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How does a country embark on large-scale R&D programs? Among R&D programs, this is an intriguing question for large scale Science and Technology (S&T) projects such as space programs, because of the necessity for large resource commitments, and the difficulty of being accountable to the taxpayers when the outcome is not always known. It can be assumed that engineers, scientists, bureaucrats, and politicians play respective roles. This paper aims to shed light on the specific role of politics, through the examples of policies of and decisions by NAKASONE Yasuhiro. Nakasone was the minister for science and technology (1959–1960, 1972), and later became the prime minister (1982–1987). He played a crucial role in establishing the Science and Technology Agency and the National Space Activities Council in the 1950s, which would be the foundational institutions responsible for space policy for the next half century. As prime minister, he decided to participate in the Space Station program. Within his vision for Japan for the 21st century, he emphasized the need for radical change in economic policy, education, defense and S&T investment. He was one of the few politicians that had vision to promote S&T and recognized the strategic value to the nation. He was able to explain to the nation why Japan should promote the development of a launch vehicle, when the engineers faced development difficulties in doing so. Thus, he was influential both in the policy layer and in promoting specific programs to support his national vision. Politics intersects with S&T projects because of the uncertainty and tradeoffs associated with these efforts. Japan did not address space programs for national security and commercial space for a long time. It is a politician's role to create institutions, to allocate resources and, more importantly, to explain to the taxpayers why policy measures or programs are necessary. R&D investment is a societal activity: it reflects the social, political, and economic situation, as well as being important for diplomacy and international relations. Bearing in mind that it would be misleading to attribute the initiation of largescale S&T projects to the leadership of a single individual, this paper will attempt to show the driving forces behind, and fundamental objective of Japan's space policy, in addition to the historical shift in that policy by examining the influence of this notable politician. • Nakasone played the key role in establishing institutions promoting space development in post-war Japan. • Nakasone made the best use of close relationships with the U.S. in promoting Japan's space activities. • Nakasone made decisions on space policy process, resource allocation with vision, thus integrating the stakeholders. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Secondary loss of response to adalimumab (ADA‐LOR) commonly occurs in patients with Crohn's disease (CD) treated with adalimumab (ADA). We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA‐LOR in adult CD patients. Methods: Patients were divided into either an ED (≥900 kcal/day) or a non‐ED group (<900 kcal/day). Cumulative non‐ADA‐LOR rates were compared between groups. The effects of ED intake to reduce ADA‐LOR were also assessed in antitumor necrosis factor‐alpha (TNF‐α)‐naïve and infliximab (IFX)‐intolerant or refractory CD patients. Serum ADA and TNF‐α levels were measured. Results: We enrolled 117 CD patients into the ED (n = 25) or non‐ED (n = 92) groups. Although the cumulative non‐ADA‐LOR rate was higher in the ED group than in the non‐ED group, ED intake was not an independent reducing factor for ADA‐LOR (adjusted hazard ratio = 0.725; 95% confidence interval: 0.448–1.180; P = 0.196) in all patients. ED intake was significantly more effective in reducing ADA‐LOR in IFX‐intolerant or refractory patients than in anti‐TNF‐α‐naïve patients in a dose‐related manner (P for interaction <0.20). Serum ADA levels did not differ between the groups. Serum TNF‐α levels were significantly lower in the ED group than in the non‐ED group at week 28 (P = 0.044) and week 52 (P = 0.043). Conclusions: Concomitant ED therapy reduced ADA‐LOR in IFX‐intolerant or refractory patients in a dose‐related manner. Reductions in the TNF‐α levels by concomitant ED intake may contribute to reduce ADA‐LOR in CD patients. [ABSTRACT FROM AUTHOR]

Background: Lithium carbonate is widely used as a first-line therapeutic agent for the depressive and manic phases of bipolar disorder. Although limb tremors and hypothyroidism are well-known side effects of lithium carbonate, other rare adverse reactions can also occur.Case Presentation: A 53-year-old Japanese woman diagnosed with lithium intoxication developed dysgeusia and glossalgia during treatment with lithium carbonate. She also showed symptoms of a swaying gait, finger tremors, and dysarthria. All of these symptoms subsided when her blood lithium concentration was reduced to a level below that which induces intoxication.Conclusions: We present a rare case of lithium carbonate-induced dysgeusia accompanied by glossalgia. Early detection of these symptoms is important in clinical settings because they can be overlooked until patients lose their appetite, which severely impairs their quality of life. [ABSTRACT FROM AUTHOR]

