CO2 Response Screen in Grass Brachypodium Reveals Key Role of a MAP Kinase in CO2-Triggered Stomatal Closure.

Plants respond to increased CO2 concentrations through stomatal closure, which can contribute to increased water use efficiency. Grasses display faster stomatal responses than eudicots due to dumbbell-shaped guard cells flanked by subsidiary cells working in opposition. However, forward genetic screening for stomatal CO2 signal transduction mutants in grasses has yet to be reported. The grass model Brachypodium distachyon is closely related to agronomically important cereal crops, sharing largely collinear genomes. To gain insights into CO2 control mechanisms of stomatal movements in grasses, we developed an unbiased forward genetic screen with an EMS-mutagenized Brachypodium distachyon M5 generation population using infrared imaging to identify plants with altered leaf temperatures at elevated CO2. Among isolated mutants, a "chill1" mutant exhibited cooler leaf temperatures than wildtype Bd21-3 parent control plants after exposure to increased [CO2]. chill1 plants showed strongly impaired high CO2-induced stomatal closure despite retaining a robust abscisic acid-induced stomatal closing response. Through bulked segregant whole-genome-sequencing analyses followed by analyses of further backcrossed F4 generation plants and generation and characterization of sodium-azide and CRISPR-cas9 mutants, chill1 was mapped to a protein kinase, Mitogen-Activated Protein Kinase 5 (BdMPK5). The chill1 mutation impaired BdMPK5 protein-mediated CO2/HCO3- sensing together with the High Temperature 1 (HT1) Raf-like kinase in vitro. Furthermore, AlphaFold2-directed structural modeling predicted that the identified BdMPK5-D90N chill1 mutant residue is located at the interface of BdMPK5 with the BdHT1 Raf-like kinase. BdMPK5 is a key signaling component that mediates CO2-induced stomatal movements and is proposed to function as a component of the primary CO2 sensor in grasses.

Dysregulation of Inflammatory Pathways in Adult Spinal Deformity Patients with Frailty.

Background/Objectives: An important aspect of the pathophysiology of frailty seems to be the dysregulation of inflammatory pathways and the coagulation system. However, an objective assessment of the impact of frailty on the recovery from surgery is not fully studied. This study sought to assess how frailty affects the recovery of adult spinal deformity (ASD) surgery using blood biomarkers. Methods: 153 consecutive ASD patients (age 64 ± 10 yr, 93% female) who had corrective spine surgery in a single institution and reached 2y f/u were included. The subjects were stratified by frailty using the modified frailty index-11 (robust [R] group or prefrail and frail [F] group). Results of commonly employed laboratory tests at baseline, 1, 3, 7, and 14 post-operative days (POD) were compared. Further comparison was performed in propensity-score matched-39 paired patients between the groups by age, curve type, and baseline alignment. A correlation between HRQOLs, major complications, and biomarkers was performed. Results: Among the propensity-score matched groups, CRP was significantly elevated in the F group at POD1,3(POD1; 5.3 ± 3.1 vs. 7.9 ± 4.7 p = 0.02, POD3; 6.6 ± 4.6 vs. 8.9 ± 5.2 p = 0.02). Transaminase was also elevated in the F group at POD3(ASD: 36 ± 15 vs. 51 ± 58 U/L, p = 0.03, ALT: 32 ± 16 vs. 47 ± 55 U/L, p = 0.04). Interestingly, moderate correlation was observed between transaminase at POD1 and 2 y SRS22 (AST; function r = -0.37, mental health r = -0.39, satisfaction -0.28, total r = -0.40, ALT; function r = -0.37, satisfaction -0.34, total r = -0.39). Conclusions: Frailty affected the serum CRP and transaminase differently following ASD surgery. Transaminase at early POD was correlated with 2 y HRQOLs. These findings support the hypothesis that there is a specific physiological basis to the frailty that is characterized in part by increased inflammation and that these physiological differences persist.

Influence of thoracolumbar kyphosis on postoperative spinal alignment in patients with Lenke type 5C adolescent idiopathic scoliosis.

