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Introduction A retroperitoneoscopic procedure for bladder neck closure has not yet been described. Case presentation Case 1 was a 56‐year‐old man who underwent clean intermittent catheterization for spastic paraplegia due to a thoracic spinal cord injury 37 years prior. Case 2 was an 80‐year‐old bedridden woman who underwent urethral catheterization after a femoral fracture and brain infarction 3 years prior. Both patients presented with Fournier's gangrene, and the urogenital region, including the necrotic urethra, was debrided. Although a permanent suprapubic catheter was established, postoperative wound healing was poor owing to continuous urine leakage from the urethral stump. Therefore, we performed retroperitoneoscopic bladder neck closure, and the urinary incontinence was completely resolved. Conclusion Retroperitoneoscopic bladder neck closure is a feasible and less invasive procedure for treating continuous urinary incontinence from the urethral stump in patients with Fournier's gangrene after surgical debridement and having a permanent suprapubic catheter.

Abstract The ability to derive retinal ganglion cells (RGCs) from human pluripotent stem cells (hPSCs) has led to numerous advances in the field of retinal research, with great potential for the use of hPSC-derived RGCs for studies of human retinal development, in vitro disease modeling, drug discovery, as well as their potential use for cell replacement therapeutics. Of all these possibilities, the use of hPSC-derived RGCs as a human-relevant platform for in vitro disease modeling has received the greatest attention, due to the translational relevance as well as the immediacy with which results may be obtained compared to more complex applications like cell replacement. While several studies to date have focused upon the use of hPSC-derived RGCs with genetic variants associated with glaucoma or other optic neuropathies, many of these have largely described cellular phenotypes with only limited advancement into exploring dysfunctional cellular pathways as a consequence of the disease-associated gene variants. Thus, to further advance this field of research, in the current study we leveraged an isogenic hPSC model with a glaucoma-associated mutation in the Optineurin (OPTN) protein, which plays a prominent role in autophagy. We identified an impairment of autophagic-lysosomal degradation and decreased mTORC1 signaling via activation of the stress sensor AMPK, along with subsequent neurodegeneration in OPTN(E50K) RGCs differentiated from hPSCs, and have further validated some of these findings in a mouse model of ocular hypertension. Pharmacological inhibition of mTORC1 in hPSC-derived RGCs recapitulated disease-related neurodegenerative phenotypes in otherwise healthy RGCs, while the mTOR-independent induction of autophagy reduced protein accumulation and restored neurite outgrowth in diseased OPTN(E50K) RGCs. Taken together, these results highlighted that autophagy disruption resulted in increased autophagic demand which was associated with downregulated signaling through mTORC1, contributing to the degeneration of RGCs.

Background/Aims During endoscopy, white spots (WS) are sometimes observed around benign or malignant colorectal tumors; however, few reports have investigated WS, and their significance remains unknown. Therefore, we investigated the significance of WS from clinical and pathological viewpoints and evaluated its usefulness in endoscopic diagnosis. Methods Clinical data of patients with lesions diagnosed as epithelial tumors from January 1, 2019, to December 31, 2020, were analyzed (n=3,869). We also performed a clinicopathological analysis of adenomas or carcinomas treated with endoscopic resection (n=759). Subsequently, detailed pathological observations of the WS were performed. Results The positivity rates for WS were 9.3% (3,869 lesions including advanced cancer and non-adenoma/carcinoma) and 25% (759 lesions limited to adenoma and early carcinoma). Analysis of 759 lesions showed that the WS-positive lesion group had a higher proportion of cancer cases and larger tumor diameters than the WS-negative group. Multiple logistic analysis revealed the following three statistically significant risk factors for carcinogenesis: positive WS, flat lesions, and tumor diameter ≥5 mm. Pathological analysis revealed that WS were macrophages that phagocytosed fat and mucus and were white primarily because of fat. Conclusions WS are cancer-related findings and can become a new criterion for endoscopic resection in the future.

