Calcineurin-mediated dephosphorylation stabilizes E2F1 protein by suppressing binding of the FBXW7 ubiquitin ligase subunit.

The transcription factor E2F1 serves as a regulator of the cell cycle and promotes cell proliferation. It is highly expressed in cancer tissues and contributes to their malignant transformation. Degradation by the ubiquitin-proteasome system may help to prevent such overexpression of E2F1 and thereby to suppress carcinogenesis. A detailed understanding of the mechanisms underlying E2F1 degradation may therefore inform the development of new cancer treatments. We here identified SCFFBXW7 as a ubiquitin ligase for E2F1 by comprehensive analysis. We found that phosphorylation of E2F1 at serine-403 promotes its binding to FBXW7 (F-box/WD repeat-containing protein 7) followed by its ubiquitination and degradation. Furthermore, calcineurin, a Ca2+/calmodulin-dependent serine-threonine phosphatase, was shown to stabilize E2F1 by mediating its dephosphorylation at serine-403 and thereby preventing FBXW7 binding. Treatment of cells with Ca2+ channel blockers resulted in downregulation of both E2F1 protein and the expression of E2F1 target genes, whereas treatment with the Ca2+ ionophore ionomycin induced upregulation of E2F1. Finally, the calcineurin inhibitor FK506 attenuated xenograft tumor growth in mice in association with downregulation of E2F1 in the tumor tissue. Impairment of the balance between the opposing actions of FBXW7 and calcineurin in the regulation of E2F1 abundance may therefore play an important role in carcinogenesis.

Albumin-Globulin Ratio Indicates the Survival Outcome of Pancreatic Cancer Cases Who Underwent Preoperative Treatment and Curative Surgical Resection.

BACKGROUND: The pretreatment albumin-globulin ratio (AGR) is a frequently used inflammation-associated factor that has been reported to have associations with the survival outcomes of various malignancies. METHODS: We retrospectively analyzed 162 patients with pancreatic cancer who underwent preoperative treatment followed by curative surgery at Nagoya University Hospital between April 2010 and December 2020. Representative nutritional status indicators of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin-globulin ratio (AGR) were calculated for each case. RESULTS: Among pretreatment blood examination parameters, only AGR (cutoff: 1.33) showed a significant difference in overall survival time (OS) and progression-free survival time (PFS) from the beginning of the preoperative treatment. Median PFS was 22.3 mo, in high AGR cases and 17.1 mo, in low AGR cases (P = 0.019). Median OS was 48.7 mo, in high AGR cases and 32.9 mo, in low AGR cases (P = 0.043). CONCLUSION: High pretreatment AGR may be a favorable prognostic factor for pancreatic cancer patients who received preoperative multimodal therapy followed by curative cancer resection. It may imply that nutritional status and inflammation control before the multimodal treatment affect the survival outcomes of pancreatic cancer cases and needs to be optimized.

Effects of changes in whole-body alignment on ipsilateral knee pain after total hip arthroplasty.

BACKGROUND: Total hip arthroplasty decreases hip pain and often reduces knee pain in patients with hip osteoarthritis. Whole-body alignment may be associated with knee pain, but to our knowledge this relationship has not been previously investigated. The purpose of this study was to investigate the effect of changes in whole-body alignment on ipsilateral knee pain in patients after total hip arthroplasty. METHODS: In total, 94 patients with unilateral hip osteoarthritis who underwent total hip arthroplasty were enrolled in this study. A visual analog scale (VAS) was used to investigate perioperative knee pain. An EOS 2D/3D X-ray system was used to quantify the whole-body alignment of the spine, pelvis, and lower extremities in the standing position. The relationship between perioperative changes in knee pain and whole-body alignment was investigated. RESULTS: Among 61 patients who had preoperative ipsilateral knee pain, pain resolved in 30 (50%) and persisted in 31 (50%) after surgery. In these patients, average ipsilateral knee pain decreased significantly after surgery, from 41 mm to 14 mm on the VAS (P < 0.01). Preoperative knee pain was correlated with femorotibial rotation, and postoperative knee pain was correlated with K-L grade, preoperative knee pain visualized analog scale, and preoperative sagittal vertical axis. Multiple linear regression identified preoperative sagittal vertical axis as significantly associated with residual postoperative ipsilateral knee pain. CONCLUSIONS: Ipsilateral knee pain decreased in half of patients after total hip arthroplasty. Patients with a considerable forward-bent posture may have residual ipsilateral knee pain after total hip arthroplasty.

Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9.

BACKGROUND: The axon guidance gene family, SLIT/ROBO pathway, controls neural network formation, which correlates with the development of several cancers. METHODS: We found through analysis of the public database that ROBO4, one of the axon guidance molecules among the SLIT/ROBO family, is significantly downregulated in primary pancreatic cancer tissues compared with adjacent normal tissues. We carried out transfection experiments using three pancreatic cancer cell lines (MiaPaCa-2, BxPC-3, and SW1990) and one pancreatic duct epithelial cell line (HPDE6c7). A total of 51 clinical samples were then examined by immunohistochemical staining to find an association between ROBO4 expression at the protein level, clinical characteristics, and surgical outcomes. RESULTS: ROBO4 overexpression suppressed the invasion and migration abilities in MiaPaCa-2 and BxPC-3, while ROBO4 siRNA transfection to SW1990 and HPDE6c7 enhanced those activities. PCR-based profiling detected MMP-9 as a candidate downstream target of ROBO4, which was validated by decreased MMP-9 activity after the ROBO4 overexpression assay. High ROBO4 expression clinical samples had significantly better overall survival rather than low ROBO4 cases (P = 0.048). CONCLUSION: These findings suggest that decreased ROBO4 expression activates malignant phenotypes in cancer cells and is correlated with poor survival outcomes in pancreatic cancer.

Utility of CT-based navigation in revision total hip arthroplasty for a patient with severe posterior pelvic tilt-case report.

BACKGROUND: Hip dislocation after total hip arthroplasty (THA) or hemi-arthroplasty is a rare but serious complication. Dislocation may be prevented by appropriate positioning of the cup angle of inclination and anteversion. CASE PRESENTATION: This report describes a 66-year-old woman who underwent revision THA using a computer tomography (CT)-based navigation system to treat an anterior dislocation after hemi-arthroplasty due to a severe posterior pelvic tilt. At initial presentation, her sagittal pelvic tilt angle, measured as anterior pelvic plane (APP) in the supine position, was 38 degrees posterior to the coronal plane. Owing to the posterior pelvic tilt, revision THA was performed using CT-based navigation, while dual mobility was utilized to reduce the risk of re-dislocation. Postoperatively, her sagittal pelvic tilt angle showed further progression over time, with an APP of 66 degrees posterior to the coronal plane in the standing position 3 years after revision THA. Simulation with the Zed Hip system showed that the risk of implant-to-implant impingement was much higher posteriorly than anteriorly. Gait analysis demonstrated hyperextension of the hip joint while walking, although hip joint function required for daily activity was maintained. CONCLUSIONS: Preoperative planning of implant orientation, based on posterior progression of pelvic tilt and accurate placement of components, is important to prevent dislocation in patients with severe posterior pelvic tilt. A dual mobility cup may also improve hip function in these patients.

The Relationship Between the Location of Uptake on Positron Emission Tomography/Computed Tomography and the Impingement Point by Computer Simulation in Femoroacetabular Impingement Syndrome With Cam Morphology.

