Clinical Outcomes of Endoscope-Assisted Vitreous Surgery for Giant Retinal Tear Detachment.

INTRODUCTION: With the advent of perfluorocarbon liquid (PFCL), the success rate of refractory giant retinal tear (GRT) detachment has dramatically improved. PFCL is a very effective tool when used properly, but in GRT detachment, it may move under the retina through the tear, so it is necessary to devise ways to prevent PFCL from migrating under the retina. Ophthalmic endoscope-assisted vitrectomy may reduce the risk of subretinal migration of PFCL, facilitate safer use of PFCL, and increase the success rate of GRT detachment. The present study aimed to describe the clinical outcomes of endoscope-assisted vitreous surgery for giant retinal detachment. METHODS: Twenty consecutive eyes from 19 patients who had undergone endoscope-assisted vitreous surgery for treatment of a GRT detachment were enrolled. Subretinal fluid drainage, extension of the rolled GRT, and endophotocoagulation under air were performed with the aid of an endoscope, without the use of PFCL. Where necessary, extension of a fixed retinal fold and internal limiting membrane peeling was performed with PFCL. RESULTS: The initial and final retinal reattachment rates were 90 and 95%, respectively. In 3 eyes, a small amount of PFCL was used, and there were no PFCL remnants. The mean follow-up duration was 18 months (range, 3-69 months). After surgery, the mean best-correlated visual acuity significantly improved from 20/514 to 20/41 (p = 0.0008). DISCUSSION/CONCLUSION: Endoscope-assisted vitreous surgery for giant retinal detachment has favourable clinical outcomes for visual acuity and retinal detachment.

[Clinical Outcomes of Endoscope-Assisted 30-Gauge Single-Needle Technique for Intrascleral Intraocular Lens Fixation].

INTRODUCTION: We have developed an endoscope-assisted single-needle technique, which is an improvement of Yamane's double-needle technique of the intrascleral intraocular lens (IOL) fixation techniques. In this surgical procedure, the IOL is manipulated in the vitreous cavity, and the IOL haptic is externalized from the eye one by one with the aid of an ophthalmic endoscope. The purpose of this study was to report the postoperative visual function and safety of this new technique. METHODS: Overall, 19 consecutive eyes (16 patients; mean age, 75.1 ± 9.6 years; mean follow-up period, 5.7 months) that underwent intrascleral IOL fixation surgery with our new technique were included in the study. Manifest refraction, uncorrected/corrected visual acuity, and corneal endothelial cell density were measured before and after surgery. Tilt and decentration of IOL were analyzed using anterior segment optical coherence tomography. RESULTS: The mean absolute prediction error (spherical equivalent) was 0.82 ± 0.52. The mean postoperative best-corrected visual acuity had significantly improved at the final visits (p = 0.02). No significant differences in the mean corneal endothelial cell density were observed between the first (2,232 ± 751 cells/mm2) and final (2,099 ± 649 cells/mm2) visits (p = 0.35). The mean IOL tilt was 8.1 ± 3.2°. There were no vision-threatening complications, such as retinal detachment, endophthalmitis, or IOL dislocation, during or after surgery. CONCLUSIONS: The endoscope-assisted single-needle technique is a safe and effective method of intrascleral IOL fixation surgery.

Clinical characteristics of participants enrolled in an early identification and healthcare management program for dementia based on cluster analysis and the effectiveness of associated support efforts.

OBJECTIVE: Although early identification and management services for dementia have become more widespread, their efficacy and the clinical characteristics of service have yet to be fully evaluated. Therefore, the objective of this study is to clarify these issues. MEASUREMENTS: The subjects were 164 Japanese users of an early identification and management program for dementia, known as the Initial-phase Intensive Support Team (IPIST), between 2013 and 2015. Nonhierarchical cluster analysis was used to derive subgroups based on cognitive status and ability in activities of daily living (ADL) and behavioral and psychological symptoms of dementia (BPSD). One-way analysis of variance was performed to evaluate differences among the groups derived by the cluster analysis. A paired t test was used to assess how the clinical status of the groups changed between baseline and follow-up. RESULTS: Four groups were identified by cluster analysis, i.e. a mild group, a moderate group, a BPSD group with moderate cognitive impairment and severe BPSD, and a severe group with severe cognitive impairment and severe BPSD. Although there were no significant improvements in cognitive impairment or ADL in any group, significant improvements were found in BPSD in the BPSD and severe BPSD groups. Caregiver burden was significantly lessened in all groups. Clinical diagnosis and long-term care insurance service utilization rates were significantly improved overall. CONCLUSION: The users of IPIST were classified into four subgroups based on their clinical characteristics. The IPIST program could improve the quality of life of people with dementia and their caregivers.

NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol η-dependent translesion DNA synthesis.

Translesion DNA synthesis, a process orchestrated by monoubiquitinated PCNA, is critical for DNA damage tolerance. While the ubiquitin-conjugating enzyme RAD6 and ubiquitin ligase RAD18 are known to monoubiquitinate PCNA, how they are regulated by DNA damage is not fully understood. We show that NBS1 (mutated in Nijmegen breakage syndrome) binds to RAD18 after UV irradiation and mediates the recruitment of RAD18 to sites of DNA damage. Disruption of NBS1 abolished RAD18-dependent PCNA ubiquitination and Polη focus formation, leading to elevated UV sensitivity and mutation. Unexpectedly, the RAD18-interacting domain of NBS1, which was mapped to its C terminus, shares structural and functional similarity with the RAD18-interacting domain of RAD6. These domains of NBS1 and RAD6 allow the two proteins to interact with RAD18 homodimers simultaneously and are crucial for Polη-dependent UV tolerance. Thus, in addition to chromosomal break repair, NBS1 plays a key role in translesion DNA synthesis.

NOVEL ENDOSCOPE-ASSISTED VITREOUS SURGERY COMBINED WITH ATMOSPHERIC ENDOSCOPIC TECHNIQUE AND/OR SUBRETINAL ENDOSCOPIC TECHNIQUE FOR RHEGMATOGENOUS RETINAL DETACHMENT WITH GRADE C PROLIFERATIVE VITREORETINOPATHY.

PURPOSE: The purpose of this study was to investigate the clinical outcomes of novel endoscope-assisted vitreous surgery techniques in patients with rhegmatogenous retinal detachment complicated by Grade C proliferative vitreoretinopathy. METHODS: Eight consecutive patients who had undergone endoscope-assisted vitreous surgery for rhegmatogenous retinal detachment complicated by Grade C proliferative vitreoretinopathy were investigated. The peripheral vitreous was cut under air with the aid of endoscopic view (atmospheric endoscopic technique), and the subretinal proliferation was removed under subretinal endoscopic observation (subretinal endoscopic technique). RESULTS: Retinal reattachment was achieved after the primary surgery without a large retinotomy and scleral buckling in each case. The mean follow-up was 16.8 months (range, 8-28 months). Atmospheric endoscopic technique was performed in all cases, and subretinal endoscopic technique was performed in three cases. After surgery, the mean best-corrected visual acuity significantly improved from 20/778 to 20/111 (P = 0.014). Although microretinal breaks occurred during the removal of vitreous using atmospheric endoscopic technique in all cases, there were no severe postoperative complications, such as retinal detachment or proliferative vitreoretinopathy. CONCLUSION: Endoscope-assisted vitreous surgery with atmospheric endoscopic technique and/or subretinal endoscopic technique is safe and effective in the treatment of rhegmatogenous retinal detachment with Grade C proliferative vitreoretinopathy.

Effects of Glucose Concentration on Ethanol Fermentation of White-Rot Fungus Phanerochaete sordida YK-624 Under Aerobic Conditions.

White-rot fungi are microorganisms capable of ethanol fermentation; however, the specific conditions activating ethanol fermentation are unclear in contrast to fermentation by yeasts. In this study, we investigated the conditions favoring ethanol fermentation by the white-rot fungus Phanerochaete sordida YK-624, which is able to produce ethanol from woody material. In aerobic stationary cultivation with various concentrations of glucose (0.8-33 g/l), the fungus produced ethanol in media containing an initial glucose concentration of 2.8 g/l or higher. The amount of glucose consumption, mycelial weight, and ethanol production on the second day of culture increased in a concentration-dependent manner at low glucose concentrations; however, these were saturated at high concentrations. Biomass yields (growth/glucose consumption) were decreased until the initial glucose concentration increased to 6.0 g/l, after which the biomass yields showed constant values at higher concentrations (12-33 g/l). On the other hand, ethanol yields increased with decreasing biomass yields. In short shaking cultivation using mycelial suspension, trace amounts of instantaneous aerobic ethanol production were observed with 1.1 and 2.1 g/l glucose, but the relative gene expression levels of key enzymes at the pyruvate branch point showed no significant differences between ethanol production and non-production conditions. From these experimental results, it appears that the white-rot fungus P. sordida YK-624 produces ethanol due to overflow in sugar metabolism under aerobic conditions, although P. sordida YK-624 prioritizes glucose utilization for respiratory growth.