Tropospheric ozone (O3) formation depends on the relative abundance of precursor species, nitrogen oxides (NOx), and volatile organic compounds (VOCs). Advancements in satellite retrievals of formaldehyde (HCHO) and nitrogen dioxide (NO2) vertical column densities (VCDs), and the corresponding HCHO/NO2 ratios (FNRs), provide the opportunity to diagnose the spatiotemporal evolution of O3 production sensitivity regimes. This study investigates trends of Ozone Monitoring Instrument (OMI)-derived summertime VCD HCHO, NO2, and FNRs in the Northern Hemisphere from 2005 to 2021. FNR trends were analyzed for polluted regions, specifically for 46 highly populated cities, over the entire 17-year period and in 2020 when global anthropogenic emissions were reduced due to COVID-19 lockdown restrictions. It was determined that OMI-derived FNRs have increased on average by ∼ 65 % across cities in the Northern Hemisphere. Increasing OMI-derived FNRs indicates a general transition from radical-limited to NOx-limited regimes. The increasing trend is driven by reduced NO2 concentrations because of emission-control strategies of NOx. OMI FNR trends were compared to ground-based in situ measurements in US cities, and it was determined that they can capture the trends in increasing FNRs (R=0.91) and decreasing NO2 (R=0.98) occurring at the surface. OMI FNRs in urban areas were higher (∼ 20 %) in 2020 for most cities studied here compared to 2019 and 2021. In addition to studying the longest period of OMI FNRs across the Northern Hemisphere to date, the capabilities and challenges of using satellite VCD FNRs to study surface-level O3 production sensitivity regimes are discussed.

Introduction Pelvic arteriovenous malformations are rare in male patients. We present a case of pelvic arteriovenous malformation involving the seminal vesicle. Case presentation A 58‐year‐old man was diagnosed with pelvic arteriovenous malformation that involved the left seminal vesicle by angiography. The patient underwent three embolization procedures and made favorable progress after the embolizations. Conclusion Herein, we report a rare case of pelvic arteriovenous malformation involving the seminal vesicle treated by embolizations with good outcome.

Study Design Retrospective study. Purpose To investigate the risk factors for allogeneic red blood cell (RBC) transfusion in adult spinal deformity (ASD) surgery. Overview of Literature Studies have not thoroughly explored the roles of intraoperative hypothermia, autologous blood donation, and hemostatic agent administration, which would provide a better understanding of the risk for perioperative RBC transfusion in ASD surgery. Methods The medical records of 151 patients with ASD who underwent correction surgery between 2012 and 2021 were retrospectively reviewed. Estimated blood loss and perioperative allogeneic transfusion were examined. Patients were categorized into two groups based on whether they received perioperative allogeneic blood transfusion. Logistic regression analysis was employed to investigate the effect of age, sex, blood type, body mass index, American Society of Anesthesiologists’ physical status, preoperative hemoglobin level, autologous blood donation, global spine alignment parameters, preoperative use of anticoagulants or antiplatelet medicine and nonsteroidal anti-inflammatory drugs, number of instrumented fusion levels, total operative duration, three-column osteotomy, lateral interbody fusion, pelvic fixation, intraoperative hypothermia, use of gelatin-thrombin based hemostatic agents, and intraoperative tranexamic acid (TXA) with simultaneous exposure by two attending surgeons. Results The estimated blood loss was 994.2±754.5 mL, and 71 patients (47.0%) received allogeneic blood transfusion. In the logistic regression analysis, the absence of intraoperative TXA use and simultaneous exposure (odds ratio [OR], 26.3; 95% confidence interval [CI], 7.6–90.9; p

Background/Aims Vedolizumab (VDZ) is a gut-selective agent with a favorable safety profile. We aimed to assess the feasibility of elective switch from other advanced therapies to VDZ and subsequent live-attenuated vaccination while continuing VDZ in patients with inflammatory bowel diseases (IBD). Methods We measured antibody titers specific for measles, rubella, mumps, and varicella viruses in IBD patients under immunosuppressive therapy. Those with negative titers and without vaccination history were judged unimmunized. Patients were administered vaccines while continuing VDZ or switched to VDZ if receiving other advanced therapies and then administered vaccines. Co-primary outcomes were the rate of maintaining disease severity after vaccination and the rate without vaccine-induced infection. Results Among 107 unimmunized patients, 37 agreed to receive live-attenuated vaccines while continuing VDZ (17 patients) or after switching to VDZ (20 patients). In the 20 patients who electively switched to VDZ, disease severity was maintained except for 1 patient who developed intestinal infection. After 54 weeks, 18 patients (90%) continued to receive VDZ, excluding 2 patients who reverted to their originally administered biologics. In all 37 patients administered live-attenuated vaccines under VDZ treatment, disease severity was maintained after vaccination. Antibody titers became positive or equivocal in 34 patients (91.9%). There were no cases of vaccine-induced infection during a median observation period of 121 weeks. Conclusions While live-attenuated vaccines are contraindicated under immunosuppressive therapy, they may be safely administered while receiving VDZ immunotherapy. Switching from other advanced therapies to VDZ and subsequently receiving live-attenuated vaccines may be a safe alternative in unimmunized patients.

