Association of Spinal Corrective Surgery With Abdominal Aorta Length in Patients With Adult Spinal Deformity.

Introduction This research aimed to explore the relationship between spinal characteristics and the length of the abdominal aorta in adult spinal deformity (ASD) patients who underwent corrective spinal surgery. We hypothesized that adjusting spinal alignment might affect the abdominal aorta's length. Methods This study included thirteen patients with ASD (average age: 63.0 ± 8.9 years; four males and nine females) who received spinal correction surgery. We measured both pre-operative and post-operative spinal parameters, including thoracolumbar kyphosis (TLK), and calculated their differences (Δ). The length of the aorta (AoL) was determined using an automated process that measures the central luminal line from the celiac artery's bifurcation to the inferior mesenteric artery. This measurement was made using contrast-enhanced computed tomography for three-dimensional aortic reconstruction. We compared the pre-operative and post-operative AoLs and their differences (Δ). The study examined the correlation between changes in spinal parameters and changes in AoL. Results Post-operatively, there was an increase in aortic length (ΔAoL: 4.2 ± 4.9 mm). There was a negative correlation between the change in TLK and the change in AoL (R2 = 0.45, p = 0.012, ß = -0.21). No significant correlations were found with other spinal parameters. Conclusions The abdominal aorta can elongate by 4.8% after spinal corrective surgery in patients with ASD. The degree of elongation of the abdominal aorta is associated with spinal alignment correction.

Measurement of Postoperative Apical Vertebral Rotation Using Radiographic Images in Adolescent Idiopathic Scoliosis-Quantitative Evaluation Using Inverse Trigonometric Functions.

Introduction: Conventional methods for analyzing vertebral rotation are limited to postoperative patients who underwent posterior fusion. A previous methodology calculated vertebral rotation using inverse trigonometric functions based on the length of the pedicle screw (PS). Accordingly, this study evaluates rotational deformity in patients with postoperative adolescent idiopathic scoliosis (AIS) using inverse trigonometric functions. Methods: This retrospective single-center study includes patients with AIS who underwent posterior fusion surgery. Postoperative radiography and computed tomography (CT) scans were retrospectively evaluated. The magnification ratio was calculated using the rod diameter (δ=lateral/frontal rod diameter), and the visible screw lengths were measured using radiographs. The rotation angle was calculated using the apex of the main curve and the lower instrumented vertebra (LIV) (rotation angle=tan-1 (lateral PS length/(δ×frontal PS length))) immediately following the surgery as well as two and five years postoperatively. The correlation between the direct CT measurement and postoperative rotation angle progression was investigated. The crankshaft phenomenon (CSP) and distal adding-on (DAO) were evaluated as postoperative deformities. CSP was defined as a 5° increase in rotation angle. Results: Seventy-eight patients (age: 15.3±2.0 years, eight boys and seventy girls) were included. The rotation angle was strongly correlated with CT rotation measurements (r=0.87). The mean rotation angle at the apex and LIV did not change within five years postoperatively (mean: 0.5±3.6° and 0.4±3.4°, respectively). CSP and DAO were observed in 6.4% and 3.8% of patients, respectively. Conclusions: The inverse trigonometric method is useful to quantitatively evaluate the postoperative rotation angle and identify CSP.

The Optimal Patient Position on the Surgical Table for Lateral Lumbar Interbody Fusion in Adult Spinal Deformity Using Three-Dimensional Computed Tomography: A Retrospective Study.

