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Aims Rifampicin is a key drug for the treatment of tuberculosis (TB). Little is known for the relationship between the rifampicin pharmacokinetics and genetic polymorphisms in the Asian population. We aimed to investigate relationship between genetic polymorphism of SLCO1B1 and rifampicin exposure and its impact on clinical outcomes in Korean patients with active pulmonary TB. Methods From February 2016 to December 2019, patients with active pulmonary TB who were taking rifampicin for >1 week were prospectively enrolled. Serial or 1-time blood sampling was conducted to determine rifampicin concentrations. The genotype of 4 single nucleotide polymorphisms of SLCO1B1 was determined. To estimate the drug clearance and exposure, population pharmacokinetics analysis was conducted. Clinical outcomes such as time to acid-fast bacteria culture conversion, chest radiograph score changes from baseline, and all-cause mortality were also evaluated. The exposure among different SLCO1B1 genotype was compared and relationship between drug exposure and clinical outcomes were explored. Results A total of 105 patients (70 males and 35 females) were included in the final analysis. The mean age of patients was 55.4 years. The mean drug clearance and exposure were 13.6 L/h and 57.9 mg h/L, respectively. The genetic polymorphisms of SLCO1B1 were not related to rifampicin clearance or exposure. As the rifampicin exposure increased, the chest radiographs improved significantly, but the duration of acid-fast bacteria culture conversion was not related to the drug exposure. Conclusion SLCO1B1 gene polymorphisms did not influence rifampicin concentrations and clinical outcomes in Korean patients with active pulmonary TB.

The purpose of this study was to develop a safe and effective method for preventing Allomyrina dichotoma nudivirus (AdNV) infection in the Korean horned beetle, Allomyrina dichotoma, found on the farms in the Republic of Korea. Mulberry leaf powder was added to fermented oak sawdust to minimize mortality in AdNV‐infected A. dichotoma. Mulberry leaves were found to contain 1‐deoxynojirimycin, which has anti‐inflammatory, antiviral, and anti‐tumor effects. Based on the proposed antiviral effects of mulberry leaves, a feed of fermented sawdust combined with 1% or 5% mulberry leaf powder was fed to AdNV‐infected second or third stage A. dichotoma larvae. The larval mortality rate was recorded over 10 weeks. The second and third instar larvae that were fed with the sawdust mixture with 5% mulberry leaf powder had mortality rates of 60% and 30%, respectively. In contrast, the control group that was fed with the sawdust without mulberry leaf powder had a mortality rate of 100%. Also, we confirmed that AdNV was not detected in the experimental group that was subjected to an outdoor application test for 8 months with mulberry leaf powder treatment. A reduced mortality rate after treatment with 1% mulberry leaf powder was observed in the field application. In addition, a comparison of the control colony and mulberry leaf treated group showed a statistical difference in growth of larvae at various states, and demonstrated the efficiency of mulberry leaf powder combined with fermented sawdust for treatment of AdNV‐ infected A. dichotoma.

This report reveals the structure of a virus extracted from the Korean horn beetle Allomyrina dichotoma. The purified virus particle was 100% identical to Allomyrina virus lef‐8 sequence registered as KM_233709.1. The structure of this virus was confirmed to be closely related to that of the Nudiviridae family, and it was rod shaped and enveloped, and observed to be of approximately the mean length of a single viral nucleocapsid of 200–210 nm and mean diameter of 100–110 nm. These results provide an insight into the structural characteristics of the Nudiviridae family that can be used for nudiviral identification.

Background and aim In a recent study, microsatellite variations (GCA tandem repeats) in the promoter region of the (kidney-type) glutaminase gene were associated with the development of hepatic encephalopathy (HE) in Spanish patients with cirrhosis. The objective of this study was to validate the relation between microsatellite variations in the glutaminase promoter region and the development of overt HE in Korean patients with liver cirrhosis. Methods We performed a prospective cohort study of 154 cirrhotic patients who underwent a glutaminase microsatellite study without previous overt HE history at baseline. The primary endpoint was the first episode of overt HE. The microsatellite length was categorized into three groups based on its repeated number, with a cutoff value of 14; 65 (42.2%), 70 (45.5 %), and 19 (12.3%) patients had the short-short, short-long, and long-long alleles, respectively. Results Over a median 3.5 years of follow-up (range = 0.1 – 4.4), overt HE developed in 28 patients (18.2 %). The 3-year cumulative incidence of overt HE was 18.4%. Multivariate Cox model indicated that past hepatocellular carcinoma history, alcoholic etiology for cirrhosis, higher model for end-stage liver disease scores and their deterioration, and serum ammonium levels were independently associated with HE development. However, microsatellite length was not associated with the development of overt HE. Conclusions In Korean patients with cirrhosis, microsatellite variations in the glutaminase promoter region were not associated with development of overt HE. Thus additional studies are needed to identify other genetic factors related to glutaminase activity in Asians with overt HE.

