Assessment of the Aryl Hydrocarbon Receptor-Mediated Effects of Aromatic Sensitizers in Paper Recycling Effluent Employing Zebrafish Embryos and in Silico Docking.

Aromatic sensitizers and related substances (SRCs), which are crucial in the paper industry for facilitating color-forming and color-developing chemical reactions, inadvertently contaminate effluents during paper recycling. Owing to their structural resemblance to endocrine-disrupting aromatic organic compounds, concerns have arisen about potential adverse effects on aquatic organisms. We focused on SRC effects via the aryl hydrocarbon receptor (AHR), employing molecular docking simulations and zebrafish (Danio rerio) embryo exposure assessments. Molecular docking revealed heightened binding affinities between certain SRCs in the paper recycling effluents and zebrafish Ahr2 and human AHR, which are pivotal components in the SRC toxicity mechanism. Fertilized zebrafish eggs were exposed to SRCs for up to 96 h post fertilization; among these substances, benzyl 2-naphthyl ether (BNE) caused morphological abnormalities, such as pericardial edema and shortened body length, at relatively low concentrations (1 µM) during embryogenesis. Gene expression of cytochrome P450 1A (cyp1a) and ahr2 was also significantly increased by BNE. Co-exposure to the AHR antagonist CH-223191 only partially mitigated BNE's phenotypic effects, despite the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin being relatively well restored by CH-223191, indicating BNE's AHR-independent toxic mechanisms. Furthermore, some SRCs, including BNE, exhibited in silico binding affinity to the estrogen receptor and upregulation of cyp19a1b gene expression. Therefore, additional insights into the toxicity of SRCs and their mechanisms are essential. The present results provide important information on SRCs and other papermaking chemicals that could help minimize the environmental impact of the paper industry. Environ Toxicol Chem 2024;43:2176-2188. © 2024 SETAC.

Pelvic Incidence As a Predictor of Proximal Junctional Kyphosis in Patients with Lenke type 5 Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To evaluate the relationship between pelvic incidence (PI) and proximal junctional kyphosis (PJK) in patients with Lenke type 5 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Although PJK is a common complication of sagittal malalignment after posterior correction and fusion surgery (PSF), few studies have assessed its risk factors. The significance of pelvic morphology in relation to PJK has been suggested but remains unclear in Lenke type 5 AIS patients. METHODS: A total of 92 patients with Lenke type 5 AIS who underwent selective thoracolumbar PSF with a minimum follow-up of two years were included. Patients were divided into PJK and non-PJK groups based on postoperative radiographs. The influence of PI on PJK occurrence was evaluated through binary logistic analysis. Subgroup analysis was performed based on the PI value (low PI,<45°; high PI, ≥ 45°) to identify factors affecting PJK occurrence. RESULTS: PJK was observed in 17.4% of the whole cohort. Binary logistic regression analysis identified low PI and large TL/L curve as a risk factor for PJK (PI, odds ratio, 0.933; TL/L curve, odds ratio, 1.080). Subgroup analysis showed that the postoperative increase in the upper instrumented vertebra slope in PJK cases was comparable in both the low and high PI groups. Meanwhile, lordotic changes in the fused area in the PJK cases were observed only in the low PI group. No difference in the Scoliosis Research Society 22 scores were observed between the two groups. CONCLUSION: From this study a low PI was identified as a risk factor for the occurrence of PJK in Lenke type 5 AIS patients. The occurrence of PJK is influenced by lordotic changes in the fused area and the limited compensatory capacity of the pelvis in patients with a low PI.

