Synthesis of Daldinans and Dynamic Stereochemistry of their Atropisomers.

The synthesis of daldinans B and E (5 and 8), 3-phenyl isoindolinones isolated from Daldinia concentrica, was achieved. The conformational properties of these isoindolinones were examined using their derivatives, revealing the presence of atropisomers. The activation free-energy barrier was estimated by the variable-temperature nuclear magnetic resonance (VT-NMR) method, and density functional theory (DFT) calculations suggested that this atropisomerization was caused by equilibration via a slow rotation around the C-3-C-8 axis.

Work engagement and associated factors among Japanese registered dietitians and dietitians: a cross-sectional study.

Healthcare services provided by registered dietitians and dietitians have been changing because of evolving lifestyles and population dynamics, leading to subsequent changes in the occupational status and experiences of these professionals. However, few studies have examined occupational stress among registered dietitians and dietitians. This study involved a cross-sectional survey to investigate the status and associated factors of work engagement among registered dietitians and dietitians, whose professions differ based on licensing processes and scope of work. A total of 3,593 questionnaires were distributed, 1,890 responses were received, and 1,654 valid questionnaires were analyzed. Work engagement was measured using the Utrecht Work Engagement Scale. Multiple regression analysis was conducted to examine the associations between work engagement and each factor. The work engagement scores of dietitians were significantly lower than those of registered dietitians. Further, work engagement was associated with age, workplace, coworker support, and effort-reward ratio for both registered dietitians and dietitians. However, exercise habit was a significant factor associated with work engagement only among dietitians. Work engagement among registered dietitians was comparable to that of typical Japanese workers, whereas it was lower among dietitians. The findings highlight the importance of considering associated factors to improve work engagement further, especially among dietitians.

Verification of quality assurance for blood culture surveillance using 6 years of data from the Japan Infection Prevention and Control Conference for National and Public University Hospitals.

The importance of blood culture has been widely recognized, and there is a need for monitoring to evaluate the accuracy of blood culture that reflects domestic healthcare systems. In this study, we assessed 6-year trends in blood culture quality assurance data. The Japan Infection Prevention and Control Conference for National and Public University Hospitals conducted yearly blood culture surveillance at 52 national public university hospitals from 2015 to 2020. Statistical analysis showed that comparison with the previous year showed significant differences in the number of blood cultures per 1000 patient-days in all years. The number of blood cultures per 1000 admissions was not significantly different in 2017 and 2018, but significant differences were shown in all other years. The multiple blood culture set rate was significantly different between non-pediatric inpatients and outpatients but not between pediatric inpatients and outpatients. The contamination rate did not differ significantly. For all parameters, significant differences were found when comparing 2015 and 2020. Our survey showed that although the sample number improved over time, even the most recent values for 2020 were lower than Cumitech's targets. It is difficult to assess whether these sample numbers are appropriate because target values have not been set for the various types of hospitals in Japan. Surveillance is a useful tool for monitoring quality assurance for blood culture. All parameters improved over the 6-year period, but it is necessary to establish a benchmark for evaluating optimization. We will continue to monitor quality assurance and work on setting benchmarks.

History of malignant neoplasia lessens oocyte developmental competence: a case-control study.

OBJECTIVE: We investigated how history of malignant neoplasia affected oocyte developmental competence. METHODS: Fifty-two cycles of assisted reproductive technology (ART) in women with a history of malignant disease (case group) were compared with fifty-two matched cycles of ART in women with no cancer history (control group). Propensity score matching involving age and body mass index was used to select controls. Oocyte developmental competence and rates of pregnancy and livebirth were compared as main outcomes. To investigate whether the cancer itself had affected oocyte developmental competence, this outcome variable was compared between case cycles with and without cancer surgical histories. RESULTS: Numbers of fertilized oocytes (FO), cleaving embryos (CE), and superior CE (SCE) were significantly lower in cases than controls. Rates of fertilization and of development to SCE from retrieved oocytes (RO), FO, or CE also were lower in cases than controls (63, 25, 39, and 43% vs. 72, 36, 50, and 55%, respectively). Cases had significantly lower rates of clinical pregnancy and livebirth per embryo transfer than controls (7.6 and 1.5% vs. 20.4 and 14.0%). Rates of development to SCE from RO, FO, and CE showed no significance for differences between cases with and without cancer operations (22, 37, and 40% vs. 31, 42, and 49%). CONCLUSIONS: A woman's history of malignant neoplasia was associated with decreased oocyte developmental competence, possibly related to patient's background factors predisposing to tumor.