Objectives: Low‐volume polyethylene glycol plus ascorbic acid (PEG‐Asc) reduces the dosage of colonoscopic bowel preparation (BP) solution, but is still poorly tolerated. Adding laxatives to the BP solution reduces the volume of fluid required, without affecting quality. This study aimed to compare 1 L PEG‐Asc plus 24 mg senna (1L‐PEG/AS) and conventional 2 L PEG‐Asc (2L‐PEG/A) regimens on BP quality and patient tolerability. Methods: A single‐center, randomized, investigator‐blinded, noninferiority trial was performed between June and August 2022. Outpatients scheduled for colonoscopy were randomized (1:1) to the 1L‐PEG/AS or 2L‐PEG/A group. The Boston Bowel Preparation Scale (BBPS) was used to evaluate BP quality. Adverse events and tolerability were surveyed using questionnaires. Results: Overall, 344 patients received 1L‐PEG/AS or 2L‐PEG/A regimens. The baseline characteristics and adverse events of the two groups were comparable. The 1L‐PEG/AS group showed noninferior adequate BP rates compared with the 2L‐PEG/A group (88% vs. 89%, P = 1.00); overall BBPS was 7.1 ± 1.5 and 7.2 ± 1.5, respectively (P = 0.39). Higher willingness to repeat the BP was observed in the 1L‐PEG/AS group (85% vs. 62%, P < 0.01). Conclusions: The 1L‐PEG/AS regimen was comparable to the 2L‐PEG/A regimen in terms of BP adequacy, requiring lower BP solution volumes, with better patient tolerance. Thus, it may be a suitable alternative to the conventional BP solution for colonoscopy. The Japan Registry of Clinical Trials (jRCT1051220043). [ABSTRACT FROM AUTHOR]

Objective: Comorbid psychiatric disorders negatively affect the survival rate of patients with some physical disorders. In liver transplant recipients, various psychiatric disorders have been identified as worsening prognosis. However, little is known about how the presence of any comorbid (overall) disorders affect the survival rate of transplant recipients. In this study, we examined the effect of overall comorbid psychiatric disorders on survival rate in liver transplant recipients. Methods: A total of 1006 recipients who underwent liver transplantation between September 1997 and July 2017 across eight transplant facilities with a psychiatric consultation-liaison team were identified consecutively. Recipients were categorized into those with comorbid psychiatric disorders and those without comorbid psychiatric disorders. In the comorbid psychiatric disorder group, psychiatric disorder diagnosis and time of diagnosis were investigated retrospectively. Results: Of the 1006 recipients, 294 (29.2%) had comorbid psychiatric disorders. Comorbid psychiatric disorders in the 1006 recipients were insomnia (N = 107, 10.6%), delirium (N = 103, 10.2%), major depressive disorder (N = 41, 4.1%), adjustment disorder (N = 19, 1.9%), anxiety disorder (N = 17, 1.7%), intellectual disability (N = 11, 1.1%), autism spectrum disorder (N = 7, 0.7%), somatic symptom disorder (N = 4, 0.4%) schizophrenia (N = 4, 0.4%), substance use disorder (N = 24, 2.4%) and personality disorder (N = 2, 0.2%). The most common time of psychiatric disorder diagnosis was within the first 3 months after liver transplantation (51.6%). The final mortality in patients with comorbid psychiatric disorder diagnosis during the five periods (pretransplant, transplant to 3 months, months to 1 year, 1 to 3 years, and over 3 years posttransplant) was 16.2%, 18.8%, 39.1%, 28.6%, and 16.2% respectively, and there were no significant differences between the five periods (χ2 = 8.05, df = 4, p = 0.09). Overall comorbid psychiatric disorders were significantly associated with shorter survival time (log-rank test: p = 0.01, hazard ratio: 1.59 [95% confidence interval: 1.14–2.21], survival rate at the endpoint [%]: 62.0 vs. 83.3). However, after adjusting for confounding variables using Cox proportional hazards regression, there was no significant effect of overall comorbid psychiatric disorders on prognosis. Conclusion: Comorbid psychiatric disorders did not affect the survival rate of liver transplant recipients in this study. [ABSTRACT FROM AUTHOR]