Comparison of Surgical Outcomes After Posterior Decompression by Junior or Senior Surgeons for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: Results From Retrospective Multicenter Cohort Study.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate surgical outcomes following posterior decompression for cervical ossification of the posterior longitudinal ligament (OPLL) when performed by board-certified spine (BCS) or non-BCS (NBCS) surgeons. METHODS: We included 203 patients with cervical OPLL who were followed for a minimum of 1 year after surgery. Demographic information, medical history, and imaging findings were collected. Clinical outcomes were assessed preoperatively and at the final follow-up using the Japanese Orthopedic Association (JOA) score and the visual analog scale (VAS) for the neck. We compared outcomes between BCS surgeons, who must meet several requirements, including experience in more than 300 spinal surgeries, and NBCS surgeons. RESULTS: BCS surgeons performed 124 out of 203 cases, while NBCS surgeons were primary in 79 cases, with 73.4% were directly supervised by a BCS surgeon. There was no statistically significant difference in surgical duration, estimated blood loss, and perioperative complication rates between the BCS and NBCS groups. Moreover, no statistically significant group differences were observed in each position of the C2-7 angle and cervical range of motion at preoperation and the final follow-up. Preoperative and final follow-up JOA scores, VAS for the neck, and JOA score recovery rate were comparable between the two groups. CONCLUSIONS: Surgical outcomes, including functional recovery, complication rates, and cervical dynamics, were comparable between the BCS and NBCS groups. Consequently, posterior decompression for cervical OPLL is considered safe and effective when conducted by junior surgeons who have undergone training and supervision by experienced spine surgeons.

Influence of slippage reduction and correction of lumbosacral kyphosis by single-level posterior lumbar interbody fusion on spinal alignment in patients with dysplastic spondylolisthesis.

PURPOSE: To investigate the influence of slippage reduction and correction of lumbosacral kyphosis by L5-S1 single-level posterior lumbar interbody fusion (PLIF) on spinal alignment and clinical outcomes including postoperative complications in patients with dysplastic spondylolisthesis (DS). METHODS: Twenty consecutive patients with symptomatic and severe DS who underwent L5-S1 single-level PLIF with a minimum of 2 years of follow-up after surgery were included. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) and visual analog scale (VAS) scores for low back and leg pain obtained on preoperative and postoperative examinations. Postoperative instrumentation failure and L5 radiculopathy were also evaluated. The preoperative and postoperative spinopelvic parameters were measured. RESULTS: The JOA score significantly improved from 21.5 ± 4.8 (preoperative) to 27.0 ± 2.5 (postoperative), with a mean recovery rate of 75.0% ± 30.4%. The VAS score for low back pain significantly improved from 44.5 ± 30.1 (preoperative) to 11.5 ± 15.9 (postoperative), and that for leg pain significantly improved from 31.0 ± 33.2 (preoperative) to 5.0 ± 10.2 (postoperative). The slip percentage (% slip) significantly improved from 59.6% ± 13.5% (preoperative) to 25.2% ± 15.0% (postoperative). The lumbosacral angle (LSA) significantly improved from 12.3° ± 9.5° (preoperative) to 1.0° ± 4.9° (postoperative). L5-S1 PLIF led to significant improvement of lumbar lordosis (from 52.0° ± 15.9° to 59.7° ± 8.0°) and pelvic incidence - lumbar lordosis mismatch (from 23.9° ± 20.6° to 13.3° ± 10.0°). Correction of lumbosacral kyphosis had a significant positive correlation with postoperative pelvic tilt (PT) (r = 0.50, P = 0.02), while postoperative % slip did not have a significant correlation with postoperative PT. CONCLUSIONS: L5-S1 PLIF for DS provided good clinical outcomes. Correction of lumbosacral kyphosis had a positive impact on regaining ideal spinopelvic balance and may be beneficial in the setting of treating DS.

Exploring 2-methyl-substituted vitamin K3 derivatives with potent inhibitory activity against the 3CL protease of SARS-CoV-2.

Since the outbreak of the pandemic, various anti-SARS-CoV-2 drugs have been developed. In particular, 3CL protease (3C-like protease, 3CLpro) is an attractive drug target because it is an essential enzyme for viral multiplication and is present only in viruses, not in humans. To date, 3CLpro inhibitors against SARS-CoV-2 such as nirmatrelvir and ensitrelvir have been launched as oral drugs in Japan, but there is still no potent drug against SARS-CoV-2, due to issues of in vivo absorption and stability. Recently, vitamin K3 was reported to show inhibitory activity against 3CLpro of SARS-CoV-2, and the mechanism of action was predicted to be the formation of a covalent bond between the thiol group of cysteine 145, the active center of 3CLpro, and the C-3 position of vitamin K3. Therefore, we synthesized derivatives in which the 2-methyl group of the vitamin K3 was systematically converted to other substituents and examined their inhibitory activity against 3CLpro of SARS-CoV-2. The results showed that the compounds with the sulfide structure showed an approximately 4-fold increase in activity over vitamin K3. These results indicated the possibility of creating new inhibitors based on vitamin K3 and its derivatives.

