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6. Lower blood glucose, hyperglucagonemia, and pancreatic [alpha] cell hyperplasia in glucagon receptor knockout mice

Author

Gelling, R.W., Du, X.Q., Dichmann, D.S., Romer, J., Huang, H., Cui, L., Obici, S., Tang, B., Holst, J.J., Fledelius, C., Johansen, P.B., Rossetti, L., Jelicks, L.A., Serup, P., Nishimura, E., and Charron, M.J.

Subjects
Cytochemistry -- Research, Mice, mutant strains -- Usage, Blood sugar -- Physiological aspects, Glucagon -- Physiological aspects, Pancreas -- Physiological aspects, Homeostasis -- Research, Hyperplasia -- Physiological aspects, Islands of Langerhans -- Physiological aspects, Bioenergetics -- Research, Energy metabolism, Body composition -- Research, Science and technology
Abstract

Glucagon, the counter-regulatory hormone to insulin, is secreted from pancreatic [alpha] cells in response to low blood glucose. To examine the role of glucagon in glucose homeostasis, mice were generated with a null mutation of the glucagon receptor ([Gcgr.sup.-/-]). These mice display lower blood glucose levels throughout the day and improved glucose tolerance but similar insulin levels compared with control animals. [Gcgr.sup.-/-] mice displayed supraphysiological glucagon levels associated with postnatal enlargement of the pancreas and hyperplasia of islets due predominantly to [alpha] cell, and to a lesser extent, [delta] cell proliferation. In addition, increased proglucagon expression and processing resulted in increased pancreatic glucogen-like peptide 1 (GLP-1) (1-37) and GLP-1 amide (1-36 amide) content and a 3- to 10-fold increase in circulating GLP-1 amide. [Gcgr.sup.-/-] mice also displayed reduced adiposity and leptin levels but normal body weight, food intake, and energy expenditure. These data indicate that glucagon is essential for maintenance of normal glycemia and postnatal regulation of islet and [alpha] and [delta] cell numbers. Furthermore, the lean phenotype of [Gcgr.sup.-/-] mice suggests glucagon action may be involved in the regulation of whole body composition.

Published
2003

10. Ireland in a warmer world; scientific predictions of the Irish climate in the twenty-first century

Author

McGrath, R. (author), Lynch, P. (author), Steele-Dunne, S.C. (author), Hanafin, J.A. (author), Nishimura, E. (author), Nolan, P. (author), Venkata Ratman, J. (author), Semmler, T. (author), Sweeney, C. (author), Wang, S. (author), McGrath, R. (author), Lynch, P. (author), Steele-Dunne, S.C. (author), Hanafin, J.A. (author), Nishimura, E. (author), Nolan, P. (author), Venkata Ratman, J. (author), Semmler, T. (author), Sweeney, C. (author), and Wang, S. (author)

Abstract

Water Management, Civil Engineering and Geosciences

Published
2008

16. Comparisons of baseline demographics, clinical presentation, and long-term outcome among patients with early, late, and very late stent thrombosis of sirolimus-eluting stents: Observations from the Registry of Stent Thrombosis for Review and Reevaluation (RESTART).

Author

Kimura T, Morimoto T, Kozuma K, Honda Y, Kume T, Aizawa T, Mitsudo K, Miyazaki S, Yamaguchi T, Hiyoshi E, Nishimura E, Isshiki T, RESTART Investigators, Kimura, Takeshi, Morimoto, Takeshi, Kozuma, Ken, Honda, Yasuhiro, Kume, Teruyoshi, Aizawa, Tadanori, and Mitsudo, Kazuaki

Published
2010
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17. Glucagon receptor knockout mice display increased insulin sensitivity and impaired ß-cell function.

Author

Sørensen H, Winzell MS, Brand CL, Fosgerau K, Gelling RW, Nishimura E, and Ahren B

Abstract

In previous studies, glucagon receptor knockout mice (Gcgr(-/-)) display reduced blood glucose and increased glucose tolerance, with hyperglucagonemia and increased levels of glucagon-like peptide (GLP)-1. However, the role of glucagon receptor signaling for the regulation of islet function and insulin sensitivity is unknown. We therefore explored beta-cell function and insulin sensitivity in Gcgr(-/-) and wild-type mice. The steady-state glucose infusion rate during hyperinsulinemic-euglycemic clamp was elevated in Gcgr(-/-) mice, indicating enhanced insulin sensitivity. Furthermore, the acute insulin response (AIR) to intravenous glucose was higher in Gcgr(-/-) mice. The augmented AIR to glucose was blunted by the GLP-1 receptor antagonist, exendin-3. In contrast, AIR to intravenous administration of other secretagogues was either not affected (carbachol) or significantly reduced (arginine, cholecystokinin octapeptide) in Gcgr(-/-) mice. In islets isolated from Gcgr(-/-) mice, the insulin responses to glucose and several insulin secretagogues were all significantly blunted compared with wild-type mice. Furthermore, glucose oxidation was reduced in islets from Gcgr(-/-) mice. In conclusion, the present study shows that glucagon signaling is required for normal beta-cell function and that insulin action is improved when disrupting the signal. In vivo, augmented GLP-1 levels compensate for the impaired beta-cell function in Gcgr(-/-) mice. [ABSTRACT FROM AUTHOR]

Published
2006
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20. Dipeptidyl peptidase IV (DPIV/CD26) degradation of glucagon. Characterization of glucagon degradation products and DPIV-resistant analogs.

Author

Hinke, S A, Pospisilik, J A, Demuth, H U, Mannhart, S, Kühn-Wache, K, Hoffmann, T, Nishimura, E, Pederson, R A, and McIntosh, C H

Abstract

Over the past decade, numerous studies have been targeted at defining structure-activity relationships of glucagon. Recently, we have found that glucagon(1-29) is hydrolyzed by dipeptidyl peptidase IV (DPIV) to produce glucagon(3-29) and glucagon(5-29); in human serum, [pyroglutamyl (pGlu)(3)]glucagon(3-29) is formed from glucagon(3-29), and this prevents further hydrolysis of glucagon by DPIV (H.-U. Demuth, K. Glund, U. Heiser, J. Pospisilik, S. Hinke, T. Hoffmann, F. Rosche, D. Schlenzig, M. Wermann, C. McIntosh, and R. Pederson, manuscript in preparation). In the current study, the biological activity of these peptides was examined in vitro. The amino-terminally truncated peptides all behaved as partial agonists in cyclic AMP stimulation assays, with Chinese hamster ovary K1 cells overexpressing the human glucagon receptor (potency: glucagon(1-29) > [pGlu(3)]glu- cagon(3-29) > glucagon(3-29) > glucagon(5-29) > [Glu(9)]glu- cagon(2-29)). In competition binding experiments, [pGlu(3)]glucagon(3-29) and glucagon(5-29) both demonstrated 5-fold lower affinity for the receptor than glucagon(1-29), whereas glucagon(3-29) exhibited 18-fold lower affinity. Of the peptides tested, only glucagon(5-29) showed antagonist activity, and this was weak compared with the classical glucagon antagonist, [Glu(9)]glucagon(2-29). Hence, DPIV hydrolysis of glucagon yields low affinity agonists of the glucagon receptor. As a corollary to evidence indicating that DPIV degrades glucagon (Demuth, et al., manuscript in preparation), DPIV-resistant analogs were synthesized. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry was used to assess DPIV resistance, and it allowed kinetic analysis of degradation. Of several analogs generated, only [D-Ser(2)] and [Gly(2)]glucagon retained high affinity binding and biological potency, similar to native glucagon in vitro. [D-Ser(2)]Glucagon exhibited enhanced hyperglycemic activity in a bioassay, whereas [Gly(2)]glucagon was not completely resistant to DPIV degradation.

Published
2000

22. Transgene expression of steel factor in the basal layer of epidermis promotes survival, proliferation, differentiation and migration of melanocyte precursors.

Author

Kunisada, T, Yoshida, H, Yamazaki, H, Miyamoto, A, Hemmi, H, Nishimura, E, Shultz, L D, Nishikawa, S, and Hayashi, S

Abstract

Mutations at the murine dominant white spotting (KitW) and steel (MgfSl) loci, encoding c-Kit receptor kinase and its ligand respectively, exert developmental defects on hematopoietic cells, melanocytes, germ cells and interstitial cells of Cajal. The expression patterns of steel factor (SLF) observed in the skin and gonads suggest that SLF mediates a migratory or a chemotactic signal for c-Kit-expressing stem cells (melanocyte precursors and primordial germ cells). By targeting expression of SLF to epidermal keratinocytes in mice, we observed extended distribution of melanocytes in a number of sites including oral epithelium and footpads where neither melanocytes nor their precursors are normally detected. In addition, enlarged pigmented spots of KitW and other spotting mutant mice were observed in the presence of the SLF transgene. These results provide direct evidence that SLF stimulates migration of melanocytes in vivo. We also present data suggesting that SLF does not simply support survival and proliferation of melanocytes but also promotes differentiation of these cells. Unexpectedly, melanocyte stem cells independent of the c-Kit signal were maintained in the skin of the SLF transgenic mice. After the elimination of c-Kit-dependent melanoblasts by function-blocking anti-c-Kit antibody, these stem cells continued to proliferate and differentiate into mature melanocytes. These melanoblasts are able to migrate to cover most of the epidermis after several months. The SLF transgenic mice described in this report will be useful in the study of melanocyte biology.

