Morphological features of lower lumbar degenerative kyphosis.

PURPOSE: Kyphosis in the lower lumbar spine (L4-S1) significantly affects sagittal alignment. However, the characteristics of the spinopelvic parameters and compensatory mechanisms in patients with lower lumbar degenerative kyphosis (LLDK) have not been described in detail. The objective of this retrospective study was to analyze the morphological characteristics in patients with sagittal imbalance due to LLDK. METHODS: In this retrospective study, we reviewed the clinical records of consecutive patients who underwent corrective surgery for adult spinal deformity (ASD) at a single institution. We defined LLDK as (i) kyphotic deformity in lower lumbar spine (L4-S1) or (ii) inappropriate distribution of lordosis (lordosis distribution index < 40%) in the lower lumbar spine. Global spine parameters of ASD patients and MRI findings were compared between those with LLDK (LLDK group) and without LLDK (control group). RESULTS: A total of 95 patients were enrolled in this study, of which the LLDK group included 14 patients (14.7%). Compared to the control, LLDK presented significantly higher pelvic incidence (62.1° vs 52.6°) and pelvic tilt (40.0° vs 33.4°), larger lordosis at the thoracolumbar junction (12.0° vs -19.6°), and smaller thoracic kyphosis (9.3° vs 26.0°). In LLDK, there was significantly less disc degeneration at L2/3 and L3/4. CONCLUSION: LLDK patients had high pelvic incidence, large pelvic tilt, and a long compensatory curve at the thoracolumbar junction and thoracic spine region.

Long-lasting increases in GABAB receptor subunit levels in hippocampal dentate gyrus of mice with a single systemic injection of trimethyltin.

We have recently shown delayed increases in GABAB receptor (GABABR) subunit protein levels in the hippocampal dentate gyrus (DG), but not in the pyramidal CA1 and CA3 regions, at 15-30 days after the systemic single administration of trimethyltin (TMT) in mice. An attempt was thus made to determine whether the delayed increases return to the control levels found in naive mice afterward. In the DG on hippocampal slices obtained at 90 days after the administration, however, marked increases were still seen in protein levels of both GABABR1 and GABABR2 subunits without significant changes in calbindin and glial fibrillary acidic protein (GFAP) levels on immunoblotting analysis. Fluoro-Jade B staining clearly revealed the absence of degenerated neurons from the DG at 90 days after the administration. Although co-localization was invariably detected between GABABR2 subunit and GFAP in the DG at 30 days on immunohistochemical analysis, GABABR2-positive cells did not merge well with GFAP-positive cells in the DG at 90 days. These results suggest that both GABABR1 and GABABR2 subunits would be tardily and sustainably up-regulated by cells other than neurons and astrocytes in the murine DG at 90 days after a systemic single injection of TMT.

Anterior Protrusion of Hydroxyapatite Blocks During Vertebroplasty for Thoracic Burst Fractures: A Case Report.

Research on complications necessitating reoperation following vertebroplasty related to hydroxyapatite (HA) blocks is limited. We present the case of a 25-year-old woman who underwent posterior fixation and vertebroplasty using HA blocks for a T12 burst fracture. Postoperative computed tomography revealed anterior protrusion of some blocks, with consequent compression of the descending aorta. We removed the protruded blocks viaa transthoracic approach and observed no aortic injuries. Although HA blocks are considered safe for vertebroplasty, surgeons should be aware of the risk of anterior protrusion and potential aortic injury.

Two-year results of single-level fixation with lateral mass screws for cervical degenerative spondylolisthesis: patient series.

