Investigation of PRDM10 and PRDM13 Expression in Developing Mouse Embryos by an Optimized PACT-Based Embryo Clearing Method.

Recent developments in tissue clearing methods have significantly advanced the three-dimensional analysis of biological structures in whole, intact tissue, providing a greater understanding of spatial relationships and biological circuits. Nonetheless, studies have reported issues with maintaining structural integrity and preventing tissue disintegration, limiting the wide application of these techniques to fragile tissues such as developing embryos. Here, we present an optimized passive tissue clearing technique (PACT)-based embryo clearing method, initial embedding PACT (IMPACT)-Basic, that improves tissue rigidity without compromising optical transparency. We also present IMPACT-Advance, which is specifically optimized for thin slices of mouse embryos past E13.5. We demonstrate proof-of-concept by investigating the expression of two relatively understudied PR domain (PRDM) proteins, PRDM10 and PRDM13, in intact cleared mouse embryos at various stages of development. We observed strong PRDM10 and PRDM13 expression in the developing nervous system and skeletal cartilage, suggesting a functional role for these proteins in these tissues throughout embryogenesis.

An in vivo cell-based assay for investigating the specific interaction between the SARS-CoV N-protein and its viral RNA packaging sequence.

The SARS-CoV nucleocapsid (N) protein serves multiple functions in viral replication, transcription, and assembly of the viral genome complex. Coronaviruses specifically package genomic RNA into assembled virions, and in SARS-CoV, it is reported that this process is driven by an interaction between the N-protein and a packaging signal encoded within the viral RNA. While recent studies have uncovered the sequence of this packaging signal, little is known about the specific interaction between the N-protein and the packaging signal sequence, and the mechanisms by which this interaction drives viral genome packaging. In this study, we developed a novel in vivo cell-based assay for examining this interaction between the N-protein and packaging signal RNA for SARS-CoV, as well as other viruses within the coronaviridae family. Our results demonstrate that the N-protein specifically recognizes the SARS-CoV packaging signal with greater affinity compared to signals from other coronaviruses or non-coronavirus species. We also use deletion mapping to identify a 151-nt region within the packaging signal sequence that is critical for N-protein-RNA binding, and conversely, we show that both the N-terminal and C-terminal domains of the N protein are necessary for recognizing the packaging RNA. These results describe, for the first time, in vivo evidence for an interaction between the SARS-CoV N-protein and its packaging signal RNA, and demonstrate the feasibility of using this cell-based assay to further probe viral RNA-protein interactions in future studies.

Residence could influence the surgical outcome after corrective surgery in adult spinal deformity: comparison study between urban and rural area in Korea.

PURPOSE: Numerous factors affect the surgical outcomes in patients with adult spinal deformity (ASD). However, no study has examined the relationship between residence and physical factors and surgical outcomes in patients with ASD. Here, we analysed the impact of residence and physical factors on the post-operative outcomes of patients with ASD residing in urban (U) and rural (R) environments. METHODS: We retrospectively reviewed data from patients who had undergone ASD surgery with sacropelvic fixation at a single institution between June 2011 and May 2017 with a minimum 1 year follow-up. We divided the patients into two groups (U and R). Preoperative demographic data were reviewed, and radiographic parameters were measured preoperatively, immediately postoperatively, at 1, 3, and 6 months, and at the final follow-up. The L4 axial paraspinal muscles were measured preoperatively using magnetic resonance imaging. RESULTS: There were 25 and 34 patients in the U and R groups, respectively. Both groups had similar preoperative demographic and radiological parameters. There were no differences between the groups in post-operative radiographic parameters, clinical outcomes, and complications, but proximal junctional kyphosis (PJK) was significantly higher in the R group. Additionally, muscle mass in the multifidus and erector spinae was lower in the R than in the U group. CONCLUSIONS: Patient residence influenced PJK in patients with ASD. Mass reduction in the trunk extensor muscle is an important and existing risk factor for PJK. Surgeons should be aware of this information for preoperative counselling, informed consent, and post-operative education of patients with ASD. These slides can be retrieved from Electronic Supplementary Material.

