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Naoya Emoto,1– 3 Mikiko Okazaki-Hada,1 Yuji Yamaguchi,1 Fumitaka Okajima,1,2 Rei Goto,4 Hitoshi Sugihara1 1Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 2Department of Diabetes, Endocrinology and Metabolism, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan; 3Diabetes & Thyroid Clinic, Sakura Chuo Hospital, Chiba, Japan; 4Graduate School of Business Administration, Keio University, Tokyo, JapanCorrespondence: Naoya EmotoDiabetes & Thyroid Clinic, Sakura Chuo Hospital, 20-4, Sakaecho, Sakura City, Chiba, 285-0014, JapanTel +81-43-486-1311Fax +81-43-486-1314Email emotonaoya1954@gmail.comPurpose: Patients with thyrotoxicosis show neuropsychological changes, and these may damage the quality of informed consent in clinical practice. Therefore, we examined patients’ real-life preferences to assess whether change in risk preferences was dependent on thyroid function state.Patients and Methods: The participants were 86 patients who were newly diagnosed with Graves’ thyrotoxicosis between 1 January and 31 December 2018 (group A), and an additional 33 euthyroid patients diagnosed before 2018 (group B). In a survey conducted via a questionnaire based on the concept of behavioral economics, we sought to determine risk preferences, rationality of choices, and other relevant factors. An identical second survey was completed 6– 12 months later by 36 patients in group A after their thyroid functions had been normalized by treatment, and by 11 euthyroid patients in group B. We performed paired analysis of the first and second surveys in 32 patients of group A and single regression analysis of a total of 140 surveys obtained from 119 patients by combining the first and second surveys of groups A and B with serum level of FT3 as an independent variable.Results: The paired analysis indicated that there was no significant difference in any survey item. The single regression analysis revealed that willingness-to-pay (WTP) for preventive medicine and monthly average out-of-pocket (OOP) expenditure on medical care were both significantly positively associated with serum level of FT3. Patients in the hyperthyroid state tend to have high WTP for preventive medicine, which may be accelerated by the anchoring effect of OOP expenditure.Conclusion: Almost all risk preferences of patients with Graves’ disease are constant, rational, and reproducible in the hyperthyroid and euthyroid states. However, medical professionals should be aware that the willingness of patients with thyrotoxicosis to pay for medical costs may change after the normalization of thyroid function.Keywords: informed consent, behavioral economics, out-of-pocket expenditure, anchoring effects

Hiroko Otake,1,* Ryoka Goto,1,* Fumihiko Ogata,1 Takumi Isaka,1 Naohito Kawasaki,1 Shinichiro Kobayakawa,2 Toru Matsunaga,3 Noriaki Nagai1 1Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, 577-8502, Japan; 2Department of Ophthalmology, Nippon Medical School, Musashi-Kosugi Hospital, Kawasaki, Kanagawa, 211-8533, Japan; 3Design and Development, SEED Co., Ltd., Kounosu-shi, Saitama, 369-0131, Japan*These authors contributed equally to this workCorrespondence: Noriaki NagaiFaculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka, 577-8502, JapanTel +81 6 4307 3640Fax +81 6 6730 1394Email nagai_n@phar.kindai.ac.jpPurpose: The multi-instillation of three commercially available (CA) eye drops [fluorometholone (FL)-, bromfenac (BF)- and levofloxacin (LV)-eye drops] has been used to manage pain and inflammation post-intraocular surgery. However, the multi-instillation of these three eye drops causes corneal damage, and the FL drops have the disadvantage of low ocular bioavailability. To overcome these problems, we prepared fixed-combination eye drops based on FL nanoparticles (FL-NPs) and BF/LV solution (nFBL-FC), and evaluated the corneal toxicity and transcorneal penetration of the nFBL-FC eye drops.Methods: FL powder was mixed in 2-hydroxypropyl-β-cyclodextrin solution containing benzalkonium chloride, mannitol and methylcellulose, and milled with a Bead Smash 12 (5500 rpm for 30 s× 30 times). The BF/LV solution was then added to the milled-dispersions to be used as nFBL-FC. The FL, BF and LV concentrations were measured by HPLC methods, and transcorneal penetration was evaluated in rabbits.Results: The FL particle size in nFBL-FC was 40– 150 nm, with only 0.0018% in liquid form. No aggregation of FL particles in the nFBL-FC was observed for 1 month. The viability of human corneal epithelial cells treated with nFBL-FC was remarkably higher than that of cells subjected to the multi-instillation of the corresponding three CA-eye drops. In addition, the corneal penetrations (AUC) of the FL, BF and LV in nFBL-FC were 4.9-, 1.8-, and 7.1-fold those of the corresponding CA-eye drops, respectively. Moreover, the caveolae-dependent endocytosis (CavME) inhibitor (nystatin) significantly prevented the transcorneal penetration of these drugs.Conclusion: We prepared fixed-combination eye drops based on FL-NPs and BF/LV solution (nFBL-FC), and show that high levels of FL-NPs and dissolved BF/LV (liquid drugs) can be delivered into the aqueous humor by the instillation of nFBL-FC. Further, we show that CavME is mainly related to the enhancement of transcorneal penetration of both the solid (NPs) and liquid drugs.Keywords: fluorometholone, bromfenac, levofloxacin, fixed-combination eye drops, corneal permeability, endocytosis