Published
1998

23. Identification and characterization of a pituitary corticotropin-releasing factor binding protein by chemical cross-linking.

Author

Nishimura, E, Billestrup, N, Perrin, M, and Vale, W

Abstract

A corticotropin-releasing factor (CRF) binding protein has been identified based on the chemical cross-linking of ovine [Nle21,m-125I-Tyr32]CRF (125I-oCRF) to bovine anterior pituitary membranes using disuccinimidyl suberate (DSS). The apparent molecular weight of the cross-linked complex determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography was approximately 75,000 and was slightly decreased in its nonreduced state, suggesting the presence of intramolecular disulfide bonds. Subtracting the molecular weight of 125I-oCRF, the binding protein appeared to have a molecular weight of approximately 70,000. The cross-linking was specific since an excess (1 microM) of an unrelated peptide (insulin) did not affect the appearance of the Mr 75,000 band. The concentration of CRF required to inhibit cross-linking by 50% was found to be similar to that determined for bovine pituitary CRF receptors by radioreceptor assay. The nonhydrolyzable GTP analogue 5'-guanylylimidodiphosphate dose dependently inhibited the cross-linking of 125I-oCRF to the Mr 70,000 protein. 50 nM of the inactive CRF analogue, [Ala14]oCRF, had no effect on the cross-linking, an observation which is consistent with this compound's low potencies in bioassays and radioreceptor assays. These results strongly suggest that this Mr 70,000 protein is the biological bovine anterior pituitary CRF receptor.

Published
1987
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24. Regulation of glucagon receptor mRNA in cultured primary rat hepatocytes by glucose and cAMP.

Author

Abrahamsen, N, Lundgren, K, and Nishimura, E

Abstract

Glucagon, the pancreatic hormone secreted in response to hypoglycemia, is a key regulator of hepatic glucose production. Since the number of specific glucagon receptors expressed on the cell surface affects the sensitivity of the liver to glucagon, we have examined the regulation of glucagon receptor mRNA levels in cultured primary rat hepatocytes. By ribonuclease protection assay we have identified glucose and intracellular cAMP as regulators of glucagon receptor mRNA expression in cultured rat hepatocytes. We observed a concentration-dependent increase in glucagon receptor mRNA expression when hepatocytes were cultured in the presence of increasing glucose. A 2-fold induction in glucagon receptor mRNA levels was obtained in hepatocytes cultured for 24 h with 22.5 mM glucose as compared with 5.5 mM glucose. Factors such as 3-isobutyl-1-methylxanthine (IBMX), isoproterenol, and forskolin, which are known to raise intracellular cAMP levels, all caused a reduction in glucagon receptor mRNA expression. IBMX alone, IBMX together with isoproterenol, and forskolin reduced glucagon receptor mRNA expression to approximately 25, 10, and 50%, respectively. Glucagon was found to dose dependently decrease glucagon receptor mRNA expression in the hepatocytes with an approximately 70% reduction in response to 100 nM glucagon. Finally, we observed a marked reduction in the number of glucagon binding sites (35% of control) after hepatocytes were cultured with the combination of IBMX and isoproterenol. These results indicate that hepatic glucagon receptor mRNA levels can be regulated by glucose and intracellular cAMP and that this is also reflected at the protein level. Furthermore, the observed effects of cAMP and glucagon suggest that this may be a means by which glucagon can down-regulate its own receptor expression.

Published
1995

25. Contractile effects of cysteamine on the guinea‐pig ileum

Author

Bakich, V., Brown, J., Kwok, Y.N., McIntosh, C., and Nishimura, E.

Abstract

1Cysteamine (β‐mercaptoethylamine HCl) (1.0–40.0 mM) induced a concentration‐dependent increase in tonic and phasic contractions of segments of guinea‐pig ileum in vitro. Myenteric plexus‐longitudinal muscle (MPLM) preparations also responded with an increase in tonic contractions but phasic contractions were either greatly reduced or absent, indicating that these were a response of the circular muscle.2Atropine (5 μM) inhibited the cysteamine‐induced contractions, whereas hexamethonium and guanethidine had no effect, suggesting that cysteamine was acting at least partly via a cholinergic mechanism involving muscarinic receptors.3Tetrodotoxin increased the phasic contractions of ileal segments, but had no effect on the tonic component.4Treatment of MPLM preparations with morphine (1 μM) resulted in a small reduction in responsiveness to cysteamine, and blocked electrically‐induced contractions by at least 90%. Since morphine acts by inhibiting acetylcholine release via hyperpolarization of intrinsic neurones, a small but significant part of the cysteamine‐induced contractions probably resulted from stimulation of acetylcholine release from intrinsic neurones.5Following a response to high cysteamine concentrations (> 15 mM) tissues were refractory to subsequent cysteamine administration. Cross‐desensitization between cysteamine and acetylcholine also occurred, as short term (1–3 min) incubation of MPLM preparations with high concentrations of either compound (1–10 μMacetylcholine or 20 mMcysteamine) resulted in a reduced responsiveness to both.6A reduced sensitivity to acetylcholine or cysteamine was obtained following long‐term (45 min) incubation with acetylcholine (1 μM). Removal of Na+from the incubation medium negated this effect. In contrast, the refractoriness to acetylcholine or cysteamine following long‐term (45 min) incubation with cysteamine (20 mM) was accentuated in low Na+medium.7It is suggested that cysteamine induces a contraction of both the circular and longitudinal muscle of the guinea‐pig ileum by stimulating the release of acetylcholine from intrinsic neurones, by an action at the level of the smooth muscle muscarinic receptor, and possibly by a non‐cholinergic mechanism. However, the mechanisms by which acetylcholine and cysteamine induce tissue refractoriness probably differ. Cysteamine (β‐mercaptoethylamine HCl) (1.0–40.0 mM) induced a concentration‐dependent increase in tonic and phasic contractions of segments of guinea‐pig ileum in vitro. Myenteric plexus‐longitudinal muscle (MPLM) preparations also responded with an increase in tonic contractions but phasic contractions were either greatly reduced or absent, indicating that these were a response of the circular muscle. Atropine (5 μM) inhibited the cysteamine‐induced contractions, whereas hexamethonium and guanethidine had no effect, suggesting that cysteamine was acting at least partly via a cholinergic mechanism involving muscarinic receptors. Tetrodotoxin increased the phasic contractions of ileal segments, but had no effect on the tonic component. Treatment of MPLM preparations with morphine (1 μM) resulted in a small reduction in responsiveness to cysteamine, and blocked electrically‐induced contractions by at least 90%. Since morphine acts by inhibiting acetylcholine release via hyperpolarization of intrinsic neurones, a small but significant part of the cysteamine‐induced contractions probably resulted from stimulation of acetylcholine release from intrinsic neurones. Following a response to high cysteamine concentrations (> 15 mM) tissues were refractory to subsequent cysteamine administration. Cross‐desensitization between cysteamine and acetylcholine also occurred, as short term (1–3 min) incubation of MPLM preparations with high concentrations of either compound (1–10 μMacetylcholine or 20 mMcysteamine) resulted in a reduced responsiveness to both. A reduced sensitivity to acetylcholine or cysteamine was obtained following long‐term (45 min) incubation with acetylcholine (1 μM). Removal of Na+from the incubation medium negated this effect. In contrast, the refractoriness to acetylcholine or cysteamine following long‐term (45 min) incubation with cysteamine (20 mM) was accentuated in low Na+medium. It is suggested that cysteamine induces a contraction of both the circular and longitudinal muscle of the guinea‐pig ileum by stimulating the release of acetylcholine from intrinsic neurones, by an action at the level of the smooth muscle muscarinic receptor, and possibly by a non‐cholinergic mechanism. However, the mechanisms by which acetylcholine and cysteamine induce tissue refractoriness probably differ.