Does minimally invasive fusion technique influence surgical outcomes in isthmic spondylolisthesis?

OBJECTIVE: To compare the clinical and radiographic results between open transforaminal interbody fusion (TLIF-O) and minimally invasive TLIF (TLIF-M) for single-level low grade isthmic spondylolisthesis (IS). METHODS: This study enrolled 45 patients who underwent single-level TLIF with low grade IS. The patients were divided into two groups according to operative method: TLIF-M (20 patients) and TLIF-O (25 patients). TLIF-O group was matched with TLIF-M. RESULTS: At one-year postoperatively, there were no significant differences in any radiologic parameters between the two groups. Perioperative results such as blood loss, operation time, and hospital stay were superior in TLIF-M than in TLIF-O. Fusion was achieved in 17 of 20 patients (85.0%) in TLIF-M and 23 of 25 (92.0%) patients in TLIF-O. Back Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores of TLIF-O were significantly lower than TLIF-M at one (back VAS, ODI) and six months (ODI) postoperatively. CONCLUSIONS: TLIF-M and TLIF-O produced similar clinical and radiological outcomes, including reduction of spondylolisthesis and disc space height restoration at one-year follow-up for single-level low grade IS. However, considering perioperative outcomes, back pain, and quality of life, TLIF-M might be a better option for single-level low grade IS compared to TLIF-O.

Ossification foci act as stabilizers in continuous-type ossification of the posterior longitudinal ligament: a comparative study between laminectomy and laminoplasty.

BACKGROUND: In multilevel ossification of the posterior longitudinal ligament (OPLL), laminectomy is an effective surgical technique; however, there is a possibility of kyphotic alignment change after surgery. Nevertheless, in the continuous type of OPLL, the ossification foci are connected and may act as stabilizers preventing alignment change. We here compare the surgical outcome of laminectomy and laminoplasty in continuous-type OPLL of the cervical spine. METHODS: Seventy-three patients who underwent cervical laminectomy or laminoplasty for continuous-type OPLL from 2004 to 2014 were enrolled. The clinical outcomes were assessed by using the neck disability index, visual analogue scale, and Japanese Orthopedic Association scoring systems. Radiological evaluation with plain lateral radiographs was performed to observe alignment changes. RESULTS: The perioperative clinical outcome with laminectomy did not differ significantly from that of laminoplasty. Kyphotic change was observed in 3 of 35 patients with laminectomy and 3 of 38 patients with laminoplasty. Although loss of lordosis was observed in both groups, the C2-7 Cobb angle, sagittal vertical axis (SVA), and T1 slope did not demonstrate significant statistical differences between laminectomy and laminoplasty. Moreover, the C2-7 SVA in the C7-included laminectomy group (33.9 ± 13.4) became greater than that in the C7-excluded laminectomy group (24.8 ± 11.3) at the final follow-up (p = 0.049). CONCLUSIONS: In continuous-type OPLL, the surgical outcome did not show any significant difference between laminectomy and laminoplasty. Laminectomy alone is also a good choice in continuous-type OPLL, similar to laminoplasty.

MR imaging features that distinguish spinal cavernous angioma from hemorrhagic ependymoma and serial MRI changes in cavernous angioma.

