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Abstract In creativity research, an important unresolved issue relates to identifying the kind of information an individual should be exposed to in order to be highly creative. We aimed to gain insights into this issue; we collected and statistically analyzed three datasets related to three large online communities (namely Cities: Skylines, SCP-wiki, and Archive of Our Own) engaged in mod development and novel writing to examine whether the quality and diversity of other people’s products referred to have a positive effect on product generation. Our analysis revealed the following three findings: (1) the quality diversity of reference products generated by others has the most positive impact on the quality of generated products when it is neither high nor low, (2) the content diversity of reference products generated by others has a negative impact on the quality of generated products, and (3) the quality of reference products generated by others has a negative impact on the quality of generated products when it is extremely high. We conclude by discussing the implications of the findings for creativity research.

Summary: Fertilized eggs initiate translation of stored mRNAs in spatially and temporally controlled manners. Here, we present a protocol for visualizing spatial and temporal translation in zebrafish embryos by fluorescence in situ hybridization and proximity ligation assay. We describe steps for labeling newly synthesized proteins and mRNA, visualizing mRNA translation and mRNA, sample mounting, and observation. Coupling detection of mRNA molecules with their translation sites is useful for understanding the molecular and cellular mechanisms that drive embryo development.For complete details on the use and execution of this protocol, please refer to Sato et al.1 and Takada et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background In Japan, the use of risperidone in combination with adrenaline is contraindicated, except in cases of anaphylaxis. Therefore, there is limited clinical evidence regarding the interaction of these two drugs. Here, we report the clinical course of a case of adrenaline-resistant anaphylactic shock induced by a contrast medium injection after a risperidone overdose. Case presentation A man in his 30s was transported to our hospital after attempting suicide by taking 10 mg of risperidone and jumping from a height of 10 m. To determine the location and severity of his injuries, he was injected with an iodinated contrast medium, after which he developed generalized erythema and hypotension and was diagnosed with anaphylactic shock. A 0.5 mg dose of adrenaline was administered with no improvement, followed by another 0.5 mg dose that did not change his blood pressure. After infusion of a sodium bicarbonate solution (8.4%), administration of fresh frozen plasma, and additional administration of adrenaline (0.6–1.2 µg/min), his blood pressure improved, and he recovered from the anaphylactic shock. Conclusions This was a rare case of a risperidone overdose followed by adrenaline-resistant anaphylactic shock. The resistance is likely associated with the high blood concentration of risperidone. Our findings indicate that the potential for decreased adrenergic responsiveness should be considered in patients undergoing risperidone treatment in the event of anaphylactic shock.

Spin-triplet exciton condensation has been predicted in perovskite cobaltites in high magnetic fields. Here, the authors report the magnetic phase diagram of LaCoO3 from magnetostriction measurements in ultrahigh magnetic fields and reveal new high-field phases with signatures of the exciton condensate.

A preschool male patient with an extensive cardiac surgical history developed refractory chylothorax after a total cavopulmonary connection. Neither lymphoscintigraphy nor single-photon emission computed tomography (SPECT)/computed tomography could identify the lymphatic system leakage sites. Non-contrast heavy T2-weighted magnetic resonance lymphangiography (MRL) was performed to visualize the lymphatic system. Nevertheless, distinguishing lymphatic ducts from other watery structures of the patient remained difficult. Therefore, non-contrast MRL and SPECT images were fused. This hybrid diagnostic tool elucidated the pathophysiology of the prolonged chylothorax; pulmonary lymphatic perfusion syndrome and illustrated the anatomical connection of the thoracic duct and an abnormally dilated lymphatic network in the neck and left hilar regions. Subsequent intranodal lymphangiography with ethiodized oil confirmed these findings. SPECT/MRL may become an alternative modality for revealing the mechanism of prolonged chylothorax by visualizing the lymphatic system when dynamic contrast-enhanced magnetic resonance lymphangiography is unavailable.

2′-5′-oligoadenylate synthetase (OAS) is one of the proteins that act as a defense mechanism against foreign RNA in cells. OAS has two functions: an antiviral effect against a wide range of virus species via the OAS/RNase L pathway with synthesized oligoadenylates and inhibition of viral replication specific to viruses of the genus Flavivirus, which is independent of enzymatic activity. Several birds have been reported to possess only one type of OAS family member, OASL, which has both enzymatic activity and inhibitory effects on flaviviral replication. However, the ostrich has two types of OASs, OAS1 and OASL, which show different functions—enzymatic and anti-flaviviral activities, respectively. In this study, emu OASs were cloned to investigate their sequence and function and elucidate the role of OASs in emus. The cloning results showed that emus had OAS1 and OASL, suggesting that emu OASs were more closely related to ostrich than to other birds. Functional investigations showed that emu OAS1 and OASL had enzymatic and anti-flaviviral activities, respectively, similar to those of the ostrich. Emus and ostriches are evolutionarily different from most birds and may be more closely related to mammalian OAS diversity.

