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Background : This cohort study was conducted to devise an approximation formula for predicting the glomerular filtration rate (GFR) after 1 year using annual medical examination data from the general population. Methods : Consecutive annual medical examination data were obtained for 41,337 inhabitants. Machine learning with the random forest method was used to assess the importance of each clinical parameter in terms of its association with estimated GFR (eGFR) after 1 year. An approximation formula was developed by multiple linear regression analysis based on the four most important clinical parameters. The relationship between the GFR after 1 year approximated by our formula and the eGFR after 1 year was analyzed using Pearson's correlation coefficient. Results : The following approximation formula was obtained by multiple linear regression analysis: approximate GFR after 1 year (mL/min/1.73 m 2 ) = -0.054 × age + 0.162 × hemoglobin - 0.085 × uric acid + 0.849 × eGFR + 11.5. The approximate GFR after 1 year was significantly and strongly correlated with the eGFR at that time (r = 0.884; p < 0.001). Conclusions : An approximation formula including age, hemoglobin, uric acid, and eGFR may be useful for predicting GFR after 1 year among members of the general population.

Proline is the most abundant amino acid in wine and beer, because the yeast Saccharomyces cerevisiae hardly assimilates proline during fermentation processes. Our previous studies showed that arginine induces endocytosis of the proline transporter Put4, resulting in inhibition of proline utilization. We here report a possible role of arginine sensing in the inhibition of proline utilization. We first found that two basic amino acids, ornithine, and lysine, inhibit proline utilization by inducing Put4 endocytosis in a manner similar to arginine, but citrulline does not. Our genetic screening revealed that the arginine transporter Can1 is involved in the inhibition of proline utilization by arginine. Intriguingly, the arginine uptake activity of Can1 was not required for the arginine-dependent inhibition of proline utilization, suggesting that Can1 has a function beyond its commonly known function of transporting arginine. More importantly, our biochemical analyses revealed that Can1 activates signaling cascades of protein kinase A in response to extracellular arginine. Hence, we proposed that Can1 regulates proline utilization by functioning as a transceptor possessing the activity of both a transporter and receptor of arginine., (© 2023 John Wiley & Sons Ltd.)

Background: Most testicular tumors are germ cell tumors; sex cord stromal tumors are infrequent, accounting for only 3-5% of testicular tumors. Unclassified sex cord stromal tumors are extremely rare. Generally, 10% of sex cord stromal tumors are malignant. We report a case of malignant unclassified sex cord stromal tumor with retroperitoneal lymph node metastasis at first visit and a corresponding literature review., Case Presentation: A 72-year-old Japanese man visited our department primarily for indolent right scrotum enlargement in September 2020. Blood biochemistry examination, urinalysis, and tumor markers (alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase) showed no abnormal findings. Contrast-enhanced computed tomography showed enlarged para-aortic lymph node (18 × 16 and 10 × 10 2  mm); a 50 × 45 2  mm mass with uneven contents was found in the right testicle. The patient underwent inguinal orchiectomy in September 2020. As per immunohistochemistry, the tumor cells were diffusely positive for SF-1 and Ki-67, partially positive for inhibin, and negative for CAM5.2, CK7, CK20, C-KIT, CD30, LCA, GATA-3, TTF-1, and PAX8. Calretinin was expressed in approximately 5% of tumor cells; thus, sex cord/gonadal stroma components were considered to be involved. The final pathological diagnosis was unclassified malignant sex cord stromal tumor. The patient was diagnosed with pT1, N1, M0, S0, and tumor-node-metastasis stage IIA disease. The patient received postoperative chemotherapy with four courses of etoposide and cisplatin therapy from November 2020. Post-chemotherapeutic computed tomography showed new metastatic lesions including lung, liver, pancreas, and para-aortic lymphadenopathy, which increased in size. Disease progression was observed. Cancer genome research was performed using the OncoGuide National Cancer Center oncopanel system; however, no gene mutation for which the drug could be expected to be effective was found. The patient opted for best supportive care at a nearby hospital and died from cancer progression in January 2022., Conclusion: We encountered a case of malignant testicular unclassified sex cord stromal tumor pathologically diagnosed as testicular tumor with retroperitoneal lymph node metastasis in a patient who underwent inguinal orchiectomy. Future data collection is necessary to establish multimodality therapy for malignant testicular unclassified sex cord stromal tumor., (© 2022. The Author(s).)