Published
1984
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26. 3

Author

James, N. W., primary, Nishimura, E. K., additional, Wilson, A. F., additional, Mukai, D. S., additional, and Lowe, J. E., additional

Published
1987
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29. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author

S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. Nauck, A Ekbom-Schnell, G Deferrari, Riccardo Schiaffini, S. Pampanelli, Khan Aka., David Hopkins, Maija Wessman, M Kamarinos, Noh J-H., O Ebisui, K McCarroll, Jeppe Sturis, Peter Nowotny, N Gorbenko, Åke Sjöholm, David G. Maggs, A E Halseth, B Cresci, A A Ortiz-Gress, A Korakovouni, O Matejkova, C E Mogensen, C J Lin, Ramon Gomis, H Seaman, C Granier, Yang C-H., F Assah, O Sanchez, Fausto Machicao, Peter G. Morris, Alberto Ortiz, A Giardinelli, D Bracaglia, A Gonzalo, S Pavlatos, Andreas Lechner, F Canovic, L Sjolind, Allan Vaag, Birgitte Bruun Nielsen, David A. Ziegler, Vito Lampasona, R Gershoni-Baruch, A. Dei Cas, H Renz, E Mena, Matthew Waltham, Kim D-M., H Levanen, D D Mick, Valentina Alexandrovna Peterkova, E Meskhishvili, Sarah Nutland, R Bustani, John R. Lindsay, M Christoforidou, A Abicht, E Harno, K Cyganek, A Fitchet, S Neelotpol, P Nikishin, P Serradas, J Hinrichsen, M Halvorson, M Chovatia, B Voet, Jinny Willis, E Parretti, M Haslbeck, M Wellard, L Teng, Julio Wainstein, J S Fischer, K. Lalic, D Roggenland, I Gich, R Anwar, Maurizio Cassader, D Serota, X J Li, R J Schotzinger, Vilmundur Gudnason, Björn Zethelius, S A Wootton, W Andrzejewski, R Rezsohazy, R Gao, T Klimentova, T Mazurek, I Bruckner, C Dohrmann, R E James, G daSilva Xavier, Kim S-Y., A Dorca, Stuart J. Pocock, Terri J. Allen, I Giovos, P B Parab, N H Andersen, P Fotinakis, Miriam Cnop, H Lee, Norbert Tennagels, Omorodola I. Abatan, F Ailett, I. Lager, D Manzella, H Hut, Larry A. Distiller, G Lip, Lim S-K., Rong Zhang, T Tsuno, Steen Knudsen, M. Bajardi, Manuel Benito, Dai Sugimoto, Melvin J. Prince, D W Dunstan, D Rankins, K A Majali, G Ozansoy, Isabella Russo, S Uçak, G Annuzzi, R Talar-Wojnarowska, K Lange, S Neugebauer-Baba, Campbell H. Thompson, Eric Renard, P. D. Mountjoy, Z Morrison, Elizabeth A. Davis, Franco Cavallo, C Corvaja, R Antuña, Craig John Currie, H Linnebjerg, He Y-L., A J Palmer, Mariola R. Chacón, H Malinska, M. Jones, R Lichnovská, K Mandes, Paolo Tessari, T Mokhort, A Laina, H. L. Y. Chan, I Schmidt, R Banks, Richard G. IJzerman, L Ksinantova, G Setti, H Vaudry, A Gallo, V Spallone, Chen J-W., Thomas Danne, A Chong, M Hallschmid, S Aczel, S Hulme, N Islam, M Hosoi, P M Ternan, P Di Bartolo, N Bishara, T Shibasaki, Martin A. Osterhoff, Im S-S., M Jecht, T Hamaguchi, S Mattera, K Ways, Elizabeth Northam, U Rajala, Reinhard W. Holl, L Yang, S Panaiotopoulos, K Horvath, R Kluge, Thora B. Bodvarsdottir, Y Dong, Irene Alemanno, C McDougall, Reimar W. Thomsen, M Campbell, W Rabl, John Öhrvik, Yuichiro Yamada, Paola Ungaro, W Benzer, Mike Sampson, Roberto Trevisan, R G Radu, Aas A-M., P E Lobo, Ricardo Scott, S M Son, Josephine M. Forbes, T A Hillier, K L Wyne, Louis L. Nguyen, J Farmer, M H Tan, Kwon H-S., J Yang, L Sandvik, Franco Folli, A K Jenum, M Nguyen, W Pratipanawatr, A L Frederiksen, Rebecca Smith, Lee H-J., A Schäfer, C Manuelli, G S Denver, T Vukovich, B Maceira, K Matsumoto, K. Chokkalingam, Nurcan Üçeyler, P Modi, Timothy M. Morgan, S Mertens, B M Singh, Michaela Riedl, K Iso, C Cucurullo, G. F. Bottazzo, M Calvani, K Hur, J Wetzels, Kazuhiro Takahashi, Y Aso, H Stammer, M G Masding, Fitsum Guebre-Egziabher, J L González-Sánchez, L Armstrong, Alberto Maran, Peter G.F. Swift, S S Popovic, J Starczynski, E Vitacolonna, Luigi Laviola, R W Gelling, Marina Cardellini, D Barilla, Rosa de Diego Martínez, W H Landschulz, Anne Mette Rosenfalck, R K Wong, Kevin E. Schneider, K Peros, Giuseppe Nanni, F Zhang, I Rákóczi, T Iburi, M Nakhjavani, X Q Zhang, S Tournis, Per Lav Madsen, Graham A. Hitman, A. Tura, K Laubner, N D Kostic, Lawrence M. Dolan, R. Sinha Roy, J A Wagner, J. 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S, Choi, D, Kim, N, Matsumoto, S, Suetsugu, M, Matsutomo, R, Pisarczyk wiza, D, Banaszak, A, Wysocki, H, Usui, H, Shikata, K, Okada, S, Ogawa, D, Yozai, K, Kido, Y, Nagase, R, Ohga, S, Tone, A, Sasaki, M, Wada, J, Unno, Y, Horiuchi, S, Mclennan, S, Kamarinos, M, Waltham, M, Dy, V, Yue, D, Zdychova, J, Komers, R, Cresci, B, Giannini, S, Manuelli, C, Giunti, S, Pinach, S, Ianni Palarchio, A, Arnaldi, L, Vittone, F, Camussi, G, Cavallo Perin, P, Gruden, G, Marshall, S, Jones, S, White, K, Brizzi, M, Dentelli, P, Rosso, A, Calvi, C, Gambino, R, Cassader, M, Salvidio, G, Deferrari, G, Pegoraro, L, Pagano, G, Cavallo perin, P, Oates, R, Ellery, C, Beebe, D, Coutcher, J, Qian, Y, Lowe, V, Appleton, T, Raunig, D, O'Neil, S, Mylari, B, Amazonas, R, Fujita, A, Doi, A, Matsuno, S, Okamoto, K, Matsumoto, E, Furuta, H, Nishi, M, Tsuno, T, Taniguchi, H, Bessho, H, Wasén, E, Isoaho, R, Mattila, K, Vahlberg, T, Kivelä, S, Irjala, K, Rigalleau, V, Lasseur, C, Perlemoine, C, Barthes, N, Raffaitin, C, Chauveau, P, Combe, C, Baillet blanco, L, Beauvieux, M, Gin, H, Heinrich, S, Steiner, T, Ott, U, Holdass, H, Fellström, B, Jardine, A, Staffler, B, Logan, J, Gimpelewicz, C, Stanciu, C, Pena, C, Serafinceanu, C, González posada, J, Hernández, D, Pérez tamajó, L, Ló, A, Herná Alarcó, M, Meneses, M, Barsotti, M, Rizzo, G, Schmauss, S, Havrdova, T, Saudek, F, Boucek, P, Adamec, M, Invitti, C, Gilardini, L, Parati, G, Mazzilli, G, Pontiggia, B, Sartorio, A, Lutgers, H, Groenier, K, Zasadzinska, G, Saryusz wolska, M, Kurktschiev, D, Majdrakova, I, Varbanova, T, Todorova, B, Bajo martinez, A, Bernal, E, Sanchez, O, Ugalde canitrot, A, Sanchez largo, E, Coca robinot, D, Fabregate, R, Calbacho, M, Marquez, J, Saban ruiz, J, Penesova, A, Cizmarova, E, Blazicek, P, De Jongh, R, Serné, E, Ijzerman, R, De Vries, G, Andersen, N, Knudsen, S, Helleberg, K, Mogensen, C, Waluś, M, Idzior waluś, B, Sztefko, K, Cieślik, G, Fedak, D, Wozniakiewicz, E, Lin, S, Guo, M, Lin, C, Liu, X, Francisco, M, Rodriguez rosas, H, Peiró martinez, I, Macías batista, A, Harte, A, Rodriguez cuenca, S, Valsamakis, G, Chetty, R, Anderson, L, Roca, P, Matyka, K, Lasalle, J, Hershon, K, Berman, L, Gibson, E, Gillen, D, Maroni, J, Simmons, D, Hiukka, A, Forder, P, Leinonen, E, Hilden, H, Fruchart, J, Keech, A, Farnier, M, Freeman, M, Macdonell, G, Perevozskaya, I, Mitchel, Y, Gumbiner, B, Didangelos, T, Athyros, V, Mikhailidis, D, Papageorgiou, A, Bouloukos, V, Pehlivanidis, A, Symeonidis, A, Elisaf, M, Mckenney, J, Insull, W, Lewin, A, Maccubbin, D, Kush, D, Schuster, H, Barter, P, Stender, S, Bonnet, J, Morrell, J, Watkins, C, Kallend, D, Stalenhoef, A, Ballantyne, C, Murin, J, Tonstad, S, Rose, H, Wilpshaar, W, Jenkins, A, Karschimkus, C, Dragicevic, G, Rowley, K, Wolthers, T, Best, J, Voet, B, Murdoch, S, Marcovina, S, Brunzell, J, Caparevic, Z, Kostic, N, Ilic, S, Sartore, G, Piarulli, F, Cantaro, S, Reitano, R, Fiore, C, Marin, R, Bassan, S, Manzato, E, Fedele, D, Solini, A, Santini, E, Thornalley, P, Babaei jadidi, R, Karachalias, N, Kupich, C, Ahmed, N, Fowler, A, Baker, A, Starczynski, J, O'Hare, P, Szepietowska, B, Szelachowska, M, Puch, U, Glebocka, A, Quinn, D, Mcternan, C, Bonser, R, Idzior walus, B, Woźniakiewicz, E, Dimitriou, K, Apostolou, O, Kontela, E, Devangelio, E, Gould, E, Serri, O, Roussin, A, Buithieu, J, Mamputu, J, Renier, G, Giordanetti, S, De Amici, E, Poggi, G, Turpini, C, Fratino, P, Garzaniti, A, Banu, I, Paries, J, Roman, G, Negrean, M, Bala, C, Nita, C, Kistorp, C, Gustafsson, F, Chong, A, Lip, G, Galatius, S, Ari, N, Sahilli, M, Ceylan isık, A, Ozansoy, G, Karasu yilmaz, C, Matteucci, E, Rosada, J, Pallini, M, Evangelista, I, Cassetti, G, Giusti, C, Giampietro, O, Capaldo, B, Galderisi, M, Cicala, S, Turco, A, Imbroinise, A, Nosso, G, D'Errico, A, De Divitiis, O, Klimontov, V, Korolyova, E, Jeltova, L, Bondar, I, Tarkun, I, Arslan, B, Canturk, Z, Tarkun, P, Agacdiken, A, Komsuoglu, B, Méneveau, N, Pierre justin, E, Alsayed, M, Sabbah, R, Paulin, S, Marcu, S, Tauveron, I, Zimmermann, C, Schiele, F, Seronde, M, Vautrin, P, Lusson, J, Thieblot, P, Bernard, Y, Mistry, A, Pye, M, Peovska, I, Maksimovic Pavlovic, J, Vavlukis, M, Pop Gorceva, D, Bosevski, M, Scognamiglio, R, Negut, C, De Kreutzenberg, S, Madonna, R, De Caterina, R, Willerson, J, Geng, Y, Vahsen, S, Ledwig, D, Ramrath, S, Frantz, S, Schmidt, I, Calvillo, L, Dienesch, C, Elbing, I, Bischoff, H, Ertl, G, Bauersachs, J, Davydov, A, Mkrtum'Yan, A, Baranova, L, Ikeda, Y, Suehiro, T, Osaki, F, Ota, K, Arii, K, Kumon, Y, Hashimoto, K, Doney, A, Morris, A, Palmer, C, Byun, S, Doo, H, Pagnin, E, Calo, L, Fadini, G, Kubaszek, A, Chai, S, Chai, Q, Rasmussen, L, Ledet, T, Wogensen, L, Lengyel, C, Varró, A, Virág, L, Magyar, J, Bíró, T, Jost, N, Skoumal, R, Nánási, P, Tóth, M, Horkay, F, Papp, J, Zacharopoulou, O, Athanaselis, S, Tsokos, N, Doupis, J, Psallas, M, Cokkinos, D, Pavlatos, S, Liatis, S, Akhobadze, T, Dzneladze, L, Samarguliani, I, Taskiran, M, Rasmussen, V, Jensen, G, Fisher, A, Petrovsky, N, Srikusalanukul, W, Budge, M, Trifunovic zamaklar, D, Zivkovic, M, Jelic, V, Vukomanovic, G, Ristic, A, Seferovic, P, Costa, J, Duarte, S, Manley, S, Sailesh, S, Venkataraman, A, Haider, Y, Groza, I, Oprean, M, Ardelean, A, Morosanu, A, Darkow, T, Vanderplas, A, Mamas, M, Mcelduff, P, Burns, J, Edwards, R, Fitchet, A, Young, R, Gibson, J, Lichiardopol, R, Niculescu, N, Totora, A, Pencea, C, Tomescu, I, Cinteza, M, Manicardi, V, Coscelli, C, Navazio, A, Catellani, E, Michelini, M, Dall'Asta, D, Guberti, A, Piazza, A, Gasparini, E, Pantaleoni, M, Guiducci, U, Manari, A, Sejil, S, Janand delenne, B, Avierinos, J, Habib, G, Labastie, N, Vague, P, Lassmann vague, V, Luźniak, P, Tatoń, J, Wojciechowska Luźniak, A, Zairis, M, Lyras, A, Patsourakos, N, Tsirimbis, V, Foussas, S, Lupón, J, Urrutia, A, Herreros, J, González, B, Coll, R, Altimir, S, Prats, M, Valle, V, Abreu padí, C, Rábago, G, Ivanova, L, Brasacchio, D, Harno, E, Keenan, A, Li, H, Lu, Z, Ke, L, Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, L, Villela, N, Laflor, C, Conde, C, Bottino, D, Dorigo, D, Bouskela, E, Pu, S, Luo, Z, Lam, K, Dan, Q, Xu, A, Shen, J, Cheng, K, Xu, J, Thamer, C, Stefan, N, Haap, M, Heller, E, Tschritter, O, De Prado, A, Ortiz, A, Ybarra, J, Gich, I, Pou, J, Ehren, M, Roggenland, D, Reinsen, B, Klein, H, Rittig, K, Stock, J, Kocher, B, Balletshofer, B, Shon, H, Chung, D, Nakatani, Y, Matsuhisa, M, Kaneto, H, Hatazaki, M, Yoshiuchi, K, Katakami, N, Kawamori, D, Ohtoshi, K, Sakamoto, K, Matsuoka, T, Ozawa, K, Ogawa, S, Hori, M, Yamasaki, Y, Zitouni, K, Harry, D, Nourooz zadeh, J, Earle, K, Olesen, P, Franco, L, Corvaja, C, Semplicini, A, Ceylan işık, A, Arı, N, Rösen, P, Lee, I, Park, K, Jung, E, Shin, D, Jo, S, Obuobie, K, Prakash, P, Hanna, F, Lazarus, J, Varadhan, L, Gurushankar, J, James, D, Sheikh, S, Gaede, P, Zou, D, Vilarrasa, N, Perez maraver, M, Mena, E, Perez, D, Setti, G, Buckingham, R, Urbančič, V, Stefanovska, A, Bernjak, A, Ažman juvan, K, Kocijančič, A, Glowania, A, Filters, T, Fosmark, D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H

