As populations grow older, the sustainability of current healthcare systems is being questioned. This paper considers what is necessary to ensure the sustainability of the healthcare system in Japan from the perspective of economics and public finance. In particular, it addresses the cost-effective use of limited medical resources. It also considers the problems of current regulations and regulatory regimes, which tend to protect vested interests. It may be necessary to carry out fundamental reforms of the regulatory system to deliver a sustainable healthcare system.

Postgraduate clinical training for physicians in Japan has been mandatory since 2004, with the provision that the system itself is to be revised every 5 years if necessary. Major revisions were implemented in 2020, involving the objectives, strategies, and evaluations of the clinical training program. Among the revisions was a section on professionalism in the first part of objectives. As one of the committee members involved in the process of this revision, I provide an explanation of the historical background, learning strategies, and assessment of professionalism in physician training.

In their role as providers of pharmaceutical products to society, pharmacists must demonstrate professionalism if they are to gain the trust of the community. The Japan Pharmaceutical Association has published the Pharmacist Platform in Japan and the Japanese Code of Ethics for Pharmacists; these resources provide clear guidelines for pharmacists and are an important component of the profession. Becoming a pharmacist involves joining a professional community and thereby pledging to accept a set of ethical standards. This concept of the pharmacy profession is shared by other countries, and the International Pharmaceutical Federation has indicated that professionalism is an issue that should be addressed in every country. This review introduces the Pharmacist Platform in Japan, the Japanese Code of Ethics for Pharmacists established by the Japan Pharmaceutical Association, and the background of each establishment.

Regulatory science underpins scientific regulations, including reflection papers, guidelines, and administrative notices, and is closely related to the quality assurance (QA) of pharmaceuticals, foods, and chemicals in our living environment. Historically, QA has been considered the basis of pharmaceutical science. Therefore, the Pharmaceutical and Medical Device Law specifies that pharmacists, as marketing directors of pharmaceutical products, are responsible for their QA. Furthermore, a pharmacist is responsible for the QA of foods and environmental chemicals by several laws; for example, as a food sanitation supervisor or an environmental sanitation training officer. This suggests that the professional expertise of pharmacists is expected in medical care where pharmaceuticals are used and in other fields associated with QA. Thus, I consider that the professionalism of a pharmacist is guided by spiritual concepts with a pragmatic attitude and conformance to these expectations.

Through many years’ experience in pharmaceutical administration, we believe that when pharmacists active in various workplaces are involved in research and development (especially clinical development) and post-marketing (especially proper usage and safety measures), they can better meet patients’ hopes and expectations based on actual conditions in clinical practice and other settings by means of mutual communication and collaboration. The International Pharmaceutical Federation believes that for the benefit of patients, pharmaceutical researchers and pharmacists should work together and that the three pillars of research, practice, and education are closely and inseparably integrated. In today’s rapidly evolving society, it is necessary—and beneficial—for pharmacists working in both government and industry to be better connected toward achieving better health care.

Worldwide interest in teaching medical professionalism has increased drastically over the past two decades and is recognized as an important core competency. It is also essential in pharmacy education. However, there is no single definition of medical professionalism owing to its multifaceted nature, leading to difficulty in understanding it. The foundational concept of professionalism are the social contract and accountability, which describe the relationship between the profession and the society which it serves. Profession must understand expectations from the society, which is trustworthy, assures competence, and devoted to the public good for the contract based on their mutual trust. In “teaching,” three basic educational actions (“setting expectations,” “providing experiences,” and “evaluating outcomes”) are required. There are two learning goals of professionalism education: the minimum goal of not doing unprofessional acts and the aspirational goal of pursuing a higher level of interiorized professionalism which leads to the professional identity formation. The true professionals are “reflective practitioners,” who have the ability to manage ambiguous problems using their interiorized professionalism in complicated situations. Therefore, reflection is one of the central concepts of professionalism education. The Professionalism Mini-Evaluation Exercise (P-MEX), an observational tool to evaluate medical professionalism, has some favorable aspects; the Japanese version is available and is a guide to specific actions for professionalism through its items, although some cautions must be exercised when using it. Considering that teaching professionalism includes not only formal but informal and hidden curricula, all of the staff in the educational environments should consider professionalism education by understanding professionalism.

Cefiderocol is a novel siderophore-conjugated cephalosporin with a catechol residue acting as an iron chelator. Cefiderocol forms a chelating complex with ferric iron and is transported rapidly into bacterial cells through iron-uptake systems. As a result, cefiderocol shows good activity against Gram-negative bacteria, including carbapenem-resistant isolates that are causing significant global health issues. Cefiderocol has been approved for clinical use in the United States and Europe, where it is being used to treat infection caused by carbapenem-resistant Gram-negative pathogens.

