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Purpose: This study aimed to quantitatively evaluate whether non-echoplanar diffusion-weighted MRI (non-EP DWI) lesion size and detectability can predict mastoid extension and complications such as labyrinthine fistula and dural exposure in middle ear cholesteatoma., Methods: This retrospective study included 120 lesions with surgically confirmed middle ear cholesteatoma. Non-EP DWI was performed within 6 months preoperatively and evaluated for lesion detectability and size measurements, including maximum axial diameter, maximum axial area, and volume. Surgical findings were used to assess mastoid extension, labyrinthine fistula, and dural exposure., Results: Of the 120 lesions, 30 were undetectable and 90 were detectable on non-EP DWI. Undetectable lesions had significantly less mastoid extension or labyrinthine fistula compared to detectable lesions (P < 0.001 - P = 0.006). The undetectable finding on non-EP DWI for identifying mastoid extension-negative lesions showed a sensitivity of 0.59, specificity of 0.95, and for labyrinthine fistula-negative lesions showed a sensitivity of 0.29, specificity of 1.00. Among the 90 detectable lesions, all size parameters (maximum axial diameter, maximum axial area, and volume) were significantly larger in cases with positive mastoid extension and positive labyrinthine fistula compared to negative cases (P < 0.001 - P = 0.005). For dural exposure, the maximum axial diameter and maximum axial area were significantly larger in positive cases (P = 0.002), but volume did not differ significantly. Optimal diagnostic cut-off values were determined for mastoid extension (8.9 mm diameter and 56 mm 2 area, both with sensitivity 0.89 and specificity 0.97), labyrinthine fistula (82 mm 2 area, sensitivity 0.47, specificity 1.00), and dural exposure (14.3 mm diameter, sensitivity 0.59, specificity 0.87; 112 mm 2 area, sensitivity 0.68, specificity 0.73)., Conclusion: Non-EP DWI lesion size and detectability can predict important operative findings in middle ear cholesteatoma. Undetectable lesions on non-EP DWI indicate a lack of mastoid extension or labyrinthine fistula, while larger detectable lesions correlate with increased risks of extension and complications.

Pyoderma gangrenosum(PG)is a rare skin disorder and its diagnosis is often delayed owing to its wound infection mimicking course. A 50-year-old woman presented to our hospital with multiple liver and bone metastases from breast cancer. A port was created on her right upper arm to administer chemotherapy. Although this treatment was successful, the port wound disrupted 10 months after treatment initiation. An infection was suspected, the port was removed, and chemotherapy was discontinued. However, another ulcer with necrotic tissue was observed in the right inguinal region. Skin biopsy revealed dense infiltration of neutrophils into the epidermis and dermis. The patient was administered prednisolone 30 mg/ day, and both wounds recovered. This case shows that, when skin necrotic ulcers are observed in patients with cancer, PG must be considered as a differential diagnosis.

Type 2 diabetes mellitus (DM) is a significant risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). With the increasing prevalence of type 2 DM and MASLD due to lifestyle changes, understanding their impact on liver health is crucial. However, the hepatocellular damage caused by glucose alone is unknown. This study investigates the effect of excess glucose on hepatocytes, focusing on oxidative stress, endoplasmic reticulum stress (ER stress), apoptosis, autophagy, and cell proliferation. We treated an immortalized-human hepatocyte cell line with excess glucose and analyzed. Excess glucose induced oxidative stress and ER stress in a time- and concentration-dependent manner, leading to apoptosis. Oxidative stress and ER stress were independently induced by excess glucose. Proteasome inhibitors and palmitic acid exacerbated glucose-induced stress, leading to the formation of Mallory-Denk body-like inclusion bodies. Despite these stresses, autophagic flux was not altered. Excess glucose also caused DNA damage but did not affect cell proliferation. This suggests that glucose itself can contribute to the progression of metabolic dysfunction-associated steatohepatitis (MASH) and carcinogenesis of HCC in patients with type 2 DM. Managing blood glucose levels is crucial to prevent hepatocyte damage and associated complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to evaluate the prognostic value of magnetic resonance imaging (MRI) findings in predicting local recurrence in patients with maxillary sinus cancer treated with super-selective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (RADPLAT)., Methods: This single-center retrospective study included consecutive patients with maxillary sinus squamous cell carcinoma, who underwent RADPLAT between October 2016 and September 2021. MRI was performed before (within 2 weeks) and 1 month after (post-treatment MRI) the start of treatment. Tumor reduction rates and pre-treatment cross-sectional areas were calculated from the maximum cross-sectional areas on pre- and post-treatment MRI T2-weighted axial images. Statistical analyses, including receiver operating characteristic analysis, were performed to assess the predictive value of the tumor reduction rates., Results: Twenty-four patients were included in this study. Recurrence occurred in seven patients with a median time of 213 days. The tumor reduction rates were significantly higher in the benign post-treatment changes group compared to the recurrence group (median, 0.814 vs. 0.174; p < 0.001). The cut-off value for the reduction rate between the groups was 0.3578. No significant difference was observed in the maximum pre-treatment cross-sectional area between the groups (p = 0.664). The inter-observer agreement for the tumor areas was excellent., Conclusions: The tumor reduction rate calculated from MRI T2-weighted images may be a predictor of local recurrence in patients with maxillary sinus cancer treated with RADPLAT. Patients with lower reduction rates may benefit from early salvage surgeries., Competing Interests: Declaration of competing interest The authors have no funding, financial relationships, or conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well. More recently, nondestructive actions of neutrophil granule proteins have been reported, such as modulation of tissue remodeling and metabolism. Here, we report a completely different mechanism by which neutrophils act nondestructively, by inserting granules directly into hepatocytes. Specifically, elastase-containing granules were transferred to hepatocytes where elastase selectively degraded intracellular calcium channels to reduce cell proliferation without cytotoxicity. In response, hepatocytes increased expression of Serpin E2 and A3, which inhibited elastase activity. Elastase insertion was seen in patient specimens of alcohol-associated hepatitis, and the relationship between elastase-mediated ITPR2 degradation and reduced cell proliferation was confirmed in mouse models. Moreover, neutrophils from patients with alcohol-associated hepatitis were more prone to degranulation and more potent in reducing calcium channel expression than neutrophils from healthy individuals. This nondestructive and reversible action on hepatocytes defines a previously unrecognized role for neutrophils in the transient regulation of epithelial calcium signaling mechanisms.

