Adrenocortical Carcinoma Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration

Adrenocortical carcinoma (ACC) is a rare malignancy with a very poor prognosis. A 77-year-old man underwent imaging studies due to poorly controlled hypertension, which revealed a mass measuring 43 mm in diameter near the left adrenal gland. There were no findings indicative of pheochromocytoma. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed for the preoperative pathological evaluation, and the findings indicated a possibility of ACC. Based on these results, curative surgery was performed. If the diagnosis of pheochromocytoma is excluded, then EUS-FNA for adrenal lesions is relatively safe. It can also be used for the preoperative diagnosis of ACC.     

Tracking the crystallization behavior of high-silica FAU during AEI-type zeolite synthesis using acid treated FAU-type zeolite

During AEI zeolite synthesis using acid treated FAU (AcT-FAU), we found the recrystallization of high-silica FAU with high crystallinity and Si/Al ratio of 6.1 using N,N-dimethyl-3,5-dimethylpiperidinium hydroxide (DMDMPOH) after 2 h, followed by the crystallization of AEI via FAU-to-AEI interzeolite conversion at a longer synthesis time. In order to understand the formation mechanism of high-silica FAU and generalize its direct synthesis, we have investigated this synthesis process. An analysis of the short-range structure of AcT-FAU revealed that it has an ordered aluminosilicate structure having a large fraction of 4-rings despite its low crystallinity. The changes in the composition of the products obtained at different synthesis times suggested that DMDMP⁺ plays a certain role in the stabilization of the FAU zeolite framework. Moreover, the results of thermogravimetric analysis showed that the thermal stability of DMDMP⁺ changed with the zeolite conversion. To the best of our knowledge, this is the first study to clarify the structure-directing effect of DMDMP⁺ on FAU zeolite formation.

A high-silica FAU was obtained during FAU-to-AEI interzeolite conversion using acid treated FAU.     

Recent progress in the use of diaziridine-based sweetener derivatives to elucidate the chemoreception mechanism of the sweet taste receptor

All sweeteners are recognized by the sweet taste receptor (T1R2–T1R3). The elucidation of the chemoreception mechanism of receptor–ligand interactions is an attractive topic for researchers. Molecular biology and computational biology techniques can reveal the proposed mechanisms for this topic. Other approaches, including chemical biology (bioorganic chemistry), have helped to identify mechanisms on the basis of molecular structure. In this mini-review, we have summarized the recent progress in the synthesis of sweetener derivatives, which includes the use of photoaffinity labeling of diazirine-based derivatives to elucidate the chemoreception of sweeteners.

The review summarized recent progress for the elucidation of the chemoreception mechanism of sweet taste receptor–sweetener interactions with photoaffinity labeling.     

Appropriate definition of diabetes using an administrative database: A cross‐sectional cohort validation study

Aims/IntroductionThe purpose of the present study was to quantify errors in the diagnosis of diabetes for use in the national database, using a sufficient population size.Materials and methodsA claims database constructed by the JMDC (Tokyo, Japan), using standardized disease classifications and anonymous record linkage, was used in this validation study. We included patients with health insurance claims data from April 2005 to March 2019 in the JMDC claims database. We excluded patients without a record of specific health checkups in Japan. Sample size calculation was based on a 5% prevalence of diabetes and 0.4% absolute accuracy (i.e., 1,250,000 individuals), to calculate the sensitivity, specificity, positive predictive value and negative predictive value.ResultsIn total, 2,999,152 patients were included in this study, of which 165,515 were classified as having diabetes based on specific health checkups (validation cohort prevalence of 5.5%). The newly devised algorithm had three elements – the diagnosis‐related codes for diabetes without suspected flag, the medication codes for diabetes and then these two codes on the same record – and yielded a sensitivity of 74.6%, positive predictive value of 88.4% and Kappa Index of 0.80 (the highest values).ConclusionsIn future claims database studies, our validated algorithms will be useful as diagnostic criteria for diabetes.     

Microglial responses after phagocytosis: Escherichia coli bioparticles,but not cell debris or amyloid beta,induce matrix metalloproteinase-9 secretion in cultured rat primary microglial cells

Upon infection or brain damage, microglia are activated to play roles in immune responses, including phagocytosis and soluble factor release. However, little is known whether the event of phagocytosis could be a trigger for releasing soluble factors from microglia. In this study, we tested if microglia secrete a neurovascular mediator matrix metalloproteinase-9 (MMP-9) after phagocytosis in vitro. Primary microglial cultures were prepared from neonatal rat brains. Cultured microglia phagocytosed Escherichia coli bioparticles within 2 hr after incubation and started to secrete MMP-9 at around 12 hr after the phagocytosis. A TLR4 inhibitor TAK242 suppressed the E. coli-bioparticle-induced MMP-9 secretion. However, TAK242 did not change the engulfment of E. coli bioparticles in microglial cultures. Because lipopolysaccharides (LPS), the major component of the outer membrane of E. coli, also induced MMP-9 secretion in a dose–response manner and because the response was inhibited by TAK242 treatment, we assumed that the LPS-TLR4 pathway, which was activated by adhering to the substance, but not through the engulfing process of phagocytosis, would play a role in releasing MMP-9 from microglia after E. coli bioparticle treatment. To support the finding that the engulfing step would not be a critical trigger for MMP-9 secretion after the event of phagocytosis in microglia, we confirmed that cell debris and amyloid beta were both captured into microglia via phagocytosis, but neither of them induced MMP-9 secretion from microglia. Taken together, these data demonstrate that microglial response in MMP-9 secretion after phagocytosis differs depending on the types of particles/substances that microglia encountered.     