PURPOSE: This study aimed to examine the changes in thoracolumbar kyphosis (TLK) following correction surgery in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS) and to evaluate its influence on postoperative spinal alignment and clinical outcomes. METHODS: Sixty-six patients with Lenke type 5C AIS were included and followed up for a minimum of 5 years after surgery. First, the patients were divided into two groups according to the preoperative TLK angle (Study 1; Kyphosis and Lordosis group). The patients were further classified into two groups according to the presence or absence of postoperative changes in TLK (Study 2; Changed and Maintained groups). Finally, the outcome variables were compared between these groups and analyzed for spinal alignment and clinical outcomes. RESULTS: In Study 1, patients demonstrated a significant kyphotic change in the Lordosis group and a significant lordotic change in the Kyphosis group postoperatively. No statistically significant differences were found between the two groups when comparing the pre- and postoperative coronal and sagittal alignment. In Study 2, there were no statistically significant differences between the Changed and the Maintained groups in each spinal alignment pre- and postoperatively. Each domain of the Scoliosis Research Society 22-item questionnaire remained unchanged at 5 years postoperation. CONCLUSION: In many patients with Lenke type 5C AIS, TLK changed significantly and approached 0° after surgery. However, the magnitude of the preoperative TLK and the presence or absence of improvement did not affect postoperative spinal alignment. Furthermore, the patients had satisfactory clinical outcomes irrespective of TLK modification. LEVEL OF EVIDENCE: III.

How coronal malalignment affects the surgical outcome in corrective spine surgery for adult symptomatic lumbar deformity.

PURPOSE: The importance of coronal alignment is unclear, while the importance of sagittal alignment in the treatment of adult patients with spinal deformities is well described. This study sought to elucidate the impact of global coronal malalignment (GCMA) in surgically treated adult symptomatic lumbar deformity (ASLD) patients. METHODS: A multicentre retrospective analysis of a prospective ASD database. GCMA was defined as GCA (C7PL-CSVL) ≥ 3 cm. GCMA is categorized based on the Obeid-Coronal Malalignment Classification (O-CM). Demographic, surgical, radiographic, HRQOL, and complication data were analysed. The risk for postoperative GCMA was analysed by univariate and multivariate analyses. RESULTS: Of 230 surgically treated ASLD patients, 96 patients showed GCMA preoperatively and baseline GCA was correlated with the baseline SRS-22 pain domain score (r = - 30). Postoperatively, 62 patients (27%, O-CM type 1: 41[18%], type 2: 21[9%]) developed GCMA. The multivariate risk analysis indicated dementia (OR 20.1[1.2-304.4]), diabetes (OR 5.9[1.3-27.3]), and baseline O-CM type 2 (OR 2.1[1.3-3.4]) as independent risk factors for postoperative GCMA. The 2-year SRS-22 score was not different between the 2 groups, while 4 GCMA patients required revision surgery within 1 year after surgery due to coronal decompensation (GCMA+ vs. GCMA- function: 3.6 ± 0.6 vs. 3.7 ± 0.7, pain: 3.7 ± 0.8 vs. 3.8 ± 0.8, self-image: 3.6 ± 0.8 vs. 3.6 ± 0.8, mental health: 3.7 ± 0.8 vs. 3.8 ± 0.9, satisfaction: 3.9 ± 0.9 vs. 3.9 ± 0.8, total: 3.7 ± 0.7 vs. 3.7 ± 0.7). Additionally, the comparisons of 2-yr SRS-22 between GCMA ± showed no difference in any UIV and LIV level or O-CM type. CONCLUSIONS: In ASLD patients with corrective spine surgery, GCMA at 2 years did not affect HRQOL or major complications at any spinal fusion extent or O-CM type of malalignment, whereas GCA correlated with pain intensity before surgery. These findings may warrant further study of the impact of GCMA on HRQOL in the surgical treatment of ASLD patients.

Impact of Surgical Resection Without Spinal Fusion for Thoracic Dumbbell Tumors on Postoperative Global Spinal Sagittal Alignment and Clinical Outcomes.