Objective: To investigate the relationship between oral frailty (OF), nutrient intake and calf circumference (CC) in middle-aged and older adults., Design: Cross-sectional study., Setting: Residents of four model districts of Shika town, Ishikawa Prefecture, Japan, using data from November 2017 to February 2018., Participants: One hundred and ninety-four residents aged ≥50 years in four model districts of Shika town. The OF total score ≥3 was defined as OF. Participants were divided into OF and non-OF groups and divided into the low-CC/kg and the high-CC/kg groups., Outcome Measures: The primary outcome is to use a two-way analysis of covariance to analyse the interaction between the two CC/kg groups and the two OF groups on nutrition intake. The secondary outcome is to use multiple regression analysis to investigate the nutrients significantly related to CC/kg when stratified by OF, with age, sex, body mass index, drinking status, smoking status and regular exercise as input covariates., Results: A two-way analysis of covariance revealed a significant interaction between the two CC/kg groups and the two OF groups on animal protein intake (p=0.039). Multiple comparisons using the Bonferroni analysis revealed a significantly lower animal protein intake in the OF group than in the non-OF group with a low CC/kg (p=0.033) but not in the group with a high CC/kg. The multiple regression analysis stratified by OF revealed a positive correlation between animal protein intake and CC/kg (p=0.002)., Conclusions: The present results revealed a significantly lower animal protein intake in the OF group than in the non-OF group in the low-CC/kg group, but no such difference was observed in the high-CC/kg group. Further longitudinal studies are needed to elucidate this relationship., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In addition to its role in pyroptosis and inflammatory cytokine maturation, caspase-4 (CASP4) also contributes to the fusion of phagosomes with lysosomes and cell migration. However, its role in cell division remains elusive. In this study, we demonstrate that CASP4 is indispensable for proper cell division in epithelial cells. Knockout of CASP4 (CASP4 KO) in HepG2 cells led to delayed cell proliferation, increased cell size, and increased multinucleation. In mitosis, CASP4 KO cells showed multipolar spindles, asymmetric spindle positioning, and chromosome segregation errors, ultimately increasing DNA content and chromosome number. We also found that phalloidin, a marker of filamentous actin, increased in CASP4 KO cells owing to suppressed actin depolymerization. Moreover, the levels of actin polymerization-related proteins, including Rho-associated protein kinase1 (ROCK1), LIM kinase1 (LIMK1), and phosphorylated cofilin, significantly increased in CASP4 KO cells. These results suggest that CASP4 contributes to proper cell division through actin depolymerization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To comprehensively summarize the clinical data and CT/MRI characteristics of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA)., Methods: Twenty-seven lesions from 25 study articles identified through a systematic review and three lesions from our institution associated with TL-LGNPPA were evaluated., Results: The mean age of the patients at diagnosis was 35.7 years, and the male-to-female ratio was nearly half. The chief complaint was nasal obstruction, followed by epistaxis. All patients underwent excision. None of the patients had neck nodes or distant metastases. All patients survived with no locoregional/distant recurrence during 3-93 months of follow-up. All lesions were located at the posterior edge of the nasal septum, attached to the nasopharyngeal parietal wall, and showed no laterality. The mean lesion diameter was 1.7 cm. The margins of lesions were well-defined and lobulated, followed by well-defined smooth margins. None of lesions were associated with parapharyngeal space or skull base destruction. All lesions were iso- and low-density on non-contrast CT. Adjacent skull base sclerosis was detected in 63.6% of lesions. High signal intensity on T2-weighted imaging and mostly iso-signal intensity on T1-weighted imaging compared to muscle tissue. Most lesions were heterogeneous and exhibited moderate contrast enhancement. Relatively large lesions (≥1.4 cm) tended to be more lobulated than smooth margins compared to relatively small lesions (<1.4 cm) (p = 0.016)., Conclusion: We summarized the clinical and radiological features of TL-LGNPPA to facilitate accurate diagnosis and appropriate management., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Liver cancer involves tumor cells rapidly