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The clinical effectiveness of robotic arm-assisted systems remains unclear for total hip arthroplasty (THA) in patients suffering from osteoarthritis secondary to developmental dysplasia of the hip (DDH).Patients with DDH who underwent primary THA were included in this study. We conducted a propensity score-matched comparison between THAs using a robotic arm-assisted system (Mako group) versus those using the manual procedure (manual group) to compare the absolute differences in cup placement angles measured using postoperative computed tomography and those planned preoperatively.A total of 217 patients with osteoarthritis due to DDH met the inclusion criteria. Eighty-four patients were matched as the Mako group and 84 as the manual group. The differences were smaller in the Mako group than the manual group in terms of both inclination and anteversion angles (1.1 ± 1.0 versus 4.2 ± 3.1, respectively; 95% CI, 2.4 to 3.8; p 0.0001, and 1.2 ± 1.1 versus 5.8 ± 4.0, respectively; 95% CI, 3.7 to 5.5; p 0.0001).The robotic arm-assisted system may provide more accurate cup placement in THA for DDH.

From mathematical models of growth to computer simulations of pigmentation, the study of shell formation has given rise to an abundant number of models, working at various scales. Yet, attempts to combine those models have remained sparse, due to the challenge of combining categorically different approaches. In this paper, we propose a framework to streamline the process of combining the molecular and tissue scales of shell formation. We choose these levels as a proxy to link the genotype level, which is better described by molecular models, and the phenotype level, which is better described by tissue-level mechanics. We also show how to connect observations on shell populations to the approach, resulting in collections of molecular parameters that may be associated with different populations of real shell specimens.The approach is as follows: we use a Quality-Diversity algorithm, a type of black-box optimization algorithm, to explore the range of concentration profiles emerging as solutions of a molecular model, and that define growth patterns for the mechanical model. At the same time, the mechanical model is simulated over a wide range of growth patterns, resulting in a variety of spine shapes. While time-consuming, these steps only need to be performed once and then function as look-up tables. Actual pictures of shell spines can then be matched against the list of existing spine shapes, yielding a potential growth pattern which, in turn, gives us matching molecular parameters. The framework is modular, such that models can be easily swapped without changing the overall working of the method. As a demonstration of the approach, we solve specific molecular and mechanical models, adapted from available theoretical studies on molluscan shells, and apply the multiscale framework to evaluate the characteristics of spines from three distinct populations ofTurbo sazae.Author summaryConnecting genotype to phenotype is a fundamental goal in developmental biology. While many studies examine this link in model organisms for which gene regulatory networks are well known, for non-model organisms, different techniques are required, and multiscale computational modeling offers a promising direction. In this paper, we develop a framework linking molecular-scale interactions to tissue-level growth and mechanics to organism-level characteristics in order to investigate spine formation inT. sazae, a species of mollusc that displays remarkable phenotypic plasticity in spine form. Our analysis uncovers a subtle but statistically significant difference in spine form between shell specimens collected from three different localities in Japan. Moreover, by tracing the difference in form through parametric differences in the multiscale framework, we provide mechanistic insight as to how environmental differences may translate to a change in form. The methodology we present may readily be extended to more detailed modeling of this system, and the conceptual framework is amenable for multiscale analysis in other systems.

NF-κB mediates transcriptional regulation crucial to many biological functions, and elevated NF-κB activity leads to autoimmune and inflammatory diseases, as well as cancer. Since highly aggressive breast cancers have few therapeutic molecular targets, clarification of key molecular mechanisms of NF-κB signaling would facilitate development of more effective therapy. In this report, we show that Tob, a member of the Tob/BTG family of antiproliferative proteins, acts as a negative regulator of the NF-κB signal in breast cancer. Studies with 35 human breast cancer cell lines reveal that Tob expression is negatively correlated with NF-κB activity. Analysis of The Cancer Genome Atlas (TCGA) database of clinical samples reveals an inverse correlation between Tob expression and NF-κB activity. Tob2, another member of the Tob/BTG family, shows no such negative correlations. Furthermore, in TNF-α treated cells, Tob associates with TNF receptor complex I to suppress polyubiquitylation of RIPK1, which results in repression of NF-kB activity. Therefore, Tob functions as a negative regulator of the NF-κB pathway and may serve as a therapeutic target for aggressive breast cancer.