Naoya Emoto,1,2 Akimi Soga,1 Izumi Fukuda,1 Kyoko Tanimura-Inagaki,1 Taro Harada,1 Hajime M Koyano,3 Rei Goto,4 Hitoshi Sugihara1 1Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 2Diabetes & Thyroid Clinic, Sakura Chuo Hospital, Chiba, Japan; 3Division of Endocrinology and Diabetes, Juntendo University Urayasu Hospital, Chiba, Japan; 4Graduate School of Business Administration, Keio University, Kanagawa, JapanCorrespondence: Naoya EmotoDiabetes & Thyroid Clinic, Sakura Chuo Hospital, 20-4, Sakaecho, Sakura City, Chiba 285-0014, JapanTel +81-43-486-1311Fax +81-43-486-1314Email emotonaoya1954@gmail.comPurpose: The risk preferences of patients with diabetes have profound effects on the progression of complications. The present study aimed to clarify whether the preferences of patients with diabetes and retinopathy are deliberately risk-seeking or irrational and whether this propensity is specific to those with retinopathy or is also found in patients without retinopathy compared with those without diabetes.Patients and Methods: A total of 394 patients with diabetes (264 without retinopathy and 130 with retinopathy) and 198 patients without diabetes agreed to participate in this survey. The questions were modified versions of those from the Japan Household Survey on Consumer Preferences and Satisfaction, which sought to determine the participants’ personal socioeconomic status and risk preferences. In the questionnaires, responses were analyzed by determining the participants’ willingness to pay for a lottery ticket and for an insurance policy. Irrational responses were defined as violations of two axioms of the Expected Utility Theory: completeness and transitivity.Results: The incidence of irrational responses increased with age and was associated with educational level. The incidence of irrational responses was significantly higher in patients with retinopathy than in those without retinopathy after adjusting for age and educational level. There was no significant difference in the incidence of irrational responses between patients with diabetes but without retinopathy and those without diabetes.Conclusion: The risk-seeking behavior of patients with diabetes and retinopathy was not deliberate but was irrational under uncertainty. Medical professionals should be aware of their patients’ propensity to make irrational decisions, which is an important risk factor for the progression of retinopathy in patients with diabetes regardless of age and educational level.Keywords: behavioral economics, expected utility theory, educational level, cognitive function

We present results from Subaru Fiber Multi Object Spectrograph near-infrared spectroscopy of 118 star-forming galaxies at z∼1.5 in the Subaru Deep Field. These galaxies are selected as [O ii]λ3727 emitters at z ≈ 1.47 and 1.62 from narrow-band imaging. We detect the Hα emission line in 115 galaxies, the [O iii]λ5007 emission line in 45 galaxies, and Hβ, [N ii]λ6584, and [S ii]λλ6716, 6731 in 13, 16, and 6 galaxies, respectively. Including the [O ii] emission line, we use the six strong nebular emission lines in the individual and composite rest-frame optical spectra to investigate the physical conditions of the interstellar medium in star-forming galaxies at z∼1.5. We find a tight correlation between Hα and [O ii], which suggests that [O ii] can be a good star formation rate indicator for galaxies at z∼1.5. The line ratios of Hα/[O ii] are consistent with those of local galaxies. We also find that [O ii] emitters have strong [O iii] emission lines. The [O iii]/[O ii] ratios are larger than normal star-forming galaxies in the local universe, suggesting a higher ionization parameter. Less massive galaxies have larger [O iii]/[O ii] ratios. With evidence that the electron density is consistent with local galaxies, the high ionization of galaxies at high redshifts may be attributed to a harder radiation field by a young stellar population and/or an increase in the number of ionizing photons from each massive star.