growing within a packed tissue environment. Patient tumor tissues reveal densely packed and deformed cells, especially at tumor boundaries, indicative of physical crowding and compression. It is not well understood how these physical signals modulate tumor evolution and therapeutic susceptibility. Here we investigate the impact of volumetric compression on liver cancer (HepG2) behavior. We find that conditioning cells under a highly compressed state leads to major transcriptional reprogramming, notably the loss of hepatic markers, the epithelial-to-mesenchymal transition (EMT)-like changes, and altered calcium signaling-related gene expression, over the course of several days. Biophysically, compressed cells exhibit increased Rac1-mediated cell spreading and cell-extracellular matrix interactions, cytoskeletal reorganization, increased YAP and β-catenin nuclear translocation, and dysfunction in cytoplasmic and mitochondrial calcium signaling. Furthermore, compressed cells are resistant to chemotherapeutics and desensitized to apoptosis signaling. Apoptosis sensitivity can be rescued by stimulated calcium signaling. Our study demonstrates that volumetric compression is a key microenvironmental factor that drives tumor evolution in multiple pathological directions and highlights potential countermeasures to re-sensitize therapy-resistant cells., Significance Statement: Compression can arise as cancer cells grow and navigate within the dense solid tumor microenvironment. It is unclear how compression mediates critical programs that drive tumor progression and therapeutic complications. Here, we take an integrative approach in investigating the impact of compression on liver cancer. We identify and characterize compressed subdomains within patient tumor tissues. Furthermore, using in vitro systems, we induce volumetric compression (primarily via osmotic pressure but also via mechanical force) on liver cancer cells and demonstrate significant molecular and biophysical changes in cell states, including in function, cytoskeletal signaling, proliferation, invasion, and chemoresistance. Importantly, our results show that compressed cells have impaired calcium signaling and acquire resistance to apoptosis, which can be countered via calcium mobilization.

Carcinoma ex pleomorphic adenoma is a carcinoma that arises from a primary or recurrent benign pleomorphic adenoma. The prevalence of epithelial-myoepithelial carcinoma is low, and this histological type accounting for only 1% of all salivary gland tumors. Here, we report a rare case of Epithelial-Myoepithelial Carcinoma ex pleomorphic adenoma of the parotid gland with a radiologic-pathologic correlation., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Aim: Ovarian tissue cryopreservation (OTC) is performed for fertility preservation in cancer patients undergoing chemotherapy. Although anti-Müllerian hormone is used as a marker for ovarian reserve, serum levels do not always correlate with the number of follicles. Additionally, the follicle development stage most affected by chemotherapy is unclear. We examined the association between serum anti-Müllerian hormone levels and the number of remaining primordial follicles after chemotherapy, as well as which follicle stage is most affected by chemotherapy before ovarian cryopreservation., Methods: Thirty-three patients who underwent OTC were divided into the chemotherapy (n = 22) and non-chemotherapy (n = 11) groups; their ovarian tissues underwent histological examination. Pathological ovarian damage induced by chemotherapy was assessed. Ovarian volumes were estimated from weights. We compared the number of follicles at each developmental stage as a percentage of primordial follicles between the groups. The relationship between serum anti-Müllerian hormone level and primordial follicle density was analyzed., Results: The chemotherapy group had a significantly lower serum anti-Müllerian hormone level, ovarian volume, and density of developing follicles than the non-chemotherapy group. Serum anti-Müllerian hormone levels correlated with primordial follicle density only in the non-chemotherapy group. The chemotherapy group had significantly lower numbers of primary and secondary follicles., Conclusions: Chemotherapy induces ovarian damage and follicle loss. However, serum anti-Müllerian hormone level does not always reflect the number of primordial follicles after chemotherapy, and chemotherapy more significantly affects primary and secondary follicles than primordial follicles. Many primordial follicles remain in the ovary after chemotherapy, supporting OTC for fertility preservation., (© 2023 Japan Society of Obstetrics and Gynecology.)