Quantitative analysis of UV photolesions suggests that cyclobutane pyrimidine dimers produced in mouse skin by UVB are more mutagenic than those produced by UVC.

The amount of photolesions produced in DNA after exposure to physiological doses of ultraviolet radiation (UVR) can be estimated with high sensitivity and at low cost through an immunological assay, ELISA, which, however, provides only a relative estimate that cannot be used for comparisons between different photolesions such as cyclobutane pyrimidine dimer (CPD) and pyrimidine(6-4)pyrimidone photoproduct (64PP) or for analysis of the genotoxicity of photolesions on a molecular basis. To solve this drawback of ELISA, we introduced a set of UVR-exposed, calibration DNA whose photolesion amounts were predetermined and estimated the absolute molecular amounts of CPDs and 64PPs produced in mouse skin exposed to UVC and UVB. We confirmed previously reported observations that UVC induced more photolesions in the skin than UVB at the same dose, and that both types of UVR produced more CPDs than 64PPs. The UVR protection abilities of the cornified and epidermal layers for the lower tissues were also evaluated quantitatively. We noticed that the values of absorbance obtained in ELISA were not always proportional to the molecular amounts of the lesion, especially for CPD, cautioning against the direct use of ELISA absorbance data for estimation of the photolesion amounts. We further estimated the mutagenicity of a CPD produced by UVC and UVB in the epidermis and dermis using the mutation data from our previous studies with mouse skin and found that CPDs produced in the epidermis by UVB were more than two-fold mutagenic than those by UVC, which suggests that the properties of CPDs produced by UVC and UVB might be different. The difference may originate from the wavelength-dependent methyl CpG preference of CPD formation. In addition, the mutagenicity of CPDs in the dermis was lower than that in the epidermis irrespective of the UVR source, suggesting a higher efficiency in the dermis to reduce the genotoxicity of CPDs produced within it. We also estimated the minimum amount of photolesions required to induce the mutation induction suppression (MIS) response in the epidermis to be around 15 64PPs or 100 CPDs per million bases in DNA as the mean estimate from UVC and UVB-induced MIS.

Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein.

In mammalian nucleotide excision repair, the DDB1-DDB2 complex recognizes UV-induced DNA photolesions and facilitates recruitment of the XPC complex. Upon binding to damaged DNA, the Cullin 4 ubiquitin ligase associated with DDB1-DDB2 is activated and ubiquitinates DDB2 and XPC. The structurally disordered N-terminal tail of DDB2 contains seven lysines identified as major sites for ubiquitination that target the protein for proteasomal degradation; however, the precise biological functions of these modifications remained unknown. By exogenous expression of mutant DDB2 proteins in normal human fibroblasts, here we show that the N-terminal tail of DDB2 is involved in regulation of cellular responses to UV. By striking contrast with behaviors of exogenous DDB2, the endogenous DDB2 protein was stabilized even after UV irradiation as a function of the XPC expression level. Furthermore, XPC competitively suppressed ubiquitination of DDB2 in vitro, and this effect was significantly promoted by centrin-2, which augments the DNA damage-recognition activity of XPC. Based on these findings, we propose that in cells exposed to UV, DDB2 is protected by XPC from ubiquitination and degradation in a stochastic manner; thus XPC allows DDB2 to initiate multiple rounds of repair events, thereby contributing to the persistence of cellular DNA repair capacity.

Radiation-Induced RhoGDIß Cleavage Leads to Perturbation of Cell Polarity: A Possible Link to Cancer Spreading.