Cavernous angiomas of the spinal cord exhibit imaging characteristics that may overlap with those of hemorrhagic ependymoma. In the present study, we aimed to identify specific magnetic resonance imaging (MRI) findings that could be used to differentiate cavernous angioma from hemorrhagic ependymoma, and to evaluate serial MRI changes in cases of cavernous angioma. We retrospectively evaluated MR images of spinal cord tumors collected at our hospital from 2007 to 2015. From this cohort of images, 11 pathologically confirmed cavernous angiomas and 14 pathologically confirmed hemorrhagic ependymomas were compared with respect to the size of the tumor, longitudinal location, axial location, enhancement pattern, syrinx, edema, tumor margin, signal intensity of T2WI, signal intensity of T1WI, and longitudinal spreading of the hemorrhage. Serial MR images of seven spinal cavernous angiomas were reviewed. Small size, eccentric axial location, minimal enhancement, and absence of edema were more frequently observed on images of cavernous angioma compared to those of hemorrhagic ependymoma (p < 0.01). Serial MRI changes in cases of cavernous angioma included increased longitudinal spreading of the hemorrhage (6/7, 86 %) and emergence of high signal intensity on T1WI (1/7, 14 %). Small size, eccentric axial location, minimal enhancement, and absence of edema are significant MRI findings that may be used to distinguish Type I and Type II spinal cavernous angiomas from hemorrhagic ependymomas. Furthermore, longitudinal spreading of the hemorrhage may be observed on follow-up MRIs of cavernous angiomas.

Anatomical parameters of fifth lumbar vertebra in L5-S1 spondylolytic spondylolisthesis from a surgical point of view.

PURPOSE: We measured the length, width, height, and angles related to both Meyerding grading system and Marchetti-Bartolozzi classification in L5-S1 spondylolytic spondylolisthesis patients to investigate the anatomical characteristics of fifth lumbar pedicles. METHODS: Seventy patients with L5-S1 spondylolytic spondylolisthesis and general spinal disease were included. Patient attributes, Meyerding grading system and Marchetti-Bartolozzi classification of spondylolisthesis, length, width, height of L4 and L5 pedicle, and the angle between pedicle and vertebral midline were measured. The heights of L5 vertebral body, divided as anterior, mid, and posterior were also measured. RESULTS: The pedicle is elongated and the angle of the pedicle is wider in cases of L5-S1 spondylolysis. Vertebral body shape was more posteriorly wedged in L5-S1 spondylolysis. Pedicles were more narrow and shorter in L5-S1 spondylolysis. CONCLUSIONS: In L5-S1 spondylolytic spondylolisthesis, a longer screw is suitable for insertion of L5 pedicle and the screw should be inserted more medially compared to patients without spondylolysis.

Predictive risk factors for mechanical complications after multilevel posterior cervical instrumented fusion.

OBJECTIVE: Mechanical complications should be considered following the correction of multilevel posterior cervical instrumented fusion. This study aimed to investigate clinical data on the patients' pre- and postoperative cervical alignment in terms of the incidence of mechanical complications after multilevel posterior cervical instrumented fusion. METHODS: Between January 2008 and December 2018, 156 consecutive patients who underwent posterior cervical laminectomy and instrumented fusion surgery of 4 or more levels and were followed up for more than 2 years were included in this study. Age, sex, bone mineral density (BMD), BMI, mechanical complications, and pre- and postoperative radiographic factors were analyzed using multivariate logistic regression analysis to investigate the factors related to mechanical complications. RESULTS: Of the 156 patients, 114 were men and 42 were women; the mean age was 60.38 years (range 25-83 years), and the mean follow-up duration of follow-up was 37.56 months (range 24-128 months). Thirty-seven patients (23.7%) experienced mechanical complications, and 6 of them underwent revision surgery. The significant risk factors for mechanical complications were low BMD T-score (-1.36 vs -0.58, p = 0.001), a large number of fused vertebrae (5.08 vs 4.54, p = 0.003), a large preoperative C2-7 sagittal vertical axis (SVA; 32.28 vs 23.24 mm, p = 0.002), and low preoperative C2-7 lordosis (1.85° vs 8.83°, p = 0.001). The clinical outcomes demonstrated overall improvement in both groups; however, the neck visual analog scale, Neck Disability Index, and Japanese Orthopaedic Association scores after surgery were significantly worse in the mechanical complication group compared with the group without mechanical complications. CONCLUSIONS: Low BMD, a large number of fused vertebrae, a large preoperative C2-7 SVA, and low C2-7 lordosis were significant risk factors for mechanical complications after posterior cervical fusion surgery. The results of this study could be valuable for preoperative counseling, medical treatment, or surgical planning when multilevel posterior cervical instrumented fusion surgery is performed.

