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Vasospastic angina (VSA) can be worsened by oral nonselective beta-blockers. Ophthalmic carteolol eye drops are non-selective beta blockers and effective against glaucoma and ocular hypertension. Systemic effects of ophthalmic beta blockers on VSA have not yet been reported. We herein report a case of VSA that developed after a patient started carteolol eye drops for ocular hypertension. Even though benidipine, a calcium channel blocker. was started, a VSA attack with incessant non-sustained ventricular tachycardia occurred. Once the carteolol eyedrops were discontinued, the VSA resolved. This case demonstrates that carteolol eye drops can induce life-threatening VSA.

Occupational exposure of pharmacists to drugs during powder drug preparation in dispensing pharmacies was investigated. First, we determined frequently prescribed tipepidine hibenzate and ambroxol hydrochloride suspended in the air of the dispensing room. The median concentration of the drugs in the air was 0.01 μg/m3 and 0.02 μg/m3, respectively; these values indicate that the air in the dispensing room was contaminated with powder drug. To estimate drug exposure during powder drug preparation, drug dust was collected near the nose of workers. Analysis of the active ingredients of the drugs used in the preparation revealed that eight drugs, including bethanechol, l-carbocisteine, and zonisamide, were detected in the range of 1.5-1220 μg/m3. Assuming that the respiratory volume of an adult was 0.008 m3/min, it was estimated that 0.4-36 μg of the ingredients were exposed per prescription by multiplying concentration, respiratory volume and sampling time (3-5 min). Furthermore, the effect of wearing a medical mask on the drug powder exposure was evaluated using a self-made apparatus. When the amount of drug powder collected on filters that is either covered with or without a medical mask was compared, the covered filter exhibited reduced drug powder accumulation to less than 10% the amount collected on the uncovered filter. The present data suggested that a medical mask might decrease the drug dust allergies in dispensing pharmacists.

The molecular conformations, packing structures and intermolecular interactions of homopentapeptides from achiral α-aminoisobutyric acid (Aib), ArSO2-(Aib)5-OMe (Ar = p-tolyl, p-bromophenyl and p-methoxyphenyl), have been investigated by single-crystal X-ray diffraction analysis. The peptides were folded in 310-helical conformations consisting of two or three consecutive ten-atom intramolecular hydrogen-bonded β-turns of type III or III′. In the packing mode, left-handed (M) and right-handed (P) 310-helical molecules formed linear network structures with head-to-tail type intermolecular hydrogen bonds. Two types of network structures consisting of homochiral sequences (⋯M⋯M⋯M⋯ or ⋯P⋯P⋯P⋯) and heterochiral sequences (⋯M⋯P⋯M⋯P⋯) were obtained depending on the functional groups or substituents of the peptides. Interestingly, peptide 1a which has a p-tolyl group crystallized differently when using a different crystallization medium.

DiethoxyP(V)tetrakis(p-methoxyphenyl)porphyrin (EtP(V)TMPP) and its fluorinated derivative (FEtP(V)TMPP) were synthesized to examine their photodynamic action. These P(V)porphyrins were aggregated in an aqueous solution, resulting in the suppression of their photodynamic activity. In the presence of human serum albumin (HSA), a water-soluble protein, the aggregation states were resolved and formed a binding complex between P(V)porphyrin and HSA. These P(V)porphyrins photosensitized the oxidation of the tryptophan residue of HSA under the irradiation of long-wavelength visible light (>630 nm). This protein photodamage was explained by the electron transfer from tryptophan to the photoexcited state of P(V)porphyrins and singlet oxygen generation. The axial fluorination reduced the redox potential of the one-electron reduction of P(V)porphyrin and increased the electron transfer rate constant. However, this axial fluorination decreased the binding constant with HSA, and the quantum yield of photosensitized HSA damage through electron transfer was decreased. The photocytotoxicity of these P(V)porphyrins to HaCaT cells was also confirmed, and FEtP(V)TMPP demonstrated stronger phototoxicity than EtP(V)TMPP. In summary, a self-aggregation of porphyrin photosensitizers and resolving by targeting biomacromolecules may be used to target selective photodynamic action. The redox potential and an association with a targeting biomolecule are the important factors of the electron transfer-mediated mechanism, which is advantageous under hypoxic tumor conditions.