Kenya Kamimura,1 Yoko Shinagawa-Kobayashi,1 Ryo Goto,1 Kohei Ogawa,1 Takeshi Yokoo,1 Akira Sakamaki,1 Satoshi Abe,1 Hiroteru Kamimura,1 Takeshi Suda,2 Hiroshi Baba,3 Takayuki Tanaka,4 Yoshizu Nozawa,5 Naoto Koyama,6 Masaaki Takamura,1 Hirokazu Kawai,1 Satoshi Yamagiwa,1 Yutaka Aoyagi,1 Shuji Terai1 1Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan; 2Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata Medical and Dental Hospital, Minami-Uonuma, Niigata, Japan; 3Division of Anesthesiology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan; 4Uonuma Eye Clinic, Uonuma, Niigata, Japan; 5Institute of Food Sciences and Technologies, Ajinomoto Co., Inc., Kawasaki, Kanagawa, Japan; 6Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Kanagawa, Japan Background: Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand–foot syndrome (HFS) is the most common, occurring in 30%–50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms. Materials and methods: To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow. Results: A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow (p = 0.009) and significantly decreased occurrence of HFS (p = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period (p = 0.035). Conclusion: The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow. Keywords: sorafenib, hepatocellular carcinoma, hand–foot syndrome, blood flow, bonito broth

Naoya Emoto,1,2 Fumitaka Okajima,1,2 Hitoshi Sugihara,2 Rei Goto3 1Department of Endocrinology, Nippon Medical School Chiba-Hokusoh Hospital, Chiba, 2Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, 3Graduate School of Business Administration, Keio University, Kanagawa, Japan Background: We have recently reported that the attitude of patients toward risk could be a factor in the progression of diabetic complications. In general, risk preference is closely related to socioeconomic status (SES), which includes factors such as age, sex, income, and educational attainment.Objective: We aimed to determine the effect of SES and behavioral propensity on the progress of diabetic complications in patients with type 2 diabetes mellitus (T2DM).Methods: We conducted a survey of 238 patients with difficult-to-control T2DM treated at a hospital in Japan using a modified behavioral economics questionnaire that included questions related to SES. The patients had been referred by general practitioners or other departments in the hospital because of poor metabolic control or unstable complications.Results: Educational attainment was significantly associated with progression of retinopathy in patients

Naoya Emoto,1 Fumitaka Okajima,1 Hitoshi Sugihara,2 Rei Goto3,4 1Division of Endocrinology, Department of Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, 2Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, 3Hakubi Center of Advanced Research, Kyoto University, Kyoto, 4Graduate School of Economics, Kyoto University, Kyoto, Japan Background: Adherence to treatment and the metabolic control of diabetes are challenging in many patients with diabetes. The theory of neuroeconomics can provide important clues for understanding unreasonable human behavior concerning decisions between outcomes occurring at different time points. Objective: We investigated patients with type 1 and type 2 diabetes to determine whether patients who are at a risk of developing complications are less risk averse. We also examined whether patients with type 1 and type 2 diabetes have different behavioral traits in decision making under risk. Methods: We conducted a behavioral economics survey of 219 outpatients, 66 with type 1 diabetes and 153 with type 2 diabetes. All patients had been referred by general practitioners or other departments in the hospital. At the time of the survey, levels of hemoglobin A1c were not significantly different between patients with type 1 and type 2 diabetes. Results: Patients with type 2 diabetes showed a lower response rate to the survey compared with patients with type 1 diabetes (71.9% vs 87.9%, P

