Intracranial solitary fibrous tumor/hemangiopericytoma: tumor reclassification and assessment of treatment outcome via the 2016 WHO classification.

PURPOSE: As per the 2016 World Health Organization (WHO) guidelines on the classification of central nervous system tumors, solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) constitute a single disease entity, known as SFT/HPC. This study provides a clinical analysis of these tumors and describes the treatment outcomes of SFT/HPCs. METHODS: This retrospective study included 76 patients with histopathologically proven SFT/HPC. Reclassification according to the 2016 WHO guideline was done for patients who were diagnosed with SFT or HPC based on the 2007 WHO classification. Recurrence-free survival (RFS) and overall survival (OS) were evaluated for all patients and subgroups. RESULTS: The median follow-up period was 77.9 months. The median RFS and OS were 126.5 and 136.8 months, respectively. The 1-, 5-, 10-, and 15-year RFS rates were 93%, 72%, 40%, and 40%, respectively. The 1-, 5-, 10- and 15-year OS rates were 97%, 89%, 54%, and 35%, respectively. In multivariable analyses, stereotactic radiosurgery (SRS; p = 0.009, hazard ratio [HR] 6.986), female sex (p = 0.023, HR 1.76), and age over 45 (p = 0.037, HR 2.74) were associated with shorter RFS. Patients who underwent SRS as initial treatment had a shorter OS than that of patients who underwent primary resection (p < 0.001, HR 12.86). CONCLUSIONS: High-grade tumors tended to have worse OS and occur extracranial metastases earlier than low-grade tumors. The median RFS was not different between grade II and III tumors. Male sex, younger age, and GTR were associated with a better RFS. A history of SRS before tumor resection was associated with a shorter RFS and OS.

Primary central nervous system lymphoma involving the hypothalamic-pituitary axis: a case series and pooled analysis.

PURPOSE: Primary central nervous system lymphoma (PCNSL) involving the hypothalamic-pituitary axis (H-P axis) is a rare intracranial neoplasm. We aimed to determine the unique characteristics and treatment outcomes of patients with PCNSL at the H-P axis and review the literature. METHODS: We retrospectively reviewed the electronic medical records of patients with PCNSL in our institute from 2000 to 2017. We analyzed patient characteristics, clinicopathologic features, imaging results, and treatment outcomes. Furthermore, we searched the PubMed database and gathered more cases from published studies to analyze patient treatment outcomes. RESULTS: A total of 488 patients were diagnosed with central nervous system lymphoma at our institute. Seven (1.4%) patients had H-P axis involvement, five had diffuse large B-cell lymphoma, and two had mucosa-associated lymphoid tissue lymphoma. All patients had anterior pituitary lobe dysfunction, and two had posterior lobe dysfunction. The median progression-free survival (PFS) for seven patients was 29.0 (range: 0.9-48.1) months, and the 3-year survival rate was 42.9%. Pooled analysis included 45 patients. The median PFS for these patients was 7.0 months (0.9-52.0), and the 2-year survival rate was 20%. Univariate and multivariate analyses revealed that the patients with visual field defects had better prognosis (p = 0.0153 and 0.043, respectively). CONCLUSION: PCNSL at the H-P axis is associated with a higher rate of pituitary dysfunction than other parasellar pathologies. PCNSL at the H-P axis has a worse treatment outcome than PCNSL at other sites. However, visual field defect is related to a favorable prognosis in these patients.

Gender and age differences in the association between work stress and incident depressive symptoms among Korean employees: a cohort study.

PURPOSE: The aim of this study was to identify gender- and age-specific occupational stress associated with depressive symptoms among Korean employees. METHODS: Data of 73,014 employees aged 18 and above who had undergone comprehensive health examinations at Kangbuk Samsung Hospital Health Screening Center, South Korea, in January 2012 and who were followed up until December 2017 were collected, and 63,959 (participation rate: 87.59%, men: 50,413, women: 13,546) were finally analyzed. A Cox proportional hazards model was used to estimate the hazard ratios and 95% confidence intervals of the relationship between occupational stress and depressive symptoms. In light of gender and age differences in the association between occupational stress and depressive symptoms, interaction and stratification by gender and age groups were tested. RESULTS: During 238,630 person-years of follow-up, case-level depressive symptoms developed in 4227 participants (an incident rate of 1.8%). There were gender differences in the relationship between job stress and incident depressive symptoms. For men, high job demand, job insecurity, lack of reward, and discomfort in their organizational climate were associated with incident depressive symptoms in all age groups. Insufficient job control was associated with the development of depressive symptoms only in midlife and organizational injustice only in early adulthood. For women, the results for high job demand, organizational injustice, and discomfort in an organizational climate were associated with the onset of depressive symptoms from early adulthood to the midlife decade. CONCLUSION: The results suggest gender and age differences in the relationship between occupational stress and incident depressive symptoms.