Introduction: Lateral lumbar interbody fusion (LLIF) techniques have been extensively used in adult spinal deformity surgery. Preoperative knowledge of the optimal position of the patient on the surgical table is essential for a safe procedure. Therefore, this study aims to determine the optimal angle for positioning the patient on the surgical table during LLIF using three-dimensional computed tomography (3DCT). Methods: Data from 59 patients (2 males, 57 females, mean age 66.3±8.6 years) with adult spinal deformities treated by performing corrective spinal surgery were included in this observational retrospective study. Simulated fluoroscopic images were obtained using 3DCT images rotated from the reference position with the spinous process of S1 as the midline to the position with the spinous process in the center of the bilateral pedicle of T12-L5. The rotation angle of each vertebra was measured and defined as the optimal rotation angle (ORA). The angle that bisected the angle between the maximum and minimum ORA was defined as the optimal mean angle of the maximum and minimum ORA (OMA) and considered the optimal angle for the patient's position on the surgical table, as this position could minimize the rotation angle of the surgical table during surgery. A multiple regression analysis was performed to predict OMA. Results: Multiple regression analysis revealed the following equation: OMA=1.959+(0.238×lumbar coronal Cobb angle)+(-0.208×sagittal vertical axis). Conclusions: When the patient is placed on the surgical table by rotating them at the OMA, the rotation of the surgical table can be reduced, ensuring a safe and efficient surgical procedure.

Factors Influencing Optimal Bracing Compliance in Adolescent Idiopathic Scoliosis: A Single Center Prospective Cohort Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To identify factors contributing to optimal bracing compliance in adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Poor brace compliance is a key factor affecting brace treatment success in AIS. Predictive factors influencing optimal brace compliance to achieve brace treatment success remain unknown. MATERIALS AND METHODS: This study included AIS patients, aged 10-15, with a Cobb angle of 20-40 degrees. Demographics data, radiographic assessments, and patient-reported outcomes (including the SRS-22r patient questionnaire) were collected. Brace compliance was monitored using in-brace thermometers, defining optimal bracing time as more than 18 hours/day. Multivariable logistic regression analysis was employed to identify predictors of optimal bracing time from the demographic and patient- reported outcomes score before bracing. RESULTS: Among 122 patients, 59.0% achieved optimal bracing time by six months. The achieved group indicated higher scores in satisfaction domain before bracing (3.3±0.7 vs. 3.1±0.6; P=0.034). Multivariable logistic regression analysis demonstrated that Satisfaction domain before bracing was an independent factor associated with achievement of the optimal bracing time (OR 1.97 [95%CI 1.00 - 3.89], P=0.049). The model with bracing at 1-month follow-up also demonstrated the bracing at 1-month was a significant factor (OR 1.52 [95%CI 1.30 - 1.79], P<0.001). CONCLUSION: Optimal bracing compliance in AIS is significantly influenced by pre-bracing satisfaction and brace compliance at earlier time point. These findings highlight the need to address psychological factors and early compliance in AIS bracing treatment. SRS-22r can be useful to identify the need for psychological support.

Machine learning algorithms for predicting Cobb angle beyond 25 degrees in female adolescent idiopathic scoliosis patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To develop a machine learning (ML) model that predicts the progression of AIS using minimal radiographs and simple questionnaires during the first visit. SUMMARY OF BACKGROUND DATA: Several factors are associated with angle progression in patients with AIS. However, it is challenging to predict angular progression at the first visit. METHODS: Among female patients with AIS treated at a single institution from July 2011 to February 2023, 1119 cases were studied. Patient data, including demographic and radiographic data based on anterior-posterior and lateral whole-spine radiographs, were collected at the first and last visits. The last visit was defined differently based on treatment plans. For patients slated for surgery or bracing, the last visit occurred just before these interventions. For others, it was their final visit before turning 18 years. Angular progression was defined as a Cobb angle greater than 25 degrees for each of the proximal thoracic (PT), main thoracic (MT), and thoracolumbar/lumbar (TLL) curves at the last visit. ML algorithms were employed to develop individual binary classification models for each type of curve (PT, MT, and TLL) using PyCaret in Python. Multiple models were explored and analyzed, with the selection of optimal models based on the area under the curve (AUC) and Recall scores. Feature importance was evaluated to understand the contribution of each feature to the model predictions. RESULTS: For PT, MT, and TLL progression, the top-performing models exhibit AUC values of 0.94, 0.89, and 0.84, and achieve recall rates of 0.90, 0.85, and 0.81. The most significant factors predicting progression varied for each curve: initial Cobb angle for PT, presence of menarche for MT, and Risser grade for TLL. CONCLUSIONS: This study introduces an ML-based model using simple data at the first visit to precisely predict angle progression in female patients with AIS.