This study aimed to validate the usefulness of parent artery complex coil protection for the treatment of wide-neck, side-branched, and ruptured aneurysms. A microcatheter was first introduced into the aneurysmal sac, and another microcatheter was introduced into the parent artery or near the orifice of the branch artery. A framing coil was deployed partially from the first microcatheter, and a protection coil was deployed from the second microcatheter to prevent protrusion of the first framing coil to the parent artery and side branches. After the first framing coil insertion, the protection coil was withdrawn to confirm the stability of the framing coil and blood flow. The procedures with this technique were successful for 3 patients. Parent artery complex coil protection can be an effective and safe coil embolization technique for the preservation of parent and side branch arteries and an alternative method for emergent ruptured cases.

Pathogenic Escherichia coli strains are important causes of several swine diseases that result in significant economic losses worldwide. In Japan, the use of antimicrobials in swine is much higher than that in other farm animals every year. Antimicrobial resistance in pathogenic E. coli strains also heavily impacts the swine industry due to the limited treatment options and an increase in the potential risk of the One Health crisis. In 2016, we investigated 684 Japanese isolates of swine pathogenic E. coli belonging to four major serogroups and reported the emergence and increase in the highly multidrug-resistant serogroups O116 and OSB9 and the appearance of colistin-resistant strains. In the present study, by expanding our previous analysis, we determined the serotypes and antimicrobial resistance of 1,708 E. coli strains isolated from diseased swine between 1991 and 2019 in Japan and found recent increases in the prevalences of multidrug-resistant strains and minor serogroup strains. Among the antimicrobials examined in this study that have been approved for animal use, a third-generation cephalosporin was found to be effective against the most isolates (resistance rate: 1.2%) but not against highly multidrug-resistant strains. We also analyzed the susceptibilities of the 1,708 isolates to apramycin and bicozamycin, both which are available for treating swine in Japan, and found that the rates of resistance to apramycin and bicozamycin were low (6.7% and 5.8%, respectively), and both antimicrobials are more effective (resistance rates: 2.7% and 5.4%, respectively) than third-generation cephalosporins (resistance rate: 16.2%) against highly multidrug-resistant strains.

Abstract Background Genus Desulfovibrio species is a sulphate-reducing anaerobic gram-negative rod that resides in the human oral cavity and intestinal tract. It was reported as the causative pathogen of bacteraemia and abdominal infections, but not renal cyst infection, and Desulfovibrio fairfieldensis has higher pathogenicity than other Desulfovibrio species. Case presentation A 63-year-old man was on haemodialysis for end-stage renal failure due to autosomal dominant polycystic kidney disease. On admission, he had a persistent high-grade fever, right lumbar back pain, and elevated C-reactive protein levels. His blood and urine cultures were negative. He received ciprofloxacin and meropenem; however, there was no clinical improvement. Contrast-enhanced computed tomography and plain magnetic resonance imaging revealed a haemorrhagic cyst at the upper pole of the right kidney. The lesion was drained. Although the drainage fluid culture was negative, D. fairfieldensis was detected in a renal cyst using a polymerase chain reaction. After the renal cyst drainage, he was treated with oral metronidazole and improved without any relapse. Conclusions To the best of our knowledge, this is the first reported case of a renal cyst infection with Desulfovibrio species. D. fairfieldensis is difficult to detect, and polymerase chain reaction tests can detect this bacterium and ensure better management for a successful recovery.

Abstract Background Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later‐line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens. Patients and methods A regional cohort study was undertaken to determine the real‐world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated. Results In total, 70 patients who received nivolumab as ≥third‐line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8–10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68–0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2‐positive status (27.3%) or microsatellite instability‐high (27.3%) status. Conclusions The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival.

Background The effect of oral microbiota on the intestinal microbiota has garnered growing attention as a mechanism linking periodontal diseases to systemic diseases. However, the salivary microbiota is diverse and comprises numerous bacteria with a largely similar composition in healthy individuals and periodontitis patients.Aim We explored how health-associated and periodontitis-associated salivary microbiota differently colonized the intestine and their subsequent systemic effects.Methods The salivary microbiota was collected from a healthy individual and a periodontitis patient and gavaged into C57BL/6NJcl[GF] mice. Gut microbial communities, hepatic gene expression profiles, and serum metabolites were analyzed.Results The gut microbial composition was significantly different between periodontitis-associated microbiota-administered (PAO) and health-associated oral microbiota-administered (HAO) mice. The hepatic gene expression profile demonstrated a distinct pattern between the two groups, with higher expression of lipid and glucose metabolism-related genes. Disease-associated metabolites such as 2-hydroxyisobutyric acid and hydroxybenzoic acid were elevated in PAO mice. These metabolites were significantly correlated with characteristic gut microbial taxa in PAO mice. Conversely, health-associated oral microbiota were associated with higher levels of beneficial serum metabolites in HAO mice.Conclusion The multi-omics approach used in this study revealed that periodontitis-associated oral microbiota is associated with the induction of disease phenotype when they colonized the gut of germ-free mice.