PURPOSE: To clarify the concordance rate of the location of uptake on positron emission tomography/computed tomography (PET/CT) and the impingement point demonstrated in computer simulation in femoroacetabular impingement (FAI) syndrome with cam morphology. METHODS: We included hip joints with FAI syndrome that underwent 18F-fluoride PET/CT. We also excluded hips with SUVmax <6. Each hip was evaluated for the region of the SUVmax point on PET/CT as well as the impingement point by computer simulation. We used ZedHip software (Lexi, Tokyo, Japan) for impingement simulation analysis based on CT data. Bony impingement is identified if there is a mesh in acetabular and femoral side contact in at least one unit. We investigated the rate of concordance between these 2 regions for each 10° flexion angle of the hip, ranging from 0° to 90°. RESULTS: Twenty-two hips of 22 patients were evaluated. The SUVmax region was most frequently distributed in the proximal middle region in 12 hips. In 18 of 22 hips (81.8%), the SUVmax region was concordant with the impingement region for at least one flexion angle. The concordance rates in 50° (P = .034), 60° (P = .007), 70° (P = .011), and 80° (P = .046) of flexion were significantly higher than in 90° of flexion. CONCLUSIONS: It was possible to visualize and clarify the detailed location of abnormal uptake in FAI syndrome patients with cam morphology by applying 18F-fluoride PET/CT. The concordance rates in 50°, 60°, 70°, and 80° of flexion were significantly higher than in 90° of flexion, which suggested that impingement may more frequently occur at less than 90° of flexion in FAI syndrome with cam morphology. LEVEL OF EVIDENCE: Level III, cross-sectional diagnostic study.

[A Case of Advanced Gastric Cancer Treated with Curative Resection after Preoperative Secondary Chemotherapy with Irinotecan after Primary Chemotherapy with Docetaxel, Cisplatin, and S-1].

A 70-year-old man was diagnosed with advanced gastric cancer based on esophagogastroduodenoscopy(EGD). Abdominal computed tomography(CT)showed swelling of the lymph nodes and invasion to the liver and pancreas. The patient was treated using combined docetaxel, cisplatin, and S-1(DCS)chemotherapy. After 2 courses of treatment, the primary tumor and lymph node metastases continued to grow. The patient was treated using secondary chemotherapy with irinotecan (CPT-11). After 1 course of treatment, the primary tumor and regional lymph nodes reduced in size. We performed curative total gastrectomy with D2 lymph node dissection. There has been no recurrence for 15 months after adjuvant chemotherapy with capecitabine and oxaliplatin(CapeOX). Therefore, CPT-11 therapy is a possible option for the management of advanced gastric cancer after DCS therapy.

A simple recovery process for biodegradable plastics accumulated in cyanobacteria treated with ionic liquids.

Here, we proposed a simple recovery process for poly(3-hydroxybutyrate) (PHB) accumulated in cyanobacteria by using ionic liquids (ILs), which dissolve cyanobacteria but not PHB. First, we investigated the effects of IL polarity on hydrogen-bonding receipt ability (ß value) and hydrogen-bonding donating ability (α value) and evaluated the subsequent dissolution of cyanobacteria. We found that ILs having α values higher than approximately 0.4 and ß values of approximately 0.9 were suitable for dissolution of cyanobacteria. In particular, 1-ethyl-3-methylimidazolium methylphosphonate ([C2mim][MeO(H)PO2]) was found to dissolve cyanobacteria components, but not PHB. Thus, we verified that PHB produced in cyanobacteria could be separated and recovered by simple filtering after dissolution of cyanobacteria in [C2mim][MeO(H)PO2]. Using this technique, more than 98 % of PHB was obtained on the filter as residues separated from cyanobacteria. Furthermore, [C2mim][MeO(H)PO2] maintained the ability to dissolve cyanobacteria after a simple recycling procedure.

Clinical Efficacy of Nasal Screening and Methicillin-Resistant Staphylococcusaureus Decolonization in Total Hip Arthroplasty without Chlorhexidine Soap or Vancomycin.