Air pollutants, such as nitrogen dioxide (NO 2 ), ozone (O 3 ), and particulate matter (PM), have been epidemiologically reported to contribute to the onset and exacerbation of asthma. We have previously shown that several proteins in atmospheric PM are allergenic in mouse asthma models and that these proteins are nitrated by atmospheric NO 2 and O 3 in chemical reactions. Based on these results, the amount of 3-nitrotyrosine (3-NT) in atmospheric PM could be an air pollution marker integrating NO 2 , O 3 , and PM. We established a method to measure 3-NT by high-performance liquid chromatography electrochemical detection (HPLC-ECD). Although this method is accurate, it requires a filter treatment process, which is time-consuming and costly for an environmental monitoring tool, in which many samples are measured simultaneously. Therefore, in this study, we investigated a simple immunoblotting method in which atmospheric PM proteins were directly transferred to a polyvinylidene fluoride (PVDF) membrane and measured using an anti-3-NT antibody (the filter blot method). The 3-NT value obtained from this method was significantly correlated (r = 0.809, p < 0.001) with that of the HPLC-ECD method, with a detection power of 0.1 μg/mL for tyrosine nitrated bovine serum albumin equivalents. Multiple regression analysis using the filter blot method showed that the amount of 3-NT in atmospheric PM was significantly associated with the published environmental measurements of O 3 and PM in the region. Therefore, the filter blot method may be useful for the environmental monitoring of 3-NT in atmospheric PM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The incidence of extrahepatic malignancies (EHMs) after hepatitis C virus (HCV) eradication by interferon (IFN)-based and IFN-free direct-acting antivirals (DAAs) treatment remains unclear., Aims: The aim was to evaluate the cumulative incidence of EHMs diagnosed for the first time after the antiviral treatments., Methods: We analyzed a total 527 patients with chronic HCV infection and without prior history of any malignancies who achieved sustained virological response by antiviral treatments, including IFN-based (n = 242) or IFN-free DAAs (n = 285). The baseline predictors for EHM occurrence were analyzed using Cox regression analysis., Results: Thirty-two patients were diagnosed with EHMs, 14 in IFN-based and 18 in IFN-free DAAs, respectively. The total duration of follow-up was 1,796 person-years in IFN-based and 823 person-years in IFN-free DAAs. The incidence of EHMs in IFN-based and IFN-free DAAs was 7.8 and 21.9 per 1,000 person-years, respectively. The cumulative incidence of EHMs was significantly higher in IFN-free DAAs than IFN-based (p = 0.002). IFN-free DAAs was a single independent predictor for incidence of EHMs (p = 0.012). As for gender, the incidence of EHMs was significantly higher in IFN-free DAAs only in the female cohort (p = 0.002). After propensity score matching, IFN-free DAAs was a single independent predictor for incidence of EHMs in the female patients (p = 0.045)., Conclusions: The incidence of EHMs after HCV eradication is higher in IFN-free DAAs than IFN-based regimens, especially in female patients. We should carefully follow-up not only HCC but also EHMs after IFN-free DAAs regimens., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The association between oral frailty (OFr) and body action has been investigated, but its association with systemic function remains unclear. Therefore, this cross-sectional study examined the association between OFr with decreased bone mineral density (BMD) and renal function in residents of Shika town, Ishikawa Prefecture, Japan aged ≥40 years. This study included 400 inhabitants. The OFr total score was assessed using three oral domains in the Kihon Checklist (a self-reported comprehensive health checklist), the number of teeth, and brushing frequency per day. Measurements were the estimated glomerular filtration rate (eGFR) and the osteo-sono assessment index (OSI). Using a two-way analysis of covariance ( p = 0.002), significantly lower OSI was indicated in the eGFR < 60 and OFr group than in the eGFR of < 60 and non-OFr group after adjusting for age, body mass index, and drinking and smoking status as confounding factors. Multiple logistic regression analysis confirmed this relationship ( p = 0.006). Therefore, lower BMD seems to be associated with lower renal function only when accompanied by OFr. Further longitudinal studies are needed to confirm these results.

The diterpene glucoside fusicoccin-A (FC-A) is a fungal phytotoxin that stabilizes the interaction of plant 14-3-3 protein and plasma membrane H + -ATPase by forming a stable ternary complex. Previous studies demonstrated that structurally modified FC-A derivatives exhibit significant antitumor activities but their synthesis involves an explosive reagent, limiting their utility and opportunities for further structure-activity-relationship studies. In this study, we synthesized a series of FC derivatives by introducing various substituents on the fusicoccan scaffold and on the glucoside moiety, and evaluated their stabilization effects on the binding of 14-3-3 to fluorescently labeled mode-1 and mode-3 phosphopeptides. The results showed that introducing an amino group at the 6'-position of the glucoside moiety improves stabilization. Furthermore, cell-based evaluation demonstrated that 6'-amino benzyl 21b exhibits higher antiproliferative activity than previously developed FC agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To determine the morphology of the fovea in the ophthalmoscopically and tomographically normal fellow eyes of patients with a unilateral idiopathic macular hole (MH) and determine the association between foveal morphological