Summary: Fertilized eggs begin to translate mRNAs at appropriate times and placements to control development, but how the translation is regulated remains unclear. Here, we found that pou5f3 mRNA encoding a transcriptional factor essential for development formed granules in a dormant state in zebrafish oocytes. Although the number of pou5f3 granules remained constant, Pou5f3 protein accumulated after fertilization. Intriguingly, signals of newly synthesized peptides and a ribosomal protein became colocalized with pou5f3 granules after fertilization and, moreover, nascent Pou5f3 was shown to be synthesized in the granules. This functional change was accompanied by changes in the state and internal structure of granules. Dissolution of the granules reduced the rate of protein synthesis. Similarly, nanog and sox19b mRNAs in zebrafish and Pou5f1/Oct4 mRNA in mouse assembled into granules. Our results reveal that subcellular compartments, termed embryonic RNA granules, function as activation sites of translation after changing physical properties for directing vertebrate development.

Background & AimsPeriodontitis increases the risk of nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms are unclear. Here, we show that gut dysbiosis induced by oral administration of Porphyromonas gingivalis, a representative periodontopathic bacterium, is involved in the aggravation of NAFLD pathology.MethodsC57BL/6N mice were administered either vehicle, P. gingivalis, or Prevotella intermedia, another periodontopathic bacterium with weaker periodontal pathogenicity, followed by feeding on a choline-deficient, l-amino acid-defined, high-fat diet with 60 kcal% fat and 0.1% methionine (CDAHFD60). The gut microbial communities were analyzed by pyrosequencing the 16S ribosomal RNA genes. Metagenomic analysis was used to determine the relative abundance of the Kyoto Encyclopedia of Genes and Genomes pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance-based metabolomics coupled with multivariate statistical analyses. Hepatic gene expression profiles were analyzed via DNA microarray and quantitative polymerase chain reaction.ResultsCDAHFD60 feeding induced hepatic steatosis, and in combination with bacterial administration, it further aggravated NAFLD pathology, thereby increasing fibrosis. Gene expression analysis of liver samples revealed that genes involved in NAFLD pathology were perturbed, and the two bacteria induced distinct expression profiles. This might be due to quantitative and qualitative differences in the influx of bacterial products in the gut because the serum endotoxin levels, compositions of the gut microbiota, and serum metabolite profiles induced by the ingested P. intermedia and P. gingivalis were different.ConclusionsSwallowed periodontopathic bacteria aggravate NAFLD pathology, likely due to dysregulation of gene expression by inducing gut dysbiosis and subsequent influx of gut bacteria and/or bacterial products.

Diamond-like carbon (DLC) is an amorphous form of carbon that contains aspects of both the diamond and graphite structures. It is composed of carbon and hydrogen, and owing to its texture, high mechanical hardness, chemical inertness, and optical transparency, DLC is widely used as a protective coating in the form of a thin film, which is applied to the surfaces of many materials. Recently, it has attracted attention as a biomedical material because of its high biocompatibility and stability [1,2]. DLC is particularly suitable to be embedded in the body owing to its low friction properties and selective cell surface attachment properties [3]. The material is currently being developed for the treatment of bone fractures [4]. However, unlike fibroblasts, the attachment of osteoblasts has not been extensively examined and no morphological data is available on how osteoblastic cells form contacts with the surface of biocompatible DLC-coated materials. Herein, such data were collected by coating DLC on the surface of silicon plates. The attachment of mouse cells to the DLC-coated plates was examined by colorimetric cell proliferation assay, and morphological observations were made using a field emission scanning electron microscope. Also, the flat cross section of the cell and plate was obtained by the ion milling method.

Obesity is an epidemic health issue with a rapid increase worldwide. It increases the risk of various diseases, including periodontal disease, an oral chronic infectious disease.