Toxicity Assessment of Mixed Exposure of Nine Perfluoroalkyl Substances at Concentrations Relevant to Daily Intake.

Per- and poly-fluoroalkyl substances (PFAS) exhibit high persistence in the environment and accumulate within the human body, warranting a thorough assessment of their toxicity. In this study, we exposed mice (male C57BL/6J mice aged 8 weeks) to a composite of nine PFAS, encompassing both long-chain PFAS (e.g., perfluorooctanoic acid and perfluorooctanesulfonic acid) and short-chain PFAS (e.g., perfluorobutanoic acid and perfluorobutanesulfonic acid). The exposure concentrations of PFAS were equivalent to the estimated daily human intake in the composition reported (1 µg/L (sum of the nine compounds), representing the maximum reported exposure concentration). Histological examination revealed hepatocyte vacuolization and irregular hepatocyte cord arrangement, indicating that exposure to low levels of the PFAS mixture causes morphological changes in liver tissues. Transcriptome analysis revealed that PFAS exposure mainly altered a group of genes related to metabolism and chemical carcinogenesis. Machine learning analysis of the liver metabolome showed a typical concentration-independent alteration upon PFAS exposure, with the annotation of substances such as glutathione and 5-aminovaleric acid. This study demonstrates that daily exposure to PFAS leads to morphological changes in liver tissues and alters the expression of metabolism- and cancer-related genes as well as phospholipid metabolism.

Influence of the timing of surgery for cervical spinal cord injury without bone injury in the elderly: A retrospective multicenter study.

BACKGROUND: Although previous studies have demonstrated the advantages of early surgery for traumatic spinal cord injury (SCI), the appropriate surgical timing for cervical SCIs (CSCIs) without bone injury remains controversial. Here, we investigated the influence of relatively early surgery within 48 h of injury on the neurological recovery of elderly patients with CSCI and no bone injury. METHODS: In this retrospective multicenter study, we reviewed data from 159 consecutive patients aged ≥65 years with CSCI without bone injury who underwent surgery in participating centers between 2010 and 2020. Patients were followed up for at least 6 months following CSCI. We divided patients into relatively early (≤48 h after CSCI, n = 24) and late surgery (>48 h after CSCI, n = 135) groups, and baseline characteristics and neurological outcomes were compared between them. Multivariate analysis was performed to identify factors associated with neurological recovery. RESULTS: The relatively early surgery group demonstrated a lower prevalence of cardiac disease, poorer baseline American Spinal Injury Association (ASIA) impairment scale grade, and lower baseline ASIA motor score (AMS) than those of the late surgery group (P < 0.030, P < 0.001, and P < 0.001, respectively). Although the AMS was lower in the relatively early surgery group at 6 months following injury (P = 0.001), greater improvement in this score from baseline to 6-months post injury was observed (P = 0.010). Multiple linear regression analysis revealed that relatively early surgery did not affect postoperative improvement in AMS, rather, lower baseline AMS was associated with better AMS improvement (P < 0.001). Delirium (P = 0.006), pneumonia (P = 0.030), and diabetes mellitus (P = 0.039) negatively influenced postoperative improvement. CONCLUSIONS: Although further validation by future studies is required, relatively early surgery did not show a positive influence on neurological recovery after CSCI without bone injury in the elderly.

Structure of a putative immature form of a Rieske-type iron-sulfur protein in complex with zinc chloride.