parameters and foveal outer nuclear layer (ONL) thickness., Design: Retrospective observational study., Participants: Two hundred three normal fellow eyes of patients with a unilateral MH and 216 normal eyes of 216 healthy subjects., Methods: All the eyes were examined using swept-source OCT. A built-in software was used to measure the average retinal and choroidal thickness in the center and in the inner 4 subfields defined in ETDRS. The total retinal thickness, thickness of 3 retinal layers at the fovea and parafovea (0.25 and 0.5 mm nasal and temporal from the fovea), and foveal floor width (FFW) were measured on a scan image of a horizontal line passing through the center of the fovea. We defined the thickness between the internal limiting membrane and outer plexiform layer as inner retinal thickness and the thickness between the external limiting membrane and retinal pigment epithelium as outer retinal thickness. Multiple regression analyses were performed with age, sex, axial length, and the presence of a posterior vitreous detachment as the dependent variables., Main Outcome Measures: OCT measurements and correlations between foveal parameters and foveal ONL thickness., Results: The fellow eyes had a thinner central retinal subfield, thinner fovea, thinner ONL at all points except at 0.5 mm nasal, significantly thicker outer retina at all points, and a wider FFW (P = 0.040 to P < 0.0001). The foveal ONL thickness was significantly and positively correlated with the central subfield retinal thickness and foveal thickness and negatively correlated with the FFW (all P < 0.0001)., Conclusions: The thinner and deeper fovea and the thinner ONL of the fellow eyes of patients with a unilateral MH make these eyes more susceptible to the formation of an MH., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Although alcohol intake is associated with chronic pain (CP) and analgesia, epidemiological studies have not yet examined the factors affecting the relationship between alcohol intake and CP in detail. Therefore, the present cross-sectional study investigated the relationship between alcohol intake and CP in community-dwelling middle-aged and elderly individuals with/without depressive symptoms. Participants comprised 2223 inhabitants of Shika town in Ishikawa prefecture, located on the Noto Peninsula facing the Sea of Japan, and included 1007 males and 1216 females. CP, depressive symptoms, and alcohol intake were assessed using a CP questionnaire, the Geriatric Depression Scale-15 and the brief-type self-administered diet history questionnaire, respectively. In males without depressive symptoms, mean alcohol intake was significantly higher at 5.70% energy (27.92 g/day) in the CP group than that of 3.75% energy (20.00 g/day) in the non-CP group. The prevalence of low back/knee pain was also significantly higher in males with than in those without depressive symptoms. The present results suggest that long-term alcohol intake is related to CP by reducing the pain threshold and enhancing nociceptive pain as a possible mechanism. However, even a low alcohol intake was associated with psychogenic pain in participants with depressive symptoms. Further studies to investigate the involvement of depressive symptoms and alcohol intake in CP and its prevention are needed.

Inhalation of particulate matter with a diameter less than 2.5 µm has been reported to exacerbates fatty liver disease. However, the components and mechanisms of particulate matter involved in hepatic lipid metabolism and autophagy have not been fully elucidated. We found that atmospheric particulate matter in Japan stimulated lipogenesis in hepatocytes even when its lipid component was removed. Furthermore, we demonstrated that particulate matter did not promote autophagosome formation but inhibited autophagic degradation in hepatocytes. In previous toxicity experiments, particulate matter collected from atmosphere often contained contaminants originating from filters. In this study, we exposed the powdery particulate matter with less contaminants collected using a cyclone and impactor system to HepG2 cells, human hepatocyte. This particulate matter induced lipogenesis and endoplasmic reticulum stress in HepG2 cells as well as previous reports of particulate matter in the USA and China. On the other hand, when autophagic flux were examined in detail, the particulate matter did not promote autophagosome formation, but inhibited autophagic degradation. Since these effects were similar to those of palmitate, a fatty acid, we prepared particulate matter in which lipid component was removed by acetone and compared the effects on HepG2 cells with those of untreated one. The particulate matter without lipid component induced lipid droplets as well as did the untreated one although it induced less endoplasmic reticulum stress. These results suggest that hepatic lipid synthesis is stimulated not only by the uptake of lipid but also by other components in the particulate matter., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To determine whether the correlations between the axial length and the aging-dependent and birth year-dependent age are significant., Design: Retrospective cross-sectional study., Methods: This study included Japanese patients ≥50 years who had undergone cataract surgery at numerous clinics from 2002 to 2020. Only 1 eye/patient was analyzed. The axial length was measured with the IOL Master. The age-dependent changes were determined by the significance of the correlation between the axial length and age by the birth year. The birth year-dependent changes were determined by the significance of the correlation between the axial length and birth year in the different age groups. The age refers to the age at the time of the cataract surgery. Spearman