We report a case of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells ocalized within the main pancreatic duct (MPD). A 61-year-old woman was referred to our hospital for evaluation of dilatation of the MPD that was detected on screening sonogram. Preoperative MR imaging revealed a small hypervascular tumor within the dilated MPD, showing high signal on R2* map and signal reduction on in-phase as compared to out-of-phase. R2* hyperintensity and in-phase signal reduction may be a characteristic feature of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, which indicates intratumoral hemorrhage even if they are small. Keywords: Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, Intratumoral hemorrhage, Intraductal growth, R2* map, Chemical-shift imaging

Concentrated polymer brush (CPB) is the polymer film with a structure that possesses greatly extended polymer chains densely grafted to substrate. CPB is known to swell in good solvents, which have high affinity for the polymer. Swollen CPB by a good solvent shows excellent micro-tribological properties such as super lubrication with the extremely low friction coefficient (μ~10-4). However, macro-tribological properties of CPB surface on steel have not been explored sufficiently. In this study, macroscopic tribological properties of a CPB on rough steel were evaluated using a block-on-ring type tribo-tester under lubrication with an ionic liquid. The CPB showed a significant friction reduction effect with the low friction coefficient of 0.005 on macroscale.

This paper describes mobile robot tactics for recovering a wheeled vehicle that has overturned. If such a vehicle were to tip over backward off its wheels and be unable to recover itself, especially in areas where it is difficult for humans to enter and work, overall work efficiency could decline significantly, not only because the vehicle is not able to perform its job, but because it becomes an obstacle to other work. Herein, the authors propose a robot-based recovery method that can be used to recover such overturned vehicles, and the authors evaluate its effectiveness. The recovery robot, which uses a mounted manipulator and hand to recover the overturned vehicle, is also equipped with a camera and a personal computer (PC). The ARToolKit software package installed on the PC detects AR markers attached to the overturned vehicle and uses the information they provide to orient itself in order to perform recovery operations. A statics analysis indicates the feasibility of the proposed method. To facilitate these operations, it is also necessary to know the distance between the robotic hand and the target position for grasping of vehicle. Therefore, a theoretical analysis is conducted, and a control system based on the results is implemented. The experimental results obtained in this study demonstrate the effectiveness of the proposed system.

Myeloid sarcoma (MS), which involves extramedullary lesions, is classified as a unique subtype of acute myeloid leukemia (AML). At present, no standard treatments for MS have been established. The patient was an 89-year-old man with myelodysplastic syndrome-excess blast-2 (MDS-EB-2) with a 2-year history of intermittent treatment with azacitidine (AZA) during a 4-year history of MDS. He developed painful cutaneous tumors 8 months after the second discontinuation of AZA. They were refractory for antibiotics and topical tacrolimus hydrate. A tumor biopsy was performed, and the histological findings of the tumor lesion showed a proliferation of tumor cells that were positive for myeloperoxidase and CD68 and negative for CD4 and CD123. The patient was diagnosed with MDS-associated MS. MDS-EB-2 quickly progressed to AML with the appearance of peripheral blood blasts and 25% bone marrow blasts. Monotherapy with reduced-dose AZA (37.5 mg/m2 for 7 days, every 4–6 weeks) was restarted, and the MS quickly disappeared. The patient’s MS was successfully treated with 16 cycles of AZA treatment over a 22-month period. There have been 10 reported cases in which MS was successfully treated with AZA. Among the 10 cases, the patient in the present case was the oldest. Treatment with reduced-dose AZA should be considered as a therapeutic option for MS in elderly patients with MDS, especially patients who are ineligible for intensive chemotherapy.

An elevated level of homocysteine (Hcy) in plasma is an independent risk factor for cardiovascular disease and central nervous system disease. Endothelial dysfunction as a result of apoptosis in endothelial cells is involved in the development and progression of these diseases. In this study, we aimed to investigate the effect of autophagy activation by amino acid starvation on Hcy-induced cytotoxicity in bovine aorta endothelial cells (BAECs). Hcy-induced lactate dehydrogenase (LDH) release was promoted by amino acid starvation. In addition, Hcy increased cleaved caspase-3 level, an indicator of apoptosis, by amino acid starvation. We revealed that oxidative stress is not involved in the Hcy-induced cytotoxicity promoted by amino acid starvation. Salazosulfapyridine (SASP), an SLC7A11 inhibitor, protected against the Hcy-induced LDH release promoted by amino acid starvation. SASP decreased the Hcy-induced cleaved caspase-3 level by amino acid starvation. We demonstrate for the first time that autophagy activation by amino acid starvation promotes Hcy-induced apoptosis in BAECs. Moreover, SLC7A11 inhibitor SASP, which is an amino acid transporter, protects against Hcy-induced apoptosis due to autophagy.