Background Faced with extremely low fertility rates and increasing numbers of low-birthweight births in Korea, we examined the factors affecting the mortality of very-low-birthweight (VLBW) infants in Korea. Methods A survey was conducted in 91 of 93 hospitals providing neonatal intensive care in Korea in 2009. Data included information on number of neonatal intensive care unit (NICU) beds, medical workforce, resources in the NICU, birth and death. Results There was approximately one NICU per 4888 births, one NICU bed per 355 births, one mechanical ventilator per 739 births, one incubator per 327 births and one board-certified neonatologist per 4683 births. Regional disparity existed in neonatal care resources and consequently in mortality rates. VLBW infants’ mortality was related to the NICU facility level, volume of VLBW infants and geographic regions. The capital city, Seoul, has the best NICU facilities and workforce, and the least mortality. Overall mortality rates before hospital discharge for

Mixed metal oxide (MMO) nanostructures co-doped uniformly by carbon and nitrogen are synthesized for the first time by annealing a terephthalate-intercalated layered double hydroxide (LDH) under ammonia gas flow. The interlayer gallery of LDH allows effective access of NH3 and the carbon source to its crystal lattice for a uniform nitrogen and carbon doping. Such co-doped MMO exhibit significantly red-shifted absorption spectra to visible light region relative to pure MMO. Photoelectrochemical water oxidation and incident-photon-to-current-conversion efficiency of LDH-derived photocatalysts demonstrate that all the visible light absorption caused by the anion doping contributes to the photocatalytic activity over the entire absorbed wavelength range of

pH values go live! A ratiometric two-photon (TP) probe (NP1, see scheme) that has a significant TP action cross-section, high photostability, negligible toxicity, and can estimate pH values in live cells and human tissues by two-photon microscopy is described. NP1 can detect the difference in pH between live cells from the gastroesophageal junction (GEJ) and the lower esophageal sphincter of patients with and without esophagitis.

The effect of infertility on the psychological well-being of couples has been the subject of increasing attention in recent years. The frustration of couples of a relatively young age (ie, in their fourth decades) provokes not only anxiety and depression but also negative effects on the relationships. The objective of this study was to evaluate the effect of a diagnosis of male infertility on anxiety and depression in the men themselves and in fertile female spouses. The prospective cross-sectional study consisted of 264 participants, 72 males diagnosed with nonobstructive azoospermia (NOA) and their fertile spouses and 60 fertile couples attending our university between January 1, 2009, and April 30, 2010. The Beck Anxiety Inventory, Beck Depression Inventory (BDI), and hormone levels were measured during initial and follow-up visits. In NOA men, follicle-stimulating hormone and luteinizing hormone were positively associated with anxiety, in contrast to testosterone, which was inversely associated with anxiety. After the diagnosis of NOA, producing no testicular sperm, the panic intensity among men increased significantly, whereas their spouses exhibited less panic. By contrast, fertile female partners of NOA men reported higher BDI scores after the initial diagnosis of azoospermia, whereas their partners recorded higher levels of depression after the absence of testicular sperm was discovered. Insomnia was the most common complaint for both sexes after the diagnosis of azoospermia. Hormonal abnormalities had a negative effect on the quality of life. Physicians and clinicians should acknowledge the immense psychosocial effect of the diagnosis of male infertility on both males and their fertile female partners.

Summary Introduction: Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiating morphologically and functionally into several mesenchymal tissues. There have been contrasting data on whether MSCs are altered in various hematologic disorders. Methods: We isolated bone marrow (BM)–derived MSCs from a patient with thalassemia syndrome to compare phenotypic and functional characteristics to those from normal healthy donor. Results: No differences were observed between MSCs from thalassemia syndrome (T-MSCs) and those from normal healthy donor in terms of morphology, phenotype, karyotype, multidifferentiation capacity. In mixed lymphocyte reaction, T-MSCs strongly inhibited the proliferation of allogeneic T cells in association with reduced proportion of CD3+, CD4+, and CD8+ cells. Furthermore, the fraction of Treg cells was increased under the culture with T-MSCs, suggesting that T-MSCs exert normal immunomodulatory function. In addition, T-MSCs expressed hematopoietic cytokines and supported hematopoiesis, which was comparable to those from normal BM-derived MSCs. Conclusion: T-MSCs exhibited normal phenotype, karyotype as well as normal immunomodulatory function, and autologous MSCs from patients with thalassemia syndrome may be an attractive source of stem cell in terms of hematopoietic support as well as immunomodulatory activity.

We briefly describe the advantages and limitations of label-free multiphoton microscopy and probe-labeled two-photon microscopy for the endomicroscopic diagnosis. The two methods are complementary and more information can be collected from tissues by combining the two methods. Therefore, parallel efforts should be directed to the development of both label-free MPM and probe-labeled TPM as the diagnostic tool.