Data analytics approach for melt-pool geometries in metal additive manufacturing.

Modern data analytics was employed to understand and predict physics-based melt-pool formation by fabricating Ni alloy single tracks using powder bed fusion. An extensive database of melt-pool geometries was created, including processing parameters and material characteristics as input features. Correlation analysis provided insight for relationships between process parameters and melt-pools, and enabled the development of meaningful machine learning models via the use of highly correlated features. We successfully demonstrated that data analytics facilitates understanding of the inherent physics and reliable prediction of melt-pool geometries. This approach can serve as a basis for the melt-pool control and process optimization.

Punicalagin suppresses methicillin resistance of Staphylococcus aureus to oxacillin.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen that is cross-resistant to most ß-lactam antibiotics. We investigated whether oxacillin, which is a ß-lactam antibiotic, alone or in combination with punicalagin can affect the penicillin binding protein 2a (PBP2a)-mediated resistance of MRSA. Susceptibility testing of punicalagin with oxacillin was performed using the microdilution and checkerboard assay and the growth curve assay. Binding affinity of punicalagin for cell wall peptidoglycan (PGN) was confirmed by an increased concentration of PGN in bacterial cultures containing punicalagin. The level of PBP2a was analyzed by western blotting. Punicalagin exhibited antimicrobial activity in the viability assay and increased the susceptibility of MRSA to oxacillin. PGN interfered with the antimicrobial activity of punicalagin and prevented the synergistic activity of punicalagin and oxacillin. Increasing the concentration of punicalagin and maintaining a constant concentration of oxacillin resulted in synergistic suppression of the expression of the mec operon (mecA, mecI, and mecR1). The production of PBP2a was suppressed by the addition of punicalagin to oxacillin. Our findings demonstrate that punicalagin potentiates the effect of oxacillin on MRSA by reducing the transcription of mecA (a gene marker for methicillin resistance), which resulted in a reduced level of PBP2a.

Impaired facial expression recognition in patients with social anxiety disorder: a case-control study.

INTRODUCTION: The aim of this study was to investigate whether social anxiety disorder (SAD) patients have low emotion recognition accuracy, take longer for emotion recognition and tended to interpret a stimulus more negatively than controls. METHODS: Fifty-six SAD patients and 56 healthy controls were participated in this study. We evaluated facial emotion recognition using a computer program in which participants chose one of seven emotions as displayed in each of 55 photographs of faces. We compared the accuracy and reaction times of the patients and controls. We further analysed which emotions were selected in the incorrect answers. RESULTS: SAD patients showed delayed reaction times for all emotions except anger and lower accuracy for fear, surprise, neutrality and happiness compared to controls. After applying Bonferroni correction, only delayed reaction time for surprise and happiness were remain significant. Neutrality was not mistaken for a negative emotion at a higher rate by SAD patients than by controls. CONCLUSION: This result suggests that the alterations of reaction time and accuracy of emotion recognition of SAD patients, especially in emotions with positive valence, play a more important role than negative bias in the cognitive aspects of SAD.

Dynamics of Methylated Cytosine Flipping by UHRF1.