A cross-sectional study of the association between effort-reward imbalance and psychologic distress among Japanese dietitians.

OBJECTIVES: This study aims to clarify dietitians' effort-reward imbalance (ERI) and examine its association with psychologic distress. METHODS: A cross-sectional survey was conducted. A total of 3593 questionnaires were distributed to dietitians in about 110 organizations and 1890 responses were received (response rate 52.6%). Hence, a total of 1743 valid questionnaires were used in the analysis. Effort-reward (ER) ratio was measured by a subscale of the ERI Questionnaire, and psychologic distress was measured by the Kessler Psychological Distress Scale (K6). The association between the ER ratio and psychologic distress was analyzed by multiple logistic regression analysis with covariates. RESULTS: The mean ER ratio was 0.83 (SD = 0.53) and ERI (ER ratio >1) prevalence was 26.3%. The mean K6 score was 7.1 (5.3), and psychologic distress (K6 score ≥5) prevalence was 62.4%. The increased psychologic distress was associated with a higher ER ratio, less support from supervisors and coworkers, and lower age and household income. ERI was significantly associated with psychologic distress, even after being adjusted for covariates. CONCLUSIONS: Dietitians experience high stress, as shown by their high ER ratio and K6 scores. Their ERI was greatly associated with psychologic distress.

Psychological distress and associated factors among Japanese nursery school and kindergarten teachers: a cross-sectional study.

The understaffing of nursery schools and kindergartens and the increasing workload of childcare workers are becoming significant issues in Japan. In this study, a cross-sectional survey was conducted to investigate the stress experienced by childcare workers and its antecedents. We distributed 2,640 questionnaires to childcare workers in Miyagi prefecture, obtaining a response rate of 51.9% (n=1,370). Finally, 1,210 valid questionnaires were used in the analysis. As a stress indicator, psychological distress was measured with the Kessler Screening Scale for Psychological Distress (K6). The mean K6 score was 7.0 (SD=5.4), and the prevalence of psychological distress (K6 score ≥5) was 60.0%. Considering work-related factors, the mean scores were as follows: supervisor support 11.8 (2.6), coworker support 12.1 (2.0), work engagement 3.2 (1.2), and effort-reward ratio 0.93 (0.53). A multivariate logistic regression analysis with adjustment for possible confounders revealed that increased psychological distress was associated with higher effort-reward ratio, lower support from supervisors and coworkers, lower work engagement, and insufficient sleep. These results suggest that elevated psychological distress is strongly associated with effort-reward imbalance, while high work engagement in childcare workers helped to reduce their distress.

Clinical evaluation of a non-purified direct molecular assay for the detection of Clostridioides difficile toxin genes in stool specimens.

Recently, a new rapid assay for the detection of tcdB gene of Clostridioides difficile was developed using the GENECUBE. The assay can directly detect the tcdB gene from stool samples without a purification in approximately 35 minutes with a few minutes of preparation process. We performed a prospective comparative study of the performance of the assay at eight institutions in Japan. Fresh residual stool samples (Bristol stool scale ≥5) were used and comparisons were performed with the BD MAX Cdiff assay and toxigenic cultures. For the evaluation of 383 stool samples compared with the BD MAX Cdiff assay, the sensitivity, and specificity of the two assays was 99.0% (379/383), 98.1% (52/53), 99.1% (327/330), respectively. In the comparison with toxigenic culture, the total, sensitivity, and specificity were 96.6% (370/383), 85.0% (51/60), and 98.8% (319/323), respectively. The current investigation indicated the GENECUBE Clostridioides difficile assay has equivalent performance with the BD MAX Cdiff assay for the detection of tcdB gene of C. difficile.

Author Correction: Structure of two purple pigments, catechinopyranocyanidins A and B from the seed-coat of the small red bean, Vigna angularis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10.