STUDY DESIGN: A retrospective comparative study. OBJECTIVES: This study investigated radiographical changes in global spinal sagittal alignment (GSSA) and clinical outcomes after tumor resection without spinal fusion in patients with thoracic dumbbell tumors. METHODS: Thirty patients with thoracic dumbbell tumors who were followed up for at least 3 years were included in this study. Variations in the outcome variables were analyzed using individual GSSA parameters measured on radiography. Clinical outcomes were assessed using the modified McCormick scale (MMCS), Japan Orthopaedic Association (JOA) score, and visual analog scale (VAS). To assess the impact of the affected levels on these outcomes, we divided the patients into three groups according to the location of the tumor (upper [T1-4], middle [T5-8], or lower [T9-12] thoracic spine). RESULTS: The GSSA parameters (cervical lordosis, T1 slope, thoracic kyphosis [global, upper, middle, and lower], thoracolumbar kyphosis, lumbar lordosis, sacral slope, pelvic incidence, and pelvic tilt) of all the patients did not change significantly after surgery. Eleven of thirty patients had preoperative gait disturbances but they could walk without support (MMCS grade I or II) at the final follow-up. The JOA score and VAS showed significant postoperative improvements. No statistically significant differences were observed in each postoperative sagittal profile or clinical outcome between the upper, middle, and lower groups. CONCLUSIONS: Tumor resection without spinal fusion did not affect the various GSSA parameters and resulted in satisfactory clinical outcomes, indicating that spinal fusion may not always be necessary when resecting thoracic dumbbell tumors.

The Effect of Age-adjusted Sagittal Alignment on the Result of Posterior Decompression Surgery for Lumbar Spinal Canal Stenosis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to compare the outcomes of posterior decompression surgery for lumbar spinal canal stenosis (LSS) in patients with preoperative sagittal malalignment to those without, after adjusting for age and sex. SUMMARY OF BACKGROUND DATA: Sagittal balance is an important factor in spine surgery and is thought to affect postoperative outcomes following LSS. However, the relationship between sagittal malalignment and postoperative outcomes has not been thoroughly examined. METHODS: We included 533 patients who underwent surgical treatment for LSS and also achieved two-year follow-up. Patients were categorized into either a malalignment (MA+) group (69 patients) or a matched-alignment (MA-) group (348 patients) based on age-adjusted preoperative sagittal alignment. We compared the baseline and two-year postoperative health-related quality of life (HRQOL) using the Visual Analog Scale and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) scores. We also calculated clinical efficacy using the minimal clinically important difference (MCID) based on JOABPEQ scores, and age- and sex-adjusted JOABPEQ scores two years after surgery. Differences between groups were examined using the Mann‒Whitney U test and χ 2 analysis, where applicable. RESULTS: Both groups showed an improved HRQOL after decompression surgery. Similar proportions of patients showed substantial improvement, as estimated by the MCID, in four out of five subdomains of the JOABPEQ. A significantly smaller proportion of patients in the MA+ group showed substantial improvement in lumbar function. The age- and sex-adjusted HRQOL scores two years after surgery were lower in the MA+ group, particularly in the lumbar function and social life function subdomains of the JOABPEQ. CONCLUSION: The effects of posterior decompression surgery alone can still be observed at least two years postoperatively for patients with LSS and concomitant sagittal malalignment. Patients with sagittal malalignment may experience lower HRQOL than those without this type of malalignment.

Radiographical Results of Adolescent Idiopathic Scoliosis with Major Curve at Proximal Thoracic Spine.

Introduction: Adolescent idiopathic scoliosis (AIS) with a major curve at the main thoracic (MT) area is classified as Lenke type 1, 2, or 3 depending on the flexibility of the proximal thoracic (PT) curve and lumbar curve. No definite classification has been established for a major curve at the PT spine. The purpose of this study is to investigate the radiographic characteristics before and after correction surgery for AIS with a major curve at the PT area. Methods: This is a retrospective cohort study at a single academic institution. Twelve patients with a major curve at the PT spine participated in our study and followed for at least two years after surgery. We evaluated the pre- and postoperative Cobb angles of the curve, curve range, location of the apex, sagittal parameters, and shoulder balance-related parameters. All patients were treated by posterior correction and fusion surgery using pedicle screw constructs. Results: The patients were classified as having a double-curve (DC) type, in which the MT curve was structural, or a single-curve (SC) type, in which the MT curve was corrected to less than 25° on supine side-bending films. The mean correction rates for the PT curve were favorable in both groups (DC, 65.7%±9.6%; SC, 39.2%±4.9%). The mean Cobb angle of the lumbar curve improved in the DC group (preoperative, 17.1°±4.0°; postoperative, 5.0°±4.2°) but deteriorated in the SC group (preoperative, 7.1°±1.2°; postoperative, 12.4°±4.4°) after surgery. Conclusions: We illustrated the postoperative radiographical changes of 12 consecutive patients with the major curve at the PT curve. Although posterior correction and fusion surgery corrected the PT curve satisfactorily in both DC and SC patients, the Cobb angle of the lumbar curve deteriorated after surgery in all SC patients. Surgeons need to pay attention to the fusion area, especially LIV, when operating the SC curve type.