In this paper, the fatigue crack growth simulation of two non-coplanar embedded cracks using the s-version finite element method is presented, and the validity and reliability of the alignment rule for two non-coplanar cracks are evaluated. According to the previous numerical and experimental studies on two non-coplanar surface cracks, the simulated fatigue crack growth behavior is categorized into five patterns to discuss the criteria for the application of the alignment rule. The results suggest that the strength of interaction between the non-coplanar embedded cracks is similar to that between non-coplanar surface cracks. Finally, the interaction of the cracks is evaluated by the stress intensity factor, and the categorization of the fatigue crack growth behavior is discussed by the stress intensity factor. It can be found that the boundary corresponding to the criteria of the application of the alignment rule can be determined as the ratio of the stress intensity factor is 4%. Thus, instead of making a decision of the fatigue crack growth pattern based on the visual inspection, the ratio of the stress intensity factor can be used, and should give more quantitative evaluation of the interaction of two non-coplanar embedded cracks.

Introduction As the clinical applications of medical genetics and genomics continue to expand, nongenetics professionals increasingly find themselves in the position of managing patients with genetic conditions. To prepare medical students to handle this future practice demand, it is imperative that they obtain skills and confidence in utilizing credible medical genetics resources to care for patients with genetic conditions. To this end, we developed active learning materials to introduce first-year medical students to these resources. Methods This approximately 2-hour session targeted first-year medical students (123 students) and combined flipped classroom and small-group collaborative case-based learning models. Students first completed a hands-on preclass exercise, which guided them in navigating the Online Mendelian Inheritance in Man website, and then attended an in-person small-group classroom activity, which provided the opportunity to apply information obtained from credible medical genetics resources to a patient case. At the conclusion of the classroom activity, students voluntarily completed an anonymous survey. Results Results of student postsession surveys showed that, regardless of previous exposure to medical genetics resources, this session increased both confidence in skills and future intention to use medical genetics resources. Discussion Since the majority of students were unfamiliar with using specialized medical genetics resources prior to this educational intervention, the session functioned as a practical introduction to these essential resources. We propose that equipping medical students with skills that support inquiry-oriented learning, particularly in the early stage of training, can cultivate the practice of lifelong learning in medical genetics.

We built a machine learning model (ML model) which input the number of daily infection cases and the other information related to COVID-19 over the past 24 days in each of 17 provinces in South Korea, and output the total increase in the number of infection cases in each of 17 provinces over the coming 24 days. We employ a combination of XGBoost and MultiOutputRegressor as machine learning model (ML model). For each province, we conduct a binary classification whether our ML model can classify provinces where total infection cases over the coming 24 days is more than 100. The result is Sensitivity = 3/3 = 100%, Specificity = 11/14 = 78.6%, False Positive Rate = 3/11 = 21.4%, Accuracy = 14/17 = 82.4%. Sensitivity = 100% means that we did not overlook the three provinces where the number of COVID-19 infection cases increased by more than100. In addition, as for the provinces where the actual number of new COVID-19 infection cases is less than 100, the ratio (Specificity) that our ML model can correctly estimate was 78.6%, which is relatively high. From the above all, it is demonstrated that there is a sufficient possibility that our ML model can support the following four points. (1) Promotion of behavior modification of residents in dangerous areas, (2) Assistance for decision to resume economic activities in each province, (3) Assistance in determining infectious disease control measures in each province, (4) Search for factors that are highly correlated with the future increase in the number of COVID-19 infection cases.

Optical coherence tomography (OCT) scanning is useful in detecting various retinal diseases. However, there are not enough ophthalmologists who can diagnose retinal OCT images in much of the world. To provide OCT screening inexpensively and extensively, an automated diagnosis system is indispensable. Although many machine learning techniques have been presented for assisting ophthalmologists in diagnosing retinal OCT images, there is no technique that can diagnose independently without relying on an ophthalmologist, i.e., there is no technique that does not overlook any anomaly, including unlearned diseases. As long as there is a risk of overlooking a disease with a technique, ophthalmologists must double-check even those images that the technique classifies as normal. Here, we show that our deep-learning-based binary classifier (normal or abnormal) achieved a perfect classification on 108,308 two-dimensional retinal OCT images, i.e., true positive rate = 1.000000 and true negative rate = 1.000000; hence, the area under the ROC curve = 1.0000000. Although the test set included three types of diseases, two of these were not used for training. However, all test images were correctly classified. Furthermore, we demonstrated that our scheme was able to cope with differences in patient race. No conventional approach has achieved the above performances. Our work has a sufficient possibility of raising automated diagnosis techniques for retinal OCT images from "assistant for ophthalmologists" to "independent diagnosis system without ophthalmologists".