Establishment of epigenetic markers to predict irradiation efficacy against oropharyngeal cancer

Irradiation, or chemoradiotherapy, is a curative treatment for oropharyngeal squamous cell carcinoma (OPSCC). Its invasiveness, however, can often negate its efficacy. Therefore, developing methods to predict which patients would benefit from irradiation is urgent. Promoter DNA hypermethylation was recently reported to correlate with favorable OPSCC prognosis. It is still unclear, however, whether there is an association between promoter DNA methylation and response to irradiation. In this study, we analyzed DNA methylation in the specimens from 40 OPSCC patients who had undergone irradiation, using the Infinium assay. Our results showed significant correlation between high levels of promoter DNA methylation and better response to treatment (P < 0.01). We used the 10 most differentially‐methylated genes between responders and non–responders to develop a panel of predictive markers for efficacy. Our panel had high sensitivity, specificity and accuracy (92%, 93% and 93%, respectively). We conducted pyrosequencing to quantitatively validate the methylation levels of 8 of the 10 marker genes (ROBO1, ULK4P3, MYOD1, LBX1, CACNA1A, IRX4, DPYSL3 and ELAVL2) obtained by Infinium. The validation by pyrosequencing showed that these 8 genes had a high prediction performance for the training set of 40 specimens and for a validation set of 35 OPSCC specimens, showing 96% sensitivity, 89% specificity and 94% accuracy. Methylation of these markers correlated significantly with better progression‐free and overall survival rates, regardless of human papillomavirus status. These results indicate that increased DNA methylation is associated with better responses to irradiation therapy and that DNA methylation can help establish efficacy prediction markers in OPSCC.     

Cytolytic Recombinant Vesicular Stomatitis Viruses Expressing STLV-1 Receptor Specifically Eliminate STLV-1 Env-Expressing Cells in an HTLV-1 Surrogate Model In Vitro

Human T-cell leukemia virus type 1 (HTLV-1) causes serious and intractable diseases in some carriers after infection. The elimination of infected cells is considered important to prevent this onset, but there are currently no means by which to accomplish this. We previously developed “virotherapy”, a therapeutic method that targets and kills HTLV-1-infected cells using a cytolytic recombinant vesicular stomatitis virus (rVSV). Infection with rVSV expressing an HTLV-1 primary receptor elicits therapeutic effects on HTLV-1-infected envelope protein (Env)-expressing cells in vitro and in vivo. Simian T-cell leukemia virus type 1 (STLV-1) is closely related genetically to HTLV-1, and STLV-1-infected Japanese macaques (JMs) are considered a useful HTLV-1 surrogate, non-human primate model in vivo. Here, we performed an in vitro drug evaluation of rVSVs against STLV-1 as a preclinical study. We generated novel rVSVs encoding the STLV-1 primary receptor, simian glucose transporter 1 (JM GLUT1), with or without an AcGFP reporter gene. Our data demonstrate that these rVSVs specifically and efficiently infected/eliminated the STLV-1 Env-expressing cells in vitro. These results indicate that rVSVs carrying the STLV-1 receptor could be an excellent candidate for unique anti-STLV-1 virotherapy; therefore, such antivirals can now be applied to STLV-1-infected JMs to determine their therapeutic usefulness in vivo.     

Development of culture-sensitive clinical teacher evaluation sheet in the Japanese context

Aim: Many instruments for evaluating clinical teaching have been developed, albeit most in Western countries. This study aims to develop a validated cultural and local context sensitive instrument for clinical teachers in an East Asian setting (Japan), Japanese Clinical Teacher Evaluation Sheet (JaCTES).

Methods: A multicenter, cross-sectional evaluation study was conducted. We collected a total of 1368 questionnaires on 304 clinical teachers, completed by residents in 16 teaching hospitals. The construct validity was examined by conducting a factor analysis and using structural equation modeling (SEM). We also assessed the reliability using generalizability analysis and decision study.

Results: Exploratory factor analysis resulted in three-factor (role model, teaching activities, and accessibility) model including 18 items. Confirmatory factor analysis was performed, using SEM. The comparative fit index was 0.931 and the root mean square error of approximation was 0.087, meaning an acceptable goodness of fit for this model. To obtain a reliable dependability-coefficient of at least 0.70 or higher, 5–8 resident responses are necessary.

Discussion and conclusion: JaCTES is the first reported instrument with validity evidence of content and internal structure and high feasibility in Japan, an East Asian setting. Medical educators should be aware of the local context and cultural aspects in evaluating clinical teachers.