The equilibrium between proliferation and apoptosis is tightly balanced to maintain tissue homeostasis in normal tissues and even in tumors. Achieving and maintaining such a balance is important for cancer regrowth and spreading after cytotoxic treatments. Caspase-3 activation and tumor cell death following anticancer therapy as well as accompanying cell death pathways are well characterized, but their association to homeostasis of cancerous tissue and tumor progression remains poorly understood. Here we proposed a novel mechanism of cancer spreading induced by caspase-3. RhoGDIß, known as a direct cleavage substrate of caspase-3, is overexpressed in many epithelial cancers. The N-terminal-truncated RhoGDIß (ΔN-RhoGDIß) is accumulated in caspase-3-activated cells. Stable expression of ΔN-RhoGDIß in HeLa cells did not induce apoptosis, but impaired directional cell migration in a wound-healing assay accompanied by a perturbed direction of cell division at the wound edge. Subcellular protein fractionation experiments revealed that ΔN-RhoGDIß but not wild-type RhoGDIß was present in the detergent-soluble cytoplasmic and nuclear fractions and preferentially associated with Cdc42. Furthermore, Cdc42 activity was constitutively inhibited by stable expression of ΔN-RhoGDIß, resulting in increased radiation-induced compensatory proliferation linking to RhoA activation. Thus, ΔN-RhoGDIß dominant-negatively regulates Cdc42 activity and contributes to loss of polarity-related functions. The caspase-3-cleaved RhoGDIß is a possible determinant to promote cancer spreading due to deregulation of directional organization of tumor cell population and inhibition of default equilibrium between proliferation and apoptosis after cytotoxic damage. J. Cell. Physiol. 231: 2493-2505, 2016. © 2016 Wiley Periodicals, Inc.

Analysis of ethanol fermentation mechanism of ethanol producing white-rot fungus Phlebia sp. MG-60 by RNA-seq.

BACKGROUND: The white-rot fungus Phlebia sp. MG-60 shows valuable properties such as high ethanol yield from several lignocellulosic materials, although white-rot fungi commonly degrade woody components to CO2 and H2O. In order to identify genes involved in ethanol production by Phlebia sp. MG-60, we compared genes differentially expressed by the ethanol producing fungus Phlebia sp. MG-60 and the model white-rot fungus Phanerochaete chrysosporium under ethanol fermenting and non-fermenting conditions using next-generation sequencing technologies. RESULTS: mRNAs from mycelia of Phlebia sp. MG-60 and P. chrysosporium under fermenting and non-fermenting conditions were sequenced using the MiSeq system. To detect differentially expressed genes, expression levels were measured in fragments per kilobase of exon per million mapped reads (FPKM). Differentially expressed genes were annotated using BLAST searches, Gene Ontology classifications, and KEGG pathway analysis. Functional analyses of differentially expressed genes revealed that genes involved in glucose uptake, glycolysis, and ethanol synthesis were widely upregulated in Phlebia sp. MG-60 under fermenting conditions. CONCLUSIONS: In this study, we provided novel transcriptomic information on Phlebia sp. MG-60, and these RNA-seq data were useful in targeting genes involved in ethanol production for future genetic engineering.

Effects of Homologous Expression of 1,4-Benzoquinone Reductase and Homogentisate 1,2-Dioxygenase Genes on Wood Decay in Hyper-Lignin-Degrading Fungus Phanerochaete sordida YK-624.

We investigated the function of 1,4-benzoquinone reductase (BQR)- and homogentisate 1,2-dioxygenase (HGD)-like genes in wood degradation by Phanerochaete sordida YK-624, which exhibits high ligninolytic activity and selectivity. We determined homologous expression in the genomic and cDNA sequences of BQR- and HGD-like genes in P. sordida YK-624 (PsBQR and PsHGD). Both genes shared high homology (≥90 % amino acid sequence similarity) with the corresponding genes in Phanerochaete chrysosporium. These genes were co-transformed with a reporter gene into an uracil auxotrophic mutant of P. sordida YK-624. The PsBQR and PsHGD co-transformants exhibited lower holocellulolytic activity and higher ligninolytic selectivity than the control transformants. In liquid culture with vanillin, both co-transformants significantly accelerated vanillin degradation. Thus, we suggest that the rapid metabolism of low-molecular weight lignin fragments, due to the homologous expression of BQR- and HGD-like genes, affects quinone redox cycling to produce hydroxyl radicals, thereby decreasing holocellulose degradation and increasing ligninolytic selectivity.

Tmem100, an ALK1 receptor signaling-dependent gene essential for arterial endothelium differentiation and vascular morphogenesis.