Risk factors for unplanned reoperation after corrective surgery for adult spinal deformity.

To determine the major risk factors for unplanned reoperations (UROs) following corrective surgery for adult spinal deformity (ASD) and their interactions, using machine learning-based prediction algorithms and game theory. Patients who underwent surgery for ASD, with a minimum of two-year follow-up, were retrospectively reviewed. In total, 210 patients were included and randomly allocated into training (70% of the sample size) and test (the remaining 30%) sets to develop the machine learning algorithm. Risk factors were included in the analysis, along with clinical characteristics and parameters acquired through diagnostic radiology. Overall, 152 patients without and 58 with a history of surgical revision following surgery for ASD were observed; the mean age was 68.9 years (SD 8.7) and 66.9 years (SD 6.6), respectively. On implementing a random forest model, the classification of URO events resulted in a balanced accuracy of 86.8%. Among machine learning-extracted risk factors, URO, proximal junction failure (PJF), and postoperative distance from the posterosuperior corner of C7 and the vertical axis from the centroid of C2 (SVA) were significant upon Kaplan-Meier survival analysis. The major risk factors for URO following surgery for ASD, i.e. postoperative SVA and PJF, and their interactions were identified using a machine learning algorithm and game theory. Clinical benefits will depend on patient risk profiles.

Clinical Effect of Transverse Process Hook with K-Means Clustering-Based Stratification of Computed Tomography Hounsfield Unit at Upper Instrumented Vertebra Level in Adult Spinal Deformity Patients.

OBJECTIVE: This study aimed to investigate the efficacy of transverse process (TP) hook system at the upper instrumented vertebra (UIV) for preventing screw pullout in adult spinal deformity surgery using the pedicle Hounsfield unit (HU) stratification based on K-means clustering. METHODS: We retrospectively reviewed 74 patients who underwent deformity correction surgery between 2011 and 2020 and were followed up for >12 months. Pre- and post-operative data were used to determine the incidence of screw pullout, UIV TP hook implementation, vertebral body HU, pedicle HU, and patient outcomes. Data was then statistically analyzed for assessment of efficacy and risk prediction using stratified HU at UIV level alongside the effect of the TP hook system. RESULTS: The screw pullout rate was 36.4% (27/74). Perioperative radiographic parameters were not significantly different between the pullout and non-pullout groups. The vertebral body HU and pedicle HU were significantly lower in the pullout group. K-means clustering stratified the vertebral body HU ≥205.3, <137.2, and pedicle HU ≥243.43, <156.03. The pullout rate significantly decreases in patients receiving the hook system when the pedicle HU was from ≥156.03 to < 243.43 (p<0.05), but the difference was not statistically significant in the vertebra HU stratified groups and when pedicle HU was ≥243.43 or <156.03. The postoperative clinical outcomes improved significantly with the implementation of the hook system. CONCLUSION: The UIV hook provides better clinical outcomes and can be considered a preventative strategy for screw-pullout in the certain pedicle HU range.

Saving Stabilizing Structure Treatment With Bilateral-Contralateral Decompression for Spinal Stenosis in Degenerative Spondylolisthesis Using Unilateral Biportal Endoscopy.