To identify yeasts involved in white-colony formation on Japanese commercial kimchi products, three types of kimchi were prepared and fermented at four different temperatures. At 4 °C, yeast colonies did not appear until 35 days, while more rapid white-colony formation occurred at higher temperatures (10, 15, and 25 °C). Combination of PCR-DGGE and direct isolation of yeasts from white colonies revealed that Kazachstania exigua and K. pseudohumilis were responsible for the white-colony formation. Inoculation of the isolated Kazachstania strains into fresh kimchi successfully reproduced white-colony formation at 15 °C but not at 4 °C. Growth experiments in liquid medium revealed that Kazachstania spp. grew fast at 15 °C even in the presence of acidulants, which are commonly added to Japanese kimchi products for prevention of yeast growth. These results suggest that white-colony formation on Japanese kimchi is caused by the genus Kazachstania, and that one of important factors determining white-colony formation is its fermentation temperature. Kimchi inoculated with 102 CFU g−1 of Kazachstania pseudohumilis after fermentation at 15 °C for 21 days (left) or at 4˚C for 51 days (right).

The objective was to evaluate the effect of replacing milk with soymilk or calcium-fortified soymilk as a part of a meal on postprandial serum phosphorus levels. This study had a randomized crossover design. Ten healthy subjects were enrolled and consumed three test meals that contained either milk, soymilk, or calcium-fortified soymilk containing the same amount of calcium as milk. Blood samples were collected at 0, 30, 60, 120, 240 and 360 min and urine samples were collected from 0 to 360 min after consuming the test meal. Serum phosphorus levels decreased the most after the ingestion of the soymilk meal, and the least after the ingestion of the milk meal. After the ingestion of each meal, serum intact parathyroid hormone levels showed an initial drop followed by a gradual rise, and these changes were more pronounced for the soymilk meal than for the milk meal and the soymilk + calcium meal. Our study shows that replacing milk with soymilk as a part of a meal may suppress the postprandial elevation in serum phosphorus levels, even when the soymilk contains the same amount of calcium as milk.

The synthesis of thioamides via the condensation reaction of thiocarboxylic acids with amines is described. Using 3-cyano-1,2,4-triazole as a favorable nucleophilic catalyst and 3-cyano-1,2,4-triazol-1-yl-tris(pyrrolidine-1-yl)phosphonium hexafluorophosphate (PyCTP) as a new phosphonium-type condensing reagent, thioamides are obtained selectively over amides, which can be attributed to the hardness of the phosphorus center of the condensing reagent.

In this paper, fatigue crack growth simulation of interacting subsurface cracks using the s-version finite element method (SFEM) is presented. In order to evaluate the accuracy and reliability of the proximity rules published by the ASME, during the fatigue crack growth simulations, the subsurface cracks are approximated to either a single elliptical crack or semi-elliptical surface crack in accordance with the proximity rules. Then, the proximity rules are slightly modified for improving the accuracy and reliability. The results of crack depth evolution calculated by the SFEM with the use of the new proximity rules suggest that the approximation to deep cracks drastically improves the accuracy of the fatigue crack growth evaluation. Thus, the approximation to deep cracks must be a promising approach for having better evaluation of fatigue crack growth of subsurface cracks.

Although zinc is an essential element for organisms, excess zinc exposure is harmful. We assessed the possible negative influence of zinc (Zn) on the freshwater fish Danio rerio during its early life stage by using Organization for Economic Cooperation and Development test guideline no. 210. Lethality of Zn after hatching occurred in a concentration dependent manner. The LC50 and lowest observed effect concentration of mortality values in the present toxicity assay were 2.31 mg/L (95% confidence limit: 1.81–3.05) and 1.5 mg/L, respectively. These values were close to the reported concentration recorded in aquatic environments. Growth inhibition was observed at 15 and 30 days post-hatching with Zn exposure of 1.5 mg/L. In general, the growth hormone (Gh)/insulin-like growth factor-I (Igf-1) axis is important for growth in fishes, and Zn exposure induced a significant reduction of igf-1 expression at the concentration that caused growth inhibition. These findings suggest that the observed growth inhibition was induced by the suppression of igf-1 expression. In addition, these results suggest that by examining gene expression on the Gh/Igf-1 axis, it may be possible to predict growth suppression by chemical exposure.