Iron-sulfur clusters are prosthetic groups of proteins involved in various biological processes. However, details of the immature state of the iron-sulfur cluster into proteins have not yet been elucidated. We report here the first structural analysis of the Zn-containing form of a Rieske-type iron-sulfur protein, PetA, from Thermochromatium tepidum (TtPetA) by X-ray crystallography and small-angle X-ray scattering analysis. The Zn-containing form of TtPetA was indicated to be a dimer in solution. The zinc ion adopts a regular tetra-coordination with two chloride ions and two cysteine residues. Only a histidine residue in the cluster-binding site exhibited a conformational difference from the [2Fe-2S] containing form. The Zn-containing structure indicates that the conformation of the cluster binding site is already constructed and stabilized before insertion of [2Fe-2S]. The binding mode of ZnCl2, similar to the [2Fe-2S] cluster, suggests that the zinc ions might be involved in the insertion of the [2Fe-2S] cluster.

Characteristics of the cervical spine and cervical cord injuries in older adults with cervical ossification of the posterior longitudinal ligament.

Although the incidence of cervical spinal cord injury (CSCI) with ossification of the posterior longitudinal ligament (OPLL) has increased in older adults, its etiology and neurological outcomes remain unknown. We identified OPLL characteristics and determined whether they influence neurological severity and improvement of CSCI in older patients. This multicenter retrospective cohort study identified 1512 patients aged ≥ 65 years diagnosed with CSCI on admission during 2010-2020. We analyzed CSCI etiology in OPLL patients. We performed propensity score-adjusted analyses to compare neurological outcomes between patients with and without OPLL. Cases were matched based on variables influencing neurological prognosis. The primary neurological outcome was rated according to the American Spine Injury Association (ASIA) impairment scale (AIS) and ASIA motor score (AMS). In 332 OPLL patients, the male-to-female ratio was approximately 4:1. Half of all patients displayed low-energy trauma-induced injury and one-third had CSCI without a bony injury. Propensity score matching created 279 pairs. There was no significant difference in the AIS grade and AMS between patients with and without OPLL during hospitalization, 6 months, and 12 months following injury. OPLL patients tended to exhibit worse neurological findings during injury; nevertheless, OPLL was not associated with poor neurological improvement in older CSCI patients.

Helicobacter pylori-negative Gastric Adenocarcinoma Mimicking Verrucous Gastritis in the Antrum: A Case Report and Literature Review.

A 46-year-old man was referred to our hospital for the examination of a flat elevated lesion with an erosion-like depression, located on the greater curvature of the antrum. Endoscopic submucosal dissection was performed. Histological findings of the resected specimen demonstrated a well-differentiated tubular adenocarcinoma with a diameter of 12 mm. No atrophy was observed in the tumor-adjacent mucosa. Serum Helicobacter pylori antibody estimation and 13C-urea breath tests yielded negative results. Immunohistochemical staining was positive for both gastric mucin and intestinal mucin. The final diagnosis was well-differentiated tubular adenocarcinoma with a gastrointestinal phenotype that originated in mucosa uninfected by H. pylori.

Is Blood Loss Greater in Elderly Patients under Antiplatelet or Anticoagulant Medication for Cervical Spine Injury Surgery? A Japanese Multicenter Survey.

Introduction: In elderly patients with cervical spinal cord injury, comorbidities such as cardiovascular and cerebrovascular diseases are common, with frequent administration of antiplatelet/anticoagulant (APAC) drugs. Such patients may bleed easily or unexpectedly during surgery despite prior withdrawal of APAC medication. Few reports have examined the precise relationship between intraoperative blood loss and history of APAC use regarding surgery for cervical spine injury in the elderly. The present multicenter database survey aimed to answer the question of whether the use of APAC drugs affected the amount of intraoperative blood loss in elderly patients with cervical spinal cord trauma. Methods: The case histories of 1512 patients with cervical spine injury at 33 institutes were retrospectively reviewed. After excluding cases without spinal surgery or known blood loss volume, 797 patients were enrolled. Blood volume loss was the outcome of interest. We calculated propensity scores using the inverse probability of treatment weighting (IPTW) method. As an alternative sensitivity analysis, linear mixed model analyses were conducted as well. Results: Of the 776 patients (mean age: 75.1±6.4 years) eligible for IPTW calculation, 157 (20.2%) were taking APAC medications before the injury. After weighting, mean estimated blood loss was 204 mL for non-APAC patients and 215 mL for APAC patients. APAC use in elderly patients was not significantly associated with surgical blood loss according to the IPTW method with propensity scoring or linear mixed model analyses. Thus, it appeared possible to perform surgery expecting comparable blood loss in APAC and non-APAC cases. Conclusions: This multicenter study revealed no significant increase in surgical blood loss in elderly patients with cervical trauma taking APAC drugs. Surgeons may be able to prioritize patient background, complications, and preexisting conditions over APAC use before injury when examining the surgical indications for cervical spine trauma in the elderly.