This paper proposes a method that provides a phase image related to the demagnetization field (Hd) within a thin-foil permanent magnet using electron holography. The observation of Hd remains a significant challenge because electron holography in principle allows only imaging of the magnetic flux density (B), which is a mixture of the contributions from magnetization (M), stray magnetic field (Hs) outside of the specimen and Hd inside of the specimen. The phase map approximating Hd, which was determined by processing of the electron holography observation from a Nd2Fe14B single-crystalline specimen, showed a good agreement with the prediction by micromagnetic theory. With respect to permanent magnets, this method can be applied to examinations about the coercivity mechanism, which is sensitive to the demagnetization field. Graphical Abstract

(Introduction) In tethered cord syndrome, the lower end of the spinal cord is moored to the caudal tissue, causing various neuropathies. Bladder dysfunction often appears early. We herein evaluated children with daytime urinary incontinence in whom tethered cord syndrome was eventually diagnosed. (Method) Eighteen children (9 males and 9 females) with daytime urinary incontinence were enrolled between March 2011 and October 2017. The causes of their urinary incontinence were investigated using spinal MRI and changes in clinical symptoms before and after untethering surgery. (Results) The average age at the first visit was 6.3 years (range: 4-9 years). Urodynamic testing and a voiding cystourethrogram (VCUG) were performed in all cases of refractory daytime incontinence, and all patients with abnormal findings on either test underwent spinal MRI. The diagnosis based on spinal MRI findings was filum lipoma in eight, occult tethered cord syndrome in four, low set conus in four, conus lipoma in one, and sacral meningeal cyst in one, patient. The average observation period after untethering surgery was 66.3 months (range: 22-116 months). All the patients achieved a cure postoperatively. Four patients were treated for nocturnal enuresis by oral medication, and three patients required urological management via clean, intermittent catheterization. (Conclusions) When treating children with daytime continence, one should consider the possibility of tethered cord syndrome, the diagnosis of which can be aided by urodynamic assessment of bladder function.

Kouichi Ohta, Atsuko Sato, Emi Fukui Department of Ophthalmology, Matsumoto Dental University, Shiojiri, Nagano, JapanCorrespondence: Kouichi OhtaDepartment of Ophthalmology, Matsumoto Dental University, 1780 Gobara, Hirooka, Shiojiri, Nagano, 399-0781, JapanTel/Fax +81-263-51-2210Email kouichi.ohta@mdu.ac.jpPurpose: A late dislocation of an in-the-bag intraocular lens (IOL) is strongly associated with pseudoexfoliation and less with retinitis pigmentosa, prior vitreoretinal surgery, and uveitis. We present our findings of late in-the-bag IOL dislocation in three patients with multiple chorioretinal atrophy associated with sarcoidosis.Methods: Observational study of three elderly female Japanese patients with a history of uveitis from sarcoidosis who presented with a late dislocation of an in-the-bag IOL.Results: The late in-the-bag IOL dislocation occurred in the convalescent/quiescent stage of the sarcoidosis. Peripheral multifocal chorioretinal atrophy was the main manifestation in all patients who were diagnosed with definite or presumed sarcoidosis. The dislocated IOLs were successfully removed and new IOLs were implanted with scleral suture fixation followed by no remarkable active uveitis.Conclusion: Clinicians should be aware that patients with peripheral multifocal chorioretinal atrophy associated with sarcoidosis can have a late in-the-bag IOL dislocation.Keywords: late in-the-bag IOL dislocation, pigmented chorioretinal atrophy, sarcoidosis, uveitis

(Objective) We reviewed the clinical efficacy of transurethral Deflux

Purpose To report a case of a full-thickness macular hole (MH) that developed after cryotherapy and intravitreal bevacizumab injection (IVB) to treat a retinal vasoproliferative tumor (VPT). Methods Case report of a man with a retinal VPT. Results A 64-year-old Japanese man complained of blurred vision in his right eye. At the initial examination, his best-corrected visual acuity (BCVA) was 20/25 in the right eye and 20/20 in the left eye. Ophthalmoscopy showed a VPT in the lower peripheral retina of the right eye. An exudative retinal detachment and hard exudates were seen around the tumor. Cryotherapy and intravitreal injections of bevacizumab (IVB) were performed. Although the exudative changes were reduced, a MH developed two months after the initial IVB treatment. He underwent 25-gauge pars plana vitrectomy, and the MH was closed. His postoperative BCVA was 20/32 and the VPT was inactive. The reduced BCVA was due to damage of the outer retinal layers. Conclusion Our findings indicate that cryotherapy and IVB are effective treatments for VPT although the possibility of developing a MH should be considered.