BACKGROUND: In surgery for cervical spondylotic myelopathy (CSM) with spondylolisthesis, there is no consensus on the correction and fixation for spondylolisthesis. The authors retrospectively studied whether the correction of single-level fixation with lateral mass screws (LMSs) could be maintained. OBSERVATIONS: The records of patients with CSM with spondylolisthesis who had been treated with posterior decompression and single-level fusion with LMSs from 2017 to 2021 were retrospectively reviewed. Radiographic measurements included cervical parameters such as C2-7 lordosis, T1 slope, and the degree of spondylolisthesis (percent slippage) before surgery, immediately after surgery, and at the final observation. Ten cases (mean age 72.8 ± 7.8 years) were included in the final analysis, and four cases (40%) were on hemodialysis. The median observation period was 26.5 months (interquartile range, 12-35.75). The mean percent slippage was 16.8% ± 4.7% before surgery, 5.3% ± 4.0% immediately after surgery, and 6.5% ± 4.7% at the final observation. Spearman's rank correlation showed a moderate correlation between preoperative slippage magnitude and correction loss (r = 0.659; p = 0.038). Other parameters showed no correlation with correction loss. LESSONS: For CSM with spondylolisthesis, single-level fixation with LMSs achieved and maintained successful correction in the 2-year observation.

Factors Associated with Retro-Odontoid Pseudotumor in Long-Term Hemodialysis Patients.

OBJECTIVE: Hemodialysis has been reported to be associated with retro-odontoid pseudotumor (ROP), but its clinical characteristics have not been well described. The purpose of the present study was to investigate the factors associated with ROP in hemodialysis patients. METHODS: A retrospective clinical study of hemodialysis patients was conducted with the evaluation of computed tomography and magnetic resonance imaging of cervical spinal lesions at a single institution from 2012 to 2020. The patients' characteristics and radiographic findings were assessed. A case-control analysis was performed between patients with ROP (ROP group) and patients without ROP (control group). RESULTS: We analyzed 46 patients. The mean duration of hemodialysis (± standard deviation) was 21.5 ± 11.8 years. The mean retro-odontoid soft tissue thickness was 4.3 ± 0.3 mm and was correlated with the duration of hemodialysis (r = 0.46, P < 0.01). Thirty patients (65.2%) were included in the ROP group. The ROP group showed a significantly longer duration of hemodialysis (24.9 ± 11.2 years vs. 15.2 ± 10.3 years, P < 0.01) and a higher incidence of osteolytic lesions in the atlantoaxial joint compared with the control group (60.0% vs. 18.8%, P < 0.01). Logistic regression analysis revealed the atlantoaxial osteolytic lesions are associated with retro-odontoid pseudotumor in hemodialysis patients (odds ratio, 5.1; 95% confidence interval, 1.1-24.2; P = 0.04). CONCLUSIONS: The existence of ROP in hemodialysis patients was associated with osteolytic lesions in the atlantoaxial joint. The finding of atlantoaxial erosive lesions in long-term hemodialysis patients requires spine surgeons to carefully evaluate the presence of ROP.

Delayed Expression of Both GABABR1 and GABABR2 Subunits in Murine Hippocampal Dentate Gyrus After a Single Systemic Injection of Trimethyltin.

Trimethyltin (TMT) has been used as a cytotoxin to neurons rather than glial cells in the mammalian hippocampus. The systemic administration of TMT led to declined fluorescence of ZnAF-2 DA staining as a marker of intact mossy fibers and increased fluorescence of Fluoro-Jade B staining as a marker of degenerated neurons during the initial 2 to 5 days after the administration with later ameliorations within 30 days in the hippocampal dentate gyrus (DG) and CA3 region in mice. On immunoblotting analysis, both GABABR1 and GABABR2 subunit levels increased during 15 to 30 days after TMT along with significant decreases in glutamatergic GluA1 and GluA2/3 receptor subunit levels during 2 to 7 days in the DG, but not in other hippocampal regions such as CA1 and CA3 regions. Immunohistochemical analysis revealed the constitutive and inducible expression of GABABR2 subunit in cells immunoreactive to an astrocytic marker as well as neuronal markers in the DG with the absence of neither GABABR1a nor GABABR1b subunit from cells positive to an astrocytic marker. These results suggest that both GABABR1 and GABABR2 subunits may be up-regulated in cells other than neurons and astroglia in the DG at a late stage of TMT intoxication in mice.

Dynamization-Posterior Lumbar Interbody Fusion for Hemodialysis-Related Spondyloarthropathy: Evaluation of the Radiographic Outcomes and Reoperation Rate within 2 Years Postoperatively.