Vero cell-adapted SARS-CoV-2 strain shows increased viral growth through furin-mediated efficient spike cleavage.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes several host proteases to cleave the spike (S) protein to enter host cells. SARS-CoV-2 S protein is cleaved into S1 and S2 subunits by furin, which is closely involved in the pathogenicity of SARS-CoV-2. However, the effects of the modulated protease cleavage activity due to S protein mutations on viral replication and pathogenesis remain unclear. Herein, we serially passaged two SARS-CoV-2 strains in Vero cells and characterized the cell-adapted SARS-CoV-2 strains in vitro and in vivo. The adapted strains showed high viral growth, effective S1/S2 cleavage of the S protein, and low pathogenicity compared with the wild-type strain. Furthermore, the viral growth and S1/S2 cleavage were enhanced by the combination of the Δ68-76 and H655Y mutations using recombinant SARS-CoV-2 strains generated by the circular polymerase extension reaction. The recombinant SARS-CoV-2 strain, which contained the mutation of the adapted strain, showed increased susceptibility to the furin inhibitor, suggesting that the adapted SARS-CoV-2 strain utilized furin more effectively than the wild-type strain. Pathogenicity was attenuated by infection with effectively cleaved recombinant SARS-CoV-2 strains, suggesting that the excessive cleavage of the S proteins decreases virulence. Finally, the high-growth-adapted SARS-CoV-2 strain could be used as the seed for a low-cost inactivated vaccine; immunization with this vaccine can effectively protect the host from SARS-CoV-2 variants. Our findings provide novel insights into the growth and pathogenicity of SARS-CoV-2 in the evolution of cell-cell transmission. IMPORTANCE: The efficacy of the S protein cleavage generally differs among the SARS-CoV-2 variants, resulting in distinct viral characteristics. The relationship between a mutation and the entry of SARS-CoV-2 into host cells remains unclear. In this study, we analyzed the sequence of high-growth Vero cell-adapted SARS-CoV-2 and factors determining the enhancement of the growth of the adapted virus and confirmed the characteristics of the adapted strain by analyzing the recombinant SARS-CoV-2 strain. We successfully identified mutations Δ68-76 and H655Y, which enhance viral growth and the S protein cleavage by furin. Using recombinant viruses enabled us to conduct a virus challenge experiment in vivo. The pathogenicity of SARS-CoV-2 introduced with the mutations Δ68-76, H655Y, P812L, and Q853L was attenuated in hamsters, indicating the possibility of the attenuation of excessive cleaved SARS-CoV-2. These findings provide novel insights into the infectivity and pathogenesis of SARS-CoV-2 strains, thereby significantly contributing to the field of virology.

Analysis of Rod Fracture at the Lumbosacral Junction Following Surgery for Adult Spinal Deformity.

STUDY DESIGN: Retrospective study. PURPOSE: This study aimed to investigate the differences in the characteristics of patients with rod fracture (RF) at the lumbosacral junction from those without RF following adult spinal deformity (ASD) surgery. OVERVIEW OF LITERATURE: RF is a major complication following ASD surgery and may require reoperation because of pain and correction loss. The lumbosacral junction is a common RF site. However, risk factors for RFs at the lumbosacral junction remain unknown. METHODS: The study included data from 100 patients who underwent ASD surgery between 2012 and 2020. Fifteen of these patients presented with RFs. Patient demographics, clinical outcomes, and radiographic parameters were evaluated in each group. RESULTS: RFs were significantly more frequent in patients with a medical history of total hip arthroplasty (THA; p=0.01) or severe obesity (p=0.04). However, no significant differences in clinical outcomes, preoperative or postoperative measurements, or changes were found between pre- and postoperative radiographic parameters within the groups. Both pre- (p=0.01) and postoperative (p=0.02) anterior disc heights were significantly greater in the RF group than in the non-RF group. In the RF group, the postoperative lordotic angles of the lumbosacral junction significantly decreased compared with preoperative angles (p=0.02). Multiple logistic regression analysis demonstrated that a THA history (odds ratio, 34.2), severe obesity (odds ratio, 14.0), and preoperative anterior disc height (odds ratio, 1.2) were significant risk factors for RFs. CONCLUSIONS: In this study, the greatest risk factors for postoperative lumbosacral RF after ASD surgery were THA history, severe obesity, and postoperative anterior disc height of ≥10. For patients at higher risk, the use of multirods is considered necessary.