Subjects
0303 health sciences, medicine.medical_specialty, business.industry, EASD, Endocrinology, Diabetes and Metabolism, Human physiology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Family medicine, Internal Medicine, Medicine, business, 030217 neurology & neurosurgery, 030304 developmental biology
Published
2004

30. Glucose-sensitive insulin with attenuation of hypoglycaemia.

Author

Hoeg-Jensen T, Kruse T, Brand CL, Sturis J, Fledelius C, Nielsen PK, Nishimura E, Madsen AR, Lykke L, Halskov KS, Koščová S, Kotek V, Davis AP, Tromans RA, Tomsett M, Peñuelas-Haro G, Leonard DJ, Orchard MG, Chapman A, Invernizzi G, Johansson E, Granata D, Hansen BF, Pedersen TA, Kildegaard J, Pedersen KM, Refsgaard HHF, Alifrangis L, Fels JJ, Neutzsky-Wulff AV, Sauerberg P, and Slaaby R

Subjects
Animals, Female, Humans, Male, Rats, Glucosides administration & dosage, Glucosides chemistry, Glucosides pharmacology, Glucosides therapeutic use, Receptor, Insulin metabolism, Swine, Macrocyclic Compounds administration & dosage, Macrocyclic Compounds chemistry, Macrocyclic Compounds pharmacology, Macrocyclic Compounds therapeutic use, Rats, Sprague-Dawley, Blood Glucose metabolism, Glucose metabolism, Hypoglycemia drug therapy, Hypoglycemia metabolism, Hypoglycemia chemically induced, Insulin administration & dosage, Insulin analogs & derivatives, Insulin metabolism, Insulin pharmacology, Insulin therapeutic use
Abstract

The risk of inducing hypoglycaemia (low blood glucose) constitutes the main challenge associated with insulin therapy for diabetes 1,2 . Insulin doses must be adjusted to ensure that blood glucose values are within the normal range, but matching insulin doses to fluctuating glucose levels is difficult because even a slightly higher insulin dose than needed can lead to a hypoglycaemic incidence, which can be anything from uncomfortable to life-threatening. It has therefore been a long-standing goal to engineer a glucose-sensitive insulin that can auto-adjust its bioactivity in a reversible manner according to ambient glucose levels to ultimately achieve better glycaemic control while lowering the risk of hypoglycaemia 3 . Here we report the design and properties of NNC2215, an insulin conjugate with bioactivity that is reversibly responsive to a glucose range relevant for diabetes, as demonstrated in vitro and in vivo. NNC2215 was engineered by conjugating a glucose-binding macrocycle 4 and a glucoside to insulin, thereby introducing a switch that can open and close in response to glucose and thereby equilibrate insulin between active and less-active conformations. The insulin receptor affinity for NNC2215 increased 3.2-fold when the glucose concentration was increased from 3 to 20 mM. In animal studies, the glucose-sensitive bioactivity of NNC2215 was demonstrated to lead to protection against hypoglycaemia while partially covering glucose excursions., (© 2024. The Author(s).)