correlations were calculated. The turning points were identified by the LOESS, NLIN, and HPMIXED procedures., Results: A total of 62,362 eyes (35,508 women, 26,854 men) were studied. The mean age was 72.9 ± 8.4 (standard deviation) years (range, 50-101 years), and the mean axial length was 23.90 ± 1.66 mm (standard deviation) (range, 19.20-37.07 mm). The birth year ranged from 1908 to 1970. Analyses of the birth year-dependent changes showed significant positive correlations in 48 of 81 (59.3%) groups for women and men. The increase in the axial length was birth year-dependent, and the turning point was 1939.4 for women and 1936.7 for men., Conclusions: The negative and significant correlation between the axial length and age is due to birth year-dependent changes. A birth year-dependent increase in axial length might have continued for several decades from the birth year of the late 1930s., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Acatalasemia is caused by genetic defect in the catalase gene. Human achatalasemia patients are able to scavenge physiological hydrogen peroxide but are vulnerable to exogenous oxidative stress. In the present study, we used an acetaminophen-induced hepatotoxicity model in acatalasemic mice to explore this vulnerability. Interestingly, the acetaminophen-induced decrease in total glutathione levels was more prolonged in acatalasemic mice. While the subunits of glutamate-cysteine ligase, a glutathione synthase enzyme, were increased by acetaminophen in the liver of wild-type mice, their expression was lower and was further reduced by acetaminophen in acatalasemic mice. This feature was also observed in immortalized hepatocytes derived from the livers of these mice. However, when catalase was knocked down in HepG2 cells, a cultured human liver cell line, the expression of glutamate-cysteine ligase subunits was increased, suggesting that the low expression of glutamate-cysteine ligase subunits in acatalasemia may be due to other mechanism than catalase deficiency. Therefore, when other factors were investigated, it was found that transforming growth factor-β1 was up-regulated by acetaminophen in the liver of acatalasemic mice, which may inhibit the expression of glutamate-cysteine ligase subunits. The results of this study suggest a new toxic mechanism of acetaminophen-induced liver injury in patients with acatalasemia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The health-promoting effects of exercise are explained by the biological adaptation to oxidative stress via maintenance of mitochondrial function especially in muscles. Although the induction of antioxidant enzymes in muscle is a useful indicator of exercise, it is not widely used due to the invasiveness of muscle biopsies. To explore more suitable biomarkers for exercise, we examined mRNA levels of antioxidant enzymes in peripheral blood mono-nuclear cells of 14 volunteers in an exercise intervention study. These results were validated in a cross-sectional study of 392 healthy individuals, and we investigated the association between exercise habits, smoking, alcohol consumption, mitochondrial DNA, malondialdehyde, and various clinical features. The 2-week exercise increased superoxide dismutase 1 at the end of exercise and superoxide dismutase 2 from week 4 onwards. In the cross-sectional study, superoxide dismutase 2 correlated positively with exercise habits and number of mitochondrial DNA, and negatively with malondialdehyde levels. Multivariate binominal regression analysis showed that superoxide dismutase 2 was positively associated with exercise habits in nonsmoking individuals. These results suggest that mRNA levels of superoxide dismutase 2 in blood might be a potentially useful biomarker for exercise in healthy individuals. This study was registered with University Hospital Medical Information Network (No: 000038034)., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2021 JCBN.)

Aims: The elevation of arginase in vascular tissues decreases nitric oxide production, which is considered as an early step of atherosclerosis in obesity. Previously, we found that arginase-1, one of arginase isozymes, was elevated in the blood plasma of obese adults. The purpose of this study is to elucidate the mechanism by which obesity increases arginase-1 levels in the blood., Main Methods: C57/BL6J male mice fed a high-fat diet (HFD) for 12 weeks were analyzed for factors related to nitric oxide/arginine metabolism and plasma exosomes. To explore the arginase secretory organs, the protein expression levels were analyzed in several organs. To further investigate the relationship between exosomal arginase-1 in plasma, blood glucose levels and arginase-1 in the liver, HepG2 (the human hepatoma cell line) was analyzed after treatment with high glucose., Key Findings: The increase in arginase activity in the plasma of HFD-fed mice was positively corelated with blood glucose levels and was accompanied by an increase in exosomal arginase-1 levels. Among the organs that highly express arginase, the liver of HFD-fed mice showed a significant increase in arginase-1. The expression of arginase-1 in exosomes and total lysates of HepG2 cells were increased by high glucose exposure., Significance: Increased exosomal arginase-1 in plasma contributes to increased plasma arginase activity in obesity. The liver is a candidate organ for the secretion of exosomal arginase-1 into plasma, and the p38 pathway induced by high glucose levels may be involved., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Bladder hernia is relatively rare in cases of inguinal hernia. In some instances, bladder hernia may be treated as inguinal hernia if bladder prolapse is not recognized. Because of the rarity of inguinal bladder hernias, there are no related