Iron is necessary for all living organisms, and bacteria that cause infections in human hosts also need ferrous ions for their growth and proliferation. In the human body, most ferric ions (Fe³⁺) are tightly bound to iron-binding proteins such as hemoglobin, transferrin, lactoferrin, and ferritin. Pathogenic bacteria express highly specific iron uptake systems, including siderophores and specific receptors. Most bacteria secrete siderophores, which are low-molecular weight metal-chelating agents, to capture Fe³⁺ outside cell. Siderophores are mainly classified as either catecholate or hydroxamate. Vibrio vulnificus, a Gram-negative pathogenic bacterium, is responsible for serious infections in humans and requires iron for growth. A clinical isolate, V. vulnificus M2799, secretes a catecholate siderophore, vulnibactin, that captures ferric ions from the environment. In our study, we generated deletion mutants of the genes encoding proteins involved in the vulnibactin mediated iron-utilization system, such as ferric-vulnibactin receptor protein (VuuA), periplasmic ferric-vulnibactin binding protein (FatB), ferric-vulnibactin reductase (VuuB), and isochorismate synthase (ICS). ICS and VuuA are required under low-iron conditions for ferric-utilization in M2799, but the alternative proteins FatB and VuuB can function as a periplasmic binding protein and a ferric-chelate reductase, respectively. VatD, which functions as ferric-hydroxamate siderophores periplasmic binding protein, was shown to participate in the ferric-vulnibactin uptake system in the absence of FatB. Furthermore, the ferric-hydroxamate siderophore reductase IutB was observed to participate in ferric-vulnibactin reduction in the absence of VuuB. We propose that ferric-siderophore periplasmic binding proteins and ferric-chelate reductases represent potential targets for drug discovery in the context of infectious diseases.

Inspired by the mechanism by which microorganisms utilize siderophores to ingest iron, four different Fe^III complexes of typical artificial siderophore ligands containing catecholate and/or hydroxamate groups, K₃[Fe^III-L_C3], K₂[Fe^III-L_C2H1], K[Fe^III-L_C1H2], and [Fe^III-L_H3], were prepared. They were modified on an Au substrate surface (Fe-L/Au) and applied as microorganism immobilization devices for fast, sensitive, selective detection of microorganisms, where H₆L_C3, H₅L_C2H1, H₄L_C1H2, and H₃L_H3 denote the tri-catecholate, biscatecholate-monohydroxamate, monocatecholate-bishydroxamate, and tri-hydroxamate type of artificial siderophores, respectively. Their adsorption properties for the several microorganisms were investigated using scanning electron microscopy (SEM), quartz crystal microbalance (QCM), and electric impedance spectroscopy (EIS) methods. The artificial siderophore-iron complexes modified on the Au substrates Fe-L_C3/Au, Fe-L_C2H1/Au, Fe-L_C1H2/Au, and Fe-L_H3/Au showed specific microorganism immobilization behavior with selectivity based on the structure of the artificial siderophores. Their specificities corresponded well with the structural characteristics of natural siderophores that microorganisms release from the cell and/or use to take up an iron. These findings suggest that release and uptake are achieved through specific interactions between the artificial siderophore-Fe^III complexes and receptors on the cell surfaces of microorganisms. This study revealed that Fe-L/Au systems have specific potential to serve as effective immobilization probes of microorganisms for rapid, selective detection and identification of a variety of microorganisms.

Microbial exudates including siderophore, which changes chemical species of actinides and lanthanides. We have investigated effects of desferrioxamine B (DFOB; one of the siderophores) and siderophore-like organic molecules (SLOM) on the adsorption of lanthanides by microbial cells, aluminium oxide (Al₂O₃), and manganese (Mn) oxides. When DFOB was present, the distribution coefficients of cerium (Ce) were measured to be lower than those of neighboring elements of lanthanum (La) and praseodymium (Pr) (Negative anomaly of Ce adsorption). Even though initial oxidation state of Ce in the solution was III, that was changed to IV after the addition of DFOB, indicating that Ce(III) was oxidized by forming complex with DFOB. When lanthanides were adsorbed by biogenic Mn(IV) oxides, negative anomaly of Ce adsorption was observed in the sorption in alkaline solution. Ce(III) was oxidized to forme the complexes of Ce(IV) with SLOM in the solution. These results show that siderophore possesses high performance of oxidation of Ce(III) to Ce(IV) during association, affectiong the adsorption behavior of Ce. After Fukushima accident, radioactive Cs accumulation by Eleutherococcus sciadophylloides (Koshiabura) caused by the dissolution of Fe from soil around the roots, that was dominated by siderophore releasing microorganisms (SB). These SBs may enhance dissolution of iron (Fe) and uranium (U) phases in the nuclear fuel debris formed in the nuclear reactors in Fukushima Daiichi nuclear power plant. Thus, in the interaction between microorganisms and radionuclides, SLOMs discharged by microorganisms are deeply involved in the chemical state change of radionuclides.