Published
2024
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31. Correction: Current Use and Discrepancies in the Adoption of Health-Related Internet of Things and Apps Among Working Women in Japan: Large-Scale, Internet-Based, Cross-Sectional Survey.

Author

Sasayama K, Nishimura E, Yamaji N, Ota E, Tachimori H, Igarashi A, Arata N, Yoneoka D, and Saito E

Abstract

[This corrects the article DOI: 10.2196/51537.]., (©Kiriko Sasayama, Etsuko Nishimura, Noyuri Yamaji, Erika Ota, Hisateru Tachimori, Ataru Igarashi, Naoko Arata, Daisuke Yoneoka, Eiko Saito. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 21.08.2024.)

Published
2024
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32. Association of hyaluronan and proteoglycan link protein 1 gene with the need of home oxygen therapy in premature Japanese infants with bronchopulmonary dysplasia.

Author

Ito M, Sasaki A, Haga M, Iwatani A, Nishimura E, Arai H, Nagano N, Suga S, Araki S, Konishi A, Onouchi Y, and Namba F

Subjects
Infant, Newborn, Infant, Female, Humans, Pregnancy, Japan, Infant, Premature, Proteoglycans genetics, Oxygen, Hyaluronic Acid, Bronchopulmonary Dysplasia genetics, Bronchopulmonary Dysplasia therapy, Extracellular Matrix Proteins
Abstract

Background: Bronchopulmonary dysplasia (BPD) has a lasting effect on the respiratory function of infants, imposing chronic health burdens. BPD is influenced by various prenatal, postnatal, and genetic factors. This study explored the connection between BPD and home oxygen therapy (HOT), and then we examined the association between HOT and a specific single-nucleotide polymorphism (SNP) in the hyaluronan and proteoglycan link protein 1 ( HAPLN1 ) gene among premature Japanese infants., Materials and Methods: Prenatal and postnatal data from 212 premature infants were collected and analyzed by four SNPs (rs975563, rs10942332, rs179851, and rs4703570) around HAPLN1 using the TaqMan polymerase chain reaction method. The clinical characteristics and genotype frequencies of HAPLN1 were assessed and compared between HOT and non-HOT groups., Results: Individuals with AA/AC genotypes in the rs4703570 SNP exhibited significantly higher HOT rates at discharge than those with CC homozygotes (odds ratio, 1.20, 95% confidence interval, 1.07-1.35, p  = .038). A logistic regression analysis determined that CC homozygotes in the rs4703570 SNP did not show a statistically significant independent association with HOT at discharge., Conclusions: Although our study did not reveal a correlation between HAPLN1 and the onset of BPD, we observed that individuals with CC homozygosity at the rs4703570 SNP exhibit a reduced risk of HOT.

Published
2024
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33. Current Use and Discrepancies in the Adoption of Health-Related Internet of Things and Apps Among Working Women in Japan: Large-Scale, Internet-Based, Cross-Sectional Survey.

Author

Sasayama K, Nishimura E, Yamaji N, Ota E, Tachimori H, Igarashi A, Arata N, Yoneoka D, and Saito E

Subjects
Humans, Female, Japan, Adult, Cross-Sectional Studies, Middle Aged, Surveys and Questionnaires, Young Adult, Mobile Applications statistics & numerical data, Women, Working statistics & numerical data, Women, Working psychology, Internet of Things statistics & numerical data
Abstract

Background: Demographic changes and a low birth rate have led to a workforce shortage in Japan. To address this issue, the government has promoted engagement of female employment. However, increased female employment can impact women's health. Using Internet of Things (IoT) and apps to manage women's health has gained attention, but few studies have focused on working women., Objective: This study aimed to clarify the current situation of working women and their use of IoT or apps to manage their health., Methods: A large-scale, nationwide internet survey was conducted among 10,000 female participants aged from 20 years to 64 years in Japan. Participants were recruited from a marketing research company's active survey panel of 5.24 million members. The survey included questions about health status, sociodemographic factors, psychological characteristics, and the use of IoT or apps for health management. We compared perceived health status and reasons for current IoT use using t tests and assessed participant characteristics that predicted IoT use using the C5.0 decision tree algorithm. Ethical approval was granted by St. Luke's International University., Results: Among participants, 14.6% (1455/10,000) currently used IoT or apps, 7% (695/10,000) used them previously, and 78.5% (7850/10,000) had never used them. Current users (42.7 years old) were older than past users (39.7 years old). Discrepancies were observed between participants' perceived health problems and the purpose for using IoT or apps, with 21.3% (2130/10,000) of all women reporting they experienced menstrual symptoms or disorders but only 3.5% (347/10,000) used IoT or apps to manage the same symptom. On the other hand, current users were more likely to use IoT or apps to manage nutrition-related problems such as underweight or obesity (405/1455, 27.8%). Device use was highest among current users, with 87.3% (1270/1455) using smartphones, 19.7% (287/1455) using smartwatches, and 13.3% (194/1455) using PCs. Decision tree analysis identified 6 clusters, the largest consisting of 81.6% (5323/6523) of non-IoT users who did not exercise regularly, while pregnant women were more likely to use IoT or apps., Conclusions: Our findings highlight the idea that woman with particular health problems (ie, menstrual symptoms or disorders and premenstrual syndrome) have lower use of IoT or apps, suggesting an unmet need for IoT and apps in specific areas., (©Kirio Sasayama, Etsuko Nishimura, Noyuri Yamaji, Erika Ota, Hisateru Tachimori, Ataru Igarashi, Naoko Arata, Daisuke Yoneoka, Eiko Saito. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 31.07.2024.)

Published
2024
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34. Enhanced disulphide bond stability contributes to the once-weekly profile of insulin icodec.

Author

Hubálek F, Cramer CN, Helleberg H, Johansson E, Nishimura E, Schluckebier G, Steensgaard DB, Sturis J, and Kjeldsen TB

Subjects
Animals, Humans, Male, Half-Life, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents pharmacokinetics, Hypoglycemic Agents chemistry, Receptor, Insulin metabolism, Sulfhydryl Compounds chemistry, Swine, Swine, Miniature, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 blood, Disulfides chemistry, Insulin administration & dosage, Insulin metabolism, Insulin chemistry, Insulin pharmacokinetics
Abstract

Insulin icodec is a once-weekly insulin analogue that has a long half-life of approximately 7 days, making it suitable for once weekly dosing. The Insulin icodec molecule was developed based on the hypothesis that lowering insulin receptor affinity and introducing a strong albumin-binding moiety would result in a long insulin half-life, provided that non-receptor-mediated clearance is diminished. Here, we report an insulin clearance mechanism, resulting in the splitting of insulin molecules into its A-chain and B-chain by a thiol-disulphide exchange reaction. Even though the substitutions in insulin icodec significantly stabilise insulin against such degradation, some free B-chain is observed in plasma samples from minipigs and people with type 2 diabetes. In summary, we identify thiol-disulphide exchange reactions to be an important insulin clearance mechanism and find that stabilising insulin icodec towards this reaction significantly contributes to its long pharmacokinetic/pharmacodynamic profile., (© 2024. The Author(s).)

Published
2024
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35. Effect of concomitant use of yokukansan on steady-state blood concentrations of donepezil and risperidone in real-world clinical practice.

Author

Saruwatari J, Kaneko T, Murata T, Narise H, Kugimoto S, Nishimura E, Tetsuka N, Ando M, Oi M, Ota M, Hamada N, Kaneda K, Furusho S, Sakamoto M, Kajiwara-Morita A, Oda K, Oniki K, Ueda K, Jono H, and Yasui-Furukori N

Abstract

Aim: Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting., Methods: A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co-treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high-performance liquid chromatography-tandem mass spectrometry and compared before and after the 8-week administration of yokukansan., Results: The plasma concentrations of donepezil and its metabolites (6-O-desmethyl-donepezil, 5-O-desmethyl-donepezil, and donepezil-N-oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8-week treatment with yokukansan., Conclusions: The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady-state blood levels of donepezil and risperidone in patients with dementia or schizophrenia., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Published
2024
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36. Correction: Effectiveness and safety of weekly paclitaxel and cetuximab as a salvage chemotherapy following immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: a multicenter clinical study.

