulative error of the inertial measurement unit can be continuously corrected. In this regard, the applicability of the VLP system can be enhanced in places where the multiple luminescent signals are hard to consistently detect. The proposed system was verified through experiments in a classroom and a corridor, and the results show an average error of less than 11 cm at travel distances of 80 to 100 m.

Peripheral Nerve-Derived Stem Cell Spheroids Induce Functional Recovery and Repair after Spinal Cord Injury in Rodents.

Stem cell therapy is one of the most promising candidate treatments for spinal cord injury. Research has shown optimistic results for this therapy, but clinical limitations remain, including poor viability, engraftment, and differentiation. Here, we isolated novel peripheral nerve-derived stem cells (PNSCs) from adult peripheral nerves with similar characteristics to neural-crest stem cells. These PNSCs expressed neural-crest specific markers and showed multilineage differentiation potential into Schwann cells, neuroglia, neurons, and mesodermal cells. In addition, PNSCs showed therapeutic potential by releasing the neurotrophic factors, including glial cell-line-derived neurotrophic factor, insulin-like growth factor, nerve growth factor, and neurotrophin-3. PNSC abilities were also enhanced by their development into spheroids which secreted neurotrophic factors several times more than non-spheroid PNSCs and expressed several types of extra cellular matrix. These features suggest that the potential for these PNSC spheroids can overcome their limitations. In an animal spinal cord injury (SCI) model, these PNSC spheroids induced functional recovery and neuronal regeneration. These PNSC spheroids also reduced the neuropathic pain which accompanies SCI after remyelination. These PNSC spheroids may represent a new therapeutic approach for patients suffering from SCI.

Prenylated Rab acceptor RABAC1 inhibits anti-apoptotic protein BCL2A1 and induces apoptosis.

The B cell lymphoma 2 (BCL2) family of proteins constitutes a critical intracellular checkpoint in the intrinsic apoptosis pathway. Among BCL2 members, the anti-apoptotic protein BCL2A1 mediates the resistance to BCL2 inhibitors and may be considered as a target for anti-cancer therapy. Here, we report that prenylated Rab acceptor 1 (RABAC1 or PRA1) inhibits the anti-apoptotic activity of BCL2A1 and induces apoptosis in AGS gastric cancer cells. Protein interaction of BCL2A1 and RABAC1 was verified by an in-vitro glutathione-S-transferase pull-down assay, immunoprecipitation, and confocal microscopy. When apoptosis was induced by cisplatin, the anti-apoptotic activity of BCL2A1 was blocked by RABAC1 expression. RABAC1 caused caspase-3 activation and decreased cell proliferation, clonogenic cell survival, and cell migration and invasion. We suggest RABAC1 as a potential therapeutic target for BCL2A1-related cancer.

Analysis of Multi-Level Simultaneous Driving Technique for Capacitive Touch Sensors.

The signal-to-noise ratio (SNR) and driving levels of capacitive touch sensors determine the applicability of these sensors to thinner displays and sensor-integrated modules. The simultaneous driving technique has been widely applied to capacitive touch sensors to cope with various types of environmental noise. A Hadamard matrix has been used to determine the driving code and multiplex capacitive signals required to increase the SNR and responsivity of touch sensors. Using multi-level Hadamard matrices, a new driving technique for sensing concurrent capacitive elements across multiple rows of a touch panel was developed. The technique provides more effective design choices than the existing bipolar driving method by supporting a variety of orders of matrices and regular capacity. The required TX voltage can be reduced by applying the Kronecker product for higher orders of simultaneous driving. A system model is presented for multiplexing capacitive signals to extract the SNR of the existing Hadamard matrices as well as one of the proposed multi-level sequences. In addition, the corresponding multi-level drivers and receivers were implemented to verify the theoretical expectations and simulation results of the proposed technique.

Quantitative analysis of unusual entrance of the vertebral artery into the cervical foramen (V2 segment) and its clinical implications.