STUDY DESIGN: Clinical case series. PURPOSE: This study aimed to report dynamization-posterior lumbar interbody fusion (PLIF), our surgical treatment for hemodialysisrelated spondyloarthropathy (HSA), and investigate patients' postoperative course within 2 years. OVERVIEW OF LITERATURE: HSA often requires lumbar fusion surgery. Conventional PLIF for HSA may cause progressive destructive changes in the vertebral endplate, leading to progressive cage subsidence, pedicle screw loosening, and pseudoarthrosis. A dynamic stabilization system might be effective in patients with a poor bone quality. Thus, we performed "dynamization-PLIF" in hemodialysis patients with destructive vertebral endplate changes. METHODS: We retrospectively examined patients with HSA who underwent dynamization-PLIF at our hospital between April 2010 and March 2018. The radiographic measurements included lumbar lordosis and local lordosis in the fused segment. The evaluation points were before surgery, immediately after surgery, 1 year after surgery, and 2 years after surgery. The preoperative and postoperative radiographic findings were compared using a paired t-test. A p-value of less than 0.05 was considered significant. RESULTS: We included 50 patients (28 males, 22 females). Lumbar lordosis and local lordosis were significantly improved through dynamization- PLIF (lumbar lordosis, 28.4°-35.5°; local lordosis, 2.7°-12.8°; p<0.01). The mean local lordosis was maintained throughout the postoperative course at 1- and 2-year follow-up (12.9°-12.8°, p=0.89 and 12.9°-11.8°, p=0.07, respectively). Solid fusion was achieved in 59 (89%) of 66 fused segments. Solid fusion of all fixed segments was achieved in 42 cases (84%). Within 2 years postoperatively, only six cases (12%) were reoperated (two, surgical debridement for surgical site infection; two, reoperation for pedicle screw loosening; one, laminectomy for epidural hematoma; one, additional fusion for adjacent segment disease). CONCLUSIONS: Dynamization-PLIF showed local lordosis improvement, a high solid fusion rate, and a low reoperation rate within 2 years of follow-up.

Association Between Paravertebral Muscle Mass and Improvement in Sagittal Imbalance After Decompression Surgery of Lumbar Spinal Stenosis.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: This study examined associated factors for the improvement in spinal imbalance following decompression surgery without fusion. SUMMARY OF BACKGROUND DATA: Several reports have suggested that decompression surgery without fusion may have a beneficial effect on sagittal balance in patients with lumbar spinal stenosis (LSS) through their postoperative course. However, few reports have examined the association between an improvement in sagittal imbalance and spinal sarcopenia. METHODS: We retrospectively reviewed 92 patients with LSS and a preoperative sagittal vertical axis (SVA) more than or equal to 40 mm who underwent decompression surgery without fusion at a single institution between April 2017 and October 2018. Patients' background and radiograph parameters and the status of spinal sarcopenia, defined using the relative cross-sectional area (rCSA) of the paravertebral muscle (PVM) and psoas muscle at the L4 caudal endplate level, were assessed. We divided the patients into two groups: those with a postoperative SVA less than 40 mm (balanced group) and those with a postoperative SVA more than or equal to 40 mm (imbalanced group). We then compared the variables between the two groups. RESULTS: A total of 29 (31.5%) patients obtained an improved sagittal imbalance after decompression surgery. The rCSA-PVM in the balanced group was significantly higher than that in the imbalanced group (P = 0.042). The preoperative pelvic incidence (PI)-lumbar lordosis (LL) mismatch (P = 0.048) and the proportion with compression vertebral fracture (P = 0.028) in the balanced group were significantly lower than those in the imbalanced group. A multivariate logistic regression analysis identified PI-LL less than or equal to 10° and rCSA-PVM more than or equal to 2.5 as significant associated factor for the improvement in spinal imbalance following decompression surgery. CONCLUSION: A larger volume of paravertebral muscles and a lower PI-LL were associated with an improvement in sagittal balance in patients with LSS who underwent decompression surgery.Level of Evidence: 3.