The intergenerational effects from chronic low-dose exposure are matters of concern. It is thus important to elucidate the radiation-induced effects of germ cell maturation, fertilization and embryonic development. It is well known that DNA methylation levels in CpG sites in gametes are reprogrammed in stages during their maturity. Furthermore, the binding of Izumo on the surface of sperm and Juno on the surface of oocytes is essential for fertilization. Thus, there is a possibility that these genes are useful indicators to evaluate fertility in mice after irradiation exposure. Therefore, in this study, we analyzed global DNA methylation patterns in the testes and gene expression of Izumo1 and Izumo1r (Juno) in the gonads of mice after neonatal acute high-dose ionizing radiation (HDR) and chronic low-dose ionizing radiation (LDR). One-week-old male and female mice were irradiated with a total dose of 4 Gy, with acute HDR at 7 days at a dose rate of 30 Gy/h and LDR continuously at a dose rate of 6 mGy/h from 7 to 35 days. Their gonads were subsequently analyzed. The results of global DNA methylation patterns in the testes showed that methylation level increased with age in the control group, the LDR group maintained its DNA methylation level, and the HDR group showed decreased DNA methylation levels with age. In the control group, the gene expression level of Izumo1 in the testis did not show age-related changes, although there was high expression at 100 days of age. However, in the LDR group, the expression level recovered after the end of irradiation, while it remained low regardless of age in the HDR group. Conversely, gene expression of Izumo1r (Izumo1 receptor) in the ovary decreased with age in the control group. Although the gene expression of Izumo1r decreased with age in the LDR group, it remained low in the HDR group. Our results indicate that LDR can induce different DNA methylation patterns, and both high- and low-dose radiation before sexual maturity might affect gametogenesis and fertility.

Abstract Porhyromonas gingivalis, a causative bacterium of periodontitis, is implicated in the etiology of rheumatoid arthritis (RA), mainly because of expressing peptidyl arginine deiminase (PAD) that generates RA-related autoantigens. However, compared with other periodontopathic bacteria, the precise role of P. gingivalis in RA is largely unknown. We found that orally administered P. gingivalis changed the gut microbiome with concomitant elevation of serum endotoxin and inflammatory markers, and impairment of the gut barrier function. Based on findings showing a relationship between gut microbiota and RA, we investigated whether the change of gut microbiota induced by P. gingivalis and Prevotella intermedia, another periodontopathic bacterium without PAD, is associated with collagen-induced arthritis (CIA). DBA/1J mice were orally administered with or without bacteria followed by induction of CIA. P. gingivalis, but not P. intermedia, administration significantly aggravated arthritis with increased interleukin-17 levels in sera and culture supernatants, increased Th17 cell proportions among mesenteric lymphocytes, and a significant change in the gut microbiome. However, P. gingivalis administration did not elevate the level of anti-citrullinated protein antibody. These results suggest a unique role of P. gingivalis in the link between periodontitis and RA by affecting the gut immune system and the gut microbiota composition.

Background: Oligonol® (OLG) is a functional food product and ingredient for cosmetics derived from a lychee fruit polyphenol. It has been reported to act on the skin as an anti-inflammatory and prevent UVB-induced skin damage. Aim: In this study, with the aim of exploring new functionalities of OLG on the scalp, we investigated the effect of OLG on human dermal papilla cells by comparing with adenosine and minoxidil at the genetic level. Method: OLG, adenosine, and minoxidil were applied to human dermal papilla cell lines for 24 h, after which VEGF, FGF-7, WNT5a, and WNT10a mRNA expressions were measured by real-time PCR analysis. Additionally, using DNA microarrays, we investigated the effect on 205 inflammation-related genes. Result: Consequently, in human dermal papilla cell lines, FGF-7 and WNT10a mRNA expression were observed in 100 µg/mL OLG-supplemented cells. The results of the DNA microarray analysis showed that 10 genes were suppressed by OLG. Conclusions: OLG may be expected to affect function of human dermal papilla cell by regulating the expression of genes related to cell proliferation and inflammation.

Pro-protein convertase subtilisin/kexin type 9 (PCSK9), a secreted serine protease, regulates serum low-density lipoprotein (LDL) cholesterol levels by targeting the degradation of LDL receptor (LDLR) in the liver. Although previous reports describe elevated levels of PCSK9 in patients with periodontitis, the mechanisms that trigger this increase in serum PCSK9 levels and induce the related inflammatory response remain unclear. In an unc93b1-deficient mouse of Porphyromonas gingivalis infection, nucleic acid antigen recognition via Toll-like receptors was found to promote PCSK9 production, suggesting an indirect role for tumor necrosis factor-α as an inducer of PCSK9 in contrast to that reported in previous studies. Furthermore, PCSK9 production was independent of the TIR domain-containing adapter-inducing interferon-β-dependent signaling pathway. These results indicate that changes in LDLR expression precede an increase in the serum PCSK9 level in the context of an infectious disease such as periodontitis.