OBJECTIVE: This study aimed to evaluate the treatment of spinal stenosis with spondylolisthesis using bilateral-contralateral unilateral biportal endoscopic (UBE) decompression to minimize facet joint damage. METHODS: We retrospectively evaluated 42 patients with grade 1 spondylolisthesis who underwent bilateral-contralateral UBE decompression between July 2018 and September 2019. To identify segmental instability, static and dynamic images from preoperative and postoperative procedures and final follow-up radiographs were reviewed. Lateral radiograph slippage ratio, sagittal motion, and facet joint preservation were evaluated. Clinical assessments were conducted using the visual analogue scale (VAS), Oswestry Disability Index (ODI), and modified MacNab criteria. RESULTS: The average final follow-up period was 26.5 ± 1.3 months. The average preoperative slip percentage was 15.70% ± 5.25%, which worsened to 18.80% ± 5.41% at the final follow-up (p < 0.005). The facet joint preservation rate was 95.6% ± 4.1% on the contralateral side. Improvements in the VAS scores (leg pain: from 7.9 ± 2.2 to 3.1 ± 0.7; p < 0.005; back pain: from 7.2 ± 3.0 to 2.8 ± 1.0; p < 0.005) were observed at the final follow-up. The mean preoperative ODI was 26.19 ± 3.42, which improved to 9.6 ± 1.0 (p < 0.005). Thirteen patients exhibited delayed focal segmental instability following decompression. Despite the absence of symptoms or improvement with conservative treatment in the majority of patients with delayed instability, two patients required fusion surgery to address the instability. Additionally, 2 patients developed facet synovial cysts, while 2 experienced spinous process fractures. CONCLUSION: Bilateral decompression with a contralateral UBE approach could be an effective and alternative treatment method to reduce instability in spinal stenosis with grade 1 spondylolisthesis.

Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting.

Intermittent fasting (IF) has been shown to reduce cardiovascular risk factors in both animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction. However, the underlying molecular mechanisms behind these effects remain unclear. To shed light on the molecular and cellular adaptations of the heart to IF, we conducted comprehensive system-wide analyses of the proteome, phosphoproteome, and transcriptome, followed by functional analysis. Using advanced mass spectrometry, we profiled the proteome and phosphoproteome of heart tissues obtained from mice that were maintained on daily 12- or 16 hr fasting, every-other-day fasting, or ad libitum control feeding regimens for 6 months. We also performed RNA sequencing to evaluate whether the observed molecular responses to IF occur at the transcriptional or post-transcriptional levels. Our analyses revealed that IF significantly affected pathways that regulate cyclic GMP signaling, lipid and amino acid metabolism, cell adhesion, cell death, and inflammation. Furthermore, we found that the impact of IF on different metabolic processes varied depending on the length of the fasting regimen. Short IF regimens showed a higher correlation of pathway alteration, while longer IF regimens had an inverse correlation of metabolic processes such as fatty acid oxidation and immune processes. Additionally, functional echocardiographic analyses demonstrated that IF enhances stress-induced cardiac performance. Our systematic multi-omics study provides a molecular framework for understanding how IF impacts the heart's function and its vulnerability to injury and disease.

Kyphoplasty versus vertebroplasty: restoration of vertebral body height and correction of kyphotic deformity with special attention to the shape of the fractured vertebrae.

STUDY DESIGN: Retrospective comparative analysis. OBJECTIVE: We analyzed kyphosis correction, vertebral height restoration, and bone cement leakage in patients treated by vertebroplasty (VP) and kyphoplasty (KP) to compare the effectiveness of VP and KP for the treatment of osteoporotic vertebral compression fractures. SUMMARY OF BACKGROUND DATA: Superior results have been reported for the use of KP for kyphotic deformity correction and collapsed vertebral height restoration. However, there are no previous comparative reports comparing the efficacy of KP versus VP according to the shapes of fractured vertebrae. METHODS: A total of 103 patients underwent either VP (n=58) or KP (n=45) for treatment of osteoporotic vertebral compression fracture between October 2006 and September 2009. We organized the patients into 6 groups according to treatment method and fracture type: VP (wedge-shaped), VP (V-shaped), VP (flat-shaped), KP (wedge-shaped), KP (V-shaped), and KP (flat-shaped). Comparisons were performed for kyphosis correction, vertebral height restoration, and cement leakage between VP and KP groups. RESULTS: KP was more effective than VP, especially for middle column height restoration and bone cement leakage prevention, for all fracture types (P value <0.05). In addition, KP was more effective in anterior height restoration and kyphosis correction in both flat and wedge-shape fractures (P value <0.05). However, posterior column vertebral height was not restored in either the KP group or the VP group. The clinical outcomes did not differ between the 2 groups (P value >0.05). CONCLUSIONS: KP has a significant advantage over VP in terms of kyphosis correction, vertebral height restoration, and cement leakage prevention. KP has an obvious advantage in terms of middle vertebral height restoration and cement leakage prevention, especially for V-shape compression fractures.