detailed reports from studies performed at a single institution. In our hospital, patients with suspected inguinal hernia undergo CT in the prone position, enabling the diagnosis of bladder hernia preoperatively. This study aimed to clarify the clinical characteristics of inguinal bladder hernias and consider noteworthy points in their laparoscopic treatment., Methods: This retrospective analysis included data from 32 consecutive patients with bladder hernia in 1126 patients with inguinal hernia. In each patient, the lengths of the hernial orifice and prolapsed bladder were measured on the CT images and intraoperatively. Totally extraperitoneal (TEP) repair was performed in all patients, who were then followed for 1 year postoperatively., Results: Inguinal bladder hernia was detected on CT in 32 of 1126 patients (2.8%). Among them, only five (15.6%) had urological symptoms such as pollakiuria or the sensation of residual urine. The 32 patients were classified into three groups according to hernia subtype: intraperitoneal (n = 12, 37.5%), para-peritoneal (n = 15, 46.9%), and extraperitoneal (n = 5, 15.6%). The prolapsed bladder of the extraperitoneal type was significantly shorter than that of the other subtypes. The prolapsed bladders were directly identified in the extraperitoneal space and repaired safely with TEP. One recurrence (3.1%) occurred 2 months postoperatively., Conclusion: Preoperative CT and TEP are useful for the definitive diagnosis and treatment of inguinal bladder hernia., (© 2020 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Hepatitis C virus (HCV) infection has been known to use autophagy for its replication. However, the mechanisms by which HCV modulates autophagy remain controversial. We used HCV-Japanese fulminant hepatitis-1-infected Huh7 cells. HCV infection induced the accumulation of autophagosomes. Morphological analyses of monomeric red fluorescent protein (mRFP)-green fluorescent protein (GFP) tandem fluorescent-tagged LC3 transfection showed HCV infection impaired autophagic flux. Autophagosome-lysosome fusion assessed by transfection of mRFP- or GFP-LC3 and immunostaining of lysosomal-associated membrane protein 1 was inhibited by HCV infection. Decrease of HCV-induced endoplasmic reticulum (ER) stress by 4-phenylbutyric acid, a chemical chaperone, improved the HCV-mediated autophagic flux impairment. HCV infection-induced oxidative stress and subsequently DNA damage, but not apoptosis. Furthermore, HCV induced cytoprotective effects against the cellular stress by facilitating the formation of cytoplasmic inclusion bodies as shown by p62 expression and by modulating keratin protein expression and activated nuclear factor erythroid 2-related factor 2. HCV eradication by direct-acting antivirals improved autophagic flux, but DNA damage persisted. In conclusion, HCV-induced ER stress correlates with autophagic flux impairment. Decrease of ER stress is considered to be a promising therapeutic strategy for HCV-related chronic liver diseases. However, we should be aware that the risk of hepatocarcinogenesis remains even after HCV eradication.

Increased circulating levels of free fatty acids, especially saturated ones, are involved in disease progression in the non-alcoholic fatty liver. Although the mechanism of saturated fatty acid-induced toxicity in the liver is not fully understood, oxidative stress may be deeply involved. We examined the effect of increased palmitic acid, the most common saturated fatty acid in the blood, on the liver of BALB/c mice via tail vein injection with palmitate. After 24 h, among several anti-oxidative stress response genes, only heme oxygenase-1 (HO-1) was significantly upregulated in palmitate-injected mice compared with that in vehicle-injected mice. Elevation of HO-1 mRNA was also observed in the fatty liver of high-fat-diet-fed mice. To further investigate the role of HO-1 on palmitic acid-induced oxidative stress, in vitro experiments were performed to expose palmitate to HepG2 cells. SiRNA-mediated knockdown of HO-1 significantly increased the oxidative stress induced by palmitate, whereas pre-treatment with SnCl 2 , a well-known HO-1 inducer, significantly decreased it. Moreover, SB203580, a selective p38 inhibitor, reduced HO-1 mRNA expression and increased palmitate-induced oxidative stress in HepG2 cells. These results suggest that the HO-1-mediated anti-oxidative stress compensatory reaction plays an essential role against saturated fatty acid-induced lipotoxicity in the liver.

While plasma arginase-1 has been suggested as a biomarker of mental status in healthy individuals, it has not been evaluated in patients with chronic liver disease. This cross-sectional study investigated the utility of plasma arginase-1 for screening mental status in patients with chronic liver disease. This study included outpatients with chronic liver disease who underwent regular check-ups at Okayama University Hospital between September 2018 and January 2019. In addition to the standard blood tests, the plasma arginase-1 level was analyzed. The patients' mental status was assessed using the Japanese version of the General Health Questionnaire-28 (GHQ-28). The associations between mental status and various parameters, including plasma arginase-1, were investigated using logistic regression analysis. Among 114 participating patients, 8 were excluded, comprising 6 with insufficient blood samples for plasma arginase-1 measurement and 2 with incomplete questionnaires. Multivariate binomial logistic regression analysis revealed that plasma arginase-1 was significantly and negatively associated with the GHQ-total score, especially somatic symptoms. Therefore, plasma arginase-1 may be a useful biomarker for assessing the mental status of outpatients with chronic liver disease.