DiethoxyP(V)tetrakis(

To clarify whether Oryzias congeners, including freshwater, brackish water, and marine medaka, would be useful models for evaluating environmental chemical effects in various aquatic ecosystems, we examined the influence of salinity on their embryo development. We also compared the toxicity values of the organotin compounds triphenyltin and tributyltin, which remain pollutants of marine and freshwater ecosystems, between Oryzias latipes (freshwater), Oryzias melastigma (brackish water), and Oryzias javanicus (saltwater). Hatching and survival rates of O. latipes were significantly decreased at a salinity of 34, whereas O. melastigma and O. javanicus were adaptable to various salinities from freshwater to seawater. The lowest observed effect concentrations of organotin compounds for survival and embryo development were the similar in the three species. The similarity of the species’ responses to organotin compounds indicated that Oryzias congeners are useful for ecological risk assessment of chemicals in a range of aquatic ecosystems, from freshwater to marine.

Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most effective chemotherapeutic drugs that are used for treatment of patients with gastrointestinal cancer cells, but its continuous administration often evokes the development of chemoresistance. In this study, we investigated alterations in antioxidant molecules and functions using a newly established CDDP-resistant variant of gastric cancer MKN45 cells, and found that aldo-keto reductase 1B10 (AKR1B10) is significantly up-regulated with acquisition of the CDDP resistance. In the nonresistant MKN45 cells, the sensitivity to cytotoxic effect of CDDP was decreased and increased by overexpression and silencing of AKR1B10, respectively. In addition, the AKR1B10 overexpression markedly suppressed accumulation and cytotoxicity of 4-hydroxy-2-nonenal that is produced during lipid peroxidation by CDDP treatment, suggesting that the enzyme acts as a crucial factor for facilitation of the CDDP resistance through inhibiting induction of oxidative stress by the drug. Transient exposure to CDDP and induction of the CDDP resistance decreased expression of peroxisome proliferator-activated receptor-γ (PPARγ) in MKN45 and colon cancer LoVo cells. Additionally, overexpression of PPARγ in the cells elevated the sensitivity to the CDDP toxicity, which was further augmented by concomitant treatment with a PPARγ ligand rosiglitazone. Intriguingly, overexpression of AKR1B10 in the cells resulted in a decrease in PPARγ expression, which was recovered by addition of an AKR1B10 inhibitor oleanolic acid, inferring that PPARγ is a downstream target of AKR1B10-dependent mechanism underlying the CDDP resistance. Combined treatment with the AKR1B10 inhibitor and PPARγ ligand elevated the CDDP sensitivity, which was almost the same level as that in the parental cells. These results suggest that combined treatment with the AKR1B10 inhibitor and PPARγ ligand is an effective adjuvant therapy for overcoming CDDP resistance of gastrointestinal cancer cells.

This Technical Memorandum (TM) summarizes the Fermilab Test Beam Faciltiy (FTBF) operations for FY2019. It is one of a series of annual publications intended to gather information in one place. This TM discusses the experiments performed at the Test Beam from November 2018 to July 2019. The experiments are listed in Table 1. Each experiment wrote a summary that was edited for clarity and is included in this report.

We attempted to prepare carbon nanofibers (CNFs) bonded chemically with alumina particles using acid-treated CNFs and aluminum secbutoxide. The structure and morphology of the boehmite deposited on the CNFs, the boundary between the CNFs and the deposited boehmite, and the thermal transformation of the deposited boehmite were investigated using Raman spectroscopy, X-ray diffraction (XRD) analysis, field-emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). The boehmite deposited not only particulately on the CNFs but also in a film-like manner on parts of the CNFs. In addition, the boehmite could deposit not only on the disordered inner walls of the CNFs but also on the ordered inner walls. By heating at 1200 degrees C, the boehmite on the CNFs was transformed into alpha-alumina and theta-alumina. At this time, some alumina particles, particularly those formed on the ordered inner walls of CNFs, fell out of the CNFs, and only those alumina particles which might chemically bond with CNFs remained on the CNFs. Finally, CNFs dotted with alumina particles with a size of, Article, CERAMICS INTERNATIONAL. 41(10):13171-13178 (2015)