Anatomical Analysis of the S1 Neural Foramen Using Three-Dimensional Computed Tomography Imaging: Insights for Effective S1 Nerve Root Block.

OBJECTIVE: The first sacral nerve root block (S1 NRB) is used to diagnose and treat lumbosacral and radicular pain. This study aims to clarify the anatomy of the S1 neural foramen using three-dimensional (3D) computed tomography (CT) images and to establish the optimal fluoroscopic angle, localize the S1 neural foramen on fluoroscopy, and determine the safe puncture depth for S1 NRB. METHODS: In this single-center cohort study, 200 patients with lumbar degenerative disease who underwent preoperative CT were enrolled. Four distinct studies were conducted using the CT data. Study 1 examined the correlation of the sacral slope angle and the supine and prone positions. Study 2 analyzed the tunnel view angle (TVA) using 3D reconstruction. Study 3 ascertained the location of the S1 neural foramen in fluoroscopy images. Study 4 investigated the safe depth for performing S1 NRB. RESULTS: The regression analysis in Study 1 revealed a correlation of the sacral slope angle and the supine and prone positions. Study 2 determined an optimal fluoroscopic TVA of approximately 30° for the S1 NRB. Study 3 found that the S1 neural foramen was located caudal to the L5 pedicle 1.7 ± 0.2 times the distance between the L4 and L5 pedicles. Study 4 revealed that the depths of the S1 neural foramen and root were 27.0 ± 2.1 mm and 16.5 ± 2.0 mm, respectively. CONCLUSIONS: Our study suggests an optimal fluoroscopic angle, a simple method to locate the S1 neural foramen on fluoroscopy, and an ideal puncture depth for a safe and effective S1 NRB.

Long-term changes in bone mineral density following adolescent idiopathic scoliosis surgery: a minimum 34-year follow-up.

PURPOSE: To investigate longitudinal changes in bone mineral density (BMD) in middle-aged female patients who underwent spinal fusion for adolescent idiopathic scoliosis (AIS). METHODS: The study subjects were 229 female patients who were diagnosed with AIS and underwent spinal fusion between 1968 and 1988. A two-step survey study was conducted on 19 female AIS patients. BMD, Z-scores, T-scores, and the prevalence of osteoporosis and osteopenia were compared between the initial (2014-2016) and second (2022) surveys. Correlations between the annual changes in Z-scores and T-scores with radiographic parameters, body mass index (BMI), and the number of remaining mobile discs were analyzed. RESULTS: BMD decreased significantly from the initial (0.802 ± 0.120 g/cm2) to the second survey (0.631 ± 0.101 g/cm2; p < 0.001). Z-scores decreased from 0.12 ± 1.09 to - 0.14 ± 1.04, while T-scores decreased significantly from - 0.70 ± 1.07 to - 1.77 ± 1.11 (p < 0.001). The prevalence of osteopenia and osteoporosis increased significantly from 36.8% to 89.5% (p = 0.002), but the increase in osteoporosis alone was not statistically significant (5.3% to 26.3%; p = 0.180). Moderate negative correlations were found between annual changes in Z-scores and both main thoracic (MT) curve (r = - 0.539; p = 0.017) and lumbar curve (r = - 0.410; p = 0.081). The annual change in T-scores showed a moderate negative correlation with the MT curve (r = - 0.411; p = 0.081). CONCLUSION: Significant reductions in BMD and an increased prevalence of osteopenia and osteoporosis were observed in middle-aged female AIS patients who had undergone spinal fusion. The decline in Z-scores in patients with AIS suggested that there was an accelerated loss of BMD compared with the general population. Larger residual curves could pose an added osteoporosis risk. Further research is needed to understand if the onset of osteoporosis in AIS patients is attributable to the condition itself or the surgical intervention.