Developing a Quantifying Device for Soft Tissue Material Prop-Erties around Lumbar Spines.

Knowing the material properties of the musculoskeletal soft tissue could be important to develop rehabilitation therapy and surgical procedures. However, there is a lack of devices and information on the viscoelastic properties of soft tissues around the lumbar spine. The goal of this study was to develop a portable quantifying device for providing strain and stress curves of muscles and ligaments around the lumbar spine at various stretching speeds. Each sample was conditioned and applied for 20 repeatable cyclic 5 mm stretch-and-relax trials in the direction and perpendicular direction of the fiber at 2, 3 and 5 mm/s. Our device successfully provided the stress and strain curve of the samples and our results showed that there were significant effects of speed on the young's modulus of the samples (p < 0.05). Compared to the expensive commercial device, our lower-cost device provided comparable stress and strain curves of the sample. Based on our device and findings, various sizes of samples can be measured and viscoelastic properties of the soft tissues can be obtained. Our portable device and approach can help to investigate young's modulus of musculoskeletal soft tissues conveniently, and can be a basis for developing a material testing device in a surgical room or various lab environments.

Influence of Frailty on Life Expectancy in Octogenarians After Lumbar Spine Surgery.

OBJECTIVE: Many studies have reported positive surgical outcomes and decreased mortality after spine surgery in the elderly population, including patients between 85 and 90 years of age. Here, in addition to patient age, we investigated the influence of frailty on short and long-term mortality in octogenarians after lumbar surgery. METHODS: We performed a retrospective analysis of 162 patients over 80 years of age who underwent posterior lumbar fusion or decompressive laminectomy between January 2011 and September 2016. We examined patient survival and modified frailty index (mFI) from medical records. RESULTS: By October 2019, 29 of 162 patients had expired (follow-up period: 1-105 months). Three-month mortality was 1.9%, and 1-year mortality was 4.9%. Frailty did not affect long-term survival at 1 year but was associated with 3-month mortality (p = 0.024). CONCLUSION: There was no relationship in long-term survival according to frailty in patients 80 years of age or older, but a difference was identified in short-term mortality. When making a surgical decision for lumbar spine surgery in frail patients over 80 years of age, surgeons should pay attention to the short-term prognosis.

Reactive oxygen species-responsive dendritic cell-derived exosomes for rheumatoid arthritis.

Although tolerogenic dendritic cell-derived exosomes (TolDex) have emerged as promising therapeutics for rheumatoid arthritis (RA), their clinical applications have been hampered by their poor in vivo disposition after systemic administration. Herein, we report the development of stimuli-responsive TolDex that induces lesion-specific immunoregulation in RA. Responsiveness to reactive oxygen species (ROS), a physiological stimulus in the RA microenvironment, was conferred on TolDex by introducing a thioketal (TK) linker-embedded poly(ethylene glycol) (PEG) on TolDex surface via hydrophobic insertion. The detachment of PEG following overproduction of ROS facilitates the cellular uptake of ROS-responsive TolDex (TKDex) into activated immune cells. Notably, TolDex and TKDex downregulated CD40 in mature dendritic cells (mDCs) and regulated secretion of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) at the cellular level. In the collagen-induced arthritis (CIA) mouse model, PEG prolonged the blood circulation of TKDex following intravenous administration and enhanced their accumulation in the joints. In addition, TKDex decreased IL-6, increased transforming growth factor-ß, and induced the CD4+CD25+Foxp3+ regulatory T cells in CIA mice. Overall, ROS-responsive TolDex might have potential as therapeutic agents for RA. STATEMENT OF SIGNIFICANCE: Tolerogenic dendritic cell-derived exosomes (TolDex) are emerging immunoregulators of autoimmune diseases, including rheumatoid arthritis (RA). However, their lack of long-term stability and low targetability are still challenging. To overcome these issues, we developed reactive oxygen species (ROS)-responsive TolDex (TKDex) by incorporating the ROS-sensitive functional group-embedded poly(ethylene glycol) linker into the exosomal membrane of TolDex. Surface-engineered TKDex were internalized in mature DCs because of high ROS-sensitivity and enhanced accumulation in the inflamed joint in vivo. Further, for the first time, we investigated the potential mechanism of action of TolDex relevant to CD40 downregulation and attenuation of tumor necrosis factor (TNF)-α secretion. Our strategy highlighted the promising nanotherapeutic effects of stimuli-sensitive TolDex, which induces immunoregulation.