Coenzyme Q10 (CoQ10) plays a key role not only as an essential electron carrier in the mitochondrial electron transport chain, but also as an antioxidant to protect cells from oxidative stress. CoQ10 supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ10 are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form). Both forms of CoQ10 supplements are commercially available, however, their kinetic difference is still unclear. In order to conduct in vivo analysis of the kinetics of ubiquinol-10 and ubiquinone-10, we succeeded in synthesizing 11C-labeled ubiquinol-10 ([11C]UQL) and ubiquinone-10 ([11C]UQN), respectively. In the present study, we aimed to investigate the kinetics of [11C]UQL and [11C]UQN, both of which were administered via the tail vein of 8-week-old male Sprague-Dawley rats. Whole-body positron emission tomography (PET) imaging was performed to follow the time course of accumulation in the liver, spleen, brain, and other organs. Then, at the two typical time points at 20 or 90 min after injection, we conducted the biodistribution study. Various organs/tissues and blood were collected, weighed and counted with a gamma counter. Percent injected dose per gram of tissue (%ID/g) was calculated as the indicator of the accumulation of each compound. As the results, at both time points, %ID/g of [11C]UQL in the cerebrum, cerebellum, white adipose tissue, muscle, kidney, and testis were higher (P < 0.05) than that of [11C]UQN: at 90-min time point, %ID/g of [11C]UQL in the brown adipose tissue was higher (P < 0.05) than that of [11C]UQN: on the contrary, %ID/g of [11C]UQL in the spleen was lower (P < 0.05) than that of [11C]UQN at 90 min. In a separate study of the metabolite analysis in the plasma, UQL injected into the tail vein of rats was almost unchanged during the PET scanning time, but UQN was gradually converted to the reduced form UQL. Therefore, the uptake values of UQL into the tissues and organs were rather accurate but those of UQN might be the sum of UQN uptake and partly converted UQL uptake. These studies suggested that the accumulation level of administered CoQ10 differs depending on its redox state, and that CoQ10 redox state could be crucial for optimization of the effective supplementation.

Structure of two purple pigments, catechiopyranocyanidins A and B from the seed-coat of the small red bean, Vigna angularis.

The small red bean, Vigna angularis, is primarily used to produce the "an-paste" component of Japanese sweets. Through the manufacturing process, the red seed-coat pigment is transferred to the colorless "an-particles", imparting a purple color. However, the major pigment in the seed coat has not yet been identified, although it is historically presumed to be an anthocyanin. Here, we report the isolation and structural determination of two hydrophobic purple pigments in the seed coat via instrumental analysis and derivatization. The new pigments, catechinopyranocyanidins A and B, contain a novel pyranoanthocyanidin skeleton condensed with a catechin and cyanidin ring system, and no sugar moieties. Catechinopyranocyanidins A and B are diastereomers with a different configuration at the catechin moiety, and both are purple in color in strongly acidic-to-neutral media. Catechinopyranocyanidins A and B are very stable under dark conditions, but, labile to light and decompose to colorless compounds. Thus, these pigments exhibit quite different chemical properties compared to simple anthocyanidins.

Synthesis of 11 C-labeled ubiquinone and ubiquinol via Pd0 -mediated rapid C-[11 C]methylation using [11 C]methyl iodide and 39-demethyl-39-(pinacolboryl)ubiquinone.

To enable positron emission tomography (PET) imaging of the in vivo kinetics of ubiquinone and ubiquinol, which is referred to as coenzyme Q10 , their 11 C-radiolabeled counterparts were synthesized herein. 11 C-Labeled ubiquinone [11 C]-1 was realized by Pd-mediated rapid C-[11 C]methylation of [11 C]CH3 I with 39-demethyl-39-(pinacolboryl)ubiquinone, prepared by Ru-catalyzed olefin metathesis of unradiolabeled ubiquinone with 2-(pinacolboryl)propene. Subsequent reduction of [11 C]-1 using Na2 S2 O4 yielded 11 C-labeled ubiquinol [11 C]-2. The synthesis time and [11 C]CH3 I-based radiochemical yield of [11 C]-1 were within 36 minutes and up to 53%, while those of [11 C]-2 were within 38 minutes and up to 39%, respectively. After radiopharmaceutical formulation, the qualities of [11 C]-1 and [11 C]-2 were confirmed to be applicable for animal PET studies. The analytical values of [11 C]-1 and [11 C]-2 are as follows: radioactivity of up to 3.5 and 1.4 GBq, molar activity of 21 to 78 and 48 to 76 GBq/µmol, radiochemical purity of greater than 99% and greater than 95%, and chemical purity of greater than 99% and 77%, respectively. The concept behind this radiolabeling procedure is that unradiolabeled natural ubiquinone can be converted to 11 C-radiolabeled ubiquinone and ubiquinol via a pinacolborane-substituted ubiquinone derivative. Each PET probe was used for molecular imaging using rats to investigate the in vivo kinetics and biodistribution of the coenzyme Q10 .