Biofilms are formed by the aggregation of microorganisms into multicellular structures that adhere to surfaces. Biofilm formation by yeast is a critical issue in clinical and industrial fields because of the strong adhesion of yeast biofilm to abiotic surfaces and tissues. Here, we clarified the arginine-mediated inhibition of biofilm formation by yeast. First, we showed that arginine inhibits biofilm formation in fungi such as Saccharomyces cerevisiae, Candida glabrata, and Cladosporium cladosporioides, but not in bacteria. In regard to the underlying mechanism, biochemical analysis indicated that arginine inhibits biofilm formation by suppressing Flo11-dependent flocculation. Intriguingly, a strain with deletion of the arginine transporter-encoding CAN1 was insensitive to arginine-mediated inhibition of biofilm formation. Finally, Can1 endocytosis appeared to be required for the inhibitory mechanism of biofilm formation by arginine. The present results could help to elucidate the molecular mechanism of yeast biofilm formation and its control., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Proline is a predominant amino acid in grape must, but it is poorly utilized by the yeast Saccharomyces cerevisiae in wine-making processes. This sometimes leads to a nitrogen deficiency during fermentation and proline accumulation in wine. In this study, we clarified that a glucose response is involved in an inhibitory mechanism of proline utilization in yeast. Our genetic screen showed that strains with a loss-of-function mutation on the CDC25 gene can utilize proline even under fermentation conditions. Cdc25 is a regulator of the glucose response consisting of the Ras/cAMP-dependent protein kinase A (PKA) pathway. Moreover, we found that activation of the Ras/PKA pathway is necessary for the inhibitory mechanism of proline utilization. The present data revealed that crosstalk exists between the carbon and proline metabolisms. Our study could hold promise for the development of wine yeast strains that can efficiently assimilate proline during the fermentation processes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Introduction/objectives: In patients who have undergone recent percutaneous coronary intervention (PCI), poor adhesion to antiplatelet agents may increase the risk of stent thrombosis and death. We aimed to investigate the adherence to different P2Y12 receptor inhibitors after PCI with drug-eluting stent in stable and unstable patients and to evaluate the factors associated with low adherence., Method: In a prospective study conducted between 2014 and 2018, the 8-item Morisky scale was applied at 30 days and 6 months post-PCI to measure P2Y12 receptor inhibitors adherence. Also, we describe the characteristics of patients using different platelet receptor P2Y12 inhibitors. Regression models were used to identify predictors of poor adherence., Results: A total of 214 patients were included (65 ± 12 years, 81% man, 61% acute coronary syndromes). Patients in the clopidogrel group were older than those in the prasugrel (68 ± 12 vs 59 ± 11 years, P < .01, respectively) or ticagrelor group (68 ± 12 vs 62 ± 12 years, P < .01). Patients with low/moderate adherence at 30 days and 6 months represented, respectively, 19.8% and 27.5% of our sample. Current smokers and preexisting cardiovascular disease at presentation were associated with lower adherence at 30 days., Conclusions: We found substantial rates of moderate and low adherence to P2Y12 receptor inhibitors early after PCI. Current smokers and preexisting cardiovascular disease at presentation were associated with a lower likelihood of adherence. These results highlight the need of monitoring adherence to medical treatment after PCI.

A series of cellulose derivatives bearing dialkyl dithiocarbamate (DTC) groups were synthesized. Their ability of sorption of arsenite (As(iii)) and heavy metals and their storage stability in the solid state were investigated. Among them, DTC-modified cellulose derived from l-proline showed the highest sorption capacity for As(iii) and heavy metals to selectively remove them from aqueous media. It also showed exellent storage stability in air at 40 °C., Competing Interests: The authors declare the following conflict of interest(s): Kanazawa University and Daicel Corporation hold or have a filed patent related to this work (Patent Application No. PCT/JP2020/21903)., (This journal is © The Royal Society of Chemistry.)