Members of the transforming growth factor-ß superfamily play essential roles in various aspects of embryonic development and physiological organ function. Among them, bone morphogenetic protein (BMP) 9 and BMP10 regulate embryonic vascular development by activating their endothelial receptor ALK1 (activin receptor-like kinase 1, also called Acvrl1). ALK1-mediated intracellular signaling is implicated in the etiologies of human diseases, but their downstream functional proteins are largely unknown. In this study, we identified Tmem100, a gene encoding a previously uncharacterized intracellular transmembrane protein, to be an embryonic endothelium-enriched gene activated by BMP9 and BMP10 through the ALK1 receptor. Tmem100 null mice showed embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied most of the vascular abnormalities observed with the Acvrl1/Alk1 deficiency. The activity of Notch- and Akt-mediated signaling, which is essential for vascular development, was down-regulated in Tmem100 null mice. Cre-mediated deletion of Tmem100 in endothelial cells was sufficient to recapitulate the null phenotypes. These data indicated that TMEM100 may play indispensable roles downstream of BMP9/BMP10-ALK1 signaling during endothelial differentiation and vascular morphogenesis.

HCMV-infected cells maintain efficient nucleotide excision repair of the viral genome while abrogating repair of the host genome.

Many viruses subvert the host cell's ability to mount and complete various DNA damage responses (DDRs) after infection. HCMV infection of permissive fibroblasts activates host DDRs at the time of viral deposition and during replication, but the DDRs remain uncompleted without arrest or apoptosis. We believe this was in part due to partitioning of the damage response and double strand break repair components. After extraction of soluble proteins, the localization of these components fell into three groups: specifically associated with the viral replication centers (RCs), diffused throughout the nucleoplasm and excluded from the RCs. Others have shown that cells are incapable of processing exogenously introduced damage after infection. We hypothesized that the inability of the cells to process damage might be due to the differential association of repair components within the RCs and, in turn, potentially preferential repair of the viral genome and compromised repair of the host genome. To test this hypothesis we used multiple strategies to examine repair of UV-induced DNA damage in mock and virus-infected fibroblasts. Comet assays indicated that repair was initiated, but was not completed in infected cells. Quantitative analysis of immunofluorescent localization of cyclobutane pyrimidine dimers (CPDs) revealed that after 24 h of repair, CPDs were significantly reduced in viral DNA, but not significantly changed in the infected host DNA. To further quantitate CPD repair, we developed a novel dual-color Southern protocol allowing visualization of host and viral DNA simultaneously. Combining this Southern methodology with a CPD-specific T4 endonuclease V alkaline agarose assay to quantitate repair of adducts, we found efficient repair of CPDs from the viral DNA but not host cellular DNA. Our data confirm that NER functions in HCMV-infected cells and almost exclusively repairs the viral genome to the detriment of the host's genome.

Present status and road map to achieve inclusive and holistic care for dementia in a Japanese community: analysis using the Delphi method.

BACKGROUND/AIMS: Dementia is a priority issue in the public health realm. However, few reports address problems of dementia in the real world or provide comprehensive road maps to solve these problems. METHODS: Nine groups of questions covering 4 topics were discussed using the Delphi method, relating to (1) current achievements and challenges regarding inclusive and holistic care in the community, (2) patients who are at a high risk of being excluded from care, (3) suggestions for a road map for the establishment of better and more inclusive medical and social care, and (4) unmet needs of patients with dementia. RESULTS: In total, 477 opinions were obtained. Family issues, psychological/behavioral symptoms, and complications secondary to physical disorders are main factors for being excluded from care. To create a road map for care we have to address the topics of reaffirming care principles, multidisciplinary coalitions, and education for stakeholders. CONCLUSION: Further effective collaboration to promote dementia care is required.

Factors associated with postoperative visual function after rhegmatogenous retinal detachment with foveal detachment.