Development of Diagnostic Techniques for Early Rheumatoid Arthritis Using Positron Emission Tomography with [11C]PK11195 and [11C]Ketoprofen Tracers.

PURPOSE: In vivo detection of pathological insults during the early stages of rheumatoid synovitis is essential to allow early anti-inflammatory treatment for prevention of joint destruction. Whether rheumatoid synovitis pathology and the efficacy of therapies can be visualized by positron emission tomography (PET) tracers specific to the inflammatory process was investigated. PROCEDURES: Using a collagen-induced experimental rat model of rheumatoid arthritis, in vivo imaging using the PET tracers [11C]PK11195, which binds to the translocator protein mainly expressed on myeloid cells, and [11C]ketoprofen, for cyclooxygenase imaging, was performed. To evaluate therapeutic efficacy, model animals were administered the tumour necrosis factor alpha blocker etanercept subcutaneously. RESULTS: [11C]PK11195 and [11C]ketoprofen uptakes were significantly higher in inflamed paws of collagen-induced arthritis rats than in normal rats. The data showed a correlation between tracer uptake values and paw swelling. After treatment with etanercept, [11C]ketoprofen uptake was significantly lower in treated animals than in untreated ones, whereas [11C]PK11195 uptake in the inflamed regions was comparable to that in the untreated group. CONCLUSIONS: With [11C]PK11195 and [11C]ketoprofen tracers, non-invasive in vivo PET imaging for rheumatoid synovitis can provide diagnostic evidence of early synovitis and allow monitoring inflammatory cell activity during treatment.

Biocompatible fluorescent silicon nanocrystals for single-molecule tracking and fluorescence imaging.

Fluorescence microscopy is used extensively in cell-biological and biomedical research, but it is often plagued by three major problems with the presently available fluorescent probes: photobleaching, blinking, and large size. We have addressed these problems, with special attention to single-molecule imaging, by developing biocompatible, red-emitting silicon nanocrystals (SiNCs) with a 4.1-nm hydrodynamic diameter. Methods for producing SiNCs by simple chemical etching, for hydrophilically coating them, and for conjugating them to biomolecules precisely at a 1:1 ratio have been developed. Single SiNCs neither blinked nor photobleached during a 300-min overall period observed at video rate. Single receptor molecules in the plasma membrane of living cells (using transferrin receptor) were imaged for ≥10 times longer than with other probes, making it possible for the first time to observe the internalization process of receptor molecules at the single-molecule level. Spatial variations of molecular diffusivity in the scale of 1-2 µm, i.e., a higher level of domain mosaicism in the plasma membrane, were revealed.

Bloodstream infection due to Mycoplasma arginini in an immunocompromised patient.

Mycoplasma arginini, an organism usually recovered from mammals, was isolated from the blood of a febrile patient with advanced non-Hodgkin lymphoma. The patient's condition improved without administration of antimycoplasmal drugs. Simulation of blood culture showed that automated blood culture instruments may fail to detect the organism.

Altered gut flora are associated with septic complications and death in critically ill patients with systemic inflammatory response syndrome.

BACKGROUND: Gut under severe insult is considered to have an important role in promoting infection and multiple organ dysfunction syndrome from the viewpoint of altered intestinal epithelium, immune system and commensal bacteria. There are few reports, however, about the relationship between gut flora and septic complications. METHODS: We analyzed gut flora in patients with systemic inflammatory response syndrome (SIRS) and evaluated key bacteria and their cutoff values for infectious complications and mortality by using classification and regression trees (CART). Eighty-one SIRS patients with a serum C-reactive protein level higher than 10 mg/dL treated in the intensive care unit (ICU) for more than 2 days were included for the study. We quantitatively evaluated nine types of bacteria in fecal samples by plate or tube technique. Two hundred seventy-one samples were analyzed using CART and logistic regression. RESULTS: The dominant factors for complication of enteritis were the minimum number of total obligate anaerobes and the maximum number of Staphylococcus and Enterococcus. The dominant factors for complication of bacteremia were the minimum numbers of total obligate anaerobes and total facultative anaerobes. The dominant factors for mortality were the numbers of total obligate anaerobes and total facultative anaerobes and age. CONCLUSIONS: A decrease in total obligate anaerobes and an increase in pathogenic bacteria in the gut are associated with septic complications and mortality in patients with SIRS. The altered gut flora may be a potential prognostic marker in SIRS patients.