Purpose We have shown distinct morphological changes of the foveal retina such as horizontally asymmetrical retinal thicknesses and displacements of the fovea toward the optic disc after successful idiopathic macular hole (MH) closure by MH surgery with internal limiting membrane (ILM) peeling. The purpose of this study was to determine whether these morphological changes will alter the stereoacuity. Setting This was a non-randomized, retrospective study conducted on patients who underwent MH surgery at the Matsumoto Dental University Hospital, Nagano, Japan. Methods Forty patients (22 women, 18 men) who underwent MH surgery with ILM peeling for a unilateral MH were studied. At >6 months after the PPV, the stereoacuity was measured with the Titmus stereotest (TST) and the TNO stereotest (TNO). The relationship between the stereoacuity and the age, MH size, best-corrected visual acuity (BCVA), foveal retinal thickness, and amount of nasal shift of the retina was determined. Results The mean postoperative BCVA was -0.05 ± 0.11 logarithm of the minimum angle of resolution (logMAR) units. The percentage of cases with good stereoacuity of ≤100 sec of arc was 87.5% with the TST and ≤240" was 90% with the TNO test. A better stereoacuity was significantly correlated with a younger age (r = 0.36, P

The magnetism of a narrow (~1.6 nm) grain boundary phase produced in a 0.1 at% Ga-doped Nd–Fe–B sintered magnet was examined using electron holography. The magnetic flux density was determined to be 0.8 ± 0.1 T, which was smaller than that for a commercial magnet free from Ga doping (~1.0 T). The presence of a ferromagnetic grain boundary phase reasonably explained the functionality of the 0.1 at% Ga-doped system, such as the improvement in the squareness of the demagnetization curve. The observations provide useful information for deeper understanding of the coercivity mechanism in Ga-doped Nd–Fe–B sintered magnets.

Modular stems are useful for total hip arthroplasty (THA) in anatomically difficult dysplasia. Here, we present mean 6.8-year outcomes of cementless primary THA using S-ROM-A (modified modular stem for Asian patients) femoral prosthesis in anatomically difficult cases.Charts of 373 patients (461 hips) undergoing THA (mean age, 58 years) were reviewed for clinical evaluation of modified Merle d'Aubigné-Postel score and Kaplan-Meier survivorship with revision for any reason as the end point. For radiographic analysis, 331 patients (412 hips) followed up for ≥5 years were included. Bearing couples were metal-on-metal (n = 145), metal-on-polyethylene (n = 120), and ceramic-on-polyethylene (n = 147). Radiography and multiplanar computed tomography were performed.No postoperative dislocation or deep infection occurred. Mean modified Merle d'Aubigné-Postel score improved significantly (10.9 points preoperatively, 16.7 points at last follow-up; P.001). Cumulative 5- and 10-year stem survival rates were 100% and 84%, respectively (95% confidence interval, 75%-93%). All stems were classified as bone ingrown fixation. Osteolysis occurred in metal-on-metal (42.8%) and metal-on-polyethylene (15.8%) groups. Mean time to osteolysis was ~3 years, with no significant difference between 3 groups (P = .264). In logistic regression, lower cup inclination angle was significantly associated with osteolysis (odds ratio, 0.914; 95% confidence interval, 0.84-0.99; P = .029).S-ROM-A femoral prosthesis achieved excellent midterm fixation, and the modular system was useful in primary THA with severe deformity. Bearing couples are potentially associated with adverse reactions to metal debris. S-ROM-A with ceramic-on-polyethylene bearing couples may be an option for anatomically difficult THA.