A rare spontaneous breast abscess due to Mycobacterium chelonae: a case report.

BACKGROUND: Mycobacterium chelonae, a nontuberculous mycobacterium, commonly causes skin, soft tissue, eye, pulmonary, catheter-related, and post-surgical infections in patients with immunosuppression or trauma. M. chelonae breast infections are rare, and most cases occur following cosmetic surgery. Here, we report the first case of spontaneous breast abscess due to M. chelonae. CASE PRESENTATION: A 22-year-old Japanese woman presented at our hospital with swelling and pain in the right breast for the past 2 weeks without any fever. She had a 19-month-old child and stopped breastfeeding 1 month after giving birth. The patient had no history of trauma or breast surgeries, no family history of breast cancer, and was not immunocompromised. Breast ultrasonography revealed a heterogeneous hypoechoic lesion with multiple fluid-filled areas suspected to be abscesses. Dynamic contrast-enhanced magnetic resonance imaging revealed a 64 × 58 × 62 mm, ill-defined, high-signal-intensity lesion with multiple ring enhancements in the upper half of the right breast. The first diagnosis was inflammatory breast cancer or granulomatous mastitis with abscess. A core needle biopsy led to drainage of pus. Gram staining did not reveal any bacteria in the pus, but the colonies from the biopsy grew on blood and chocolate agar cultures. Mass spectrometry detected M. chelonae in these colonies. Histopathological findings revealed mastitis without malignancy. The patient's treatment regimen was oral clarithromycin (CAM) based on susceptibility. Three weeks later, although the pus had reduced, the induration in the breast did not resolve; therefore, multidrug antibiotic treatment was initiated. The patient received amikacin and imipenem infusion therapy for 2 weeks, followed by continuation of CAM. Three weeks later, tenderness in the right breast recurred with slight pus discharge. Hence, minocycline (MINO) was added to the treatment. The patient stopped CAM and MINO treatment 2 weeks later. There was no recurrence 2 years after treatment. CONCLUSION: We report a case of M. chelonae breast infection and abscess formation in a 22-year-old Japanese woman without obvious risk factors. M. chelonae infection should be considered in cases of intractable breast abscess, even in patients without immunosuppression or trauma.

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study.

Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated. Material and methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese. Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI. Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.

Clinical Features of Recurrent Spinal Cord Tumors.