DNA methylation patterns, which are critical for gene expression, are replicated by DNA methyltransferase 1 (DNMT1) and ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) proteins. This replication is initiated by the recognition of hemimethylated CpG sites and further flipping of methylated cytosines (mC) by the Set and Ring Associated (SRA) domain of UHRF1. Although crystallography has shed light on the mechanism of mC flipping by SRA, tools are required to monitor in real time how SRA reads DNA and flips the modified nucleobase. To accomplish this aim, we have utilized two distinct fluorescent nucleobase surrogates, 2-thienyl-3-hydroxychromone nucleoside (3HCnt) and thienoguanosine (thG), incorporated at different positions into hemimethylated (HM) and nonmethylated (NM) DNA duplexes. Large fluorescence changes were associated with mC flipping in HM duplexes, showing the outstanding sensitivity of both nucleobase surrogates to the small structural changes accompanying base flipping. Importantly, the nucleobase surrogates marginally affected the structure of the duplex and its affinity for SRA at positions where they were responsive to base flipping, illustrating their promise as nonperturbing probes for monitoring such events. Stopped-flow studies using these two distinct tools revealed the fast kinetics of SRA binding and sliding to NM duplexes, consistent with its reader role. In contrast, the kinetics of mC flipping was found to be much slower in HM duplexes, substantially increasing the lifetime of CpG-bound UHRF1, and thus the probability of recruiting DNMT1 to faithfully duplicate the DNA methylation profile. The fluorescence-based approach using these two different fluorescent nucleoside surrogates advances the mechanistic understanding of the UHRF1/DNMT1 tandem and the development of assays for the identification of base flipping inhibitors.

Microwave-Assisted Protein Digestion in a Plate Well for Facile Sampling and Rapid Digestion.

Protein digestion is one of the most important processes in proteomic analysis. Here, we report microwave-assisted protein digestion in a plate well, which allows for facile sampling as well as rapid protein digestion based on the combination of highly stable enzyme immobilization and 3D printing technologies. Trypsin (TR) was immobilized on polystyrene-based nanofibers via an enzyme coating (EC) approach. The EC with stabilized TR activity was assembled with the 3D-printed structure in the plate well (EC/3D), which provides two separated compartments for the solution sampling and the TR-catalyzed protein digestion, respectively. EC/3D can effectively prevent the interference of sampling by accommodating EC in the separated compartment from the sampling hole in the middle. EC/3D in the plate well maintained its protein digestion performance under shaking over 160 days. Microwave irradiation enabled the digestion of bovine serum albumin within 10 min, generating the MALDI-TOF MS results of 75.0% sequence coverage and 61 identified peptides. EC/3D maintained its protein digestion performance under microwave irradiation after 30 times of recycled uses. EC/3D in the plate well has demonstrated its potential as a robust and facile tool for the development of an automated protein digestion platform. The combination of stable immobilized enzymes and 3D-printed structures can be potentially utilized not only for the protein digestion, but also for many other enzyme applications, including bioconversion and biosensors.

Binge eating is associated with trait anxiety in Korean adolescent girls: a cross sectional study.

BACKGROUND: Binge eating occurs more frequently in women than in men, and is known to be related to psychological factors such as stress, depression, and anxiety. This study examined the relationship between binge eating and depression, trait anxiety, and perceived stress in Korean adolescents. METHODS: Four hundred girls (aged 17-18 years) from two high schools located in Seoul completed self-report questionnaires. In total, 327 participants returned reliable responses, and were included in the final study. Binge eating was measured using the Bulimic Inventory Test Edinburgh. The questionnaire also included the Perceived Stress Scale (PSS), Trait Anxiety (TA) of State-Trait Anxiety Inventory, Anxiety Sensitivity Inventory (ASI), and Beck Depression Inventory (BDI). RESULTS: The binge-eating group had higher BMI than the control group. The binge-eating group showed higher scores than control on the PSS, BDI, ASI, and TA. The TA was most highly correlated with binge eating. From logistic regression analysis, TA was revealed to be the only factor that raised the risk of binge eating, whereas PSS, BDI, and ASI showed no statistical significance. CONCLUSION: Although binge eating was correlated with perceived stress, depression, and trait anxiety, when their influences were controlled, only binge eating appeared to be associated with trait anxiety.

Petascale supercomputing to accelerate the design of high-temperature alloys.

Recent progress in high-performance computing and data informatics has opened up numerous opportunities to aid the design of advanced materials. Herein, we demonstrate a computational workflow that includes rapid population of high-fidelity materials datasets via petascale computing and subsequent analyses with modern data science techniques. We use a first-principles approach based on density functional theory to derive the segregation energies of 34 microalloying elements at the coherent and semi-coherent interfaces between the aluminium matrix and the θ'-Al2Cu precipitate, which requires several hundred supercell calculations. We also perform extensive correlation analyses to identify materials descriptors that affect the segregation behaviour of solutes at the interfaces. Finally, we show an example of leveraging machine learning techniques to predict segregation energies without performing computationally expensive physics-based simulations. The approach demonstrated in the present work can be applied to any high-temperature alloy system for which key materials data can be obtained using high-performance computing.

Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position.

Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5'- and 3'-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix.

An Aspect of the History of Medicine in Ancient Korea as Examined through Silla Buddhist Monks'Annotations on the "Chapter on Eliminating Disease"in the Sutra of Golden Light (Suvarnabhasa-sutra).

Nearly nothing is known of medicine in ancient Korea due to insufficient materials. With several extant prescriptions and esoteric methods of treating diseases alone, it is impossible to gauge in depth the management of medicine during this period. If one exception were to be cited, that would be the fact that the annotations for understanding the contents on Indian medicine in the "Chapter on Eliminating Disease" in the Sutra of Golden Light, a Buddhist sutra originating from India, reflected the medical knowledge of Buddhist monks from Silla (57 BC-935 AD) who were active immediately after the nation's unification of the two other kingdoms on the Korean Peninsula (668 AD) such as Wonhyo (617-686 AD), Gyeongheung (620?-700? AD), and Seungjang (684-? AD). Along with those by other monks, these annotations are collected in the Mysterious Pivot of the Sutra of Golden Light, which was compiled by Gangyo(835-871 AD), a Japanese monk from the Heian era (794-1185 AD). Representative versions of the "Chapter on Eliminating Disease" in the Sutra of Golden Light include: a classical Chinese translation by the Indian monk Dharmaksema (385-433 AD); the eight-volume edition by Chinese monk Baogui, which differs little from the preceding work in terms of the contents of the "Chapter on Eliminating Disease"; and the ten-volume edition by Yijing (635-713 AD), who had full-fledged knowledge of Indian medicine. When the contents of the annotations thus collected are examined, it seems that Wonhyo had not been aware of the existence of the ten-volume edition, and Gyeongheung and Seungjang most certainly used the ten-volume edition in their annotations as well. Especially noteworthy are Wonhyo's annotations on the Indian medical knowledge found in the "Chapter on Eliminating Disease" in the Sutra of Golden Light. Here, he made a bold attempt to link and understand consistently even discussions on Indian and Buddhist medicine on the basis of the traditional East Asian medical theory centering on the yin-yang and five phases (wuxing). In accordance with East Asia's theory of the seasonal five phases, Wonhyo sought to explain aspects of Indian medicine, e.g., changes in the four great elements (catvari maha-bhutani) of earth, water, fire, and wind according to seasonal factors and their effect on the internal organs; patterns of diseases such as wind (vata)-induced disease, bile (pitta)-induced disease, phlegm (slesman)-induced disease, and a combination (samnipata) of these three types of diseases; pathogenesis due to the indigestion of food, as pathological mechanisms centering on the theory of the mutual overcoming (xiangke) of the five phases including the five viscera (wuzang), five flavors (wuwei), and five colors (wuse). They existed in the text contents on Indian medicine, which could not be explicated well with the existing medical knowledge based on the theory of the five phases. Consequently, he boldly modified the theory of the five phases in his own way for such passages, thus attempting a reconciliation, or harmonization of disputes (hwajaeng), of the two medical systems. Such an attempt was even bolder than those by earlier annotators, and Wonhyo's annotations came to be accepted by later annotators as one persuasive explanation as well. In the case of Gyeongheung and Seungjang, who obtained and examined the ten-volume edition, a new classical Chinese translation produced following Wonhyo's death, annotated the "Chapter on Eliminating Disease" based on their outstanding proficiency in Sanskrit and knowledge of new Indian and Buddhist medicine. This fact signifies that knowledge of the eight arts of Ayurvedic medicine in India was introduced into Silla around the early 8th century. The medical knowledge of Wonhyo, Gyeongheung, and Seungjang demonstrates that intellectual circles in contemporary Silla were arenas in which not only traditional East Asian medicine as represented by works such as the Inner Canon of the Yellow Emperor (Huangdi Neijing) but also Indian medicine of Buddhism coexisted in almost real time.

Tautomers of a Fluorescent G Surrogate and Their Distinct Photophysics Provide Additional Information Channels.