Objectives. Several serum biomarkers have been reported to increase in periodontitis patients as possible mediators linking periodontal inflammation to systemic diseases. However, the relationship between periodontitis and urine biomarkers is still unclear. The aim of this cross-sectional study was to investigate potential urine biomarkers of periodontitis in a Japanese population. Materials and Methods. This study included 108 male subjects, and microbiological and clinical parameters were evaluated as a periodontitis marker. The correlation between nine urine biomarkers (typically used to diagnose kidney disease) and periodontal parameters was analyzed. Based on the findings, β2-microglobulin (β2-MG) and neutrophil gelatinase-associated lipocalin (NGAL) were selected for comparison and multivariate regression analysis, and the Kruskal–Wallis test followed by Bonferroni correction was used to identify differences in their concentrations between the three periodontitis groups (severe, moderate, and no/mild periodontitis). Results. β2-MG and NGAL exhibited a significant correlation with clinical parameters of periodontitis. The prevalence of clinical parameters such as bleeding on probing and number of sites with probing depth (PD) ≥ 6 mm were greater in the β2-MG high group (≥300 μg/g creatinine) than in the normal group (P=0.017 and 0.019, respectively). Multivariate regression analysis indicated that the number of sites with PD ≥ 6 mm was independently associated with urine β2-MG. Moreover, the number of sites with the clinical attachment level (CAL) ≥ 6 mm was greater in the NGAL high group (highest quartile) (P=0.041). Multivariate regression analysis showed that the number of sites with CAL ≥ 6 mm was associated independently with urine NGAL. Finally, β2-MG was significantly higher in the severe periodontitis subjects compared to the no/mild periodontitis subjects. Conclusion. The significant association between urine β2-MG or NGAL and periodontitis was revealed. These biomarkers can potentially be used to screen for or diagnose periodontitis. This trial is registered with the UMIN Clinical Trials Registry UMIN000013485.

Osteopenia/osteoporosis and sarcopenia are common geriatric diseases among older adults and harm activities of daily living (ADL) and quality of life (QOL). Osteosarcopenia is a unique syndrome that is a concomitant of both osteopenia/osteoporosis and sarcopenia. This review aimed to summarize the related factors and clinical outcomes of osteosarcopenia to facilitate understanding, evaluation, prevention, treatment, and further research on osteosarcopenia. We searched the literature to include meta-analyses, reviews, and clinical trials. The prevalence of osteosarcopenia among community-dwelling older adults is significantly higher in female (up to 64.3%) compared to male (8–11%). Osteosarcopenia is a risk factor for death, fractures, and falls based on longitudinal studies. However, the associations between osteosarcopenia and many other factors have been derived based on cross-sectional studies, so the causal relationship is not clear. Few studies of osteosarcopenia in hospitals have been conducted. Osteosarcopenia is a new concept and has not yet been fully researched its relationship to clinical outcomes. Longitudinal studies and high-quality interventional studies are warranted in the future.

Geriatric patients with hip fractures often experience overlap in problems related to nutrition, including undernutrition, sarcopenia, and frailty. Such problems are powerful predictors of adverse responses, although few healthcare professionals are aware of them and therefore do not implement effective interventions. This review aimed to summarize the impact of undernutrition, sarcopenia, and frailty on clinical outcomes in elderly individuals with hip fractures and identify successful strategies that integrate nutrition and rehabilitation. We searched PubMed (MEDLINE) and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant literature published over the last 10 years and found that advanced interventions targeting the aforementioned conditions helped to significantly improve postoperative outcomes among these patients. Going forward, protocols from advanced interventions for detecting, diagnosing, and treating nutrition problems in geriatric patients with hip fractures should become standard practice in healthcare settings.

The study aimed to investigate the impact of physical intervention and the amount of nutritional intake on the increase in tongue strength and swallowing function in older adults with sarcopenia. From November 2018 and May 2019, older patients with sarcopenia who were admitted for rehabilitation were analyzed. The intervention employed in the study was the usual physical and occupational therapy for two months. Tongue strength was measured before and after two months of treatment. Data on tongue strength, the amount of energy and protein intake, intervention time, and swallowing function were examined. A total of 95 sarcopenic older patients were included (mean age 83.4 ± 6.5 years). The mean tongue strength after the intervention was significantly increased from 25.4 ± 8.9 kPa to 30.5 ± 7.6 kPa as a result of the treatment (p < 0.001). After adjusting the confounding factors in the multivariable models, an energy intake of ≥30 kcal/kg/day and a protein intake of ≥1.2 g/kg/day based on the ideal body weight had a significant impact on the increase in tongue strength after the treatment (p = 0.011 and p = 0.020, respectively). Swallowing function assessed using the Mann Assessment of Swallowing Ability was significantly increased after the treatment (mean difference between pairs: 1.12 [0.53–1.70]; p < 0.001). Physical intervention and strict nutritional management for older inpatients with sarcopenia could be effective to improve tongue strength and swallowing function.