Introduction: Only a few reports have described the clinical features of recurrent spinal cord tumors. This study aimed to report the recurrence rates (RRs), radiographic imaging, and pathological features of various histopathological recurrent spinal cord tumors using a large sample size. Methods: This study adopted the retrospective observational study design using a single-center study setting. We retrospectively reviewed 818 consecutive individuals operated for spinal cord and cauda equina tumors between 2009 and 2018 in a university hospital. We first determined the number of surgeries and then the histopathology, duration to reoperation, number of surgeries, location, degree of tumor resection, and tumor configuration of the recurrent cases. Results: A total of 99 patients (46 men and 53 women) who underwent multiple surgeries were identified. The mean duration between the primary and second surgeries was 94.8 months. A total of 74 patients underwent surgery twice, 18 patients thrice, and 7 patients 4 or more times. The recurrence sites were broadly distributed over the spine, with mainly intramedullary (47.5%) and dumbbell-shaped (31.3%) tumors. The RRs for each histopathology were as follows: schwannoma, 6.8%; meningioma and ependymoma, 15.9%; hemangioblastoma, 15.8%; and astrocytoma, 38.9%. The RRs after total resection were significantly lower (4.4%) than that after partial resection. Neurofibromatosis-associated schwannomas had a higher RR than sporadic schwannomas (p<0.001, odds ratio [OR]=8.54, 95% confidence interval [95% CI]: 3.67-19.93). Among the meningiomas, the RR increased to 43.5% in ventral cases (p<0.001, OR=14.36, 95% CI: 3.66-55.29). Within the ependymomas, partial resection (p<0.001, OR=2.871, 95% CI: 1.37-6.03) was found to be significantly correlated with recurrence. Dumbbell-shaped schwannomas exhibited a higher RR than non-dumbbell-shaped ones. Furthermore, dumbbell-shaped tumors other than schwannoma had a higher RR than dumbbell-shaped schwannomas (p<0.001, OR=16.0, 95% CI: 5.518-46.191). Conclusions: Aiming for total resection is essential to prevent recurrence. Dumbbell-shaped schwannomas and ventral meningiomas exhibited higher RR requiring revision surgery. As for dumbbell-shaped tumors, spinal surgeons should pay attention to the possibilities of non-schwannoma histopathologies.

Novel O/W Emulsions by Utilizing a Vesicle/Disc Transformation of Polyether Modified Silicone.

Emulsification is an important technology in the field of cosmetics and household products. Emulsions are in non-equilibrium state; therefore, the products vary depending on the preparation process, and their state changes with time. Furthermore, it is known empirically that different types of oils have different emulsification properties (preparation and stability). For these reasons, the variables in emulsification research are numerous and complicated to analyze. As a result, many industrial applications have had to rely on empirical rules. In this study, emulsions with a lamellar liquid crystalline phase as an adsorption layer at the emulsion interface were investigated. The characteristics of O/W emulsions formed with the excess solvent phases (aqueous and oil phases) separated from the lamellar liquid crystalline phase were investigated based on the phase equilibrium of the ternary system.As a result, it was found that by agitating the aqueous phase containing dispersed vesicles of emulsifier (polyether modified silicone) together with the oil phase, an emulsion with a uniform interfacial membrane of lamellar liquid crystalline phase could be obtained. The emulsions prepared by this method were found to have good stability against coalescence. The process of transformation from vesicles to the uniform liquid crystal interfacial membrane during the emulsification process was clarified by a freeze-fracture transmission electron micrograph and the calculation of interfacial membrane thickness based on precise particle size analysis. Furthermore, the emulsification properties of polyether-modified silicones were clarified using polar oils and silicone oils, which are a combination of high/low and low/high compatibility with hydrophilic (polyethylene glycol) and lipophilic (polydimethylsiloxane) groups of polyether modified silicone, respectively. It is expected that this research will lead to the evolution of various functionalities in products in the fields of cosmetics, household products, food, pharmaceuticals, paint and others.

Natural history and surgical outcomes of idiopathic spinal cord herniation.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: Although surgery is frequently selected for the treatment of idiopathic spinal cord herniation (ISCH), its impact on functional outcomes has yet to be fully understood given the limited number of patients in previous studies. This study aims to evaluate the symptomatic history and surgical outcomes of ISCH. SETTING: Three institutions in Japan. METHODS: A total of 34 subjects with ISCH were retrospectively enrolled and followed up for at least 2 years. Demographic information, imaging findings, and clinical outcomes were collected. Functional status was assessed using the JOA score. RESULTS: The types of neurologic deficit were monoparesis, Brown-Sequard, and paraparesis in 5, 17, and 12 cases, with their mean disease duration being 1.2, 4.2, and 5.8 years, respectively. Significant differences in disease duration were observed between the monoparesis and Brown-Sequard groups (p < 0.01) and between the monoparesis and paraparesis groups (p = 0.04). Surgery promoted significantly better recovery rates from baseline. Correlations were observed between age at surgery and recovery rate (p < 0.01) and between disease duration and recovery rate (p = 0.04). The mean recovery rates were 82.6%, 51.6%, and 29.1% in the monoparesis, Brown-Sequard, and paraparesis groups, respectively. The monoparesis group had a significantly higher recovery rate than did the Brown-Sequard (p = 0.045) and paraparesis groups (p < 0.01). CONCLUSIONS: Longer disease duration was correlated with the progression of neurologic deficit. Older age, and worse preoperative neurologic status hindered postoperative functional recovery. These results highlight the need to consider surgical timing before neurologic symptoms deteriorate.