Nonsurgical treatment outcomes for surgical candidates with lumbar disc herniation: a comprehensive cohort study.

Physicians often encounter surgical candidates with lumbar disc herniation (LDH) who request non-surgical management even though surgery is recommended. However, second opinions may differ among doctors. Therefore, a prospective comprehensive cohort study (CCS) was designed to assess outcomes of nonsurgical treatment for surgical candidates who were recommended to undergo surgery for LDH but requested a second opinion. The CCS includes both randomized and observational cohorts, comprising a nonsurgery cohort and surgery cohort, in a parallel fashion. Crossover between the nonsurgery and surgery cohorts was allowed at any time. The present study was an as-treated interim analysis of 128 cases (nonsurgery cohort, n = 71; surgery cohort, n = 57). Patient-reported outcomes included visual analogue scores for the back (VAS-B) and leg (VAS-L), the Oswestry Disability Index, the EuroQol 5-Dimension instrument, and the 36-Item Short-Form Health Survey (SF-36), which were evaluated at baseline and at 1, 3, 6, 12, and 24 months. At baseline, age and SF-36 physical function were significantly lower in the surgery cohort than in the nonsurgery cohort (p < 0.05). All adjusted outcomes significantly improved after both nonsurgical and surgical treatment (p < 0.05). The nonsurgery cohort showed less improvement of VAS-B and VAS-L scores at 1 month (p < 0.01), but no difference between cohorts was observed thereafter for 24 months (p > 0.01). Nonsurgical management may be a negotiable option even for surgical candidates in the shared decision-making process.

Which Is More Predictive Value for Mechanical Complications: Fixed Thoracolumbar Alignment (T1 Pelvic Angle) Versus Dynamic Global Balance Parameter (Odontoid-Hip Axis Angle).

OBJECTIVE: In this study, we investigate about relationship between postoperative global sagittal imbalance and occurrence of mechanical complications after adult spinal deformity (ASD) surgery. In global sagittal balance parameters, odontoid-hip axis (OD-HA) angle and T1 pelvic angle (TPA) were analyzed. METHODS: Between January 2009 and December 2016, 199 consecutive patients (26 males and 173 females) with ASD underwent corrective fusion of more than 4 levels and were followed up for more than 2 years. Immediate postoperative and postoperative 2 years whole spine x-rays were checked for evaluating immediate postoperative OD-HA, TPA, and other parameters. In clinical outcomes, back and leg pain visual analogue scale, Scoliosis Research Society-22 spinal deformity questionnaire (SRS-22), Oswestry Disability Index (ODI), 36- item Short Form Health Survey (SF-36) were evaluated. RESULTS: Based on the occurrence of mechanical complications, a comparative analysis was performed for each parameter. In univariable analysis, mechanical complications were significantly much more occurred in OD-HA abnormal group (odds ratio [OR], 3.296; p < 0.001; area under the curve [AUC] = 0.645). In multivariable analysis, the result was much more related (OR, 2.924; p = 0.001; AUC = 0.727). In contrast, there was no significant difference between normal and the occurrence of mechanical complications in TPA. In clinical outcomes (normal vs. abnormal), the differences of SRS-22 (0.88 ± 0.73 vs. 0.68 ± 0.64, p = 0.042), ODI (-24.72 ± 20.16 vs. -19.01 ± 19.95, p = 0.046), SF-36 physical composite score (19.33 ± 18.55 vs. 12.90 ± 16.73, p = 0.011) were significantly improved in OD-HA normal group. CONCLUSION: The goal of ASD surgery is to improve patient life quality through correction. In our study, TPA was associated with spinopelvic parameter and OD-HA angle was associated with health-related quality of life and complications. OD-HA angle is predictable factor for mechanical complications after ASD surgery.