Author

WakasakiI T, Manako T, YasumatsuI R, Hara H, Toh S, Masuda M, YamauchiID M, Kuratomi Y, Nishimura E, Takeuchi T, Matsuo M, Jiromaru R, Hashimoto K, Komune N, and Nakagawa T

Abstract

[This corrects the article DOI: 10.1371/journal.pone.0271907.]., (Copyright: © 2024 WakasakiI et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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37. Piceatannol Upregulates SIRT1 Expression in Skeletal Muscle Cells and in Human Whole Blood: In Vitro Assay and a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial.

Author

Tanaka K, Kawakami S, Mori S, Yamaguchi T, Saito E, Setoguchi Y, Matsui Y, Nishimura E, Ebihara S, and Kawama T

Abstract

Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, is reported to promote fat metabolism. This study investigated whether PIC affects sirtuin 1 (SIRT1) expression and metabolic factors in C2C12 skeletal muscle cells. C2C12 myotubes were stimulated with PIC, and alterations in gene expression, protein levels, mitochondrial DNA content, and fatty acid levels were assessed using real-time PCR, Western blotting, and Nile red staining. Furthermore, we examined changes in SIRT1 expression following the consumption of a test food containing 100 mg PIC for 2 weeks among adults with varying age and body mass index ranges. Both PIC and passion fruit seed extract induced SIRT1 expression in C2C12 myotubes to a greater extent than resveratrol. PIC also increased the expression of genes associated with mitochondrial biogenesis and fatty acid utilization, increased mitochondrial DNA content, and suppressed oleic acid-induced fat accumulation. Moreover, participants who consumed PIC exhibited significantly higher SIRT1 mRNA expression in whole blood compared to those in the placebo group. These findings suggest that PIC induces SIRT1 expression both in vitro and in the human body, which may promote mitochondrial biosynthesis and fat metabolism.

Published
2024
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38. Comparison of complications of intrascleral fixation according to the extent of vitrectomy.

Author

Yamada M, Nishimura E, Watanabe S, Yoshino M, Tokunaga Y, Sugiyama N, and Soda M

Subjects
Humans, Lens Implantation, Intraocular methods, Retrospective Studies, Visual Acuity, Sclera surgery, Postoperative Complications epidemiology, Postoperative Complications surgery, Vitrectomy adverse effects, Vitrectomy methods, Lenses, Intraocular
Abstract

Background: Intraocular lens (IOL) fixation is performed after intraoperative anterior or total vitrectomy. This study aimed to compare the intraoperative and postoperative complications of these two techniques., Methods: This retrospective study included 235 eyes that underwent intrascleral fixation surgery at our hospital between July 2014 and January 2021. The eyes were classified into the anterior vitrectomy group (A-vit group; 134 eyes) and the pars plana vitrectomy group (PPV group; 101 eyes). The age, preoperative and postoperative best-corrected visual acuity, observation period, preoperative and postoperative intraocular pressure, and the incidence of intraoperative and postoperative complications were assessed., Results: Intrascleral fixation was performed more frequently in the PPV group, and a significant difference was observed between the eyes with a history of vitrectomy and eyes with scleral buckles (p = 0.00041). In terms of the incidence of postoperative complications following intrascleral fixation, the incidence of low intraocular pressure postoperative was higher in the PPV group than that in the A-vit group, and a significant difference was observed between the two groups (p = 0.01)., Conclusions: The visual outcome and complications following intrascleral fixation did not differ according to the extent of vitreous excision., (© 2024. The Author(s).)

Published
2024
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39. 'It's more emotionally based': Prince Edward Island horse owner perspectives of horse weight management.

Author

Ross M, Proudfoot K, Campbell Nishimura E, Morabito E, Merkies K, Mitchell J, and Ritter C

Abstract

Horse obesity is a growing concern that can result in negative welfare. The role horse owners play in horse weight management is not well understood. This study aimed to: (1) explore the attitudes, beliefs, and perceptions of owners with overweight or obese horses regarding their horses' weight; and (2) understand the motivators and barriers for owners to implement, improve and maintain weight management-related strategies. A semi-structured interview guide based on the Theoretical Domains Framework was developed. Qualitative interviews were conducted with 24 owners in Prince Edward Island, Canada whose horse(s) were previously classified as overweight or obese by a veterinarian. Interviews were analysed using template analysis, organising patterns in the data into a codebook and overarching themes. Owners believed horse weight management was important, however, their perceived complexity of the issue made the implementation of the weight management practices difficult. Owners held conflicting perceptions, viewing overweight horses as well cared for, yet recognised these horses were at increased risk for negative health outcomes. Ultimately, participants felt emotionally torn about compromising their horse's mental well-being to address weight issues. Owners considered the practicality of weight-management strategies, the strategies' effectiveness, and whether recommended strategies aligned with their beliefs regarding good horse care practices. Knowledge was embedded into owners' understanding of horse weight, however, some highlighted that traditional knowledge dominates the equine industry hindering systemic industry change. Increased understanding of the effectiveness and impacts of weight management strategies on horses and fostering a society that recognises and accepts horses within a healthy weight range are warranted., Competing Interests: None., (© The Author(s) 2024.)

Published
2024
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40. Rare malignant neoplasm of the esophagus: current status and future perspectives.

Author

Yoshinami Y, Nishimura E, Hosokai T, Yamamoto S, Matsuda S, Nomura M, Kawakubo H, Kato K, and Kitagawa Y

Subjects
Humans, Esophageal Neoplasms pathology, Esophageal Squamous Cell Carcinoma, Melanoma, Carcinoma, Neuroendocrine, Gastrointestinal Stromal Tumors, Carcinosarcoma pathology
Abstract

Esophageal cancer is common worldwide, including in Japan, and its major histological subtype is squamous cell carcinoma. However, there are some rare esophageal cancers, including neuroendocrine neoplasm, gastrointestinal stromal tumor, carcinosarcoma and malignant melanoma. The biological and clinical features of these cancers differ from those of esophageal squamous cell carcinoma. Therefore, different treatment strategies are needed for these cancers but are based on limited evidence. Neuroendocrine neoplasm is mainly divided into neuroendocrine tumor and neuroendocrine carcinoma by differentiation and the Ki-67 proliferation index or mitotic index. Epidemiologically, the majority of esophageal neuroendocrine neoplasms are neuroendocrine carcinoma. The treatment of neuroendocrine carcinoma is similar to that of small cell lung cancer, which has similar morphological and biological features. Gastrointestinal stromal tumor is known to be associated with alterations in the c-KIT and platelet-derived growth factor receptor genes and, if resectable, is treated in accordance with the modified Fletcher classification. Carcinosarcoma is generally resistant to both chemotherapy and radiotherapy and requires multimodal treatments such as surgery plus chemotherapy to achieve cure. Primary malignant melanoma is resistant to cytotoxic chemotherapy, but immune checkpoint inhibitors have recently demonstrated efficacy for malignant melanoma of the esophagus. This review focuses on the current status and future perspectives for rare cancer of the esophagus., (© The Author(s) 2023. Published by Oxford University Press.)

Published
2024
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41. Projections of maternal mortality ratios in Bangladesh.

Author

Nishimura E, Yoneoka D, Rahman MO, Yonekura Y, Kataoka Y, and Ota E

Subjects
Humans, Bangladesh epidemiology, Female, Pregnancy, Health Facilities, Maternal Mortality
Abstract

Background: The objective of this study was to predict when Bangladesh would achieve Sustainable Development Goal Target 3.1, which is to reduce the maternal mortality ratio (MMR) to less than 70 per 100 000 live births., Methods: We used secondary data from the 1993 to 2017 Bangladesh Demographic and Health Surveys and other sources to project the MMR until 2060 under several scenario assumptions using an autoregressive moving average model with exogenous variables (ARMAX). Explanatory variables were selected based on the three delays model, and a reference forecast and four practical scenarios were simulated: Scenario 1 assumed a 4% annual increase in institutional deliveries, Scenario 2 followed the national goals, the reference forecast and Scenario 3 varied in terms of district-wise increase rates (Scenario 3 had a lower rate of increase), and Scenario 4 assumed minimal changes in institutional deliveries., Results: Scenario 1 was the earliest, with an MMR of <70 per 100 000 live births in 2026. Scenario 2 would meet the target of <70 per 100 000 live births in 2029. The reference forecast had the third lowest MMR, with 69.78 per 100 000 live births (95% prediction intervals (PI) = 32.44 to 107.11) in 2049. Although the MMR for Scenario 3 decreased slowly, it would not reduce below 70 per 100 000 live births by 2060. Scenario 4, which had the highest MMR, also resulted in the MMR not reducing below 70 per 100 000 live births by 2060., Conclusions: To increase the institutional delivery rate and reduce the MMR, as in Scenarios 1 and 2, it is necessary to improve the institutional delivery rate in regions with low institutional delivery rates. Additionally, health facilities need to provide appropriate quality medical care to increase the institutional delivery rate and contribute to a decrease in the MMR, as shown by the results of this study., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Published
2024
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42. Antenatal corticosteroids in specific groups at risk of preterm birth: a systematic review.