Hydroxyl Group Acetylation of Quercetin Enhances Intracellular Absorption and Persistence to Upregulate Anticancer Activity in HepG2 Cells.

Quercetin, a flavonoid compound widely distributed in many plants, is known to have potent antitumor effects on several cancer cells. Our previous study revealed that the acetylation of quercetin enhanced its antitumor effect. However, the mechanisms remain unknown. This study aimed to elucidate the bioavailability of acylated quercetin in the HepG2 cell model based on its antitumor effect. The positions of quercetin 3,7,3',4'-OH were acetylated as 3,7,3',4'-O-tetraacetylquercetin (4Ac-Q). The inhibitory effect of 4Ac-Q on HepG2 cell proliferation was assessed by measuring cell viability. The apoptosis was characterized by apoptotic proteins and mitochondrial membrane potential shifts, as well as mitochondrial reactive oxygen species (ROS) levels. The bioavailability of 4Ac-Q was analyzed by measuring the uptake and metabolites in HepG2 cells with high performance liquid chromatography (HPLC)-photodiode array detector (PDA) and-ultraviolet/visible detector (UV/Vis). The results revealed that 4Ac-Q enhanced the inhibitory effect on HepG2 cell proliferation and induced its apoptosis significantly higher than quercetin. Protein array analysis of apoptosis-related protein indicated that 4Ac-Q increased the activation or expression of pro-apoptotic proteins, including caspase-3, -9, as well as second mitochondria-derived activator of caspases (SMAC), and suppressed the expression of apoptosis inhibiting proteins such as cellular inhibitor of apoptosis (cIAP)-1, -2, Livin, Survivin, and X-linked inhibitor of apoptosis (XIAP). Furthermore, 4Ac-Q stimulated mitochondrial cytochrome c release into the cytosol by enhancing ROS level and depolarizing the mitochondrial membrane. Finally, the analysis of uptake and metabolites of 4Ac-Q in HpG2 cells with HPLC-PDA and -UV/Vis revealed that 4Ac-Q was metabolized to quercetin and several different acetylated quercetins which caused 2.5-fold higher quercetin present in HepG2 cells than parent quercetin. These data demonstrated that acetylation of the quercetin hydroxyl group significantly increased its intracellular absorption. Taken together, our findings provide the first evidence that acetyl modification of quercetin not only substantially augments the intracellular absorption of quercetin but also bolsters its metabolic stability to elongate its intracellular persistence. Therefore, acetylation could serve as a strategic approach to enhance the ability of quercetin and analogous flavonoids to suppress cancer cell proliferation.

Median Arcuate Ligament and Origin of the Celiac Artery Proximity Change in Patients after Surgery to Correct Adult Spinal Deformity: Potential Risk Factors for Acute Celiac Artery Compression Syndrome.

Introduction: This study aimed to determine whether the proximity of the median arcuate ligament (MAL) and the celiac artery (CA) changes in patients following surgery to correct adult spinal deformity (ASD). We hypothesized that the distance between the MAL and the CA shortens after corrective spinal surgery, which may cause acute celiac artery compression syndrome (ACACS). Methods: A total of 89 patients (68.4±7.6 years; 7 men/82 women) with ASD treated with spinal correction surgery were included in the present retrospective study. The level of the MAL, CA, and distance between the MAL and the CA (DMC) were determined via reconstructed computed tomography. MAL overlap was determined preoperatively and postoperatively. Results: The MAL and CA moved caudally following surgery. On average, after surgery, no changes in DMC were observed. We found preoperative MAL overlap in 32 (36%) patients, who also had postoperative MAL overlap. No patients showed any MAL overlap postoperatively. Conclusions: Contrary to our hypothesis, the distance between the MAL and the CA did not shorten, and emerging MAL overlap was not observed postoperatively.