Purpose: Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a known risk factor for periprosthetic joint infection (PJI). In our facility, preoperative prophylaxis with mupirocin without the chlorhexidine soap scrub or vancomycin was consistently implemented for more than 15 years. This study aimed to evaluate the current screening and treatment of intranasal MRSA colonization in our elective primary THA patient population. Methods: All patients who underwent primary THA between April 2011, and March 2021 were included in this analysis. All patients were screened preoperatively for nasal MRSA approximately 1 month before surgery. Patients with nasal MRSA contamination are treated with topical mupirocin to eradicate the bacteria before surgery. The patients were examined again approximately two weeks before surgery. We evaluated the current screening and treatment of intranasal colonization with MRSA in our elective primary total hip arthroplasty (THA) patient population. Results: Out of 6251 patients, 106 (1.7%) had nasal MRSA contamination. The bacteria were not eradicated in three (3.6%) patients at the second screening. Twenty-two joints (0.35%) out of the 6251 had deep infections. Only 1 patient out of the 106 MRSA nasal carriers suffered from PJI. Twenty-one of the 6145 non-carriers had PJI. The difference between the prevalence of nasal MRSA contamination and the incidence of deep infections was not statistically significant. Conclusion: Our findings suggest that screening of all patients for nasal MRSA before THA followed by mupirocin calcium treatment if needed is sufficient PJI prophylaxis.

Uterine diverticulum mimicking endometriotic cyst of the ovary.

Uterine diverticulum is a rare congenital malformation caused by abnormal fusion of the Müllerian ducts. The diagnosis of uterine diverticulum is difficult, and it is often misdiagnosed as a Müllerian duct anomaly, degenerated uterine fibroid, or ovarian cyst. We herein report a case of uterine diverticulum mimicking an ovarian endometriotic cyst. A multiparous woman with a history of normal vaginal delivery underwent magnetic resonance imaging for investigation of lower abdominal pain and fever. A 155-mm cystic lesion was observed on the ventral side of the uterus. The content of the cyst showed high signal intensity on T1- and T2-weighted images with precipitates of low signal intensity on the dorsal side, suggesting an endometriotic cyst of the ovary. Surgical and pathological findings revealed that the cyst was pedunculated from the anterior uterine body and composed of 3 layers: CD10-positive endometrium, a smooth muscle layer, and serosa. A uterine diverticulum was definitively diagnosed.

Bayesian multidimensional nominal response model for observer study of radiologists.

PURPOSE: This study proposes a Bayesian multidimensional nominal response model (MD-NRM) to statistically analyze the nominal response of multiclass classifications. MATERIALS AND METHODS: First, for MD-NRM, we extended the conventional nominal response model to achieve stable convergence of the Bayesian nominal response model and utilized multidimensional ability parameters. We then applied MD-NRM to a 3-class classification problem, where radiologists visually evaluated chest X-ray images and selected their diagnosis from one of the three classes. The classification problem consisted of 150 cases, and each of the six radiologists selected their diagnosis based on a visual evaluation of the images. Consequently, 900 (= 150 × 6) nominal responses were obtained. In MD-NRM, we assumed that the responses were determined by the softmax function, the ability of radiologists, and the difficulty of images. In addition, we assumed that the multidimensional ability of one radiologist were represented by a 3 × 3 matrix. The latent parameters of the MD-NRM (ability parameters of radiologists and difficulty parameters of images) were estimated from the 900 responses. To implement Bayesian MD-NRM and estimate the latent parameters, a probabilistic programming language (Stan, version 2.21.0) was used. RESULTS: For all parameters, the Rhat values were less than 1.10. This indicates that the latent parameters of the MD-NRM converged successfully. CONCLUSION: The results show that it is possible to estimate the latent parameters (ability and difficulty parameters) of the MD-NRM using Stan. Our code for the implementation of the MD-NRM is available as open source.

A case of non-ampullary duodenal adenosquamous carcinoma with successful emergency pancreaticoduodenectomy for gastrointestinal hemorrhage.