PURPOSE: Unusual entrance of the vertebral artery into the cervical transverse foramen (UE-V2S) is a relatively common clinical anomaly. Because spinal surgeons should understand the anatomical characteristics and clinical implications of this condition, we aimed to provide a description based on a very large number of UE-V2S anomaly cases. METHODS: We retrospectively analyzed 2207 three-dimensional head-and-neck computed tomographic angiograms (CTAs) that did not have specific vascular abnormalities. After confirming which cases had an unusual vertebral artery (VA) entrance into the transverse foreman (TF), we measured their vertebral artery diameter (VAD), transverse foramen area (TFA) and bilateral pedicle width (PW) from C3 to C7. The shortest horizontal distance from the vertical line in the medial margin of the TF to VA (D-TFVA) was measured in the extra-osseous region to estimate the exact location of the extra-osseous VA, except at the C7 level. RESULTS: An unusual V2 entrance was observed in 11.4 % (252 patients) of all 2207 consecutive patients and 6.5 % (268 courses) of all 4414 courses. The prevalence rankings for the different measures were as follows: unilateral UE-V2S = E5 > E4 > E7 > E3; bilateral UE-V2S = E5 (bilateral) > E4 (Rt) with E5 (Lt) > E4 (bilateral). Generally, the VAD of the anomaly side was statistically smaller than the normal contralateral side, which can induce a smaller TFA value at all sub-axial levels. Cervical pedicle fixation was preferable in the adjacent lower segment of unusual VA entrance level than the normal side in this study due to a broader PW, which was evident on the anomaly side. However, there was no statistical evidence that the side of the C7 entrance of the VA had a narrow PW. The lowest D-TFVA value was -3.8, indicating that we should take care not to exceed 3.8 mm medially into the vertical line of the medial TF wall during dissection when taking an anterior cervical approach. CONCLUSIONS: To avoid an unexpected VA injury and to improve the efficiency of even routine cervical operations, spinal surgeons should determine whether the patient has a UE-V2S and have a full understanding of the clinical characteristics of this anomaly.

Anatomical feasibility for safe occipital condyle screw fixation.

PURPOSE: The occipital condyle (OC) screw can be a viable alternative option for the occipito-cervical fixation. However, the risk of vertebral artery (VA) injury during the direct OC screw fixation has not been adequately assessed. The purpose of this study was to establish the course of the VA (V3) relative to the nearby osseous structures to estimate the feasibility of OC screw fixation and describe its anatomical relationship depending on patient's age and sex. METHODS: A total of 387 three-dimensional computed tomographic angiograms (3D-CTA) were used and compared between two age groups. The vertebral artery diameter and two kinds of bony space were measured. The occipito-C1 arch space (O-C1S) and VA-occipital bone distance (VOD, six entry points) were measured on both sides. The feasibility of direct OC screw fixation can be represented by the VOD value; the minimum feasible value was determined to be 4 mm. Angular measurements (O-C1A and O-C2A) were also taken to assess their relationship to the bony space. RESULTS: The mean value of the O-C1S ranged from 9.0 to 9.9 mm. The mean value of the VOD ranged from 3.2 to 3.5 mm, and the proportion of individuals for which direct OC screw fixation was considered feasible ranged from 32 to 42 % in both age groups and there was no significant difference between two age groups. The VOD value was not affected by laterality or by gender (P > 0.05). The mean kyphosis of the O-C1A (-5° ± 5.2°, range -22° to 8°) was significantly smaller in the young age group compared to the older age group (-7.6° ± 5.3°, range -26° to 2°). The mean lordosis of the O-C2A (12.4° ± 6.4°, range 3°-33°) was significantly higher in the young age group compared to the older age group (10.4° ± 6.4°, range 0°-36°). CONCLUSIONS: The direct OC screw fixation was not possible in a considerable number of cases due to the limited space and the position of the VA regardless of age group. Only about one quarter (21-24 %) of all patients was affordable to place the direct OC screw bilaterally. There was more space available to place the direct OC screw when the angle of the upper cervical spine is more kyphotic.

Sequential alignment change of the cervical spine after anterior cervical discectomy and fusion in the lower cervical spine.