Assessment of the Initial Diagnostic Accuracy of a Fragility Fracture of the Sacrum: A Study of 56 Patients.

STUDY DESIGN: Retrospective study. PURPOSE: To investigate the clinical manifestations of a fragility fracture of the sacrum (FFS) and the factors that may contribute to a misdiagnosis. OVERVIEW OF LITERATURE: The number of patients diagnosed with FFS has increased because of extended life expectancy and osteoporosis. Patients with FFS may report nonspecific symptoms, such as back, buttock, groin, and/or leg pain, leading to a misdiagnosis and a delay in definitive diagnosis. METHODS: Fifty-six patients (13 males and 43 females) with an average age of 80.2±9.2 years admitted to the hospital for FFS between 2006 and 2021 were analyzed retrospectively. The following patient data were collected using medical records: pain regions, a history of trauma, initial diagnoses, and rates of fracture detection using radiography, computed tomography (CT), and magnetic resonance imaging (MRI). RESULTS: Forty-one patients presented with low back and/or buttock pain, nine presented with groin pain, and 17 presented with thigh or leg pain. There was no history of trauma in 18 patients (32%). At the initial visit, 27 patients (48%) were diagnosed with sacral or pelvic fragility fractures. In contrast, 29 patients (52%) were initially misdiagnosed with lumbar spine disease (23 patients), hip joint diseases (three patients), and buttock bruises (three patients). Fracture detection rates for FFS were 2% using radiography, 71% using CT, and 93% using MRI. FFS was diagnosed definitively using an MRI with a coronal short tau inversion recovery (STIR) sequence. CONCLUSIONS: Some patients with FFS have leg pain with no history of trauma and are initially misdiagnosed as having lumbar spine disease, hip joint disease, or simple bruises. When these clinical symptoms are reported, we recommend considering FFS as one of the differential diagnoses and performing lumbar or pelvic MRIs, particularly coronal STIR images, to rule out FFS.

Incidence and Potential Risk Factors of Superior Mesenteric Artery Syndrome After Spinal Corrective Surgery in Patients with Adult Spinal Deformity.

OBJECTIVE: This study aimed to determine the incidence and potential risk factors of superior mesenteric artery syndrome (SMAS) after corrective spinal surgery in patients with adult spinal deformity (ASD). METHODS: In total, 102 patients (67.6 ± 8.4 years; 8 male/94 female; body mass index (BMI); 22.4 ± 3.6 kg/m2) with ASD treated by spinal correction surgery were enrolled. Preoperative and postoperative spinal parameters, including thoracolumbar kyphosis (TLK: T10-L2) and upper lumbar lordosis (ULL: L1-L4) were measured. To evaluate the potential risk factors of SMAS, the angle and the distance between the superior mesenteric artery and aorta, the aortomesenteric angle (AMA) and aortomesenteric distance (AMD), were evaluated pre- and postoperatively. Based on the postoperative AMA, AMD, and abdominal symptoms, the patients were diagnosed with SMAS. Correlations between demographic data or spinal parameters and AMA and AMD were assessed. RESULTS: Two (2.0%) patients were diagnosed with SMAS. Postoperative TLK significantly correlated with postoperative AMA (P = 0.013, 0.046). Postoperative ULL was significantly correlated with postoperative AMD (ß = -0.27; P = 0.014). CONCLUSION: The incidence of SMAS after corrective spinal surgery in patients with ASD was 2.0%. Postoperative smaller TLK and greater ULL can be risk factors for developing SMAS. Spine surgeons should avoid overcorrection of the upper lumbar spine in the sagittal plane to prevent SMAS.

The Association Between Corrective Surgery for Adult Spinal Deformity and Serum Levels of Hepatobiliary Enzymes.