BACKGROUND: Although most duodenal carcinomas are pathological adenocarcinomas, a small number of cases have been reported of adenosquamous carcinoma, characterized by variable combinations of two malignant components: adenocarcinoma and squamous cell carcinoma. However, owing to the small number of cases of non-ampullary duodenal adenosquamous carcinoma, there have been no reported cases of emergency pancreaticoduodenectomy for gastrointestinal hemorrhage due to non-ampullary duodenal adenosquamous carcinoma. CASE PRESENTATION: A 66-year-old Japanese male presented to the referring hospital with a chief complaint of abdominal pain, diarrhea, and dark urine that had persisted for 1 month. The patient was referred to our hospital because of liver dysfunction on a blood examination. Laboratory results of the blood on the day of admission showed that total and direct bilirubin levels (12.0 mg/dl and 9.6 mg/dl) were markedly increased. An endoscopic retrograde biliary drainage tube was inserted for the treatment of obstructive jaundice, and imaging studies were continuously performed. Contrast-enhanced computed tomography and endoscopy revealed an ill-defined lesion involving the second portion of the duodenum, predominantly along the medial wall, and measuring 60 mm in diameter. No metastases were observed by positron emission tomography. Pancreaticoduodenectomy was planned based on the pathological findings of poorly differentiated adenocarcinoma. However, 2 days before the scheduled surgery, the patient experienced hemorrhagic shock with melena. Owing to poor hemostasis after endoscopic treatment and poor control of hemodynamic circulation despite blood transfusion, radiological embolization and hemostasis were attempted but were incomplete. An emergency pancreaticoduodenectomy was performed after embolizing the route from the gastroduodenal artery and pseudoaneurysm area to reduce bleeding. The operation was completed using an anterior approach without Kocherization or tunneling due to the huge tumor. The operation time was 4 h and 32 min, and blood loss was 595 mL The pathological diagnosis was adenosquamous carcinoma. The postoperative course was uneventful with 17 day hospital stay and the patient is currently well, with no signs of recurrence 9 months after surgery. CONCLUSIONS: This report presents an extremely rare case of successful emergency pancreaticoduodenectomy for gastrointestinal hemorrhage caused by non-ampullary duodenal adenosquamous carcinoma.

The Efficacy and Safety of a Low Relative Dose Intensity of Cabazitaxel in Patients With Metastatic Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Clinical trials have shown that the efficacy of a reduced dose of cabazitaxel (20 mg/m2 every 3 weeks) was not inferior to that of the standard dose (25 mg/m2 every 3 weeks). However, the efficacy of even lower relative dose intensities, such as 20 mg/m2 every 4 weeks, have not been evaluated conclusively. The aim of this study was to investigate the efficacy and safety of a low relative dose intensity of cabazitaxel in patients with metastatic castration-resistant prostate cancer in the real world. PATIENTS AND METHODS: We retrospectively analyzed 101 consecutive patients treated with cabazitaxel for docetaxel-refractory metastatic castration-resistant prostate cancer. The progression-free and overall survival after introduction of cabazitaxel and prostate-specific antigen response rate were assessed as oncological outcome measures. RESULTS: The patients were divided into two groups (relative dose intensity >60%, n=74 and ≤60%, n=27). Both progression-free and overall survivals were significantly better in the >60% group than in the ≤60% group (median 5 and 2 months, p<0.01, and 15 and 6 months, p<0.01, respectively). In multivariate analyses, visceral metastasis and relative dose intensity ≤60% were prognostic factors for shorter progression-free and overall survivals (p=0.04, p<0.01, respectively). The incidence of adverse events was not significantly different between groups. CONCLUSION: The cabazitaxel relative dose intensity ≤60% group had significantly shorter progression-free and overall survivals than the >60% group, whereas the incidence of adverse events was not significantly different. The results suggested that reducing the relative dose intensity of cabazitaxel to ≤60% may not be recommended.

Role of the M point phonons for the dynamical stability of B2 compounds.