We aimed to investigate the changes in urodynamics and voiding cystourethrogram parameters on pre- and post-untethering surgery in patients aged under 2 years with filum lipoma.Sixty-two patients were enrolled in this study. The changes in urodynamics and voiding cystourethrogram parameters were compared before untethering surgery and 6 months after untethering surgery. These parameters were bladder volume, bladder deformity, vesicoureteral reflux during voiding cystourethrogram, detrusor overactivity, bladder compliance, and post-void residual volume in urodynamics.Bladder volume during voiding cystourethrogram and bladder compliance increased significantly from 89.8 ± 49.5 mL to 114.5 ± 50.5 mL (P = 0.0069) and 10.2 ± 6.2 mL/mmHAccording to voiding cystourethrogram results, bladder function and urodynamics in patients with filum lipoma significantly improved after untethering surgery. Non-invasive assessment based on measurements of post-void residual should be considered as a postoperative follow-up method.

In cold regions, the road surface sometimes deforms from frost heaving of the subgrade. For this reason, road construction in the cold regions of Japan is done by using non-frost heaving materials for the layers within the frost penetration depth of the subgrade. In Japan, materials generated at road construction sites are reused in order to make effective use of resources. Measures are taken when the materials generated from construction are unsuitable for use as subgrade materials. One method for improving such soil is by adding a solidifier. To use solidified soil, which is a material improved by the addition of a solidifying agent, for the subgrade in cold regions, such soil must have sufficient strength and must not be susceptible to freezing. Quality control of subgrades made with solidified soil is expense and time consuming. Therefore, a simple method has been called for. To develop such a method, we experimentally solidified some poor-quality soil specimens and investigated their strength and frost heave susceptibility by several types of tests. The tests revealed that a strength much higher than that required for ordinary subgrade is needed to use solidified soils as subgrade materials. It was also found that a method involving impact acceleration can be applied for quality control checks of a subgrade made with solidified soil.

For rational drug design, it is essential to predict the binding mode of protein-ligand complexes. Although various machine learning-based models have been reported that use convolutional neural networks (deep learning) to predict binding modes from three-dimensional structures, there are few detailed reports on how best to construct and use datasets. Here, we examined how different datasets affected the prediction of the binding mode of CYP3A4 by a three-dimensional neural network when the number of crystal structures for the target protein was limited. We used four different training datasets: one large, general dataset containing various protein complexes and three smaller, more specific datasets containing complexes with CYP3A4-like pockets, complexes with CYP3A4-binding ligands, and complexes with CYP protein family members. We then trained models with different combinations of datasets with or without subsequent fine-tuning and evaluated the binding mode prediction performance of each model. The best receiver operating characteristic (ROC) area under the curve (AUC) model with respect to area under the receiver operating characteristic curve was obtained by training with a combination of the general protein and CYP family datasets. However, the ROC AUC-recall balanced model was obtained by training with this combination of datasets followed by fine-tuning with the CYP3A4-binding ligands dataset. Our results suggest that datasets that balance protein functionality and data size are important for optimizing binding mode prediction performance. In addition, datasets with large median binding pocket sizes may be important for the binding mode prediction specifically of CYP3A4.

Canalization, an intrinsic robustness of development to external (environmental) or internal (genetic) perturbations, was first proposed over half a century ago. However, whether the robustness to environmental stress (environmental canalization [EC]) and to genetic variation (genetic canalization) are underpinned by the same molecular basis remains elusive. The recent discovery of the involvement of two endoplasmic reticulum (ER)-associated DnaJ genes in developmental buffering, orthologues of which are conserved across Metazoa, indicates that the role of ER-associated DnaJ genes might be conserved across the animal kingdom. To test this, we surveyed the ER-associated DnaJ chaperones in the nematode Caenorhabditis elegans. We then quantified the phenotype, in the form of variance and mean of seam cell counts, from RNA interference knockdown of DnaJs under three different temperatures. We find that seven out of eight ER-associated DnaJs are involved in either EC or microenvironmental canalization. Moreover, we also found two DnaJ genes not specifically associated with ER (DNAJC2/dnj-11 and DNAJA2/dnj-19) were involved in canalization. Protein expression pattern showed that these DnaJs are upregulated by heat stress, yet not all of them are expressed in the seam cells. Moreover, we found that most of the buffering DnaJs also control lifespan. We therefore concluded that a number of DnaJ chaperones, not limited to those associated with the ER, are involved in canalization as a part of the complex system that underlies development.