Background and objective The surgery to correct adult spinal deformity (ASD) is associated with a rare, but life-threatening complication called acute celiac artery compression syndrome (ACACS). To our knowledge, there is currently no study in the literature regarding the abnormal elevation of serum levels of hepatobiliary enzymes after surgery to correct the deformity. In light of this, the purpose of this study was to investigate this potential association. Materials and methods We collected data on 74 patients with ASD who underwent correction surgery at our institution. A Spearman's rank-order correlation was used to assess the association between serum levels of hepatobiliary enzymes and spinal parameters. Factors showing a correlation coefficient of 0.2 or more were combined in a stepwise multiple regression analysis. Results The mean age of the patients was 68.4 ± 7.7 years; the study comprised six men and 68 women. In our stepwise multiple regression analysis, there were two valid models that included spinal parameters as independent variables: changes in lactate dehydrogenase (LDH) - changes in thoracolumbar kyphosis (TLK) (B -0.0025 ± 0.0007, p<0.01), and changes in LDH - preoperative T12-L1 kyphosis (B 0.0031 ± 0.001, p<0.01). Additionally, both valid models contained median arcuate ligament (MAL) overlap defined as MAL crossing the base of the celiac artery (CA) as a significant independent variable. Conclusions Greater sagittal correction of TLK, larger preoperative T12-L1 kyphosis, and MAL overlap were factors associated with an elevated serum level of LDH. Although few patients were reported to have clinically severe symptoms, "potential" ACACS due to a temporary blood flow disturbance can occur in this patient population.

Genetic engineering strategy for generating a stable dsRNA virus vector using a virus-like codon-modified transgene.

IMPORTANCE: The stabilities of transgenes in RNA virus vectors differ between the genes of interest, but the molecular mechanisms determining genetic stability remain unknown. This study demonstrated that the stability of a transgene was affected by the nucleotide composition, and altering the codon usage of transgenes to resemble that of the viral genome significantly increased transgene stability in double-stranded RNA virus vectors. The virus-like codon modification strategy enabled generation of stable rotavirus and mammalian orthoreovirus vectors, which could be developed as machinery for gene delivery to the intestines and/or respiratory organs. This technology has further potential to be expanded to other RNA viruses.

Risk Factors for Cage Subsidence in Minimally Invasive Lateral Corpectomy for Osteoporotic Vertebral Fractures.

Introduction: This study aims to investigate risk factors for cage subsidence following minimally invasive lateral corpectomy for osteoporotic vertebral fractures. Methods: Eight males and 13 females (77.2±6.0 years old) with osteoporotic vertebral fractures who underwent single corpectomy using a wide-footprint expandable cage with at least a 1-year follow-up were retrospectively included. The endplate cage (EC) angle was defined as the angle between the vertebral body's endplate and the cage's base on the cranial and caudal sides. A sagittal computed tomography scan was performed immediately after surgery and at the final follow-up, with cage subsidence defined as subsidence of ≥2 mm on the cranial or caudal side. Risk factors were analyzed by dividing cases into groups with (n=6) and without (n=15) cage subsidence. Results: No significant differences were noted in age, bone mineral density, number of fixed vertebrae, sagittal parameters, preoperative and final kyphosis angle, amount of kyphosis angle correction, bone union, screw loosening, and number of other vertebral fractures preoperatively and 1-year postoperatively between the two groups. No difference was noted in cranial EC angle, but a significant difference was noted in caudal EC angle in the group with (10.7±4.1°) and without (4.7±4.2°) subsidence (P=0.008). Logistic regression analysis with the dependent variable as presence or absence of subsidence showed that caudal EC angle (>7.5°) was a significant factor (odds ratio: 20, 95% confidence interval: 1.655-241.7, P=0.018). Conclusions: In minimally invasive lateral corpectomy for osteoporotic vertebral fractures, a cage tilted more than 7.5° to the caudal vertebral endplate is a risk factor for cage subsidence. The cage should be placed as perpendicular to the endplate as possible, especially to the caudal vertebral body, to avoid cage subsidence.

Impact of Brace-Related Stress on Brace Compliance in Adolescent Idiopathic Scoliosis: A Single-Center Comparative Study Using Objective Compliance Measurement and Brace-Related Stress.