PURPOSE: The cervical spine has a linear chain of correlation or reciprocal relationship regionally (within the cervical spine) and globally (head to whole spine). The purpose of this study was to assess the sequential alignment change of the regional and global cervical spine after two-level anterior cervical discectomy and fusion (ACDF) performed on the lower cervical spine. METHODS: This study included 61 patients (mean age 56 ± 8.6 years; range 35-70 years) who underwent ACDF at C5-6-7 with a plate-cage construct and whose C-spine neutral lateral radiographs showed an identical degree of horizontal gaze (occipital slope) peri-operatively. We compared the change in cervical curvature from the occiput to C7 with the absolute value (slope angle) and relative value (between two different slopes). We also investigated the correlated change in multiple angular parameters according to the change in the occipital slope. RESULTS: The occipital slope was significantly correlated with the value of the C1-slope (r = 0.33) and C2- slope (r = 0.51). The value of the center of the sellar turcica-C7 sagittal vertical axis (St-SVA) was very closely related to the C1-slope (r = -0.83), C2-slope (r = -0.8), C2-7 angle (r = -0.43), and C2-5 angle (r = -0.46). The amount of angular change at the surgical level (C5-7A) was 5.8° (2.9° -> 8.5°), and the sum of the change in the C5-slope and C7-slope was 6° (3.1° + 2.9°). In general, the C2-5 angle decreased about 3°, in proportion to the upward inclination of C5-slope (3.1°), because the C2-slope was fixed. However, patients who showed improvement in cervical alignment (greatly increased C5-7 lordosis or greatly decreased St-SVA after surgery) often had upper cervical slope change (C1-s and C2-s). CONCLUSIONS: The ACDF procedure itself can induce regional slope change (C5-s and C7-s) directly at the surgical level and can also influence upper cervical slope change (C1-s and C2s) indirectly. Then the change in the upper cervical spine can induce a change in the St-CVA and spino-cranial angle (SCA).

The effect of C1 bursting fracture on comparative anatomical relationship between the internal carotid artery and the atlas.

PURPOSE: To describe the effect of the C1 bursting fracture on the location of the internal carotid artery (ICA) around the atlas. METHODS: The authors analyzed the morphology of the atlas and the ICA in 15 patients with C1 bursting fracture and compared with control group (77 patients) without any pathology. All patients were evaluated with CT angiography for the anatomical assessment. The laterality of the ICA, the distances of the ICA from the midline, anterior tubercle, and ventral surface of the C1 lateral mass were compared between two groups. The distance between the lateral margin of the longus capitis muscle and the inner edge of the transverse foramen was also measured. RESULTS: Medially located ICA was more common in the C1 bursting fracture group than control group (76.7 vs 42.8 %). There were no significant differences between 2 groups for the distance from the midline, anterior tubercle, and ventral surface of the C1 lateral mass, respectively. The distance of the longus capitis muscle to transverse foramen was 2.52 ± 2.09 and 4.15 ± 3.09 mm in each group, and there was statistically significant difference (p < 0.01). CONCLUSIONS: Lateral displacement of the bony structure of C1 bursting fracture changes the relative location of the ICA medially, which increase the injury risk during the bicortical C1 screw insertion. These data suggest that CT angiography or enhanced CT scans can give critical information to choose the ideal fixation technique and the proper trajectory of the screws for C1 bursting fracture.

Metagenomic insight of nitrogen metabolism in a tannery wastewater treatment plant bioaugmented with the microbial consortium BM-S-1.

Nitrogen (N) removal in a tannery wastewater treatment plant was significantly enhanced by the bioaugmentation of the novel consortium BM-S-1. In order to identify dominant taxa responsible for N metabolisms in the different stages of the treatment process, Illumina MiSeq Sequencer was used to conduct metagenome sequencing of the microbial communities in the different stages of treatment system, including influent (I), buffering (B), primary aeration (PA), secondary aeration (SA) and sludge digestion (SD). Based on MG-RAST analysis, the dominant phyla were Proteobacteria, Bacteroidetes and Firmicutes in B, PA, SA and SD, whereas Firmicutes was the most dominant in I before augmentation. The augmentation increased the abundance of the denitrification genes found in the genera such as Ralstonia (nirS, norB and nosZ), Pseudomonas (narG, nirS and norB) and Escherichia (narG) in B and PA. In addition, Bacteroides, Geobacter, Porphyromonasand Wolinella carrying nrfA gene encoding dissimilatory nitrate reduction to ammonium were abundantly present in B and PA. This was corroborated with the higher total N removal in these two stages. Thus, metagenomic analysis was able to identify the dominant taxa responsible for dissimilatory N metabolisms in the tannery wastewater treatment system undergoing bioaugmentation. This metagenomic insight into the nitrogen metabolism will contribute to a successful monitoring and operation of the eco-friendly tannery wastewater treatment system.

Restoration of lumbopelvic sagittal alignment and its maintenance following transforaminal lumbar interbody fusion (TLIF): comparison between straight type versus curvilinear type cage.