Alzheimer's disease-causing presenilin-1 mutations have deleterious effects on mitochondrial function.

Mitochondrial dysfunction and oxidative stress are frequently observed in the early stages of Alzheimer's disease (AD). Studies have shown that presenilin-1 (PS1), the catalytic subunit of γ-secretase whose mutation is linked to familial AD (FAD), localizes to the mitochondrial membrane and regulates its homeostasis. Thus, we investigated how five PS1 mutations (A431E, E280A, H163R, M146V, and Δexon9) observed in FAD affect mitochondrial functions. Methods: We used H4 glioblastoma cell lines genetically engineered to inducibly express either the wild-type PS1 or one of the five PS1 mutants in order to examine mitochondrial morphology, dynamics, membrane potential, ATP production, mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), oxidative stress, and bioenergetics. Furthermore, we used brains of PS1M146V knock-in mice, 3xTg-AD mice, and human AD patients in order to investigate the role of PS1 in regulating MAMs formation. Results: Each PS1 mutant exhibited slightly different mitochondrial dysfunction. Δexon9 mutant induced mitochondrial fragmentation while A431E, E280A, H163R, and M146V mutants increased MAMs formation. A431E, E280A, M146V, and Δexon9 mutants also induced mitochondrial ROS production. A431E mutant impaired both complex I and peroxidase activity while M146V mutant only impaired peroxidase activity. All PS1 mutants compromised mitochondrial membrane potential and cellular ATP levels were reduced by A431E, M146V, and Δexon9 mutants. Through comparative profiling of hippocampal gene expression in PS1M146V knock-in mice, we found that PS1M146V upregulates Atlastin 2 (ATL2) expression level, which increases ER-mitochondria contacts. Down-regulation of ATL2 after PS1 mutant induction rescued abnormally elevated ER-mitochondria interactions back to the normal level. Moreover, ATL2 expression levels were significantly elevated in the brains of 3xTg-AD mice and AD patients. Conclusions: Overall, our findings suggest that each of the five FAD-linked PS1 mutations has a deleterious effect on mitochondrial functions in a variety of ways. The adverse effects of PS1 mutations on mitochondria may contribute to MAMs formation and oxidative stress resulting in an accelerated age of disease onset in people harboring mutant PS1.

Retrospective Study on Accuracy of Intraoperative Frozen Section Biopsy in Spinal Tumors.

OBJECTIVE: Histologic types and grades are critical in the diagnosis and treatment of spinal tumors. Intraoperative frozen section is a fast and easy method in confirming pathologic diagnosis during the operation. This study was undertaken to reveal the accuracy of intraoperative frozen section biopsy in order to make proper treatment plans. METHODS: This retrospective study concerned patients who underwent spinal tumor surgeries from 1 January, 2012 to 31 December, 2016. Frozen section biopsy and permanent biopsy were compared, and cases that had differences were counted. RESULTS: Thirty-seven cases out of 324 patients had discrepancies (11.4%). In discrepant cases 11 cases were ependymoma (29.7%) and 6 cases were schwannoma (16.2%). Among 34 patients who were finally diagnosed with an ependymoma, 11 cases had discrepancies, which was the highest mismatch rate among tumor final pathologic types. By frozen biopsy, astrocytoma (n = 5) and ependymoma (n = 5) turned out to be the most discrepant pathologic types and 16 frozen section biopsy cases were "null." Frozen biopsy astrocytoma (n = 5) mostly turned out to be ependymoma in 4 cases. CONCLUSIONS: Pathologic findings from frozen biopsy for spinal cord tumors could not be corresponded to final diagnosis, especially when the results of frozen biopsy were ependymoma or astrocytoma. Therefore careful decision making for treatment plans is required.