Monensin, an Na(+) ionophore, regulates many cellular functions including apoptosis. However, there has been no report about the antitumoral effect of monensin on acute myelogenous leukemia (AML). Here, we investigated the antiproliferative effect of monensin on AML cells in vitro and in vivo. Monensin efficiently inhibited the proliferation of all of 10 AML cell lines, with IC(50) of about 0.5 microM. DNA flow cytometric analysis indicated that monensin induced a G(1) and/or a G(2)-M phase arrest in these cell lines. To address the mechanism of the antiproliferative effect of monensin, we examined the effect of monensin on cell cycle-related proteins in HL-60 cells. The levels of CDK6, cyclin D1 and cyclin A were decreased. In addition, monensin not only increased the p27 level but also enhanced its binding with CDK2. Furthermore, the activities of CDK2- and CDK6-associated kinases reduced by monensin were associated with hypophosphorylation of Rb protein. Monensin also induced apoptosis in AML cells including HL-60 cells. The apoptotic process of HL-60 cells was associated with changes in Bax, caspase-3, caspase-8 and mitochondria transmembrane potential (Deltapsi(m)). In particular, monensin (i.p. at a dose of 8 mg/kg thrice weekly) significantly reduced the tumor size of BALB/c mice that were inoculated s.c. with its derived cell line, WEHI-3BD cells (69% growth inhibition relative to control group; p < 0.05). Tumors from monensin-treated mice exhibited increased apoptosis, and these tumor were immunohistochemically more stained with Bax, Fas and p53 antibodies than control tumors. In conclusion, this is the first report that monensin potently inhibits the proliferation of AML cells.

The worldwide production of rice bran is above 27.3 million tons per year. Rice bran contains various nutrients such as protein, fat, carbohydrate, cellulose, minerals, and vitamins, etc. making it...

Objectives To evaluate the findings of tetralogy of Fallot in various fetal sonographic views. Methods We reviewed the fetal sonograms and medical records of 20 fetuses with prenatal diagnosis of tetralogy of Fallot. We analyzed the indications for targeted sonography, the abnormalities seen in various sonographic views, the postnatal echocardiographic and angiographic findings and autopsy findings. Results The most common indication for targeted sonography was an abnormal (n = 12) or inadequate (n = 3) finding on sonographic screening in which the abnormality was most frequently found on the three-vessel view (n = 9). The key pathological features of tetralogy of Fallot were uniformly demonstrated in the ventricular outflow tract, three-vessel and short-axis views. The ductus arteriosus was small in 70% of cases and not identifiable in the remaining fetuses. In three of six fetuses with no identifiable ductus, the ductus was shown to be absent at autopsy. The direction of ductal flow was variable. Conclusion The key features of tetralogy of Fallot were always demonstrable in the ventricular outflow tract, three-vessel and short-axis views. The most common reason for referral was the abnormal three-vessel view. Copyright © 1999 International Society of Ultrasound in Obstetrics and Gynecology

An efficient synthesis of dihydroindenofurans was carried out starting from the Baylis–Hillman adducts via a Pd-catalyzed 5-endo-trig-carbopalladation and enolate O-alkylation cascade as a key step. This is the first example of enolate O-alkylation with a C(sp3)-bound palladium intermediate.

The Baylis-Hillman reaction, which involves the coupling of activated vinyl compounds with electrophiles under the catal-ytic influence of a tertiary amine, gives rise to adducts, so called Baylis-Hillman adducts, with a new stereocenter and has proven to be a very useful carbon-carbon bond-forming method in the synthesis of highly functionalized molecules.

An efficient InCl3-catalyzed hydration protocol of nitriles to amides was developed. The reaction was carried out in toluene at refluxing temperature with the aid of acetaldoxime as an effective water surrogate to produce amides in high yields.

We developed an efficient method for the introduction of –CH 2 EWG moiety at the β-position of 2-cycloalken-1-ones via a Pd-catalyzed decarboxylative protonation protocol.

An efficient palladium-catalyzed two-step protocol for the synthesis of Baylis–Hillman adducts of acrylamide was developed. The method involved the preparation of Baylis–Hillman adducts of acrylonitrile and a Pd-catalyzed hydration of nitrile with acetaldoxime.

We disclosed an efficient synthetic method of 2,4,5-trisubstituted 1,4-pentadienes from Baylis–Hillman adducts via the Pd-catalyzed decarboxylation–elimination protocol as the key step.

An efficient synthetic protocol of fully substituted α-pyrones has been developed starting from the Baylis–Hillman adducts. Subsequent Diels–Alder reaction of the α-pyrones and DMAD produced poly-substituted aromatic compounds in high yields.

An efficient palladium-catalyzed protocol for the hydration of nitrile to amide with acetaldoxime has been developed. A plausible mechanism was suggested involving the first Pd(II)-catalyzed nitrile–oxime coupling and the following disruption of the intermediate into amide and acetonitrile in a concerted manner.

We found a brand-new method for the generation of aryne from methyl 2-bromobenzoates via the Pd-mediated concomitant δ-carbon elimination and decarboxylation. The generated arynes underwent Pd-mediated [2+2+2] cycloaddition to give triphenylenes.