PURPOSE: To evaluate a radiological and clinical difference between the curvilinear type cages compared to the straight type cages for the restoration of lumbopelvic sagittal alignment and its maintenance after transforaminal lumbar interbody fusion (TLIF) procedure. METHODS: 68 patients who underwent single-level TLIF using either the straight type or curvilinear type cage were retrospectively reviewed. Assessment of the lumbopelvic parameters and the height of disc space was performed before surgery as well as 2 days, 6 and 12 months after surgery. Clinical outcome was assessed using VAS and ODI. RESULTS: The curvilinear type cages were positioned more anteriorly than the straight type. Restoration of the segmental lordosis (SL) in the curvilinear group was significantly greater than the straight group and at 12 months of follow-up, the straight group showed greater decrease in the disc height than the curvilinear group. The straight group failed to show improvement of lumbar lordosis (LL), while the curvilinear group showed significant restoration of LL and could maintain it to the 6 months of follow-up. In both groups, pelvic tilt was significantly decreased and it lasted to 6 months in the straight group; whereas in the curvilinear group, it was maintained to the last follow-up of 12 months. There were no significant differences between the two groups in mean VAS and ODI score over the follow-up period. CONCLUSIONS: This study demonstrates that the curvilinear type cage is superior to the straight type cage in improving the SL and maintaining both the restored lumbopelvic parameters and elevated disc height. These results could be attributable to the anterior position of the curvilinear cage which permits easy restoration of segmental lordosis and less sinking of cages.

Full-scale biological treatment of tannery wastewater using the novel microbial consortium BM-S-1.

In order to develop a more effective and eco-friendly treatment technology, a full-scale tannery wastewater treatment plant with a sludge digestion system was augmented with a novel microbial consortium (BM-S-1). The aim of this study was to determine if the BM-S-1 could successfully treat the tannery wastewater in a full-scale treatment system without chemical pretreatment and to investigate effect of the augmentation on sludge production. Chemical oxygen demand (COD), total nitrogen (TN), total phosphorus (TP), chromium (Cr) and mixed liquor suspended solids (MLSS) were measured to monitor treated water quality and treatment efficiency. Microbial community structures in the treatment were also examined using pyrosequencing analysis of 16S rRNA gene and quantitative PCR (qPCR) of the nitrous oxide reductase gene (nosZ). The removal efficiencies of COD, TN, TP, and Cr were estimated to be 98.3%, 98.6%, 93.6%, and 88.5%, respectively, while the system without a continuous augmentation was broken down. The pyrosequencing analysis showed Brachymonas denitrificans to be the most dominant microbial population in the buffering tank (B; 37.5%). Potential polymeric substance degraders (Clostridia), sulfate reducers (Desulfuromonas palmitatis), and sulfur oxidizers (uncultured Thiobacillus) were dominant in the sludge digestion (SD) tank. The denitrifiers assayed by nosZ qPCR were dominant in B and SD. These microbial communities appeared to play important roles in removing nutrients and odor, and reducing sludge in the wastewater treatment plant without chemical pretreatment.

Lordosis distribution index for predicting mechanical complications after long-level fusion surgery: comparison of Global Alignment and Proportion score and Roussouly classification.

OBJECTIVE: Both the Global Alignment and Proportion (GAP) score and Roussouly classification account for the lordosis distribution index (LDI), but the LDI of the GAP score (G-LDI) is typically set to 50%-80%, while the LDI of the Roussouly classification (R-LDI) varies depending on the degree of pelvic incidence (PI). The objective of this study was to validate the ability of the G-LDI to predict mechanical complications and compare it with the predictive probability of R-LDI in patients with long-level fusion surgery. METHODS: A total of 171 patients were divided into two groups: 93 in the nonmechanical complication group (non-MC group) and 78 in the mechanical complication group (MC group). The mean age of the participants was 66.79 ± 8.56 years (range 34-83 years), and the mean follow-up period was 45.49 ± 16.20 months (range 24-62 months). The inclusion criteria for the study were patients who underwent > 4 levels of fusion and had > 2 years of follow-up. The predictive models for mechanical complications using the G-LDI and R-LDI were analyzed using binomial logistic regression and receiver operating characteristic analyses. RESULTS: There was a significant correlation between R-LDI and PI (r = -0.561, p < 0.001), while there was no correlation between G-LDI and PI (r = 0.132, p = 0.495). In reference to G-LDI, most patients in the non-MC group were classified as having alignment (72, 77.4%), while the MC group had an inhomogeneous composition (aligned: 34, 43.6%; hyperlordosis: 37, 47.4%). The agreement between the G-LDI and R-LDI was moderate (κ = 0.536, p < 0.001) to fair (κ = 0.383, p = 0.011) for patients with average or large PI, but poor (κ = -0.255, p = 0.245) for those with small PI. The areas under the curve for the G-LDI and R-LDI were 0.674 (95% CI, 0.592-0.757) and 0.745 (95% CI, 0.671-0.820), respectively. CONCLUSIONS: The R-LDI, which uses a PI-based proportional parameter, enables individual quantification of LL for all PI sizes and has been shown to have a higher accuracy in classifying cases and a stronger correlation with the risk of mechanical complications compared with G-LDI.