Serum urate levels are determined by the balance between uric acid production and uric acid excretion capacity from the kidneys and intestinal tract. Dysuricemia, including hyperuricemia and hypouricemia, develops when the balance shifts towards an increase or a decrease in the uric acid pool. Hyperuricemia is mostly a multifactorial genetic disorder involving several disease susceptibility genes and environmental factors. Hypouricemia, on the other hand, is caused by genetic abnormalities. The main genes involved in dysuricemia are xanthine oxidoreductase, an enzyme that produces uric acid, and the urate transporters urate transporter 1/solute carrier family 22 member 12 (URAT1/SLC22A12), glucose transporter 9/solute carrier family 2 member 9 (GLUT9/SLC2A9) and ATP binding cassette subfamily G member 2 (ABCG2). Deficiency of xanthine oxidoreductase results in xanthinuria, a rare disease with marked hypouricemia. Xanthinuria can be due to a single deficiency of xanthine oxidoreductase or in combination with aldehyde oxidase deficiency as well. The latter is caused by a deficiency in molybdenum cofactor sulfurase, which is responsible for adding sulphur atoms to the molybdenum cofactor required for xanthine oxidoreductase and aldehyde oxidase to exert their action. URAT1/SLC22A12 and GLUT9/SLC2A9 are involved in urate reabsorption and their deficiency leads to renal hypouricemia, a condition that is common in Japanese due to URAT1/SLC22A12 deficiency. On the other hand, ABCG2 is involved in the secretion of urate, and many Japanese have single nucleotide polymorphisms that result in its reduced function, leading to hyperuricemia. In particular, severe dysfunction of ABCG2 leads to hyperuricemia with reduced extrarenal excretion.

Recently, feeding damage by the olive weevil Pimelocerus (Dyscerus) perforatus Roelofs, which utilizes olive trees (Olea europaea Linne) as a host plant, has become the biggest obstacle to olive cultivation in Japan. We previously identified several volatile plant-derived natural products that exhibit repellent activity against olive weevils. In this study, we conducted a pilot test of repellents in an olive orchard along with the use of insecticide. During three consecutive years from 2021 to 2023, the first year was the observation period, and the second and third years were set aside for a trial period for o-vanillin and geraniol as repellents, respectively. Using o-vanillin, the number of adult olive weevil outbreaks decreased to almost half a year in the experimental area, the use of geraniol then resulted in a drastic reduction of the number of individual olive weevils in the experimental area. In contrast, adults and larvae outbreaks increased in the control area without a repellent, despite the use of insecticide. These results indicate that the volatile repellents drove the olive weevils away and kept them at bay in the field. Based on the observations, we will be able to provide a new approach for the control of olive cultivation, including fruit and leaves used for commercial purposes, following integrated pest management (IPM) practices, such as reducing environmental poisoning from intense insecticides, and returning olive weevils to their original habitat outside of olive orchards.

Docetaxel (DTX) is a key drug used in perioperative chemotherapy for breast cancer. Edema is a known adverse effect of DTX, but its effect on health-related QOL (HRQOL) is unclear. In this study, we evaluated the effects of edema caused by administration of DTX on HRQOL in patients with early-stage breast cancer. We prospectively investigated patients diagnosed with early-stage breast cancer (stage I–III) who received 4 cycles of DTX as preoperative or postoperative chemotherapy between September 2021 and December 2022 at Yamanashi Prefectural Central Hospital. The circumference of each extremity was measured at each administration of DTX, and limb edema was evaluated by Common Terminology Criteria for Adverse Events version 5.0. HRQOL was evaluated using SF-12 version 2, which has a range of 0–100 (national standard, 50), and compared between the presence and absence of grade 2 or higher edema and between before and after administration of DTX. Twenty patients met the eligibility criteria and were included in the study. There was no difference in the HRQOL score according to whether grade 2 limb edema was present. The median HRQOL summary scores before and after administration of DTX were 51.1 and 50.8 (p=0.763), respectively, for mental health, 52.6 and 49.4 (p=0.005) for physical health, and 38.9 and 37.5 (p=1.000) for role/social health. We found no direct effect of DTX-induced limb edema on HRQOL in patients with early-stage breast cancer. However, HRQOL summary scores indicated that administration of DTX reduced physical health in these patients.

In Japan, only few hospitals have pharmacists in their secondary emergency rooms to record medication history and provide drug information in real time. In this study, we investigated the benefits of pharmacist intervention in secondary emergency rooms by comparing the time taken by the pharmacists and non-pharmacists in the emergency room to record the medication history in the electronic medical record and the accuracy of its content. The study period was from September 1 to September 30, 2022, and included patients who were transported to our hospital for emergency care between 9:00 and 16:30. We compared the time taken between the patient’s arrival until the recording of their medication history and the accuracy of the record by the emergency room pharmacists and non-pharmacists (paramedics or medical clerks). The study included 58 patients whose medication histories were collected by pharmacists, and 11 patients whose histories were collected by non-pharmacists. For pharmacists, the median time to record medication history in the electronic medical record was 12 min, whereas for non-pharmacists, it was 19 min, which was significantly different (p=0.015). The pharmacists accurately recorded the medication history of 98.3% (57/58) of patients, whereas non-pharmacists accurately recorded it for only 54.5% (6/11) of patients, with a significant difference (p<0.01). We observed that in secondary emergency rooms, when pharmacists were responsible for recording the patients’ medication histories, it resulted in rapid and accurate sharing of medication history.