Although many binary compounds have the B2 (CsCl-type) structure in the thermodynamic phase diagram, an origin of the dynamical stability is not understood well. Here, we focus on 416 compounds in the B2 structure extracted from the Materials Project, and study the dynamical stability of those compounds from first principles. We demonstrate that the dynamical stability of the B2 compounds lies in whether the lowest frequency phonons around the M point in the Brillouin zone are endowed with a positive frequency, except for VRu. We show that the interatomic interactions up to the fourth nearest neighbor atoms are necessary for stabilizing such phonon modes, which should determine the minimum cutoff radius for constructing the interatomic potentials of binary compounds with guaranteed accuracy.

Deep learning model for the automatic classification of COVID-19 pneumonia, non-COVID-19 pneumonia, and the healthy: a multi-center retrospective study.

This retrospective study aimed to develop and validate a deep learning model for the classification of coronavirus disease-2019 (COVID-19) pneumonia, non-COVID-19 pneumonia, and the healthy using chest X-ray (CXR) images. One private and two public datasets of CXR images were included. The private dataset included CXR from six hospitals. A total of 14,258 and 11,253 CXR images were included in the 2 public datasets and 455 in the private dataset. A deep learning model based on EfficientNet with noisy student was constructed using the three datasets. The test set of 150 CXR images in the private dataset were evaluated by the deep learning model and six radiologists. Three-category classification accuracy and class-wise area under the curve (AUC) for each of the COVID-19 pneumonia, non-COVID-19 pneumonia, and healthy were calculated. Consensus of the six radiologists was used for calculating class-wise AUC. The three-category classification accuracy of our model was 0.8667, and those of the six radiologists ranged from 0.5667 to 0.7733. For our model and the consensus of the six radiologists, the class-wise AUC of the healthy, non-COVID-19 pneumonia, and COVID-19 pneumonia were 0.9912, 0.9492, and 0.9752 and 0.9656, 0.8654, and 0.8740, respectively. Difference of the class-wise AUC between our model and the consensus of the six radiologists was statistically significant for COVID-19 pneumonia (p value = 0.001334). Thus, an accurate model of deep learning for the three-category classification could be constructed; the diagnostic performance of our model was significantly better than that of the consensus interpretation by the six radiologists for COVID-19 pneumonia.

A chemically-defined plastic scaffold for the xeno-free production of human pluripotent stem cells.

Clinical use of human pluripotent stem cells (hPSCs) is hampered by the technical limitations of their expansion. Here, we developed a chemically synthetic culture substrate for human pluripotent stem cell attachment and maintenance. The substrate comprises a hydrophobic polyvinyl butyral-based polymer (PVB) and a short peptide that enables easy and uniform coating of various types of cell culture ware. The coated ware exhibited thermotolerance, underwater stability and could be stored at room temperature. The substrate supported hPSC expansion in combination with most commercial culture media with an efficiency similar to that of commercial substrates. It supported not only the long-term expansion of examined iPS and ES cell lines with normal karyotypes during their undifferentiated state but also directed differentiation of three germ layers. This substrate resolves major concerns associated with currently used recombinant protein substrates and could be applied in large-scale automated manufacturing; it is suitable for affordable and stable production of clinical-grade hPSCs and hPSC-derived products.

Prediction of pelvic mobility using whole-spinal and pelvic alignment in standing and sitting position in total hip arthroplasty patients.