Thienoguanosine ((th) G) is an isomorphic nucleoside analogue acting as a faithful fluorescent substitute of G, with respectable quantum yield in oligonucleotides. Photophysical analysis of (th) G reveals the existence of two ground-state tautomers with significantly shifted absorption and emission wavelengths, and high quantum yield in buffer. Using (TD)-DFT calculations, the tautomers were identified as the H1 and H3 keto-amino tautomers. When incorporated into the loop of (-)PBS, the (-)DNA copy of the HIV-1 primer binding site, both tautomers are observed and show differential sensitivity to protein binding. The red-shifted H1 tautomer is strongly favored in matched (-)/(+)PBS duplexes, while the relative emission of the H3 tautomer can be used to detect single nucleotide polymorphisms. These tautomers and their distinct environmental sensitivity provide unprecedented information channels for analyzing G residues in oligonucleotides and their complexes.

Conquering 2-aminopurine's deficiencies: highly emissive isomorphic guanosine surrogate faithfully monitors guanosine conformation and dynamics in DNA.

The archetypical fluorescent nucleoside analog, 2-aminopurine (2Ap), has been used in countless assays, though it suffers from very low quantum yield, especially when included in double strands, and from the fact that its residual emission frequently does not represent biologically relevant conformations. To conquer 2Ap's deficiencies, deoxythienoguanosine (d(th)G) was recently developed. Here, steady-state and time-resolved fluorescence spectroscopy was used to compare the ability of 2Ap and d(th)G, to substitute and provide relevant structural and dynamical information on a key G residue in the (-) DNA copy of the HIV-1 primer binding site, (-)PBS, both in its stem loop conformation and in the corresponding (-)/(+)PBS duplex. In contrast to 2Ap, this fluorescent nucleoside when included in (-)PBS or (-)/(+)PBS duplex fully preserves their stability and exhibits a respectable quantum yield and a simple fluorescence decay, with marginal amounts of dark species. In further contrast to 2Ap, the fluorescently detected d(th)G species reflect the predominantly populated G conformers, which allows exploring their relevant dynamics. Being able to perfectly substitute G residues, d(th)G will transform nucleic acid biophysics by allowing, for the first time, to selectively and faithfully monitor the conformations and dynamics of a given G residue in a DNA sequence.

Clinical symptoms associated with suicidality in patients with panic disorder.

BACKGROUND: Patients with panic disorder have higher rates of suicide than the general population. Among panic disorder subjects, early onset, female gender, alcohol abuse, and mood disorder increase the risk of suicidality. However, less is known about the unique relationships between discrete DSM-IV panic symptoms and higher suicidality. Therefore, in the current study we examined the panic symptom profile that is associated with higher suicidality in a sample of outpatients with panic disorder. METHODS: This cross-sectional study included 427 patients diagnosed with current panic disorder on the basis of the DSM-IV-TR. In order to assess the contribution of the clinical variables, a univariate logistic regression was carried out examining the relationships between the demographic variables, suicidality from the suicide module of the Korean version of the MINI International Neuropsychiatric Interview Plus, and DSM-IV panic symptoms. Additionally, a multivariate logistic regression was performed to identify specific panic symptoms that were significant risk factors for suicidality among patients with current panic disorder. RESULTS: We found that 74 (17.33%) panic disorder patients experienced high suicidality. Univariate analyses showed that high suicidality was significantly associated with a younger age (OR = 13.66; 95% CI 2.68-69.70), comorbid depressive disorders (OR = 4.57; 95% CI 2.57-8.11), and the following panic symptoms: palpitations (OR = 2.20; 95% CI 0.90-5.35), trembling (OR = 0.61; 95% CI 0.362-1.18), nausea or abdominal distress (OR = 1.77; 95% CI 0.96-3.27), fear of losing control or going crazy (OR = 2.18; 95% CI 1.12-4.23), and paresthesia (OR = 1.57; 95% CI 0.83-2.98). Multivariate logistic regression analyses demonstrated that specific panic symptoms, such as palpitations (adjusted OR = 2.69; 95% CI 1.08-6.73) and fear of losing control or going crazy (adjusted OR = 2.28; 95% CI 1.21-4.31), were related to suicidality after controlling for confounding factors. CONCLUSION: Some panic symptoms (e.g. palpitations and fear of losing control or going crazy) are associated with a risk of suicidality among patients with panic disorder. A priori identification of high-risk suicidal subjects could lead to effective treatment strategies for panic disorder.

In vitro Potential Effect of Morin in the Combination with ß-Lactam Antibiotics Against Methicillin-Resistant Staphylococcus aureus.