Chromosomal rearrangements can reduce fitness of heterozygotes and can thereby prevent gene flow. Therefore, such rearrangements can play a role in local adaptation and speciation. In particular, inversions are considered to be a major potential cause for chromosomal speciation. There are two closely related, partially sympatric lineages of ascidians in the genus Ciona, which we call type-A and type-B animals in the present study. Although these invertebrate chordates are largely isolated reproductively, hybrids can be found in wild populations, suggesting incomplete prezygotic barriers. Although the genome of type-A animals has been decoded and widely used, the genome for type-B animals has not been decoded at the chromosomal level. In the present study, we sequenced the genomes of two type-B individuals from different sides of the English Channel (in the zone of sympatry with type-A individuals) and compared them at the chromosomal level with the type-A genome. Although the overall structures were well conserved between type A and type B, chromosomal alignments revealed many inversions differentiating these two types of Ciona; it is probable that the frequent inversions have contributed to separation between these two lineages. In addition, comparisons of the genomes between the two type-B individuals revealed that type B had high rates of inversion polymorphisms and nucleotide polymorphisms, and thus type B might be in the process of differentiation into multiple new types or species. Our results suggest an important role of inversions in chromosomal speciation of these broadcasting spawners.

Simple Summary Molecular hydrogen (MH) reportedly exerts therapeutic effects against inflammatory diseases by alleviating oxidative stress. We investigated the cardiovascular protective effects of molecular hydrogen water (MHW) intake using high-fat diet-induced obesity (DIO) mice. We observed that MHW intake for 2 weeks did not improve the blood sugar level or body weight but decreased heart weight in DIO mice. Notably, MHW intake alleviated oxidative stress in both the heart and the adipose tissue. Moreover, it improved cardiac hypertrophy and restored left ventricular function in DIO mice, and promoted the histological conversion of energy storage to expenditure in adipose tissues with the upregulation of thermogenic and cardiovascular protective genes. Furthermore, MHW restored endothelial progenitor cell (EPC) bioactivity to maintain vascular homeostasis. Taken together, MHW intake exerts cardiovascular protective effects in DIO mice. Hence, MHW intake is a potential prophylactic strategy against cardiovascular disorders in metabolic syndrome. Abstract Molecular hydrogen (MH) reportedly exerts therapeutic effects against inflammatory diseases as a suppressor of free radical chain reactions. Here, the cardiovascular protective effects of the intake of molecular hydrogen water (MHW) were investigated using high-fat diet-induced obesity (DIO) mice. MHW was prepared using supplier sticks and degassed water as control. MHW intake for 2 weeks did not improve blood sugar or body weight but decreased heart weight in DIO mice. Moreover, MHW intake improved cardiac hypertrophy, shortened the width of cardiomyocytes, dilated the capillaries and arterioles, activated myocardial eNOS-Ser-1177 phosphorylation, and restored left ventricular function in DIO mice. MHW intake promoted the histological conversion of hypertrophy to hyperplasia in white and brown adipose tissues (WAT and BAT) with the upregulation of thermogenic and cardiovascular protective genes in BAT (i.e., Ucp-1, Vegf-a, and eNos). Furthermore, the results of a colony formation assay of bone-marrow-derived endothelial progenitor cells (EPCs) indicated that MHW activated the expansion, differentiation, and mobilization of EPCs to maintain vascular homeostasis. These findings indicate that the intake of MHW exerts cardiovascular protective effects in DIO mice. Hence, drinking MHW is a potential prophylactic strategy against cardiovascular disorders in metabolic syndrome.