Resection of Cervical Dumbbell-Shaped Schwannoma Using Posterior Unilateral Approach: Impact on Postoperative Cervical Function and Clinical Outcomes.

STUDY DESIGN: A retrospective comparative study. OBJECTIVES: This study aimed to evaluate the radiographical changes in cervical sagittal alignment (CSA) and clinical outcomes after tumor resection using a posterior unilateral approach without spinal fixation for patients with cervical dumbbell-shaped schwannoma (DS). METHODS: Seventy-three patients with DS who were followed up for at least 2 years were included. The Eden classification was used to designate the types of DS. The CSA and range of motion (ROM) were analyzed using radiographs. The clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) score and JOA cervical myelopathy questionnaire. RESULTS: The CSA in the neutral, flexion, and extension position and cervical ROM were not significantly reduced in the follow-up period. The JOA scores showed significant improvement after surgery. The postoperative radiographic parameters and clinical outcomes of Eden type II or III DS, which needed facetectomy for the resection, did not show any statistically significant difference compared with those of Eden type I tumor, which was resected without facetectomy. Fifty-two cases (71.2%) achieved gross total resection, whereas 21 cases (28.8%) remained in partial resection (PR). One case underwent reoperation due to the regrowth of the remnant tumor whose margin was at the entrance of the intervertebral foramen. CONCLUSIONS: Tumor resection using the posterior unilateral approach preserved CSA and resulted in favorable clinical outcomes in patients with DS. When the resection ends in PR, the proximal margin of the remnant tumor should be located distally away from the entrance of the foramen to prevent regrowth.

10-year Longitudinal MRI Study of Intervertebral Disk Degeneration in Patients With Lumbar Spinal Canal Stenosis After Posterior Lumbar Decompression Surgery.

STUDY DESIGN: A prospective longitudinal magnetic resonance imaging (MRI) study. OBJECTIVE: The objective of this study was to describe the progression of intervertebral disk (IVD) degeneration in patients who underwent posterior decompression surgery for lumbar spinal canal stenosis (LSS). SUMMARY OF BACKGROUND DATA: IVD degeneration contributes to the pathogenesis of LSS; however, the long-term consequences of degenerative changes after decompression surgery remain unknown. MATERIALS AND METHODS: Of 258 consecutive patients who underwent posterior lumbar decompression surgery for LSS, 62 who underwent MRI at their 10-year follow-up were included; 17 age-matched asymptomatic volunteers were analyzed as controls. Three MRI findings representing IVD degeneration were graded on their severity: decrease in signal intensity, posterior disk protrusion (PDP), and disk space narrowing (DSN). Clinical outcome was assessed using the low back pain (LBP) score from the Japanese Orthopaedic Association scoring system. We examined the association between the progression of degenerative changes on MRI and LBP/associated factors using logistic regression adjusting for age at baseline and sex. RESULTS: The severity of IVD degeneration tended to be higher in patients with LSS than asymptomatic volunteers at both baseline and follow-up. IVD degeneration progressed in all patients during the 10-year follow-up period. Progression of decrease in signal intensity and PDP was observed at L1/2 in 73% and at L2/3 in 34%, respectively (the highest frequencies in the lumbar spine). Progression of DSN was highest at L4/5 in 42%. The rates of PDP and DSN progression during the 10-year follow-up period tended to be greater in patients with LSS than in asymptomatic volunteers. No significant difference in the proportion of LBP deterioration was evident for individuals with and without MRI findings of progression. CONCLUSIONS: Our study reveals a natural history of the long-term postoperative course of IVD degeneration after posterior decompression surgery for LSS. Compared with healthy controls, patients with LSS seemed to be predisposed to IVD degeneration. Lumbar decompression surgery may promote the progression of DSN; however, progression of IVD degeneration after lumbar decompression surgery was not associated with worsening LBP scores.

MPK12 in stomatal CO2 signaling: function beyond its kinase activity.