Morin, a plant-derived flavonol, is known to be an effective inhibitor of Gram-positive bacteria. In this study, we explored the combined effect of morin with ß-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen. The anti-MRSA activity of morin was investigated by the broth microdilution method, checkerboard dilution test, and time-kill curve assay. The expression of the resistant protein, penicillin-binding protein (PBP2a) encoded by mecA, was analyzed by the Western blotting method in the presence of morin and oxacillin. An increased susceptibility of MRSA toward oxacillin was observed in the presence of morin. The protein level of PBP2a was reduced when MRSA (ATCC 33591) was treated with the combination of morin and oxacillin, indicating that the combination of morin and oxacillin potentiates the killing effect against MRSA. The present study indicates that the killing effect by the combinative treatment of morin and ß-lactam antibiotic is dependent on the PBP2a-mediated resistance mechanism.

Association between Hypertriglyceridemia and Lacunar Infarction in Type 2 Diabetes Mellitus.

BACKGROUND: Although recent studies have shown that the elevation of serum triglyceride (TG) is related to the increased incidence of ischemic stroke, the relationship between hypertriglyceridemia and subtypes of ischemic stroke is largely unknown. This study attempted to evaluate whether hypertriglyceridemia is associated with lacunar stroke in diabetes mellitus (DM). METHODS: A total of 2141 consecutive patients with acute ischemic stroke were enrolled from March 2005 to April 2014, excluding the subjects with undetermined/other determined etiology or no lipid data. We compared the lipid profiles among stroke subtypes. The estimated serum TG levels and the interaction between DM and stroke subtypes were determined by analysis of covariance (ANCOVA) and Tukey's multiple comparison. RESULTS: In ANCOVA test, the difference of estimated TG between DM and non-DM patients was largest in small-vessel occlusion (SVO; 159.7 [95% confidence interval {CI}, 143.2-176.2] versus 122.4 [95% CI, 106.1-138.7]), and a significant interaction was observed between DM and stroke subtypes for TG levels (P = .013) but not for total cholesterol (P = .363), low-density lipoprotein cholesterol (P = .171), or high-density lipoprotein cholesterol (P = .231). By Tukey's multiple comparison, SVO was consistently associated with DM for serum TG levels (P < .001). CONCLUSIONS: In acute ischemic stroke with DM, serum TG level was significantly associated with lacunar infarction adjusting for other lipid profiles and vascular risk factors. Further studies are warranted to reveal the pathophysiologic implication of hypertriglyceridemia for lacunar infarction in type 2 DM.

[Applying the Methodology and Practice of Microhistory: The Diary of a Confucian Doctor, Yi Mun-gǒn (1495-1567)].

Since microhistory's approach to the past is based on an understanding of and a sympathy for the concrete details of human lives, its area of interests overlaps with the history of medicine and medical humanities, which examine illness and health. If we put a specific region and society in a specific period under a microscope and increase the magnifying power, we can understand the numerous network connections among the body, illness management, and medicine and how multilayered were the knowledge and power applied to them. And this approach of using microhistory to illuminate medical history can be more effective than any other historical approach. This article focuses on Yi Mun-gǒn's extensive volumes of Mukchaeilgi (Mukchae's diary) in approaching medical history from the perspective of microhistory. Simply defined, this work is a Confucian scholar-doctor's diary. Its author, Yi Mun-gǒn, played the role of a Confucian doctor, although not professionally, during his 23-year exile, after serving in a high governmental office on the senior grade of the third court rank. Thanks to this extensive and detailed diary, we can now get adetailed andthorough picture of his medical practice in the Sǒngju region, 270 kilometers southeast of Seoul, where he was exiled. This article aims to understand the state of medical practice in the Sǒngju region in the 16thcentury through the"zoom-in" method adopted by microhistory. In particular, I will focus on the following three aspects:1) Yi Mun-gǒn's motivation for and method of medical study, 2)the character of Yi Mun-gǒn'spatient treatment as hwarin (the act of life-saving), and 3) the plural existence of various illness management methods, including pyǒngjǒm (divination of illness), sutra-chanting, exorcism, and ch'oje (ritual toward Heaven). All three aspects are closely related to Confucianism. First, Yi Mun-gǒn decided to acquire professional-level medical knowledge in order to practice the Confucian virtue of filial piety. He sharpened his medical knowledge during the process of caring for his ill mother. In Confucian Chosǒn society, a patient was encouraged to be deeply involved in the process of his or her medical treatment and the space of clinical treatment was not an exclusive domain for the doctor, but for public discussion, where both doctor and patient participated in making the best medical choices. In this atmosphere, a patient's family members would also naturally learn the clinical process, not unlike today's interns learning from renowned doctors. Second, after studying medicine up to a professional level, Yi Mun-gǒn administered the "life-saving" medicine to many people, yet he did not open his doors to all individuals. His medicine was practiced within his social network of blood, regional, and intellectual relations, where priority was established according to the level of closeness to himself, according to Confucian ideology. Nevertheless, because he did partially accept patients outside of these networks, his practice setin motion the symbolic system of Confucian ideal of universal "life-saving."Third, in the Sǒngju region during the 16thcentury, various methods of treating illnesses-such as medicine, divination, sutra-chanting, exorcism, and kumyǒngsisik (life-saving, food-offering ritual)-co-existed and were selected according to individual conditions. Confucianism did not want to either acknowledge or outright reject most of these methods, except for officially acknowledged medicine, at that time. In fact, this coexistence was inevitable because there was not one entirely effective means of curing illness at that time. Also, the system of Confucian ideology was not powerful enough to enforce what it championed. On the contrary, behind the outer austerity of Confucian society, people sought out unorthodox methods, such as exorcism, Buddhism, and Taoism-ironically, in order to practice the important Confucian values of filial piety and patrilineage in the face of their parents' or sons'illnesses. It was only after the emergence of modern ideology and methodology of hygiene, which had the ability to control epidemics and prioritize the preservation of the life of individuals and the population, following the opening of the port in the late 19th century, that this pluralistic culture for illness management became much less prevalent.