Platelets express the imidazoline (I)-receptor, I 1 and I 2 , as well as the α 2 -adrenoceptor. Although dexmedetomidine, a selective α 2 -adrenoceptor agonist with some affinity for the I-receptor is expected to affect platelet function, the effects of dexmedetomidine on platelet functions remain unclear. In the present study, we investigated the effects of dexmedetomidine on human platelet functions in vitro . The effects of dexmedetomidine on platelet aggregation were examined using aggregometers. The formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in platelets was measured by an enzyme immunoassay. In addition, P-selectin expression in platelets was estimated by flow cytometry. We showed that dexmedetomidine enhances platelet aggregation. But in the presence of yohimbine, an α 2 -antagonist, dexmedetomidine suppressed platelet aggregation. Efaroxan, an I 1 -antagonist, and methylene blue, a soluble guanylate cyclase inhibitor, abolished the suppressive effect of dexmedetomidine, whereas idazoxan, an I 2 -antagonist, showed no effect. Dexmedetomidine suppressed cAMP formation and enhanced P-selectin expression in platelets, and these effects were inhibited by yohimbine. Dexmedetomidine increased cGMP formation in platelets in the presence of yohimbine, and this increase was suppressed by efaroxan. These results demonstrated that dexmedetomidine has both enhancing and suppressive effects on human platelet functions through its action on the α 2 -adrenoceptor and on the I 1 -imidazoline receptor, respectively. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in the solute carrier organic anion transporter family, member 2a1 gene (SLCO2A1), which encodes a prostaglandin (PG) transporter, have been identified as causes of chronic nonspecific multiple ulcers in the small intestine; however, the underlying mechanisms have not been revealed. We, therefore, evaluated the effects of systemic knockout of Slco2a1 (Slco2a1−/−) and conditional knockout in intestinal epithelial cells (Slco2a1ΔIEC) and macrophages (Slco2a1ΔMP) in mice with dextran sodium sulphate (DSS)-induced acute colitis. Slco2a−/− mice were more susceptible to DSS-induced colitis than wild-type (WT) mice, but did not spontaneously develop enteritis or colitis. The nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 (NLRP3) inflammasome was more strongly upregulated in colon tissues of Slco2a−/− mice administered DSS and in macrophages isolated from Slco2a1−/− mice than in the WT counterparts. Slco2a1ΔMP, but not Slco2a1ΔIEC mice, were more susceptible to DSS-induced colitis than WT mice, partly phenocopying Slco2a−/− mice. Concentrations of PGE2 in colon tissues and macrophages from Slco2a1−/− mice were significantly higher than those of WT mice. Blockade of inflammasome activation suppressed the exacerbation of colitis. These results indicated that Slco2a1-deficiency increases the PGE2 concentration, resulting in NLRP3 inflammasome activation in macrophages, thus exacerbating intestinal inflammation. [ABSTRACT FROM AUTHOR]

Objectives: Although tacrolimus is useful as an induction therapy in patients with ulcerative colitis (UC), information regarding the long-term outcome after tacrolimus therapy is insufficient. The aim of this study was to evaluate the clinical significance of the pretreatment neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor in patients with UC receiving tacrolimus, to aid treatment selection. Materials and methods: Patients with moderate-to-severe active UC who received oral tacrolimus induction therapy and subsequent immunomodulatory maintenance therapy at our hospital between 2009 and 2017 and who showed clinical response at week 12, were retrospectively enrolled. Cox regression analysis was conducted to study the prognostic role of the pretreatment NLR. The combined impact of the NLR and other known prognostic factors was investigated with multivariate regression. Results: Among 45 patients included in this study, 21 patients experienced relapse during a median follow-up period of 16.6 months. Multivariate Cox regression analysis identified the pretreatment NLR (hazard ratio [HR]: 0.82, 95% confidence interval [CI]: 0.72–0.94, P < 0.01) and the use of immunomodulators at the start of tacrolimus treatment (HR: 0.18, 95% CI: 0.05–0.66, P = 0.01) as independent predictors of clinical relapse. Conclusions: The pretreatment NLR is an independent prognostic factor in patients with UC treated with tacrolimus. [ABSTRACT FROM AUTHOR]