Doxorubicin (DOX) is widely used for the treatment of a wide range of cancers such as breast and lung cancers, and malignant lymphomas, but is generally less efficacious in gastrointestinal cancers. The most accepted explanation for the DOX refractoriness is its resistance development. Here, we established DOX-resistant phenotypes of human gastric MKN45 and colon LoVo cells by continuous exposure to incremental concentrations of the drug. While the parental MKN45 and LoVo cells expressed carbonyl reductase 1 (CBR1) highly and moderately, respectively, the gain of DOX resistance further elevated the CBR1 expression. Additionally, the DOX-elicited cytotoxicity was lowered by overexpression of CBR1 and inversely strengthened by knockdown of the enzyme using small interfering RNA or pretreating with the specific inhibitor quercetin, which also reduced the DOX refractoriness of the two resistant cells. These suggest that CBR1 is a key enzyme responsible for the DOX resistance of gastrointestinal cancer cells and that its inhibitor is useful in the adjuvant therapy. Although CBR1 is known to metabolize DOX to a less toxic anticancer metabolite doxorubicinol, its overexpression in the parental cells hardly show significant reductase activity toward low concentration of DOX. In contrast, the overexpression of CBR1 increased the reductase activity toward an oxidative stress-derived cytotoxic aldehyde 4-oxo-2-nonenal. The sensitivity of the DOX-resistant cells to 4-oxo-2-nonenal was lower than that of the parental cells, and the resistance-elicited hyposensitivity was almost completely ameliorated by addition of the CBR1 inhibitor. Thus, CBR1 may promote development of DOX resistance through detoxification of cytotoxic aldehydes, rather than the drug's metabolism.

The Japanese rock ptarmigan Lagopus muta japonica breeds only in limited alpine areas at high elevations (> 2,500 m a.s.l.) in Japan. The estimated population size is about 2,000 birds and their breeding distribution is subdivided into several local areas, in each of which they may be at risk of local extinction. We estimated age-specific demographic parameters of the core population breeding on Mt. Norikura in Gifu and Nagano prefecture in Japan. We also estimated population viability using deterministic and stochastic population models. Age-specific fertility (the number of female offspring that survived to the next breeding season per female) was 0.417 ± 0.086, 0.490 ± 0.080, 0.513 ± 0.153, 0.435 ± 0.078, 0.562 ± 0.139, 0.580 ± 0.122 (mean ± SE) for ages 1-6+, respectively. The annual survival rate was 0.739 ± 0.047, 0.624 ± 0.064, 0.513 ± 0.087, 0.732 ± 0.151, 0.447 ± 0.220, 0.486 ± 0.089. The population growth rate, evaluated by use of a deterministic projection-matrix model, predicted a stable popul...

Summary: Various techniques for nail reconstruction have been reported until now; however, a simple one providing good esthetic results was difficult to find. Arterialized venous toenail flap is a free flap that includes the nail bed and matrix with a pedicle formed solely by the subcutaneous vein of the toe. The use of this flap is minimally invasive and easy, and the flap has a high survival rate. The mechanism of graft survival remains unknown given the nonphysiologic circulation. To the best of our knowledge, no studies have explained this mechanism with reference to detailed postoperative course. We herein present 2 cases of nail reconstruction performed using arterialized venous toenail flap. We analyzed the postoperative course in detail, which enabled us to postulate on the mechanism of graft survival.

We herein discovered a highly resistant clinical isolate of Pseudomonas aeruginosa with MICs to amikacin, gentamicin, and arbekacin of 128 μg/mL or higher in a drug sensitivity survey of 92 strains isolated from the specimens of Yoka hospital patients between January 2009 and October 2010, and Achromobacter xylosoxidans was separated from this P. aeruginosa isolate. The sensitivity of this bacterium to 29 antibiotics was investigated. The MICs of this A. xylosoxidans strain to 9 aminoglycoside antibiotics were: amikacin, gentamicin, arbekacin, streptomycin, kanamycin, neomycin, and spectinomycin, 1,024 μg/mL or ≥ 1,024 μg/mL; netilmicin, 512 μg/mL; and tobramycin, 256 μg/mL. This strain was also resistant to dibekacin. This aminoglycoside antibiotic resistant phenotype is very rare, and we are the first report the emergence of A. xylosoxidans with this characteristic.