We report a rare case of spontaneous pneumoperitoneum. An 82-year-old Japanese male patient was referred to our hospital because of constipation and abdominal pain. Abdominal computed tomography revealed a large amount of feces in the colon and rectum, and free air in the abdomen. Based on these findings, the patient was diagnosed with gastrointestinal perforation. Emergency exploratory laparotomy was performed. Neither perforation nor ischemic changes were recognized in the digestive tract. The patient's defecation was managed postoperatively until discharge on the 13th postoperative day. The authors assumed that free air, which was released after a mucosal injury due to the internal pressure caused by the presence of a large amount of feces in the colon and rectum, had penetrated the bowel wall through the bowel mucosa. We herein report the present case while also reviewing the pertinent literature.

Epalrestat (EPS) is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Recently, we found that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH) in rat Schwann cells. GSH plays a crucial role in protecting endothelial cells from oxidative stress, thereby preventing vascular diseases. Here we show that EPS increases GSH levels in not only Schwann cells but also endothelial cells. Treatment of bovine aortic endothelial cells (BAECs), an in vitro model of the vascular endothelium, with EPS caused a dramatic increase in intracellular GSH levels. This was concomitant with the up-regulation of glutamate cysteine ligase, an enzyme catalyzing the first and rate-limiting step in de novo GSH synthesis. Moreover, EPS stimulated the expression of thioredoxin and heme oxygenase-1, which have important redox regulatory functions in endothelial cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates the expression of antioxidant genes. EPS increased nuclear Nrf2 levels in BAECs. Nrf2 knockdown by siRNA suppressed the EPS-induced glutamate cysteine ligase, thioredoxin-1, and heme oxygenase-1 expression. Interestingly, LY294002, an inhibitor of phosphatidylinositol 3-kinase, abolished the EPS-stimulated GSH synthesis, suggesting that the kinase is associated with Nrf2 activation induced by EPS. Furthermore, EPS reduced the cytotoxicity induced by H2O2 and tert-butylhydroperoxide, indicating that EPS plays a role in protecting cells from oxidative stress. Taken together, the results provide evidence that EPS exerts new beneficial effects on endothelial cells by increasing GSH, thioredoxin, and heme oxygenase-1 levels through the activation of Nrf2. We suggest that EPS has the potential to prevent several vascular diseases caused by oxidative stress.

Schwann cell injury is caused by diabetic neuropathy. The apoptosis of Schwann cells plays a pivotal role in diabetic nerve dysfunction. Glycolaldehyde is a precursor of advanced glycation end products that contribute to the pathogenesis of diabetic neuropathy. In this study, we examined whether glycolaldehyde induces endoplasmic reticulum (ER) stress and apoptosis in rat Schwann cells. Schwann cells treated with 500 μM glycolaldehyde showed morphological changes characteristic of apoptosis. Glycolaldehyde activated apoptotic signals, such as caspase-3 and caspase-8. Furthermore, it induced ER stress response involving RNA-dependent protein kinase-like ER kinase (PERK), inositol-requiring ER-to-nucleus signal kinase 1α (IRE1α), and eukaryotic initiation factor 2α (eIF2α). In addition, glycolaldehyde activated CCAAT/enhancer-binding homologous protein (CHOP), an ER stress response factor crucial to executing apoptosis. Knockdown of nuclear factor E2-related factor 2 (Nrf2), which is involved in the promotion of cell survival following ER stress, enhanced glycolaldehyde-induced cytotoxicity, indicating that Nrf2 plays a protective role in the cytotoxicity caused by glycolaldehyde. Taken together, these findings indicate that glycolaldehyde is capable of inducing apoptosis and ER stress in Schwann cells. The ER stress induced by glycolaldehyde may trigger the glycolaldehyde-induced apoptosis in Schwann cells. This study demonstrated for the first time that glycolaldehyde induced ER stress.

Several in vivo studies suggest that nanoparticles (smaller than 100 nm) have the ability to reach the brain tissue. Moreover, some nanoparticles can penetrate into the brains of murine fetuses through the placenta by intravenous administration to pregnant mice. However, it is not clear whether the penetrated nanoparticles affect neurogenesis or brain function. To evaluate its effects on neural stem cells, we assayed a human neural stem cell (hNSCs) line exposed in vitro to three types of silica particles (30 nm, 70 nm, and

Epalrestat (EPS), approved in Japan, is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Here we report that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH), which is important for protection against oxidative injury, through transcription regulation. Treatment of Schwann cells with EPS caused a dramatic increase in intracellular GSH levels. EPS increased the mRNA levels of γ-glutamylcysteine synthetase (γ-GCS), the enzyme catalyzing the first and rate-limiting step in de novo GSH synthesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a central role in regulating the expression of γ-GCS. ELISA revealed that EPS increased nuclear Nrf2 levels. Knockdown of Nrf2 by siRNA suppressed the EPS-induced GSH biosynthesis. Furthermore, pretreatment with EPS reduced the cytotoxicity induced by H2O2, tert-butylhydroperoxide, 2,2'-azobis (2-amidinopropane) dihydrochloride, and menadione, indicating that EPS plays a role in protecting against oxidative stress. This is the first study to show that EPS induces GSH biosynthesis via the activation of Nrf2. We suggest that EPS has new beneficial properties that may prevent the development and progression of disorders caused by oxidative stress.