When the soil generated during road or river excavation work is too soft to be used as a material, it can be improved by the use of solidifiers such as cement and lime. However, if an embankment has excessive strength as a result of solidification, the embankment may be difficult to re-excavate. High-strength embankments may fail if they are constructed on soft ground and are not able to follow the behavior of that ground. For this reason, there is a demand for a material whose strength development can be controlled even when a solidifier is added. As a solution to this issue, we investigated the use of crushed solidified soil. Crushed solidified soil is produced by adding a solidifier to soil and then crushing the soil in the middle of the solidification process. It is considered that the type and amount of solidifier and the timing for crushing have considerable influence on the physical properties and strength of the product. Therefore, we investigated the physical properties and strength of the crushed solidified soil and constructed two types of full-scale embankments on soft ground. We compared the deformation characteristics of these two embankments. We found that the crushed solidified soil had lower strength than the solidified soil and that the physical properties and strength of the material depended on the time elapsed before crushing of the solidified soil. Furthermore, it was found that the embankment by solidified crushed soil follows the deformation of soft ground

Seminal vesicle cysts are usually congenital and frequently accompanied by upper urinary tract abnormalities due to mesonephric duct maldevelopment. Zinner syndrome, first described in 1914, refers to a triad of features consisting of seminal vesicle cysts, ejaculatory duct obstruction, and unilateral (mostly ipsilateral) renal agenesis. We herein present four pediatric patients with Zinner syndrome diagnosed at a children's medical center. A remnant ureteral structure was observed in three (75%) patients. Interestingly, a multicystic dysplastic kidney was present in one (25%) patient before it eventually disappeared. These findings suggest possible involvement of renal dysgenesis rather than agenesis in Zinner syndrome.

Objectives To investigate the frequency of vesicoureteral reflux, and the relationship of pretransplant decreased bladder capacity and post-transplant vesicoureteral reflux in children undergoing kidney transplantation. Methods A voiding cystourethrography was carried out in 172 pediatric kidney transplantation recipients before, and 4 months after, transplantation to evaluate bladder capacity and vesicoureteral reflux. The correlation of post-transplant vesicoureteral reflux with pretransplant bladder capacity, vesicoureteral reflux in the native kidney and the method of ureteral reimplantation (intravesical/extravesical) was analyzed. Atrophic bladder was defined as having ≤50% functional bladder capacity (age in years + 2) × 25 (mL) or ≤150 mL in patients aged >10 years. Results Bladder capacity increased remarkably after transplantation in both post-transplant vesicoureteral reflux- group (from 180 to 253 mL) and vesicoureteral reflux+ group (from 82 to 171 mL). Voiding cystourethrography showed vesicoureteral reflux in 12 cases of kidney transplantation (7%; grade 1: 2, grade 2: 3, grade 3: 7). Pretransplant atrophic bladder was an independent risk factor of post-transplant vesicoureteral reflux (P = 0.004, hazard ratio 9.5). There was no difference in renal function between the vesicoureteral reflux- group and vesicoureteral reflux+ group at 4 months to 5 years post-transplantation. Conclusions Pretransplant atrophic bladder is a risk factor of post-transplant vesicoureteral reflux in pediatric patients. However, bladder capacity can remarkably increase after transplantation, and kidney function in the post-transplant vesicoureteral reflux+ group is stable.

To evaluate the clinical accuracy of several estimated glomerular filtration rates (eGFR) using cystatin-C to measure renal function in Japanese renal donors.In total, 61 healthy, potential renal donors were assessed. The average age was 42.7 years (range: 27-67). We evaluated the GFR based on the 24-hour creatinine clearance (Ccr) using 24-hour urine collection, eGFR based on serum creatinine (eGFRcr), and cystatin-C (eGFRcys) levels using an equation developed by the Japanese Society of Nephrology, the average of the eGFRcr and eGFRcys (eGFRave) rates, and an eGFR based on a combination of serum creatinine and cystatin-C values using an equation developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The association between Ccr and each eGFR was evaluated using Pearson's r and the Bland-Altman plot.Pearson's correlation coefficient analysis revealed a significant correlation between the Ccr and the eGFRcr (r = 0.62, P .0001), eGFRave (r = 45, P = .0003), and eGFRcr-cys (r = 0.451, P = .0014). The Bland-Altman study suggested that each eGFR had a low level of agreement with the Ccr because the latter was higher than each eGFR. On the other hand, the eGFRave had the highest level of agreement with CCr × 0.715.The eGFRave may provide a simple and useful method of evaluating renal function in living renal transplant donors.