The standing T1-L1 pelvic angle: a useful radiographic predictor of proximal junctional kyphosis in adult spinal deformity.

OBJECTIVE: Proximal junctional kyphosis (PJK), which can worsen a patient's quality of life, is a common complication following the surgical treatment of adult spinal deformity (ASD). Although various radiographic parameters have been proposed to predict the occurrence of PJK, the optimal method has not been established. The present study aimed to investigate the usefulness of the T1-L1 pelvic angle in the standing position (standing TLPA) for predicting the occurrence of PJK. METHODS: The authors retrospectively extracted data for patients with ASD who underwent minimum 5-level fusion to the pelvis with upper instrumented vertebra between T8 and L1. In the present study, PJK was defined as ≥ 10° progression of the proximal junctional angle or reoperation due to progressive kyphosis during 1 year of follow-up. The following parameters were analyzed on whole-spine standing radiographs: the T1-pelvic angle, conventional thoracic kyphosis (TK; T4-12), whole-thoracic TK (T1-12), and the standing TLPA (defined as the angle formed by lines extending from the center of T1 and L1 to the femoral head axis). A logistic regression analysis and a receiver operating characteristic curve analysis were performed. RESULTS: A total of 50 patients with ASD were enrolled (84% female; mean age 74.4 years). PJK occurred in 19 (38%) patients. Preoperatively, the PJK group showed significantly greater T1-pelvic angle (49.2° vs 34.4°), conventional TK (26.6° vs 17.6°), and standing-TLPA (30.0° vs 14.9°) values in comparison to the non-PJK group. There was no significant difference in the whole-thoracic TK between the two groups. A multivariate analysis showed that the standing TLPA and whole-thoracic TK were independent predictors of PJK. The standing TLPA had better accuracy than whole-thoracic TK (AUC 0.86 vs 0.64, p = 0.03). The optimal cutoff value of the standing TLPA was 23.0° (sensitivity 0.79, specificity 0.74). Using this cutoff value, the standing TLPA was the best predictor of PJK (OR 8.4, 95% CI 1.8-39, p = 0.007). CONCLUSIONS: The preoperative standing TLPA was more closely associated with the occurrence of PJK than other radiographic parameters. These results suggest that this easily measured parameter is useful for the prediction of PJK.

Surgical treatment for cervical spine injury in nonagenarians: A report of three cases.

Among the elderly, even minor injuries can cause cervical spine fractures. With the increasing number of nonagenarians, the opportunities for treatment of cervical spine injuries in nonagenarians are getting to be more common. Conservative therapy is often chosen in nonagenarians with cervical spine injuries because of high risk associated with surgical treatment; however, we present herein the cases of three patients in nonagenarians who underwent surgical treatment for cervical spine injury. After a fall, three cases of nonagenarians who lived alone and independent were diagnosed with a Jefferson fracture and minor dislocated type II odontoid fracture, a C4 fracture with diffuse idiopathic skeletal hyperostosis, and a fracture-dislocation of C2, respectively. Their past medical history included several diseases, but we decided that spine surgery under general anesthesia was acceptable based on their pre-injury condition. We performed posterior fixation for all cases. As a result, while two patients developed postoperative minor complications, all cases showed favorable postoperative courses. They acquired independent or partially assisted walking and were transferred to the hospital for rehabilitation. If fundamental activity of daily living and general condition permit, posterior fixation seems to be a good choice even in nonagenarians.

Pelvic incidence change on the operating table.