A Fluorescent Adenosine Analogue as a Substrate for an A-to-I RNA Editing Enzyme.

Adenosine to inosine RNA editing catalyzed by ADAR enzymes is common in humans, and altered editing is associated with disease. Experiments using substrate RNAs with adenosine analogues at editing sites are useful for defining features of the ADAR reaction mechanism. The reactivity of ADAR2 was evaluated with RNA containing the emissive adenosine analogue thieno[3,4-d]-6-aminopyrimidine ((th)A). This nucleoside was incorporated into a mimic of the glutamate receptor B (GluR B) mRNA R/G editing site. We found that (th)A is recognized by AMV reverse transcriptase as A, and is deaminated rapidly by human ADAR2 to give (th)I. Importantly, ADAR reaction progress can be monitored by following the deamination-induced change in fluorescence of the (th)A-modified RNA. The observed high (th)A reactivity adds to our understanding of the structural features that are necessary for an efficient hADAR2 reaction. Furthermore, the new fluorescent assay is expected to accelerate mechanistic studies of ADARs.

Isomorphic emissive GTP surrogate facilitates initiation and elongation of in vitro transcription reactions.

The fastidious behavior of T7 RNA polymerase limits the incorporation of synthetic nucleosides into RNA transcripts, particularly at or near the promoter. The practically exclusive use of GTP for transcription initiation further compounds this challenge, and reactions with GTP analogs, where the heterocyclic nucleus has been altered, have not, to our knowledge, been demonstrated. The enzymatic incorporation of (th)GTP, a newly synthesized isomorphic fluorescent nucleotide with a thieno[3,4-d]pyrimidine core, is explored. The modified nucleotide can initiate and maintain transcription reactions, leading to the formation of fully modified and highly emissive RNA transcripts with (th)G replacing all guanosine residues. Short and long modified transcripts are synthesized in comparable yields to their natural counterparts. To assess proper folding and function, transcripts were used to assemble a hammerhead ribozyme with all permutations of natural and modified enzyme and substrate strands. The (th)G modified substrate was effectively cleaved by the natural RNA enzyme, demonstrating the isomorphic features of the nucleoside and its ability to replace G residues while retaining proper folding. In contrast, the (th)G modified enzyme showed little cleavage ability, suggesting the modifications likely disrupted the catalytic center, illustrating the significance of the Hoogsteen face in mediating appropriate contacts. Importantly, the ribozyme cleavage reaction of the emissive fluorescent transcripts could be followed in real time by fluorescence spectroscopy. Beyond their utility as fluorescent probes in biophysical and discovery assays, the results reported point to the potential utility of such isomorphic nucleosides in probing specific mechanistic questions in RNA catalysis and RNA structural analysis.