Protein phosphorylation is a major molecular switch involved in the regulation of stomatal opening and closure. Previous research defined interaction between MAP kinase 12 and Raf-like kinase HT1 as a required step for stomatal movements caused by changes in CO2 concentration. However, whether MPK12 kinase activity is required for regulation of CO2 -induced stomatal responses warrants in-depth investigation. We apply genetic, biochemical, and structural modeling approaches to examining the noncatalytic role of MPK12 in guard cell CO2 signaling that relies on allosteric inhibition of HT1. We show that CO2 /HCO3 - -enhanced MPK12 interaction with HT1 is independent of its kinase activity. By analyzing gas exchange of plant lines expressing various kinase-dead and constitutively active versions of MPK12 in a plant line where MPK12 is deleted, we confirmed that CO2 -dependent stomatal responses rely on MPK12's ability to bind to HT1, but not its kinase activity. We also demonstrate that purified MPK12 and HT1 proteins form a heterodimer in the presence of CO2 /HCO3 - and present structural modeling that explains the MPK12:HT1 interaction interface. These data add to the model that MPK12 kinase-activity-independent interaction with HT1 functions as a molecular switch by which guard cells sense changes in atmospheric CO2 concentration.

Long-Term Clinical, Radiographic, and Cost Analysis of Corrective Spine Surgery for Adult Symptomatic Lumbar Deformity With a Mean of 7.5 years Follow-Up.

STUDY DESIGN: Multicenter retrospective study. OBJECTIVE: This study reports long-term clinical and radiographic outcomes in surgically treated patients with adult symptomatic lumbar deformity (ASLD). SUMMARY OF BACKGROUND DATA: The short-term results of corrective spinal surgery for ASLD are often favorable despite a relatively high complication profile. However, long-term outcomes have not been completely characterized. METHODS: A total of 169 surgically treated consecutive ASLD patients (≥50 yr) who achieved minimum 5 year follow-up were included (average 7.5 yr observation window, average age 67±8 yr, 96% female). The subjects were stratified by current age (50s, 60s, and 70s) and compared. Kaplan-Meier analysis was used to estimate the cumulative incidence of unplanned reoperation stratified by age group. Initial and overall direct costs of surgery were also analyzed. RESULTS: The SRS-22 at final follow-up was similar among the three groups (50s, 60s, and 70s; 4.0±0.5 vs. 3.8±0.7 vs. 3.8±0.7, respectively). The overall major complication rate was 56%, and 12% experienced late complications. The cumulative reoperation rate was 23%, and 4% required late reoperation. Patients in their 70s had a significantly higher reoperation rate (33%) and overall complication rate (65%). However, the late complication rate was not significantly different between the three groups (9% vs. 12% vs. 13%). Sagittal alignment was improved at two years and maintained to the final follow-up, whereas reciprocal thoracic kyphosis developed in all age groups. The direct cost of initial surgery was $45K±9K and increased by 13% ($53K±13K) at final follow-up. CONCLUSIONS: Long-term surgical outcomes for ASLDs were favorable, with a relatively low rate of late-stage complications and reoperations, as well as reasonable direct costs. Despite the higher reoperation and complication rate, ASLD patients of more advanced age achieved similar improvement to those in the younger age groups.

Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression.

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).

Abrogation of LBX1 in skeletal muscle results in hypoplastic limbs and progressive kyphosis in mice.

LBX1 is a gene located near a single-nucleotide polymorphism, rs11190870, which is highly associated with susceptibility to adolescent idiopathic scoliosis. However, the potential involvement of LBX1 in the etiology of this spinal deformity has not been elucidated. In this study, we aimed to determine whether the lack of LBX1 in skeletal muscle results in spinal deformities in mice. We generated mutant mice in which the Lbx1 allele was conditionally excised under the control of a human muscle actin promoter. Mice lacking LBX1 from the skeletal muscle were fertile and available. The mutant mice had hypoplastic forelimbs and weighed less than control animals, but otherwise, there were no overt anomalies. The mice did not exhibit a scoliosis-like spinal deformity; however, they developed moderate kyphosis as they grew old. These observations indicated that LBX1 is involved in limb development and potentially in the maintenance of spinal curvature/alignment in mice.