Author

Saito K, Nishimura E, Ota E, Namba F, Swa T, Ramson J, Lavin T, Cao J, and Vogel JP

Subjects
Infant, Newborn, Pregnancy, Humans, Female, Cesarean Section, Adrenal Cortex Hormones therapeutic use, Fetal Growth Retardation, Chorioamnionitis, Premature Birth prevention & control, Diabetes, Gestational drug therapy
Abstract

Objective: This study aimed to synthesise available evidence on the efficacy of antenatal corticosteroid (ACS) therapy among women at risk of imminent preterm birth with pregestational/gestational diabetes, chorioamnionitis or fetal growth restriction (FGR), or planned caesarean section (CS) in the late preterm period., Methods: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Library, Web of Science and Global Index Medicus was conducted for all comparative randomised or non-randomised interventional studies in the four subpopulations on 6 June 2021. Risk of Bias Assessment tool for Non-randomised Studies and the Cochrane Risk of Bias tool were used to assess the risk of bias. Grading of Recommendations Assessment, Development and Evaluations tool assessed the certainty of evidence., Results: Thirty-two studies involving 5018 pregnant women and 10 819 neonates were included. Data on women with diabetes were limited, and evidence on women undergoing planned CS was inconclusive. ACS use was associated with possibly reduced odds of neonatal death (pooled OR: 0.51; 95% CI: 0.31 to 0.85, low certainty), intraventricular haemorrhage (pooled OR: 0.41; 95% CI: 0.23 to 0.72, low certainty) and respiratory distress syndrome (pooled OR: 0.59; 95% CI: 0.45 to 0.77, low certainty) in women with chorioamnionitis. Among women with FGR, the rates of surfactant use (pooled OR: 0.38; 95% CI: 0.23 to 0.62, moderate certainty), mechanical ventilation (pooled OR: 0.42; 95% CI: 0.26 to 0.66, moderate certainty) and oxygen therapy (pooled OR: 0.48; 95% CI: 0.30 to 0.77, moderate certainty) were probably reduced; however, the rate of hypoglycaemia probably increased (pooled OR: 2.06; 95% CI: 1.27 to 3.32, moderate certainty)., Conclusions: There is a paucity of evidence on ACS for women who have diabetes. ACS therapy may have benefits in women with chorioamnionitis and is probably beneficial in FGR. There is limited direct trial evidence on ACS efficacy in women undergoing planned CS in the late preterm period, though the totality of evidence suggests it is probably beneficial., Prospero Registration Number: CRD42021267816., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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43. Factors associated with father-infant bonding during the COVID-19 pandemic: an internet-based cross-sectional study in Japan.

Author

Nishimura E, Shoki R, Kato M, Yoneoka D, Okawa S, Tabuchi T, and Ota E

Subjects
Child, Male, Infant, Newborn, Female, Pregnancy, Humans, Infant, Japan epidemiology, Cross-Sectional Studies, Pandemics, Internet, Mothers, COVID-19 epidemiology
Abstract

The COVID-19 pandemic has forced lifestyles changes and affected the relationships between fathers and their infants. However, the factors associated with paternal-infant bonding have not been clarified. This study aimed to explore the factors associated with father-infant bonding during the COVID-19 pandemic in Japan. This cross-sectional study used data from a nationwide survey and the Japanese version of the Mother-to-Infant Bonding Scale (MIBS) to measure father-infant bonding. The participants were divided into two groups depending on their partners' parity. A linear regression model (Gauss-Markov-type) was used for both groups. A total of 1055 men were included in the analysis. Of these men, 521 (49.4%) had a primipara partner, and 534 (50.6%) had a multipara partner. No significant differences were found between the two groups' MIBS-J scores. Fathers' mental health, relationship with the partner and family members, abusive behavior towards children, wanted pregnancy, and the youngest child's Neonatal Intensive Care Unit admission history were associated with father-infant bonding. Regarding factors related to COVID-19, caring for the child while the partner is at home has a negative impact on bonding, while fear related to infection with COVID-19 has no negative impact on bonding., (© 2023. Springer Nature Limited.)

Published
2023
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44. Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross-sectional analysis of baseline data from the PR-IAH study.

Author

Sakane N, Kato K, Hata S, Nishimura E, Araki R, Kouyama K, Hatao M, Matoba Y, Matsushita Y, Domichi M, Suganuma A, Sakane S, Murata T, and Wu FL

Abstract

Background: Hypoglycemia in type 1 diabetes (T1D) is associated with mortality and morbidity, especially when awareness of hypoglycemia is impaired. This study aimed to investigate the protective and risk factors for impaired awareness of hypoglycemia (IAH) in adults with T1D., Methods: This cross-sectional study enrolled 288 adults with T1D (mean age, 50.4 ± 14.6 years; male, 36.5%; diabetes duration, 17.6 ± 11.2 years; mean HbA1c level, 7.7 ± 0.9%), who were divided into IAH and non-IAH (control) groups. A survey was conducted to assess hypoglycemia awareness using the Clarke questionnaire. Diabetes histories, complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem-solving abilities, and treatment data were collected., Results: The prevalence of IAH was 19.1%. Diabetic peripheral neuropathy was associated with an increased risk of IAH (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.13-5.91; P = 0.014), while treatment with continuous subcutaneous insulin infusion and hypoglycemia problem-solving perception scores were associated with a decreased risk of IAH (OR, 0.48; 95% CI, 0.22-0.96; P = 0.030; and OR, 0.54; 95% CI, 0.37-0.78; P = 0.001, respectively). There was no difference in continuous glucose monitoring use between the groups., Conclusion: We identified protective factors in addition to risk factors for IAH in adults with T1D. This information may help manage problematic hypoglycemia., Trial Registration: University hospital Medical Information Network (UMIN) Center: UMIN000039475). Approval date 13 February 2020., (© 2023. The Author(s).)

Published
2023
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45. Effectiveness of the Internet of Things for Improving Working-Aged Women's Health in High-Income Countries: Protocol for a Systematic Review and Network Meta-analysis.

Author

Yamaji N, Nitamizu A, Nishimura E, Suzuki D, Sasayama K, Rahman MO, Saito E, Yoneoka D, and Ota E

Abstract

Background: Women often experience many unique health issues and conditions throughout their working lives. The Internet of Things (IoT) is a system of interrelated digital devices that can enable data exchanges over a network without human-to-human or human-to-computer interaction. The usage of applications and IoT in improving women's health has recently increased worldwide. However, there has been no consensus on the effectiveness of IoT in improving women's health outcomes., Objective: This systematic review and network meta-analysis (NMA) aims to assess and synthesize the role of apps and the IoT in improving women's health and to identify the ranking of interventions for ensuring better results for each stated outcome., Methods: Our systematic review and NMA will be conducted in accordance with the guidelines of the Cochrane Handbook. We will comprehensively search the following electronic databases: PubMed (including MEDLINE), Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature (ie, CINAHL), PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry, along with other resources to identify relevant randomized controlled trials that have assessed the effects of various apps and the IoT with regard to improving working-aged women's health in high-income countries. We will segment and analyze the results of the included studies based on age categories (women undergoing a preconception period, those undergoing gestational and postpartum periods, and menopausal and pre- and postmenopausal women) and the medical history (women who have a specific medical condition-eg, cancer or diabetes-and women who do not have them) separately. Two independent reviewers will perform the study selection, data extraction, and quality assessment. Our primary outcomes include health status, well-being, and quality of life. We will perform pairwise meta-analysis and NMA to estimate the direct, indirect, and relative effects of apps and the IoT on women's health outcomes. We will also assess the hierarchy of interventions, statistical inconsistencies, and certainties of evidence for each outcome., Results: We plan to conduct the search in January 2023 and are currently discussing search strategies with the literature search specialists. The final report is planned for submission to a peer-reviewed journal in September 2023., Conclusions: To the best of our knowledge, this review will be the first to identify the ranking of IoT intervention for ensuring working-aged women's health outcomes. These findings may be of great use to researchers, policy makers, and others with an interest in the field., Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42022384620; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=384620., International Registered Report Identifier (irrid): PRR1-10.2196/45178., (©Noyuri Yamaji, Aya Nitamizu, Etsuko Nishimura, Daichi Suzuki, Kiriko Sasayama, Md. Obaidur Rahman, Eiko Saito, Daisuke Yoneoka, Erika Ota. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.04.2023.)

Published
2023
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46. Role of Maternal and Child Health Handbook on Improving Maternal, Newborn, and Child Health Outcomes: A Systematic Review and Meta-Analysis.