Modeling of the brain-lung axis using organoids in traumatic brain injury: an updated review.

Clinical outcome after traumatic brain injury (TBI) is closely associated conditions of other organs, especially lungs as well as degree of brain injury. Even if there is no direct lung damage, severe brain injury can enhance sympathetic tones on blood vessels and vascular resistance, resulting in neurogenic pulmonary edema. Conversely, lung damage can worsen brain damage by dysregulating immunity. These findings suggest the importance of brain-lung axis interactions in TBI. However, little research has been conducted on the topic. An advanced disease model using stem cell technology may be an alternative for investigating the brain and lungs simultaneously but separately, as they can be potential candidates for improving the clinical outcomes of TBI.In this review, we describe the importance of brain-lung axis interactions in TBI by focusing on the concepts and reproducibility of brain and lung organoids in vitro. We also summarize recent research using pluripotent stem cell-derived brain organoids and their preclinical applications in various brain disease conditions and explore how they mimic the brain-lung axis. Reviewing the current status and discussing the limitations and potential perspectives in organoid research may offer a better understanding of pathophysiological interactions between the brain and lung after TBI.

Evolution of sagittal spinal shape for the development of thoracic ossification of ligamentum flavum.

Thoracic ossification of the ligamentum flavum (TOLF) is a rare pathology for which limited research exists. While it is known that mechanical factors play a role in the development of TOLF, little is currently understood about the sagittal alignment and related mechanical stress involved in its development. This study aims to describe the sagittal alignment of patients with TOLF based on the pathologic evolution of the Roussouly classification. The current study evaluated the preoperative Roussouly type in consecutive patients who underwent posterior decompressive laminectomy with or without posterior screw fixation for TOLF between January 2015 and December 2021. The post-evolution sagittal alignments were analyzed using the classic Roussouly classification based on sacral slope (SS). To determine the pre-evolution Roussouly type, the patients were retrospectively classified using their individual PI and PT values. Lumbopelvic parameters and morphological index including inflection point (IP), lumbar apex (LA), and lordosis distribution index (LDI) were also evaluated. Forty-three patients (21 women and 22 men) were included; their mean age was 64.21 ±â€…11.01 years (range 43-81). The most affected level was T10-11 (48.83%). The mean PI was 50.81 ±â€…9.56°, the mean SS was 33.11 ±â€…8.61°and the mean PT was 17.69 ±â€…7.89°. According to the post-evolution Roussouly classification, type 2 shape was the most frequently observed type (n = 23, 53.5%) in the post-evolution classification while type 3 was the most common type observed in the pre-evolution classification (n = 22, 51.5% and P = .00). The level of IP and LA in type 3 moved caudally (around L2 and L4/5 level, respectively) and the LDI increased (77.98 ±â€…8.08%) than the normal standard value. The authors found that the majority of the patients had a false type 2 spine, which had evolved pathologically from Roussouly type 3 and exhibited increased LDI, a lowered level of IP, and a lowered level of LA. These changes of spinal shape, including the transition to long hypolordosis and increased length of the thoracic kyphosis, may have accentuated tensile stress at the lower thoracic spine and contributed to the development of TOLF.

WITHDRAWN: Effect of Therapeutic Hypothermia on Cognitive Impairment in a Mouse Model of Ischemia-Reperfusion Injury.

Ahead of Print article withdrawn by publisher.

Therapeutic effect of a hydrogel-based neural stem cell delivery sheet for mild traumatic brain injury.