Introduction: Platelet-rich plasma obtained by centrifuging peripheral blood can promote osteogenesis owing to its abundant growth factors but has drawbacks, including rapid growth factor loss and inconsistent effects depending on donor factors. To overcome these issues, we were the first in the world to use freeze-dried human induced pluripotent stem cell-derived megakaryocytes and platelets (S-FD-iMPs) and found that they have osteogenesis-promoting effects. Since turbulence was found to activate platelet biogenesis and iPS cell-derived platelets can now be produced on a clinical scale by a device called VerMES, this study examined the osteogenesis-promoting effect and safety of clinical-scale FD-iMP (V-FD-iMPs) for future human clinical application. Method: We administered either S-FD-iMPs, V-FD-iMPs, or saline along with artificial bone to the lumbar spine of 8-week-old male Sprague–Dawley rats (n = 4 each) and evaluated bone formation by computed tomography (CT) and pathology. Next, we administered V-FD-iMPs or saline along with artificial bone to the lumber spines of 5-week-old male New Zealand White rabbits (n = 4 each) and evaluated the bone formation by CT and pathology. Rats (n = 10) and rabbits (n = 6) that received artificial bone and V-FD-iMPs in the lumbar spine were also observed for 6 months for adverse events, including infection, tumor formation, and death. Results: Both V-FD-iMPs and S-FD-iMPs significantly enhanced osteogenesis in the lumber spines of rats in comparison with the controls 8 weeks postoperatively, with no significant differences between them. Furthermore, V-FD-iMPs vigorously promoted osteogenesis in the lumber spines of rabbits 8 weeks postoperatively. In rats and rabbits, V-FD-iMPs showed no adverse effects, including infection, tumor formation, and death, over 6 months. Conclusion: These results suggest that V-FD-iMPs promote safe osteogenesis.

The fragmentation reactions of neutron-rich unstable nuclei 81Ga and 82Ge at 250 MeV/nucleon have been studied in order to search the optimal mean for the production of very neutron-rich nuclei in the vicinity of 78Ni. The newly measured cross sections were compared with various calculations, showing a good agreement with EPAX3.01. The present work provides experimental insights into the two-step scheme—fragmentation following fission—as a method to produce very neutron-rich nuclei through a combination of ISOL and fragmentation of post-accelerated beams of unstable nuclei. Our results enable an evaluation of the potential of the two-step scheme in the production of very neutron-rich nuclei for the 78Ni region. The two-step scheme using fragmentation of a post-accelerated 81Ga beam could be an option to produce neutron-rich nuclei around 78Ni when the 81Ga beam intensity reaches 1.0×108 pps, compared to the one-step scheme with fission of 238U.

Enzyme replacement therapy (ERT) with recombinant human α-galactosidase A (α-Gal A) drugs (agalsidases) has been successfully used for treatment of Fabry disease, and three kinds of agalsidases are now available in Japan. To compare the biochemical characteristics of these drugs, especially focusing on their incorporation into cultured fibroblasts and organs/tissues of Fabry mice, we performed in vitro, cell, and animal experiments.The results revealed that there were no differences in the kinetic parameters and enzyme activity between these agalsidases. But their affinity for domain 9 of cation-independent mannose 6-phosphate receptor (CI-M6PR), which exists in various cells, was higher in the order: agalsidase beta biosimilar 1 (agalsidase beta BS) > agalsidase beta > agalsidase alfa, which almost coincided with the experimental results regarding the efficiency of their incorporation into cultured fibroblasts derived from a Fabry mouse. The results of animal experiments using Fabry mice revealed that the incorporation of the agalsidases into the kidneys and heart, where CI-M6PRs are widely distributed, was efficient in the order: agalsidase beta/agalsidase beta BS > agalsidase alfa, which reflected the degree of reduction of glycosphingolipids accumulated in the organs/tissues. On the other hand, no differences in the efficiency of their uptake or reduction of the accumulated substances were observed in the liver, probably due to asialoglycoprotein receptors expressed on the surface of hepatocytes.This information will be useful for making a suitable ERT plan for individual Fabry patients with various backgrounds and for developing new ERT drugs in the future.