The present paper describes step-climbing tactics using a wheeled robot and a hand cart that has a hand brake. The robot has two arms that are used to hold or push the handle of the cart and a lower extendable wheel mechanism that can push against the bottom of the cart. Some of the manipulator joints are controlled passively when moving over the step. To lift the front wheels of the cart, the robot holds the handle steady and pushes against the bottom of the cart using the extendable wheel mechanism. This action is similar to that performed by a human. The robot then pushes the entire cart forward so that the front wheels of the cart are above the step. When the rear wheels of the cart have climbed the step, the upper-arm links of the manipulators are pressed against the robot chest to allow the robot to push the cart. When the cart has fully climbed the step, the robot then uses the cart to climb the step. The present paper describes the details of the robot system, and theoretical analyses were performed to determine the requirement of masses and the centers of gravity of both vehicles to lift the cart. Experiments were also carried out in which the robot was controlled using an intranet connection, and the results demonstrated the effectiveness of the proposed method.

Advances in genomic microbial taxonomy have opened the way to create a more universal and transparent concept of species but is still in a transitional stage towards becoming a defining robust criteria for describing new microbial species with minimum features obtained using both genome and classical polyphasic taxonomies. Here we performed advanced microbial taxonomies combined with both genome-based and classical approaches for new agarolytic vibrio isolates to describe not only a novel Vibrio species but also a member of a new Vibrio clade. Two novel vibrio strains (Vibrio astriarenae sp. nov. C7T and C20) showing agarolytic, halophilic and fermentative metabolic activity were isolated from a seawater sample collected in a coral reef in Okinawa. Intraspecific similarities of the isolates were identical in both sequences on the 16S rRNA and pyrH genes, but the closest relatives on the molecular phylogenetic trees on the basis of 16S rRNA and pyrH gene sequences were V. hangzhouensis JCM 15146T (97.8% similarity) and V. agarivorans CECT 5085T (97.3% similarity), respectively. Further multilocus sequence analysis (MLSA) on the basis of 8 protein coding genes (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA, and topA) obtained by the genome sequences clearly showed the V. astriarenae strain C7T and C20 formed a distinct new clade protruded next to V. agarivorans CECT 5085T. The singleton V. agarivorans has never been included in previous MLSA of Vibrionaceae due to the lack of some gene sequences. Now the gene sequences are completed and analysis of 100 taxa in total provided a clear picture describing the association of V. agarivorans into pre-existing concatenated network tree and concluded its relationship to our vibrio strains. Experimental DNA-DNA hybridization (DDH) data showed that the strains C7T and C20 were conspecific but were separated from all of the other Vibrio species related on the basis of both 16S rRNA and pyrH gene phylogenies (e.g., V. agarivorans CECT 5085T, V. hangzhouensis JCM 15146T V. maritimus LMG 25439T, and V. variabilis LMG 25438T). In silico DDH data also supported the genomic relationship. The strains C7T also had less than 95% average amino acid identity (AAI) and average nucleotide identity (ANI) towards V. maritimus C210, V. variabilis C206, and V. mediterranei AK1T, V. brasiliensis LMG 20546T, V. orientalis ATCC 33934T, and V. sinaloensis DSM 21326. The name Vibrio astriarenae sp. nov. is proposed with C7 as the type strains. Both V. agarivorans CECT 5058T and V. astriarenae C7T are members of the newest clade of Vibrionaceae named Agarivorans.

The Brazilian Legal Amazon is an extensive territory in which different factors influence the dynamics of forest fires. Currently, the Brazilian government has two tools in the public domain and free of charge, PRODES and BDQueimadas, to monitor and make decisions to combat deforestation and forest fires. This work aimed to evaluate and correlate the forest fire alerts and deforestation in the Amazon Forest in the state of Pará. The analyses were based on carrying out a diagnosis of forest fires and deforestation; the behavior of forest fires and deforestation over the last twenty years; the statistical relationship between deforestation and forest fires and their spatialization. This work identified that Pará is the state in the Legal Amazon with the highest occurrence of forest fires and deforestation. Deforestation in the four-year period Jan/2003-Dec/2006 showed a higher rate compared to the four-year periods Jan/2011-Dec/2018. A high correlation was found between forest fire alerts and increases in deforestation. There is a spatial relationship between cities with greater increases in deforestation and high numbers of fire alerts. In relation to the occurrence of forest fires and deforestation, the south of the state was the most critical region and the north had lower rates. [ABSTRACT FROM AUTHOR]