Objective To determine whether a cash-for-work programme during the annual food insecurity period in Bangladesh improved nutritional status in poor rural women and children. Methods The panel study involved a random sample of 895 households from over 50 000 enrolled in a cash-for-work programme between September and December 2007 and 921 similar control households. The height, weight and mid-upper arm circumference of one woman and child aged less than 5 years from each household were measured at baseline and at the end of the study (mean time: 10 weeks). Women reported 7-day household food expenditure and consumption on both occasions. Changes in parameters were compared between the two groups. Findings At baseline, no significant difference existed between the groups. By the study end, the difference in mean mid-upper arm circumference between women in the intervention and control groups had widened by 2.29 mm and the difference in mean weight, by 0.88 kg. Among children, the difference in means between the two groups had also widened in favour of the intervention group for: height (0.08 cm; P< 0.05), weight (0.22 kg; P< 0.001), mid-upper arm circumference (1.41 mm; P< 0.001) and z-scores for height-for-age (0.02; P< 0.001), weight-for-age (0.17; P< 0.001), weight-for-height (0.23; P< 0.001) and mid-upper arm circumference (0:12; P< 0.001). Intervention households spent more on food and consumed more protein-rich food at the end of the study. Conclusion The cash-for-work programme led to greater household food expenditure and consumption and women's and children's nutritional status improved. Objectif Determiner si un programme de remuneration en especes du travail lors de la periode d'insecurite alimentaire annuelle au Bangladesh a ameliore l'etat nutritionnel des femmes et des enfants pauvres vivant dans les zones rurales. Methodes Le panel d'etude a concerne un echantillon aleatoire de 895 menages sur plus de 50 000 menages engages dans un programme de remuneration en especes du travail entre septembre et decembre 2007, mais aussi 921 menages de controle semblables. La taille, le poids et la circonference du bras a mi-hauteur de la femme et d'un enfant de moins de 5 ans de chaque menage ont ete mesures au debut et a la fin de l'enquete (duree moyenne: 10 semaines). Dans les deux groupes, les femmes ont indique des depenses et une consommation alimentaire pour 7 jours pour le menage. Les modifications des parametres ont ete comparees entre les deux groupes. Resultats Au depart, les deux groupes ne presentaient aucune difference significative. A la fin de l'etude, la difference dans la circonference du bras a mi-hauteur entre les femmes du groupe d'intervention et le groupe de controle avait augmente de 2,29 mm et la difference dans le poids moyen de 0,88 kg. Chez les enfants, la difference dans les moyennes entre les deux groupes avaient egalement augmente en faveur du groupe d'intervention comme suit: taille (0,08 cm; P < 0,05), poids (0,22 kg; P Conclusion Le programme de remuneration en especes du travail a entraine une augmentation des depenses et de la consommation alimentaires des menages. De plus, l'etat nutritionnel des femmes et des enfants s'est ameliore. Objetivo Determinar si el programa Dinero por Trabajo mejoro el estado nutricional de las mujeres y los ninos mas desfavorecidos de las zonas rurales de Bangladesh durante un periodo de un ano de inseguridad alimentaria. Metodos El estudio de cohortes comprendio una muestra aleatoria de 895 hogares, de entre los mas de 50 000 inscritos en el programa Dinero por Trabajo, entre septiembre y diciembre de 2007, y 921 hogares de caracteristicas similares como grupo de control. En cada hogar se midieron la altura, el peso y la circunferencia braquial de una mujer y de un nino menor de 5 anos al inicio y al final del estudio (duracion media: 10 semanas). En ambas ocasiones, las mujeres informaron sobre los gastos y el consumo alimentarios semanales de sus hogares. Se compararon los cambios parametricos existentes en los dos grupos. Resultados Al inicio del estudio no se observo ninguna diferencia significativa entre los grupos. AI final del estudio, la diferencia en la circunferencia media braquial entre las mujeres del grupo de intervencion y el de control habia aumentado 2,29 mm y la diferencia en el peso medio era de 0,88 kg. Entre los ninos, la diferencia de las medias entre los dos grupos tambien habia aumentado a favor del grupo de intervencion: altura (0,08 cm, p < 0,05), peso (0,22 kg, p < 0,001), circunferencia braquial (1,41 mm, p Conclusion El programa Dinero por Trabajo tuvo como resultado un mayor gasto en y consumo de alimentos en los hogares y una mejora del estado nutricional de mujeres y ninos., Introduction Cash-for-work programmes are usually associated with disasters and emergencies and have been implemented in Afghanistan, Bangladesh, Haiti, Indonesia, Pakistan and Uganda. (1) Many organisations employed cash interventions after the [...]