Factors Affecting the Waiting Time from Injury to Surgery in Elderly Patients with a Cervical Spine Injury: A Japanese Multicenter Survey.

OBJECTIVE: The management of cervical spine injuries in the elderly is often complicated by the presence of multiple medical comorbidities, and it is not uncommon for preoperative testing to reveal other conditions that require the postponement of surgery. However, the factors that affect the waiting time from injury to surgery have not been clarified. The purpose of this multicenter database study was to analyze the clinical features and identify the factors affecting the number of days waited between injury and surgery in elderly patients with a cervical spine injury. METHODS: We retrospectively reviewed the case histories of 1512 Japanese patients with a cervical spinal injury, who were seen at 33 institutions. After excluding patients who were not initially receiving a surgery for cervical spinal injury, 694 patients were ultimately analyzed. Based on a multivariate mixed model, we determined the factors related to the number of days from injury to surgery. RESULTS: The mean time from injury to surgery was 12.3 days. Multivariate analysis revealed delays of 10.7 days for a renal disorder, 7.3 days for anticoagulant use, and 15.2 days for non-surgical thoracolumbar fracture as factors prolonging wait time. In contrast, a C3 or lower spine injury was significantly associated with a shortening of 9.5 days to surgery. CONCLUSIONS: This multicenter database study identified several factors influencing the time between injury and cervical spine surgery in elderly patients. While renal impairment, anticoagulant use, and non-surgical thoracolumbar fracture may increase the number of days to surgery, trauma to C3 or lower may expedite surgical treatment.

A multicenter study of 1-year mortality and walking capacity after spinal fusion surgery for cervical fracture in elderly patients.

BACKGROUND: The 1-year mortality and functional prognoses of patients who received surgery for cervical trauma in the elderly remains unclear. The aim of this study is to investigate the rates of, and factors associated with mortality and the deterioration in walking capacity occurring 1 year after spinal fusion surgery for cervical fractures in patients 65 years of age or older. METHODS: Three hundred thirteen patients aged 65 years or more with a traumatic cervical fracture who received spinal fusion surgery were enrolled. The patients were divided into a survival group and a mortality group, or a maintained walking capacity group and a deteriorated walking capacity group. We compared patients' backgrounds, trauma, and surgical parameters between the two groups. To identify factors associated with mortality or a deteriorated walking capacity 1 year postoperatively, a multivariate logistic regression analysis was conducted. RESULTS: One year postoperatively, the rate of mortality was 8%. A higher Charlson comorbidity index (CCI) score, a more severe the American Spinal Cord Injury Association impairment scale (AIS), and longer surgical time were identified as independent factors associated with an increase in 1-year mortality. The rate of deterioration in walking capacity between pre-trauma and 1 year postoperatively was 33%. A more severe AIS, lower albumin (Alb) and hemoglobin (Hb) values, and a larger number of fused segments were identified as independent factors associated with the increased risk of deteriorated walking capacity 1 year postoperatively. CONCLUSIONS: The 1-year rate of mortality after spinal fusion surgery for cervical fracture in patients 65 years of age or older was 8%, and its associated factors were a higher CCI score, a more severe AIS, and a longer surgical time. The rate of deterioration in walking capacity was 33%, and its associated factors were a more severe AIS, lower Alb, lower Hb values, and a larger number of fused segments.