An EF-hands protein, centrin-1, is an EGTA-sensitive SUMO-interacting protein in mouse testis.

A multifunctional calcium-binding protein, centrin-1, is specifically expressed in male germ cells, certain neurons and ciliated cells. We identified centrin-1 as a protein interacting with SUMO-2/3 using yeast two-hybrid screening of a mouse testicular cDNA library. In bead halo assays, the interaction between centrin-1 and SUMO-2/3 was reduced in the presence of EGTA and facilitated by the addition of CaCl2. immunostaining of seminiferous tubules in 35-day-old mouse testes revealed that cells in the layer containing spermatogonia showed colocalization of SUMO-2/3 with centrin-1 in cytoplasmic spots. Identification of centrin-1 as the EGTA-sensitive SUMO-2/3-interacting protein indicates the possible role of calcium in modulating the centrin-1-SUMO-2/3 interaction and suggests the importance of this interaction in mouse testis.

General method for the (11)C-labeling of 2-arylpropionic acids and their esters: construction of a PET tracer library for a study of biological events involved in COXs expression.

Cyclooxygenase (COX) is a critical enzyme in prostaglandin biosynthesis that modulates a wide range of biological functions, such as pain, fever, and so on. To perform in vivo COX imaging by positron emission tomography (PET), we developed a method to incorporate (11)C radionuclide into various 2-arylpropionic acids that have a common methylated structure, particularly among nonsteroidal anti-inflammatory drugs (NSAIDs). Thus, we developed a novel (11)C-radiolabeling methodology based on rapid C-[(11)C]methylation by the reaction of [(11)C]CH(3)I with enolate intermediates generated from the corresponding esters under basic conditions. One-pot hydrolysis of the above [(11)C]methylation products also allows the synthesis of desired (11)C-incorporated acids. We demonstrated the utility of this method in the syntheses of six PET tracers, [(11)C]Ibuprofen, [(11)C]Naproxen, [(11)C]Flurbiprofen, [(11)C]Fenoprofen, [(11)C]Ketoprofen, and [(11)C]Loxoprofen. Notably, we found that their methyl esters were particularly useful as proradiotracers for a study of neuroinflammation. The microPET studies of rats with lipopolysaccharide (LPS)-induced brain inflammation clearly showed that the radioactivity of PET tracers accumulated in the inflamed region. Among these PET tracers, the specificity of [(11)C]Ketoprofen methyl ester was demonstrated by a blocking study. Metabolite analysis in the rat brain revealed that the methyl esters were initially taken up in the brain and then underwent hydrolysis to form pharmacologically active forms of the corresponding acids. Thus, we succeeded in general (11)C-labeling of 2-arylpropionic acids and their methyl esters as PET tracers of NSAIDs to construct a potentially useful PET tracer library for in vivo imaging of inflammation involved in COXs expression.

Synbiotics decrease the incidence of septic complications in patients with severe SIRS: a preliminary report.

The purpose of this study was to evaluate if synbiotic therapy can correct the deteriorated gut flora and environment in patients with severe systemic inflammatory response syndrome (SIRS). Twenty-nine SIRS patients, who fulfilled a serum C-reactive protein (CRP) level >10 mg/dl, received synbiotics (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides) (S group) and were compared with previous observations in 26 patients without synbiotics (NS group). Analysis of fecal flora confirmed that patients in the S group had significantly greater levels of beneficial Bifidobacterium, Lactobacillus, and total organic acids (particularly short-chain fatty acids) than those in the NS group. The incidence of infectious complications such as enteritis, pneumonia, and bacteremia was significantly lower in the S group than in the NS group. Synbiotics maintain the gut flora and environment and decrease the incidence of septic complications in patients with severe SIRS. Further randomized controlled study is necessary to determine the effects of synbiotics.

Bacterial arthritis caused by Leptotrichia amnionii.

Leptotrichia amnionii is an organism that rarely causes female genital tract infection. We describe a case of a male patient with arthritis on the left knee joint due to this organism.