OBJECTIVE: There are no effective clinically applicable treatments for neuronal dysfunction after mild traumatic brain injury (TBI). Here, we evaluated the therapeutic effect of a new delivery method of mouse neural stem cell (mNSC) spheroids using a hydrogel, in terms of improvement in damaged cortical lesions and cognitive impairment after mild TBI. METHODS: mNSCs were isolated from the subventricular zone and subgranular zone by a hydrogel-based culture system. GFP-transduced mNSCs were generated into spheroids and wrapped into a sheet for transplantation. Male C57BL/6J mice were randomly divided into four groups: sham operation, TBI, TBI with mNSC spheroids, and TBI with mNSC spheroid sheet transplantation covering the damaged cortex. Histopathological and immunohistochemical features and cognitive function were evaluated 7, 14, and 28 days after transplantation following TBI. RESULTS: Hydrogel-based culture systems and mNSC isolation were successfully established from the adult mice. Essential transcription factors for NSCs, such as SOX2, PAX6, Olig2, nestin, and doublecortin (DCX), were highly expressed in the mNSCs. A transplanted hydrogel-based mNSC spheroid sheet showed good engraftment and survival ability, differentiated into TUJ1-positive neurons, promoted angiogenesis, and reduced neuronal degeneration. Also, TBI mice treated with mNSC spheroid sheet transplantation exhibited a significantly increased preference for a new object, suggesting improved cognitive function compared to the mNSC spheroids or no treatment groups. CONCLUSION: Transplantation with a hydrogel-based mNSC spheroid sheet showed engraftment, migration, and stability of delivered cells in a hostile microenvironment after TBI, resulting in improved cognitive function via reconstruction of the damaged cortex. STATEMENT OF SIGNIFICANCE: This study presents the therapeutic effect of a new delivery method of mouse neural stem cells spheroids using a hydrogel, in terms of improvement in damaged cortical lesions and cognitive impairment after traumatic brain injury. Collagen/fibrin hydrogel allowed long-term survival and migratory ability of NSCs spheroids. Furthermore, transplanted hydrogel-based mNSCs spheroids sheet showed good engraftment, migration, and stability of delivered cells in a hostile microenvironment, resulting in reconstruction of the damaged cortex and improved cognitive function after TBI. Therefore, we suggest that a hydrogel-based mNSCs spheroids sheet could help to improve cognitive impairment after TBI.

Autophagy and mitophagy-related extracellular mitochondrial dysfunction of cerebrospinal fluid cells in patients with hemorrhagic moyamoya disease.

We aimed to investigate whether mitochondrial dysfunction in extracellular cerebrospinal fluid (CSF), which is associated with autophagy and mitophagy, might be involved in neurological outcomes in adult patients with hemorrhagic moyamoya disease (MMD) whose pathogenesis related to poor outcomes is not well-known. CSF samples were collected from 43 adult MMD patients and analyzed according to outcomes at 3 months. Fluorescence-activated cell sorter analysis (FACS) and the JC-1 red/green ratio were used to assess mitochondrial cells and intact mitochondrial membrane potential (MMP). We performed quantitative real-time polymerase chain reaction and Western blotting analyses of autophagy and mitophagy-related markers, including HIF1α, ATG5, pBECN1, BECN1, BAX, BNIP3L, DAPK1, and PINK1. Finally, FACS analysis with specific fluorescence-conjugated antibodies was performed to evaluate the potential cellular origin of CSF mitochondrial cells. Twenty-seven females (62.8%) with a mean age of 47.4 ± 9.7 years were included in the study. Among 43 patients with hemorrhagic MMD, 23 (53.5%) had poor outcomes. The difference in MMP was evident between the two groups (2.4 ± 0.2 in patients with poor outcome vs. 3.5 ± 0.4 in patients with good outcome; p = 0.02). A significantly higher expression (2-ΔCt) of HIF1α, ATG5, DAPK1 followed by BAX and BNIP3L mRNA and protein was also observed in poor-outcome patients compared to those with good outcomes. Higher percentage of vWF-positive mitochondria, suggesting endothelial cell origins, was observed in patients with good outcome compared with those with poor outcome (25.0 ± 1.4% in patients with good outcome vs. 17.5 ± 1.5% in those with poor outcome; p < 0.01). We observed the association between increased mitochondrial dysfunction concomitant with autophagy and mitophagy in CSF cells and neurological outcomes in adult patients with hemorrhagic MMD. Further prospective multicenter studies are needed to determine whether it has a diagnostic value for risk prediction.