CD71 is an immunohistochemical marker used in diagnosing acute myeloid leukemia (AML) M6-Er in humans; however, to our knowledge, it has not been reportedly used for immunohistochemistry in veterinary medicine. We evaluated the pathologic features of AML M6-Er in a retrovirus-negative cat and used CD71 to support the diagnosis. A 4-y-old spayed female Scottish Fold cat was presented with lethargy, anorexia, and fever. Whole-blood PCR assay results for pro feline leukemia virus/pro feline immunodeficiency virus and feline vector-borne diseases were negative. Early erythroid precursors were observed in the peripheral blood smear. Fine-needle aspiration of the enlarged spleen and splenic lymph node showed many early erythroid precursors. Bone marrow aspirate smears revealed erythroid hyperplasia with 68.4% erythroid lineage and 3.6% rubriblasts. Dysplastic cells infiltrated other organs. The patient was diagnosed with myelodysplastic syndrome, progressing to the early phase of AML M6-Er. The patient died on day 121 despite multidrug treatments. Postmortem examination revealed neoplastic erythroblasts infiltrating the bone marrow and other organs. Neoplastic cells were immunopositive for CD71 but immunonegative for CD3, CD20, granzyme B, von Willebrand factor, CD61, myeloperoxidase, and Iba-1. Although further studies are necessary for the application of CD71, our results supported the morphologic diagnosis of AML M6-Er.

Purpose: To examine the anatomic and visual outcomes after removal of foveal hard exudates through a macular hole created by subretinal balanced salt solution (BSS) injection., Methods: This was a retrospective, consecutive, case series. Six patients (7 eyes) underwent vitrectomy with removal of foveal hard exudates. All patients were women and the mean age was 65 years (range from 55 to 71). All patients had a history of panretinal photocoagulation. Previous treatments included intravitreal anti-vascular endothelial growth factor injection in one eye and vitrectomy in both eyes of one patient. The geometric mean preoperative decimal visual acuity was 0.11 (range from 0.08 to 0.3). The mean postoperative follow-up period was 12 months (range from 6 to 19). The status of lens was two phakic and five pseudophakic. Surgical procedures included simultaneous cataract surgery if phakic, creation of posterior vitreous detachment if not present, internal limiting membrane (ILM) peeling and a gas or air tamponade. Manual subretinal BSS injection using 38-gauge needle was performed at ILM-peeled area. Removal of foveal hard exudates was conducted by the water flow through the macular hole created during subretinal BSS injection., Results: Foveal hard exudates decreased in all cases early after surgery. The geometric mean final decimal visual acuity was 0.31 (range from 0.1 to 0.9). Visual acuity improved more than 0.2 LogMAR units in six eyes and unchanged in one eye. There was no severe complication and recurrence of macular edema., Conclusion: This procedure may be effective for foveal hard exudates in diabetic patients.

Unique properties and potential applications of 2D materials draw much attention for mass production of thin-layer 2D materials. Ball milling exfoliation of 2D materials has been rarely used, in spite of a promising dry phase production method, because of the superficial information in the mechanism and the effect of the operating parameters on the yield, size and thickness. Here, we investigate systematically the ball milling operating parameters in the exfoliation of bulk MoS 2 in the presence of sodium cholate (SC) as an exfoliant. The yield and dimensions of the exfoliated MoS 2 nanosheet were monitored by changing the parameters such as the weight ratio of bulk MoS 2 and SC (SC/MoS 2 ), the filling ratio in the volume of milling ball and container (φ), milling ball size (d B ), milling revolution speed (n R ), and initial mass of bulk MoS 2 ([Formula: see text]). The yield of exfoliation is found to be 95% at the optimum ball milling conditions (SC/MoS 2  = 0.75, φ = 50%, [Formula: see text] = 0.20 g). In addition, yield and size of the exfoliated MoS 2 were controlled by the conditions of the ball milling. As for the evaluation of the exfoliated MoS 2 , we developed a novel method by use of the XRD profile to determine the size and thickness of the ball-milled MoS 2 powder with less than 30% difference from those determined by the well-known absorption method. Finally, the size and thickness of the MoS 2 nanosheets prepared by ball milling exfoliation were correlated with their electrocatalytic and photoelectrocatalytic activities.

Objectives: Desmoplastic ameloblastoma (DA) is one of the rare pathological variants of ameloblastoma. The purpose of this study is to investigate CT and MR imaging findings of DA., Methods: We retrospectively evaluated six DA cases that were gathered from four different hospitals and confirmed histopathologically with resected specimens. Two radiologists who specialized in head and neck imaging retrospectively interpreted and reviewed pretreatment CT and MR imaging findings., Results: On CT, all DAs presented with well-defined border and low internal attenuation. Regarding locularity, five cases showed honeycomb-like lesions and one showed a unilocular lesion. Bone expansions were seen in all patients and located on the labial side in four cases. On MR imaging, all DAs showed well-defined borders and solid moderately low signal intensities with small cystic high signal intensities on T2-weighted images and intermediate signal intensity on T1-weighted images. Five DAs showed linear low signal intensity on T1- and T2-weighted images. Gd-DTPA-enhanced MR imaging was performed in three cases, and all cases showed moderate enhancement. Dynamic-enhanced MR imaging was performed in two of them, and persistent enhancement was detected., Conclusion: Our findings strongly suggest that MR imaging should also be consulted, particularly for honeycomb-like lesions with well-defined margins, bone expansion and anterior location on radiographs or CT. Additionally, findings by MR imaging such as solid low-signal-intensity, hyperintense cystic foci and persistent enhancement pattern will suggest the diagnosis of DA.