Introduction: This study aimed to investigate the brace compliance and clinical background of patients with adolescent idiopathic scoliosis (AIS) who demonstrate different degrees of psychological brace-related stress. Methods: Forty-five patients initiating brace treatment with a Cobb angle between 25° and 45° were included. Patients receiving brace treatment for AIS were administered a questionnaire for brace-related stress (i.e., the Japanese version of the Bad Sobernheim Stress Questionnaire-Brace [JBSSQ-brace]). Based on their scores, we allocated the patients into two stress groups: mild-stress (≥16 points) and below-moderate-stress (<16 points). We investigated the character of brace compliance and brace-related psychological stress in all patients and compared the demographics and brace compliance between both groups. Results: Forty-one of 45 patients completed the study. The mean JBSSQ-brace scores were 18.7±5.1, 19.1±5.2, and 18.7±5.0 points at the 1-month, 4-month, and 1-year follow-ups, respectively. There was no significant change in JBSSQ-brace scores over one year after the brace prescription (P=0.332). There was no difference in-brace compliance between seasons during the first month of brace prescription (P=0.252). Both groups' overall brace compliance was comparable (below-moderate: 17.1±7.1 h/day vs. mild: 20.4±3.0 h/day; P=0.078). The mild-stress group showed better compliance than the below-moderate-stress group on weekdays (below-moderate: 17.0±6.9 h/day vs. mild: 20.5±2.8 h/day; P=0.048) and at nighttime (below-moderate: 82.3%±27.0%/nighttime vs. mild: 93.8%±12.4%/nighttime; P=0.008). Conclusions: Overall, brace compliance was comparable among patients with different brace-related stress, but brace compliance during weekdays and nighttime was significantly better in the mild-stress group.

Efficient Selective Adsorption of SARS-CoV-2 via the Recognition of Spike Proteins Using an Affinity Spongy Monolith.

Since the outbreak of COVID-19, SARS-CoV-2, the infection has been spreading to date. The rate of false-negative result on a polymerase chain reaction (PCR) test considered the gold standard is roughly 20%. Therefore, its accuracy poses a question as well as needs improvement in the test. This study reports fabrication of a substrate of an anti-spike protein (AS)-immobilized porous material having selective adsorption toward a spike protein protruding from the surface of SARS-CoV-2. We have employed an organic polymer substrate called spongy monolith (SPM). The SPM has through-pores of about 10 µm and is adequate for flowing liquid containing virus particles. It also involves an epoxy group on the surface, enabling arbitrary proteins such as antibodies to immobilize. When antibodies of the spike protein toward receptor binding domain were immobilized, selective adsorption of the spike protein was observed. At the same time, when mixed analytes of spike proteins, lysozymes and amylases, were flowed into an AS-SPM, selective adsorption toward the spike proteins was observed. Then, SARS-CoV-2 was flowed into the BSA-SPM or AS-SPM, amounts of SARS-CoV-2 adsorption toward the AS-SPM were much larger compared to the ones toward the BSA-SPM. Furthermore, rotavirus was not adsorbed to the AS-SPM at all. These results show that the AS-SPM recognizes selectively the spike proteins of SARS-CoV-2 and may be possible applications for the purification and concentration of SARS-CoV-2.

Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe acute respiratory symptoms in humans. Controlling the coronavirus disease pandemic is a worldwide priority. The number of SARS-CoV-2 studies has dramatically increased, and the requirement for analytical tools is higher than ever. Here, we propose monolayered-intestinal epithelial cells (IECs) derived from human induced pluripotent stem cells (iPSCs) instead of three-dimensional cultured intestinal organoids as a suitable tool to study SARS-CoV-2 infection. Differentiated IEC monolayers express high levels of angiotensin-converting enzyme 2 and transmembrane protease serine 2 (TMPRSS2), host factors essential for SARS-CoV-2 infection. SARS-CoV-2 efficiently grows in IEC monolayers. Using this propagation system, we confirm that TMPRSS2 inhibition blocked SARS-CoV-2 infection in IECs. Hence, our iPSC-derived IEC monolayers are suitable for SARS-CoV-2 research under physiologically relevant conditions.

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.