Abstract Topological insulators (TI) hold significant potential for various electronic and optoelectronic devices that rely on the Dirac surface state (DSS), including spintronic and thermoelectric devices, as well as terahertz detectors. The behavior of electrons within the DSS plays a pivotal role in the performance of such devices. It is expected that DSS appear on a surface of three dimensional(3D) TI by mechanical exfoliation. However, it is not always the case that the surface terminating atomic configuration and corresponding band structures are homogeneous. In order to investigate the impact of surface terminating atomic configurations on electron dynamics, we meticulously examined the electron dynamics at the exfoliated surface of a crystalline 3D TI (Bi $$_2$$ 2 Se $$_3$$ 3 ) with time, space, and energy resolutions. Based on our comprehensive band structure calculations, we found that on one of the Se-terminated surfaces, DSS is located within the bulk band gap, with no other surface states manifesting within this region. On this particular surface, photoexcited electrons within the conduction band effectively relax towards DSS and tend to linger at the Dirac point for extended periods of time. It is worth emphasizing that these distinct characteristics of DSS are exclusively observed on this particular surface.

Abstract The intermediate-range order of covalently bonded glasses has been extensively studied in terms of their diffraction peaks observed at low scattering angles; these peaks are called the first sharp diffraction peaks (FSDPs). Although the atomic density fluctuations originating from the quasilattice planes are a critical scientific target, direct experimental observations of these fluctuations are still lacking. Here, we report the direct observation of the atomic density fluctuations in silica glass by energy-filtered angstrom-beam electron diffraction. The correspondence between the local electron diffraction patterns of FSDPs and the atomic configurations constructed based on the X-ray and neutron diffraction results revealed that the local atomic density fluctuations originated from the quasi-periodic alternating arrangements of the columnar chain-like atomic configurations and interstitial tubular voids, as in crystals. We also discovered longer-range fluctuations associated with the shoulder of the FSDP on the low-Q side. The hierarchical fluctuations inherent in materials could aid in the elucidation of their properties and performance.

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

Abstract Background Perinatal mental health, such as postpartum depression, is an important issue that can threaten the lives of women and children. It is essential to understand the risk factors in advance and intervene before they can lead to postnatal depression. The risk factors of postpartum depression are reported to vary considerably in Japan. This study aimed to evaluate the risk factors for women with high Edinburgh Postnatal Depression Scale (EPDS) scores and to find women who may need our intervention to prevent postpartum depression. Methods This was a retrospective observational study conducted at a single center. At the one-month check-up after birth, the EPDS test was performed in 1625 women who gave birth at our hospital from 2008 to 2016. We evaluated maternal, birth, neonatal and social factors and the breastfeeding status from medical records. Thereafter, we examined the factors that contributed to a high EPDS score. Results There were 284 women in the high-score group with an EPDS of ≥ 9, and 1341 women in the low-score group with an EPDS score ≤ of 8. Maternal mental disorders and neonatal transport were significantly associated with high EPDS scores. Conversely, exclusive breastfeeding was significantly associated with the low-score EPDS group. Conclusions The principal factor for high EPDS scores was a mental disease. Based on this result, we suggest that early intervention in women at high risk for postpartum depression could prevent serious consequences such as abuse and suicide.

Introduction Patients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome have high risks of uterine and cutaneous leiomyomas and renal cell carcinoma (RCC), which are caused by germline mutation of the fumarate hydratase (FH) gene. RCC lesions are mostly high‐grade tumors with a poor prognosis. Case presentation A 37‐year‐old man who had previously undergone treatment for a left RCC was referred to our hospital with a diagnosis of right RCC. Robot‐assisted partial nephrectomy was performed, and the pathological diagnosis revealed fumarate hydratase (FH)‐deficient RCC. The left RCC, which was originally diagnosed as mucinous tubular and spindle cell carcinoma, was reviewed and diagnosed as FH‐deficient RCC. The patient's father and uncle both died of RCC, and the father's tumor was also immunohistochemically proven to be FH‐deficient RCC. Conclusion HLRCC‐related RCC should be considered in a differential diagnosis of young patients with a family history of RCC.