The mammalian forelimb is adapted to different functions including postural, locomotor, feeding, exploratory, grooming and defence. Comparative studies on morphology of the mammalian scapula have been performed in an attempt to establish the functional differences in the use of the forelimb. In this study, a total of 102 scapulae collected from 66 species of animals, representatives of all major taxa from rodents, sirenians, marsupials, pilosa, cetaceans, carnivores, ungulates, primates and apes, were analysed. Parameters measured included scapular length, width, position, thickness, area, angles and index. Structures included supraspinous and infraspinous fossae, scapular spine, glenoid cavity, acromium and coracoid processes. Images were taken using computed tomographic (CT) scanning technology (CT-Aquarium, Toshiba and micro CT-LaTheta, Hotachi, Japan), and measurement values were acquired and processed using Avizo computer software and CanvasTM 11 ACD systems. Statistical analysis was performed using Microsoft Excel 2013. Results obtained showed that there were differences in morphological characteristics of scapula between mammals with arboreal locomotion and living in forest and mountainous areas and those with leaping and terrestrial locomotion living in open habitat or savannah. Differences were seen in the ratio of maximum length and maximum width, the orientation of scapular spine and the horizontal length of acromion and coracoid processes. The cause for the statistical grouping of the animals and the way the scapular shape covaries with habitat and to the type of locomotion and speed are discussed in detail., (© 2019 Blackwell Verlag GmbH.)

Competing Interests: Competing interests: None

Background: Depressive symptoms are independently associated with an increased risk of cardiovascular disease (CVD) among individuals with non-diagnosed CVD. The mechanisms underlying this association, however, remain unclear. Inflammation has been indicated as a possible mechanistic link between depression and CVD., Objectives: This study evaluated the association between persistent depressive symptoms and the onset of low-grade inflammation., Methods: From a database of 1,508 young (mean age: 41 years) individuals with no CVD diagnosis who underwent at least two routine health evaluations, 134 had persistent depressive symptoms (Beck Depression Inventory - BDI ≥ 10, BDI+) and 1,374 had negative symptoms at both time points (BDI-). All participants had been submitted to repeated clinical and laboratory evaluations at a regular follow-up with an average of 26 months from baseline. Low-grade inflammation was defined as plasma high-sensitivity C-Reactive Protein (CRP) concentrations > 3 mg/L. The outcome was the incidence of low-grade inflammation evaluated by the time of the second clinical evaluation., Results: The incidence of low-grade inflammation was more frequently observed in the BDI+ group compared to the BDI- group (20.9% vs. 11.4%; p = 0.001). After adjusting for sex, age, waist circumference, body mass index, levels of physical activity, smoking, and prevalence of metabolic syndrome, persistent depressive symptoms remained an independent predictor of low-grade inflammation onset (OR = 1.76; 95% CI: 1.03-3.02; p = 0.04)., Conclusions: Persistent depressive symptoms were independently associated with low-grade inflammation onset among healthy individuals.

The present study was conducted to clarify whether the meiotic stage of porcine oocytes has the highest sensitivity to hyperthermia during in vitro maturation by evaluating meiotic competence and DNA damage. Oocytes were exposed to 41 °C for 12 h at various intervals during 48 h of maturation culture. When the oocytes were exposed to 41 °C from 12 to 24 h of the maturation culture, the proportion of oocytes reaching metaphase II (MII) decreased as compared to the control oocytes cultured at 38.5 °C (P < 0.05). Moreover, the proportions of DNA fragmentation in all oocytes exposed to 41 °C in each culture period after 12 h from the start of maturation culture were significantly higher (P < 0.05) than for the control oocytes. When the meiotic stage of oocytes cultured at 38.5 °C between 12 and 24 h was examined, the majority of oocytes remained at the germinal vesicle (GV) stage at 12 h and approximately half of the oocytes reached metaphase I (MI) at 24 h. These results indicate that the meiotic stage of porcine oocytes having the highest sensitivity to hyperthermia during in vitro maturation is a transition period from the GV stage to the MI stage.

A single dose of pegfilgrastim or the daily administration of colony-stimulating factors can be used to prevent febrile neutropenia. This may delay the detection of rapidly progressive infections among cancer patients undergoing chemotherapy. We report a case of Pseudomonas aeruginosa bacteremic pneumonia that occurred in a patient receiving pegfilgrastim.