Does surgery improve neurological outcomes in older individuals with cervical spinal cord injury without bone injury? A multicenter study.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate the neurological outcomes of older individuals treated with surgery versus conservative treatment for cervical spinal cord injury (CSCI) without bone injury. SETTING: Thirty-three medical institutions in Japan. METHODS: This study included 317 consecutive persons aged ≥65 years with CSCI without bone injury in participating institutes between 2010 and 2020. The participants were followed up for at least 6 months after the injury. Individuals were divided into surgery (n = 114) and conservative treatment (n = 203) groups. To compare neurological outcomes and complications between the groups, propensity score matching of the baseline factors (characteristics, comorbidities, and neurological function) was performed. RESULTS: After propensity score matching, the surgery and conservative treatment groups comprised 89 individuals each. Surgery was performed at a median of 9.0 (3-17) days after CSCI. Baseline factors were comparable between groups, and the standardized difference in the covariates in the matched cohort was <10%. The American Spinal Injury Association (ASIA) impairment scale grade and ASIA motor score (AMS) 6 months after injury and changes in the AMS from baseline to 6 months after injury were not significantly different between groups (P = 0.63, P = 0.24, and P = 0.75, respectively). Few participants who underwent surgery demonstrated perioperative complications such as dural tear (1.1%), surgical site infection (2.2%), and C5 palsy (5.6%). CONCLUSION: Conservative treatment is suggested to be a more favorable option for older individuals with CSCI without bone injuries, but this finding requires further validation.

Revisiting the concept of peptide bond planarity in an iron-sulfur protein by neutron structure analysis.

The planarity of the peptide bond is important for the stability and structure formation of proteins. However, substantial distortion of peptide bonds has been reported in several high-resolution structures and computational analyses. To investigate the peptide bond planarity, including hydrogen atoms, we report a 1.2-Šresolution neutron structure of the oxidized form of high-potential iron-sulfur protein. This high-resolution neutron structure shows that the nucleus positions of the amide protons deviate from the peptide plane and shift toward the acceptors. The planarity of the H─N─C═O plane depends strongly on the pyramidalization of the nitrogen atom. Moreover, the orientation of the amide proton of Cys75 is different in the reduced and oxidized states, possibly because of the electron storage capacity of the iron-sulfur cluster.

Risk factors for early-onset radiographical adjacent segment disease in patients with spondylolytic spondylolisthesis after single-level posterior lumbar interbody fusion.

BACKGROUND CONTEXT: The risk factors for radiographical adjacent segment disease (ASD) in patients with degenerative spondylolisthesis have been previously reported. However, there are only few reports on patients with spondylolytic spondylolisthesis who underwent single-level posterior lumbar interbody fusion (PLIF). PURPOSE: The study aimed to investigate the risk factors for radiographical ASD in patients with L5-S1 spondylolytic spondylolisthesis who underwent single-level PLIF. STUDY DESIGN/SETTING: A retrospective study PATIENT SAMPLE: This study retrospectively reviewed 135 consecutive patients (91 men and 44 women) with symptomatic L5-S1 spondylolytic spondylolisthesis who underwent single-level PLIF. OUTCOME MEASURES: The pre- and postoperative (at the final follow-up) spinopelvic parameters, % slip, sacral slope, lumbar lordosis (LL), pelvic tilt, pelvic incidence (PI), PI minus LL (PI - LL), lumbosacral angle, C7 sagittal vertical axis, and thoracic kyphosis were measured using standing radiographs. METHODS: Radiographical ASD was defined as disc height loss (>3 mm), increase of posterior angulation (>5°), or progression of spondylolisthesis (>3 mm) between the pre- and postoperative radiographs. Pfirrmann's classification was used to evaluate disc degeneration. The radiographical parameters and changes between the pre- and postoperative values were evaluated and compared for the non-ASD and ASD groups. Binary logistic regression analysis was performed to evaluate the adjusted associations between each potential explanatory variable and ASD development. RESULTS: The radiographical ASD incidence was 11%. Additionally, 60% of the patients with ASD had radiographical ASD at 1 year and all cases of radiographical ASD in this follow-up period occurred within 3 years after the initial surgery. The mean period of ASD occurrence after initial surgery was 21.7 ± 12.6 months. No patients required reoperation for radiographical ASD. Multivariate analysis revealed that a preoperative (odds ratio [OR], 5.9; 95% confidence interval [CI], 1.2-28.9; p=.03) and a postoperative (OR, 6.5; 95% CI, 1.2-34.5; p=.03) PI - LL of ≥15° were risk factors for radiographical ASD. CONCLUSIONS: Pre- and postoperative PI - LL value mismatch was identified as significant independent risk factors for radiographical ASD in patients with L5-S1 spondylolytic spondylolisthesis. Obtaining larger lordosis at L5-S1 may be the key to preventing radiographical ASD.