PURPOSE: Dislocation is a major complication after total hip arthroplasty (THA), and pelvic stiffness is reportedly a significant risk factor for dislocation. This study aimed to investigate spinopelvic alignment, and identify preoperative factors associated with postoperative pelvic mobility. METHODS: We enrolled 78 THA patients with unilateral osteoarthritis. The sagittal spinopelvic alignment in the standing and sitting position was measured using an EOS imaging system before and 3 months after THA. We evaluated postoperative pelvic mobility, and defined cases with less than 10° of sacral slope change as pelvic stiff type. The preoperative characteristics of those with postoperative stiff type, and preoperative factors associated with risk of postoperative stiff type were evaluated. RESULTS: Sagittal spinopelvic alignment except for lumbar alignment were significantly changed after THA.A total of 13 patients (17%) were identified as postoperative pelvic stiff type. Preoperative lower pelvic and lumbar mobility were determined as significant factors for prediction of postoperative pelvic stiff type. Among these patients, nine patients (69%) did not have pelvic stiffness before THA. Preoperative factor associated with the risk of postoperative pelvic stiff type in those without preoperative stiffness was lower lumbar lordosis in standing position by multivariate regression analysis. CONCLUSION: Spinopelvic alignments except lumber alignment was significantly changed after THA. The lower pelvic mobility and lumbar alignment were identified as the preoperative predictive factors for postoperative pelvic mobility. Evaluation of preoperative lumbar alignment may be especially useful for the prediction in patients with hip contractures, for these patients may possibly experience the extensive perioperative change in pelvic mobility.

Postoperative excessive external femoral rotation in revision total hip arthroplasty is associated with muscle weakness in iliopsoas and gluteus medius and risk for hip dislocation.

BACKGROUND: Excessive external femoral rotation (FR) can functionally increase stem anteversion (SA) and is often observed at an early stage after surgery in revision total hip arthroplasty (THA). This study was conducted to investigate the prevalence of external FR, identify the factors associated with external FR, and determine the association of FR and other factors with hip dislocation in revision THA. METHODS: We enrolled 51 revision THA patients (55 hip cases). The patient background, angle of anatomical and functional SA, FR angle, sizes and densities of muscles around the hip joint, impingement distance, and consequence of postoperative hip dislocation were assessed by reviewing their medical history and imaging data that includes computed tomography (CT) scans before and after surgery. RESULTS: Forty-five hip cases (81.8%) showed external FR (mean 13.0°). External FR was significantly correlated with anatomical SA (r = - 0.54) and increase in functional SA (r = 0.36), which was significantly correlated with impingement distance (r = 0.46). The independent factors associated with external FR in multivariate analysis were the anatomical SA, CT densities of the psoas, gluteus medius and maximus muscles, and 2-stage revision (R2 = 0.559). During follow-up period, eight cases of revision THA showed hip dislocation. FR, functional SA, impingement distance, CT density of psoas and gluteus medius muscle, body mass index, number of past operation, and ratio of 2-stage revision THA were significantly different between cases with dislocation and non-dislocation. The odds ratio of FR and impingement distance for hip dislocation was identified as 1.061(95% confidence interval (CI): 1.011-1.114) and 0.901 (95% CI 0.820-0.991), respectively. CONCLUSIONS: Revision THA frequently causes an external FR that functionally increases the SA and impingement risk, particularly in hips with 2-stage revision with psoas and gluteus medius muscle atrophy. Patients who have undergone revision THA and have an excessive external FR may require careful monitoring for possible hip dislocation due to hip joint instability and impingement.

Quantized folding of plasmid DNA condensed with block catiomer into characteristic rod structures promoting transgene efficacy.

Highly regulated folding of plasmid DNA (pDNA) through polyion complexation with the synthetic block catiomer, poly(ethylene glycol)-block-poly(L-lysine) (PEG-PLys), was found to occur in such a way that rod structures are formed with a quantized length of 1/2(n + 1) of the original pDNA length folding by n times. The folding process of pDNA was elucidated with regard to rigidity of the double-stranded DNA structure and topological restriction of the supercoiled closed-circular form, and a mechanism based on Euler's buckling theory was proposed. Folded pDNA exhibited higher gene expression efficiency compared to naked pDNA in a cell-free transcription/translation assay system, indicating that the packaging of pDNA into a polyion complex core surrounded by a PEG palisade is a promising strategy for constructing nonviral gene carrier systems. Extension of this finding may provide a reasonable model to further understand the packaging mechanism of supercoiled DNA structures in nature.