PURPOSE: While a change in the pelvic incidence (PI) after long spine fusion surgery has been reported, no studies have examined the change in the PI on the operating table. The present study examined the PI-change on the operating table and elucidated the patients' background characteristics associated with this phenomenon. METHODS: This study included patients who underwent lumbar posterior spine surgery and had radiographs taken in a full-standing position preoperatively and a pelvic lateral radiograph in the prone position in the operative room. The patients with PI-change on the operating table (PICOT; PICOT group) and without PICOT (control group) were compared for their background characteristics and preoperative radiographic parameters. RESULTS: There were 128 eligible patients (62 males, 66 females) with a mean age (± standard deviation) of 69.9 ± 11.7 (range: 25-93) years old. Sixteen patients (12.5%) showed a decrease in the PI > 10°, which indicated placement in the PICOT group. The preoperative lumbar lordosis (LL) and PI-LL in the PICOT group were significantly worse than those in the control group (LL: 20.8 ± 16.6 vs. 30.6 ± 16.2, p = 0.0251, PI-LL: 33.9 ± 19.0 vs. 17.3 ± 14.8, p < 0.0001). The PICOT group had a higher proportion of patients who underwent fusion surgery than the control group, but the difference was not significant (62.5% vs. 44.6%, p = 0.1799). CONCLUSION: A decreased PI was observed in some patients who underwent lumbar posterior surgery on the operating table before surgery. Patients with a PI decrease on the operating table had a significantly worse preoperative global alignment than those without such a decrease. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Medialization of Common Carotid Artery Is Associated with Cervical Kyphosis.

INTRODUCTION: Reportedly, the medialization of the common carotid artery (MCCA) to be a vascular anomaly with a potential risk of intraoperative carotid artery injury. Nevertheless, among spine surgeons, the presence of MCCA has not been well recognized. METHODS: We retrospectively reviewed consecutive patients who underwent cervical radiographs and magnetic resonance imaging (MRI) examinations in a single spine center. Using MRI, the MCCA grade was classified into grades 1 to 3 in order of severity. Radiographic measurement included C2-C7 angles as cervical lordosis, cervical sagittal vertical axis (C-SVA), T1 slope (T1S), and T1S-cervical lordosis mismatch. We compared each patient's background and radiographic parameters between patients with each of the three MCCA grades. The continuous variables were compared using the Jonckheere-Terpstra trend test and the proportions were compared using the Cochran-Armitage trend test to investigate the trend of variables in three grades. RESULTS: The present study included data from 133 eligible patients (65 males and 68 females) with a mean age of 63.7 (±14.2) years. The details of MCCA grading were as follows: grade 1, n=101; grade 2, n=27; and grade 3, n=5. With an increasing MCCA grade, age (61.9±14.0, 68.2±13.8, and 76.4±9.4 years for grades 1, 2, and 3, respectively, p=0.005) and proportion of female (p<0.001) had an increasing trend, whereas cervical lordosis had a decreasing trend (11.7±13.5°, 7.0±14.5°, and -10.0±19.2° for grades 1, 2, and 3, respectively, p=0.011). CONCLUSIONS: Several patient backgrounds including the female gender, older age, and kyphotic alignment were determined as MCCA risk factors. Careful preoperative neck vasculature assessment would avoid a catastrophic complication during anterior cervical surgery.

Assessing the Risk of Intracranial Aneurysm Rupture Using Morphological and Hemodynamic Biomarkers Evaluated from Magnetic Resonance Fluid Dynamics and Computational Fluid Dynamics.