Impact of leg numbness on patient satisfaction following decompression surgery for lumbar spinal stenosis.

Decompression surgery is the most common surgical treatment for lumbar spinal stenosis (LSS). Relatively low satisfaction rate was reported. Patients often complaint of residual numbness despite significant pain relief. We hypothesized that numbness had a significant impact on patient satisfaction, but had not been evaluated, which is associated with low satisfaction rate. This study aimed to examine how much numbness is associated with patient satisfaction. We retrospectively reviewed prospectively collected data from consecutive patients who underwent decompression without fusion for LSS. We evaluated the Numeric Rating Scale (NRS) scores of low back pain (LBP), leg pain, and leg numbness preoperatively and at the final follow-up visit. Improvement was evaluated using minimum clinically important differences (MCIDs). Patient satisfaction was evaluated using the question, "How satisfied are you with the overall result of your back operation?". There are four possible answers consisting of "very satisfied (4-point)", "somewhat satisfied (3-point)", "somewhat dissatisfied (2-point)", or "very dissatisfied (1-point)". Spearman correlation was used to evaluate the association between patient satisfaction and reaching MCIDs. A total of 116 patients were included. All three components had correlation with patient satisfaction with the correlation efficient of 0.30 in LBP, 0.22 in leg pain, and 0.33 in numbness. Numbness had greatest correlation efficient value. We showed that numbness has a greater impact than leg/back pain on patient satisfaction in patients undergoing decompression for LSS. We suggest not only LBP and leg pain but also numbness should be evaluated pre- and postoperatively.

Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use.

Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10-40 with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10-10 ) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10-8 ), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10-4 ). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).

Split conformation of Chaetomium thermophilum Hsp104 disaggregase.

Hsp104 and its bacterial homolog ClpB form hexameric ring structures and mediate protein disaggregation. The disaggregated polypeptide is thought to thread through the central channel of the ring. However, the dynamic behavior of Hsp104 during disaggregation remains unclear. Here, we reported the stochastic conformational dynamics and a split conformation of Hsp104 disaggregase from Chaetomium thermophilum (CtHsp104) in the presence of ADP by X-ray crystallography, cryo-electron microscopy (EM), and high-speed atomic force microscopy (AFM). ADP-bound CtHsp104 assembles into a 65 left-handed spiral filament in the crystal structure at a resolution of 2.7 Å. The unit of the filament is a hexamer of the split spiral structure. In the cryo-EM images, staggered and split hexameric rings were observed. Further, high-speed AFM observations showed that a substrate addition enhanced the conformational change and increased the split structure's frequency. Our data suggest that split conformation is an off-pathway state of CtHsp104 during disaggregation.

One-Pot Tandem Michael Addition/Enantioselective Conia-Ene Cyclization Mediated by Chiral Iron(III)/Silver(I) Cooperative Catalysis.

The first one-pot tandem Michael addition/enantioselective Conia-ene cyclization of N-protected prop-2-yn-1-amines with 2-methylene-3-oxoalkanoates promoted by chiral iron(III)/silver(I) cooperative catalysts has been developed. Alkyl 4-methylenepyrrolidine-3-acyl-3-carboxylates, which can be transformed into ß-proline derivatives, are obtained in high yield with high enantioselectivity.