Author

Nishimura E, Rahman MO, Ota E, Toyama N, and Nakamura Y

Abstract

The objective of this review is to assess and synthesize the role of the maternal and child health (MCH) handbook on improving healthcare service utilization, behavior change, and health outcomes for women and children. A systematic search of all relevant existing reports was conducted on 14 January 2021, using the following online bibliographic databases: PubMed, EMBASE, MEDLINE, The Cochrane Library, Academic Search Premier, Emcare, APA PsycINFO, and Web of Science. Two reviewers independently performed study selection, data extraction, and quality assessment. We included 7 trials from 1430 articles, and a total of 2643 women. As overall risk of bias assessment, most domains of the Cochrane risk-of-bias assessment tool showed a high or unclear risk of bias. The risk of ≥6 antenatal care (ANC) visits was 19% higher (RR 1.19, 95% CI 1.09 to 1.30, I2 = 47%, 2 studies, 955 women, moderate certainty of evidence) and skilled birth attendants during delivery was 13% higher (RR 1.13, 95% CI 1.04 to 1.24, I2 = 0%, 2 studies, 1094 women, low certainty of the evidence) in the intervention group than in the control group. The MCH handbook can increase maternal health service utilization and early breastfeeding practice. It also leads to a sense of autonomy during ANC, better communication with healthcare providers, and support from family members.

Published
2023
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47. Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection.

Author

Nakayama T, Azegami T, Kiso M, Imai M, Uraki R, Hayashi K, Hishikawa A, Yoshimoto N, Nakamichi R, Sugita-Nishimura E, Yoshida-Hama E, Kawaoka Y, and Itoh H

Subjects
Animals, Mice, Antibodies, Viral, Disease Models, Animal, Lipopolysaccharides, SARS-CoV-2, COVID-19, Plasminogen Activator Inhibitor 1, Sepsis
Abstract

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global pandemic. Although several vaccines targeting SARS-CoV-2 spike proteins protect against COVID-19 infection, mutations affecting virus transmissibility and immune evasion potential have reduced their efficacy, leading to the need for a more efficient strategy. Available clinical evidence regarding COVID-19 suggests that endothelial dysfunction with thrombosis is a central pathogenesis of progression to systemic disease, in which overexpression of plasminogen activator inhibitor-1 (PAI-1) may be important. Here we developed a novel peptide vaccine against PAI-1 and evaluated its effect on lipopolysaccharide (LPS)-induced sepsis and SARS-CoV-2 infection in mice. Administration of LPS and mouse-adapted SARS-CoV-2 increased serum PAI-1 levels, although the latter showed smaller levels. In an LPS-induced sepsis model, mice immunized with PAI-1 vaccine showed reduced organ damage and microvascular thrombosis and improved survival compared with vehicle-treated mice. In plasma clot lysis assays, vaccination-induced serum IgG antibodies were fibrinolytic. However, in a SARS-CoV-2 infection model, survival and symptom severity (i.e., body weight reduction) did not differ between vaccine- and vehicle-treated groups. These results indicate that although PAI-1 may promote the severity of sepsis by increasing thrombus formation, it might not be a major contributor to COVID-19 exacerbation., (© 2023. The Author(s).)

Published
2023
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48. Comparison of changes in body-fat mass and reflux esophagitis among reconstruction methods for proximal gastrectomy.

Author

Nishimura E, Irino T, Matsuda S, Fukuda K, Nakamura R, Kawakubo H, and Kitagawa Y

Subjects
Humans, Proton Pump Inhibitors, Postoperative Complications epidemiology, Postoperative Complications prevention & control, Postoperative Complications surgery, Gastrectomy methods, Retrospective Studies, Esophagitis, Peptic etiology, Esophagitis, Peptic prevention & control, Esophagitis, Peptic surgery, Stomach Neoplasms surgery, Gastroesophageal Reflux prevention & control, Gastroesophageal Reflux surgery, Gastroesophageal Reflux etiology
Abstract

Background: Although proximal gastrectomy (PG) is a function-preserving surgical option, it remains unclear as to which reconstruction method can prevent reflux and maintain body composition., Methods: Patients who underwent PG at Keio University between April 2011 and November 2018 were analyzed. Changes in the subcutaneous and visceral adipose tissues were comparatively assessed before and after a year of surgery for three common reconstruction methods. We also compared the endoscopic findings of reflux esophagitis and the number of patients prescribed with proton-pump inhibitor after a year of surgery., Results: This study included 76 patients, of which 33 patients underwent esophagogastrostomy with a circular stapler (CS), 35 under double flap (DF) reconstruction, and 8 underwent double tract (DT) reconstruction. Comparing esophagogastrostomy (CS and DF) and DT showed that esophagogastrostomy could significantly preserve both subcutaneous and visceral adipose tissues (P < 0.001 and P = 0.04, respectively). However, the change in the subcutaneous and visceral adipose tissues was comparable between CS and DF. As for reflux esophagitis, DF showed the lowest incidence rate for esophagitis and the least number of patients who were prescribed a proton-pump inhibitor., Conclusion: DF is a relatively better reconstruction method for preserving fat mass and preventing reflux among the three common reconstruction methods., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Published
2023
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49. Association of Impaired Awareness of Hypoglycemia with Driving Safety and Hypoglycemia Problem-solving Abilities among Patients with Type 1 Diabetes in Japan: The PR-IAH Study.

Author

Sakane N, Kato K, Hata S, Nishimura E, Araki R, Kouyama K, Hatao M, Matoba Y, Matsushita Y, Domichi M, Suganuma A, Sakane S, Murata T, and Wu FL

Subjects
Adult, Humans, Middle Aged, Glycated Hemoglobin, Cross-Sectional Studies, Japan epidemiology, Awareness, Hypoglycemic Agents adverse effects, Blood Glucose, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 1 epidemiology, Hypoglycemia etiology
Abstract

Objective Patients with type 1 diabetes (T1D) and impaired awareness of hypoglycemia (IAH) are at an elevated risk of experiencing automobile accidents. We therefore investigated the association of IAH with driving safety and hypoglycemia problem-solving abilities in adults with T1D. Methods This cross-sectional survey used Gold's method in adult patients with T1D at the National Hospital Organization (NHO) Hospital from February 14, 2020, to October 31, 2021. The participants were divided into control and IAH groups. The data included information on demographics, worries and distress regarding hypoglycemia, hypoglycemia problem-solving abilities, and adverse driving events. Patients We enrolled 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%) from NHO collaborating centers in Japan. Results Among a total of 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%), the prevalence rate of IAH was 11.6% [95% confidence interval (CI): 7.8-16.4%]. IAH was significantly associated with near-miss car accidents (odds ratio: 5.41; 95% CI:1.64-17.80). Diabetic peripheral neuropathy was associated with an increased risk of IAH, while treatment with continuous subcutaneous insulin infusion was not associated with a decreased risk of IAH. The average hypoglycemia problem-solving perception, detection control, and seeking preventive strategies scores in the IAH group were significantly reduced compared with those in the control group. Conclusion IAH was associated with an increased risk of near-miss car accidents among adults with T1D. Furthermore, good hypoglycemia problem-solving abilities were associated with a decreased risk of IAH.

Published
2023
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50. Hyper-active RAS/MAPK introduces cancer-specific mitotic vulnerabilities.

Author

Herman JA, Romain RR, Hoellerbauer P, Shirnekhi HK, King DC, DeLuca KF, Osborne Nishimura E, Paddison PJ, and DeLuca JG

Subjects
Aneuploidy, Carcinogenesis metabolism, Cell Cycle Proteins metabolism, Chromosome Segregation, Humans, Kinetochores metabolism, Microtubules metabolism, Mitosis genetics, Spindle Apparatus metabolism, Neoplasms metabolism, Protein Serine-Threonine Kinases genetics
Abstract

Aneuploidy, the incorrect number of whole chromosomes, is a common feature of tumors that contributes to their initiation and evolution. Preventing aneuploidy requires properly functioning kinetochores, which are large protein complexes assembled on centromeric DNA that link mitotic chromosomes to dynamic spindle microtubules and facilitate chromosome segregation. The kinetochore leverages at least two mechanisms to prevent aneuploidy: error correction and the spindle assembly checkpoint (SAC). BubR1, a factor involved in both processes, was identified as a cancer dependency and therapeutic target in multiple tumor types; however, it remains unclear what specific oncogenic pressures drive this enhanced dependency on BubR1 and whether it arises from BubR1's regulation of the SAC or error-correction pathways. Here, we use a genetically controlled transformation model and glioblastoma tumor isolates to show that constitutive signaling by RAS or MAPK is necessary for cancer-specific BubR1 vulnerability. The MAPK pathway enzymatically hyperstimulates a network of kinetochore kinases that compromises chromosome segregation, rendering cells more dependent on two BubR1 activities: counteracting excessive kinetochore-microtubule turnover for error correction and maintaining the SAC. This work expands our understanding of how chromosome segregation adapts to different cellular states and reveals an oncogenic trigger of a cancer-specific defect.

Published
2022
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