PURPOSE: Evaluate in vivo hemodynamic and morphological biomarkers of intracranial aneurysms, using magnetic resonance fluid dynamics (MRFD) and MR-based patient specific computational fluid dynamics (CFD) in order to assess the risk of rupture. METHODS: Forty-eight intracranial aneurysms (10 ruptured, 38 unruptured) were scrutinized for six morphological and 10 hemodynamic biomarkers. Morphological biomarkers were calculated based on 3D time-of-flight magnetic resonance angiography (3D TOF MRA) in MRFD analysis. Hemodynamic biomarkers were assessed using both MRFD and CFD analyses. MRFD was performed using 3D TOF MRA and 3D cine phase-contrast magnetic resonance imaging (3D cine PC MRI). CFD was performed utilizing patient specific inflow-outflow boundary conditions derived from 3D cine PC MRI. Univariate analysis was carried out to identify statistically significant biomarkers for aneurysm rupture and receiver operating characteristic (ROC) analysis was performed for the significant biomarkers. Binary logistic regression was performed to identify independent predictive biomarkers. RESULTS: Morphological biomarker analysis revealed that aneurysm size [P = 0.021], volume [P = 0.035] and size ratio [P = 0.039] were statistically significantly different between the two groups. In hemodynamic biomarker analysis, MRFD results indicated that ruptured aneurysms had higher oscillatory shear index (OSI) [OSI.max, P = 0.037] and higher relative residence time (RRT) [RRT.ave, P = 0.035] compared with unruptured aneurysms. Correspondingly CFD analysis demonstrated significant differences for both average and maximum OSI [OSI.ave, P = 0.008; OSI.max, P = 0.01] and maximum RRT [RRT.max, P = 0.045]. ROC analysis revealed AUC values greater than 0.7 for all significant biomarkers. Aneurysm volume [AUC, 0.718; 95% CI, 0.491-0.946] and average OSI obtained from CFD [AUC, 0.774; 95% CI, 0.586-0.961] were retained in the respective logistic regression models. CONCLUSION: Both morphological and hemodynamic biomarkers have significant influence on intracranial aneurysm rupture. Aneurysm size, volume, size ratio, OSI and RRT could be potential biomarkers to assess aneurysm rupture risk.

Outcomes of an Intraoperative Povidone-Iodine Irrigation Protocol in Spinal Surgery for Surgical Site Infection Prevention.

STUDY DESIGN: This was a retrospective observational study. OBJECTIVE: The aim of this study was to evaluate the efficacy of our new protocol for preventing postoperative surgical site infection (SSI) following spinal surgery. SUMMARY OF BACKGROUND DATA: SSI following spinal surgery is a serious postoperative complication. Several studies have recently assessed the effectiveness of wound irrigation with povidone-iodine (PVP-I) for SSI prevention, but no consensus has been reached as to how PVP-I should be used in clinical practice. We formed a PVP-I irrigation protocol focusing on the pharmacological properties of PVP-I. This study aimed to evaluate the efficacy and safety of our protocol for preventing SSI. MATERIALS AND METHODS: All cases of spinal surgery at our hospital between October 2011 and September 2016 were retrospectively reviewed. The exclusion criteria were PVP-I allergy, prior surgical debridement for infection, and implant removal surgery. The patients were subdivided into those who had received normal saline irrigation after 90 seconds of 1% PVP-I pooling every 1.5 hours (study group) or only routine saline irrigation every 1.5 hours (control group). The study and control groups comprised of 177 and 146 patients, respectively. This study compared the rate of SSI with and without the use of the PVP-I irrigation protocol. RESULTS: The SSI rates were 1.7% for the study group (3/177 patients) and 3.4% for the control group (5/146 patients), showing no significant statistical difference (P=0.32). There were no cases of deep SSI in the study group, whereas there were 4 cases in the control group. The deep SSI rate significantly decreased in the study group (P=0.027). No adverse events occurred in the study group. CONCLUSION: In this study, 90 seconds of 1% PVP-I pooling every 1.5 hours followed by saline irrigation demonstrated the effectiveness of our protocol for the prevention of postoperative deep SSI after spinal surgery.

Hypoxia affects Slc7a5 expression through HIF-2α in differentiated neuronal cells.

An imbalance of branched-chain amino acids (BCAAs) in the brain may result in neuropathological conditions, such as autism spectrum disorders. The L-type amino acid transporter 1 (LAT1), encoded by the solute carrier transporter 7a5 (Slc7a5) gene, is critical for maintaining normal levels of BCAAs in the brain. However, our understanding of the mechanisms that regulate the expression of LAT1/Slc7a5 in neurons is currently limited. Here, we demonstrate that hypoxic conditions result in upregulated expression of Slc7a5 in differentiated neuronal cells (Neuro2A cells induced to differentiate using all-trans retinoic acid). Mechanistically, hypoxia-induced expression of Slc7a5 is markedly reduced by short hairpin RNA (shRNA)-mediated knockdown of hypoxia-inducible factor 2α (HIF-2α), but not by shRNA targeting HIF-1α, in differentiated neuronal cells. Moreover, hypoxia increased the binding of HIF-2α to the proximal promoter of Slc7a5 in differentiated neuronal cells. These results indicate that hypoxia directly enhances the recruitment of HIF-2α to the proximal promoter of Slc7a5, resulting in its upregulated expression in differentiated neuronal cells. These findings indicate that Slc7a5 may be a novel gene responsive to hypoxia in a HIF-2α-dependent manner in differentiated neuronal cells.