S-1 is an anticancer agent that consists of tegafur, gimeracil, and oteracil potassium at a molar ratio of 1:0.4:1. S-1 is used to treat metastatic and resectable gastric cancer. However, the extensive use of S-1 in clinical practice results in watery eyes, a serious clinical problem, which worsens patients' quality of life. Although repeated instillation of artificial tears is recommended, therapy or prophylaxis against S-1-induced ocular toxicity has not been established. In the present study, we evaluated the alleviating effects of repeated artificial tear instillation on S-1-induced ocular toxicity in dogs. Ten beagle dogs (5 males and 5 females) were orally administered 3 mg/kg/day of S-1 for up to 21 days. Five drops of artificial tears were instilled to the left eye, eight times daily, within 6 hr after S-1 administration. The mean cornea staining score tended to be low in the left eye with repeated artificial tear instillation. In 4 out of 10 dogs, the corneal staining score of the left eye was more than 2-fold lower than that of the right eye. The incidence of dogs indicating normal tear drainage increased and stenosed tear drainage decreased by repeated artificial tear instillation. In conclusion, we demonstrated that artificial tear instillation can alleviate corneal surface damage induced by S-1 in dogs.

Background: The effect of socioeconomic stressors on the incidence of cardiovascular disease (CVD) is currently open to debate. Using time-series analysis, our study aimed to evaluate the relationship between unemployment rate and hospital admission for acute myocardial infarction (AMI) and stroke in Brazil over a recent 11-year span., Methods and Results: Data on monthly hospital admissions for AMI and stroke from March 2002 to December 2013 were extracted from the Brazilian Public Health System Database. The monthly unemployment rate was obtained from the Brazilian Institute for Applied Economic Research, during the same period. The autoregressive integrated moving average (ARIMA) model was used to test the association of temporal series. Statistical significance was set at p<0.05. From March 2002 to December 2013, 778,263 admissions for AMI and 1,581,675 for stroke were recorded. During this time period, the unemployment rate decreased from 12.9% in 2002 to 4.3% in 2013, while admissions due to AMI and stroke increased. However, the adjusted ARIMA model showed a positive association between the unemployment rate and admissions for AMI but not for stroke (estimate coefficient=2.81±0.93; p=0.003 and estimate coefficient=2.40±4.34; p=0.58, respectively)., Conclusions: From 2002 to 2013, hospital admissions for AMI and stroke increased, whereas the unemployment rate decreased. However, the adjusted ARIMA model showed a positive association between unemployment rate and admissions due to AMI but not for stroke. Further studies are warranted to validate our findings and to better explore the mechanisms by which socioeconomic stressors, such as unemployment, might impact on the incidence of CVD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Poor dentition and/or dental infection due to insufficient oral care are presumed to be risk factors for infective endocarditis (IE). We present a case of endocarditis caused by Granulicatella adiacens and Sjögren's syndrome (SS) with oral complications diagnosed simultaneously. A 67-year-old woman was admitted to our hospital with fever, general fatigue, arthralgia, and back pain. She was diagnosed with primary SS according to the criteria of the American-European Consensus Group. Transthoracic echocardiography carried out to examine her persistent fever revealed vegetation formation (14 × 5 mm) on the aortic valve and her blood cultures were positive for G. adiacens . According to modified Duke's criteria, she was also diagnosed with IE. She underwent aortic valve replacement and was administered ampicillin with gentamicin for 6 weeks following surgery. G. adiacens , which is formerly known as one of the nutritionally variant streptococci, is found as part of the normal microbiota of the oral cavity. The patient had chronic periodontitis associated with SS that likely predisposed to G. adiacens bacteremia and subsequent seeding of the aortic valve. Patients with SS may be at risk of IE because of the increased risk of bacteremia from oral complications such as dental caries or periodontal disease. An association between SS and IE has not yet been reported. Our case indicates that SS may be the underlying pathology in patients with IE due to an oral bacterium.

Streptococcus agalactiae ( S. agalactiae ) is a major cause of invasive disease in neonates and pregnant women, but has also recently been observed among non-pregnant adults, especially elderly persons or persons with underlying chronic disease. S. agalactiae is also a rare cause of infective endocarditis, and most cases require early surgery. We report the case of a 43-year-old previously healthy man who experienced rapid progressive culture-negative infective endocarditis with aortic valve vegetation and severe aortic regurgitation, which was complicated by lumbar spondylodiscitis. Emergency aortic valve replacement was performed on the day of his admission, which revealed a congenital bicuspid aortic valve was ruptured by the vegetation. The resected aortic valve specimen was submitted for 16S ribosomal RNA gene sequencing, which revealed that the pathogen was S. agalactiae . Therefore, S. agalactiae should be considered a potentially causative pathogen in cases of rapid progressive infective endocarditis, even if it occurs in a non-pregnant immunocompetent adult.