PURPOSE: To investigate pre-, intra-, and postoperative factors influencing postoperative visual acuity, degree of metamorphopsia, and retinal sensitivity after vitrectomy in patients with rhegmatogenous retinal detachment and foveal detachment. METHODS: We reviewed retrospectively 33 consecutive eyes of 32 patients, who underwent vitrectomy for rhegmatogenous retinal detachment with foveal detachment between August 2018 and October 2020 and obtained retinal reattachment. Pre-, intra-, and postoperative characteristics were comprehensively analyzed using multivariate models to evaluate the presence of factors influencing best-corrected visual acuity, vertical/horizontal metamorphopsia scores using M-CHARTS (Inami & Co., Ltd., Tokyo, Japan), and retinal sensitivity using the MP-3 (NIDEK Co., Aichi, Japan) at 1-year postoperatively. RESULTS: Preoperative total retinal detachment was the only factor significantly associated with worse best-corrected visual acuity at 1-year postoperatively (ß = 0.589, P<0.001). Intraoperative internal limiting membrane peeling (ß = 0.443, P = 0.003) and longer duration after recognizing visual dysfunction (ß = 0.425, P = 0.005) were significantly associated with higher vertical metamorphopsia scores at 1 year. The horizontal metamorphopsia score was significantly related to the duration after recognizing visual dysfunction (ß = 0.457, P = 0.008). The disappearance of the EZ line on optical coherence tomography at 3 months postoperatively (ß = -0.638, P<0.001) was significantly associated with lower retinal sensitivity at 1 year. CONCLUSIONS: Our study findings suggest that best-corrected visual acuity, metamorphopsia, and retinal sensitivity at 1 year after vitrectomy for rhegmatogenous retinal detachment with foveal detachment are influenced by distinct factors.

Biotransformation and detoxification of tetrabromobisphenol A by white-rot fungus Phanerochaete sordida YK-624.

The bulky phenolic compound tetrabromobisphenol A (TBBPA) is a brominated flame retardant used in a wide range of products; however, it diffuses into the environment, and has been reported to have toxic effects. Although it is well-known that white-rot fungi degrade TBBPA through ligninolytic enzymes, no other metabolic enzymes have yet been identified, and the toxicity of the reaction products and their risks have not yet been examined. We found that the white-rot fungus Phanerochaete sordida YK-624 converted TBBPA to TBBPA-O-ß-D-glucopyranoside when grown under non-ligninolytic-enzyme-producing conditions. The metabolite showed less cytotoxicity and mitochondrial toxicity than TBBPA in neuroblastoma cells. From molecular biological and genetic engineering experiments, two P. sordida glycosyltransferases (PsGT1c and PsGT1e) that catalyze the glycosylation of TBBPA were newly identified; these enzymes showed dramatically different glycosylation activities for TBBPA and bisphenol A. The results of computational analyses indicated that the difference in substrate specificity is likely due to differences in the structure of the substrate-binding pocket. It appears that P. sordida YK-624 takes up TBBPA, and reduces its cytotoxicity via these glycosyltransferases.

Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin.

During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression.

Urinary FSP1 is a biomarker of crescentic GN.

Fibroblast-specific protein 1 (FSP1)-expressing cells accumulate in damaged kidneys, but whether urinary FSP1 could serve as a biomarker of active renal injury is unknown. We measured urinary FSP1 in 147 patients with various types of glomerular disease using ELISA. Patients with crescentic GN, with or without antinuclear cytoplasmic antibody-associated GN, exhibited elevated levels of urinary FSP1. This assay had a sensitivity of 91.7% and a specificity of 90.2% for crescentic GN in this sample of patients. Moreover, we found that urinary FSP1 became undetectable after successful treatment, suggesting the possible use of FSP1 levels to monitor disease activity over time. Urinary FSP1 levels correlated positively with the number of FSP1-positive glomerular cells, predominantly podocytes and cellular crescents, the likely source of urinary FSP1. Even in patients without crescent formation, patients with high levels of urinary FSP1 had large numbers of FSP1-positive podocytes. Taken together, these data suggest the potential use of urinary FSP1 to screen for active and ongoing glomerular damage, such as the formation of cellular crescents.

Structural health monitoring of sabo check dams with cosmic-ray muography.

Debris dams have a crucial role in consolidation of river basins and allow erosion control, flood protection in mountainous areas. Many of these infrastructures have operated over five decades, thus structural health monitoring (SHM) of these infrastructures became timely due to their aging. Utilizing new techniques is required for inspecting a large number of dams and deciding about their reinforcement or reconstruction. In this work, we propose cosmic-ray muography as a complementary tool for the SHM of debris dams. We conducted the first muographic surveying of a sabo check dam in the Karasu River, Gunma, Japan. The average mass density image was produced with a spatial resolution of 0.5 m through the dam. The comparison of density data reconstructed by muography and gamma-ray logging suggest the internal deterioration of dam in the region where cement released out from the embankment body.