Mechanism and regulation of DNA damage recognition in nucleotide excision repair.

Nucleotide excision repair (NER) is a versatile DNA repair pathway, which can remove an extremely broad range of base lesions from the genome. In mammalian global genomic NER, the XPC protein complex initiates the repair reaction by recognizing sites of DNA damage, and this depends on detection of disrupted/destabilized base pairs within the DNA duplex. A model has been proposed that XPC first interacts with unpaired bases and then the XPD ATPase/helicase in concert with XPA verifies the presence of a relevant lesion by scanning a DNA strand in 5'-3' direction. Such multi-step strategy for damage recognition would contribute to achieve both versatility and accuracy of the NER system at substantially high levels. In addition, recognition of ultraviolet light (UV)-induced DNA photolesions is facilitated by the UV-damaged DNA-binding protein complex (UV-DDB), which not only promotes recruitment of XPC to the damage sites, but also may contribute to remodeling of chromatin structures such that the DNA lesions gain access to XPC and the following repair proteins. Even in the absence of UV-DDB, however, certain types of histone modifications and/or chromatin remodeling could occur, which eventually enable XPC to find sites with DNA lesions. Exploration of novel factors involved in regulation of the DNA damage recognition process is now ongoing.

Predictors of confirmatory test results for the diagnosis of primary hyperaldosteronism in hypertensive patients with an aldosterone-to-renin ratio greater than 20. The SHRIMP study.

It remains unknown which surrogate markers can predict diagnostic test results for primary hyperaldosteronism (PA). The Secondary Hypertension Registry Investigation in Mie Prefecture (SHRIMP) study has sequentially and prospectively recruited 128 patients with hypertension with an aldosterone-to-renin ratio (ARR) greater than 20, evaluated the differences among essential hypertension (EHT), idiopathic hyperaldosteronism (IHA), and aldosterone-producing adenoma (APA), and analyzed the predictors for the confirmatory tests. The patients underwent saline-loading, captopril-challenge, and upright furosemide-loading tests. Carotid, renovascular, and cardiac echography, brachial ankle pulse wave velocity (baPWV), endothelial function, nocturnal blood pressure decline, and the apnea hypopnea index were evaluated. Multivariate regression analyses showed that the plasma aldosterone concentration (PAC) at screening was a strong predictor of the saline and captopril test results. The plasma renin activity (PRA) at screening, urine ß2-microglobulin, and left ventricular mass index (LVMI) were independent predictors for the captopril test. The estimated saline PAC and captopril 60 and 90 min ARRs predicted by the equations were highly correlated with the real values. The ROC curve analysis showed PAC at screening among each of predictors for the diagnostic tests and PAC after the saline-loading test had the highest diagnostic abilities of APA. Patients with IHA were older and had glucose intolerance and increased U-Alb/gCre and resistive indices. In patients with APA, the levels of U-Alb/gCre and urine ß2-microglobulin were increased, and levels of insulin and the HOMA-IR were decreased. In conclusion, our proposed equations may be useful for estimating saline PAC and captopril ARR. Diagnostic predictors may differ for each confirmatory test.

The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis.

Erk5 belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by Mek5, Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrate that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr249, which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser206 in the linker region known to trigger its proteasomal degradation by Smurf1. Smads transcriptionally activated the expression of Sox9 in mesenchymal cells. Accordingly, removal of one Sox9 allele in mesenchymal cells from Erk5-deficient mice rescued some abnormalities of skeletogenesis. These findings highlight the importance of the Mek5-Erk5-Smurf-Smad-Sox9 axis in mammalian skeletogenesis.