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Abstract: Significant evidence of linkage to type 2 diabetes (T2D) has been shown in a relatively broad region on chromosome 20q, where the hepatocyte nuclear factor-4α (HNF4A) has been noted as a positional candidate. To systematically evaluate genetic susceptibility to T2D in the relevant region, we examined the disease association by using 1145 SNPs in two-step screening in the Japanese population. The marker screening enabled us to identify significant disease association in the lipopolysaccharide binding protein (LBP) but not in the HNF4A locus. In a 17.7-Mb interval screened, the strongest association was identified for a SNP, rs2232592, located in the intron of LBP, with an estimated odds ratio of 1.73 (95% CI 1.30–2.31) (P =0.0002) in the whole study panel involving 675 case and 474 control subjects. Our data suggest that the LBP gene may confer genetic susceptibility to T2D and this warrants further replication study. [Copyright &y& Elsevier]

The history of hitherto existing pharmacology in Japan presented here is authored in commemoration of the 150th anniversary of Naunyn-Schmiedeberg's Archives of Pharmacology. After the publication of the new book of anatomy "Anatomische Tabellen" translated into Japanese in 1774, the foundation of understanding the medical science was gradually formed in Japan under seclusion policy, and, since the Meiji Restoration of 1868, the modernization of Japanese medicine was rapidly fostered on the basis of German medicine. Thus, the Japanese government officially adopted German medicine, and the philosophy and practice of German medical schools were incorporated. Most of the medical texts used in Japan were of German origins, often in Dutch translations, and many Japanese physicians and medical researchers studied abroad in Germany. The start of experimental pharmacology in Japan was also made up by Japanese disciples of Oswald Schmiedeberg, who was the one of founders of the Archives in 1873. Additionally, it was customary for professor candidates in charge of pharmacology in medical faculties in Japan to go to Germany and study pharmacology. Through such historical circumstances, the Japanese Pharmacology Society has been established to fulfill the responsibility for contributing internationally to world-class research achievements in the field of medical sciences by supplying numerous talented pharmacologists. During the course of the development of experimental pharmacology in Japan, the Archives has provided an excellent stage for many Japanese pharmacologists to publish their research outcomes to proliferate them internationally. Without German medicine influence, Japanese pharmacology would not have been what it is today., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Criminals in Japan with mental disorders face penal servitude in prison or treatment under the Medical Treatment and Supervision Act, depending on their ability to take responsibility for their criminal acts. Forensic psychiatric nurses caring for this group may face various ethical issues., Objective: This study aimed to identify ethical issues forensic psychiatric nurses in Japan encountered., Method: We used the Ethical Issues Scale to conduct a survey among forensic healthcare ward nurses and analyzed the data using descriptive statistics. We also conducted semistructured interviews with individual nurses who provided signed consent and responded to the initial survey on ethical issues they encountered. These data were analyzed using Berelson's content analysis., Results: Of 175 nurses, 131 answered our survey. The most frequently encountered ethical issue was "protecting patients' rights and human dignity," and the most disturbing ethical issue was "providing nursing care with possible health risks." Seventy-seven percent of the nurses chose to discuss with peers when resolving the ethical issues. Seventeen nurses who were interviewed described these forensic psychiatric nursing-related ethical distresses and conflicts: difficulty in discharge management, prevention of violence and self-harm, compulsory treatment, patient care, and negative emotions toward patient., Conclusion: Forensic psychiatric nurses in Japan face difficulties regarding respecting patients' rights. They strive to respect patients' rights by using their expertise as nurses while sharing their difficulties with colleagues. It is important to develop a support system for social reintegration to solve ethical issues., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Carnitine deficiency contributes to developing various pathological conditions, such as cardiac dysfunction, muscle weakness, and erythropoietin-resistant anemia in patients undergoing hemodialysis. However, a conclusion has not been reached concerning the prevalence and the effect of carnitine deficiency in patients undergoing peritoneal dialysis (PD). In this study, the prevalence of carnitine deficiency and the clinical factors associated with carnitine deficiency were investigated in 60 patients undergoing PD. The median age of the patients was 62.5 years (52.5-72.5 years), the proportion of male sex was 44/60 (73.3%), and the median PD period was 24 months (12-45 months). Carnitine deficiency (acyl carnitine/free carnitine ratio >0.4) was detected in 56/60 (93%) patients. Multiple regression analysis showed that the erythropoietin resistance index was independently associated with carnitine deficiency (β = 0.283, p  = 0.04). These results suggest that carnitine plays pivotal roles in hematogenesis in patients undergoing PD.

Forensic nursing is the application of forensic science to nursing. It provides direct patient care with relation to violence, abuse, crime, victimization and exploitation. Forensic nurses integrate forensic and nursing sciences in their assessment and care of victims and perpetrators. In the U.S.A., Canada and Europe, forensic nursing practice involves advocating for the collection of evidence and reporting of crimes. Additionally, forensic nurses treat victims and perpetrators for their trauma, their families, communities and the systems that respond to them. Through its practice, forensic nursing contributes to public health by preventing health hazards caused by violence and crime. This report considers the possibility of the development of forensic nursing in Japan. We propose that the development of forensic nursing is necessary.

Forensic nursing scientifically obtains and preserves the criminal damage from victims of domestic violence, child abuse, elder abuse, sexual violence and other related forms of violence. This was developed in North America in the 1980s, and has carried out appropriate nursing care while protecting the human rights of victims. Serious crime in Japan has been increasing, and it would seem that forensic nursing opportunities should expand as well. However, in Japan, there hasn't been much discussion about forensic nursing. Theorizing that support for clinical forensic nursing should be recognized and relevant, we carried out a survey of 581 clinical nurses to investigate the development of forensic nursing in Japan. 93 clinical nurses (16.0%) had a low level of familiarity with forensic nursing; however, 324 nurses (56.3%) had encountered patients who had suffered violence. 264 nurses (45.4%) had a feeling of wanting to be involved in forensic nursing, but were not confident with the knowledge and technology, while 144 nurses (24.8%) were concerned about the larger responsibility they would have. 400 nurses (68.8%) hoped to receive specialized knowledge and technical education. It is necessary to establish an education system for forensic nursing in accordance with the educational status-quo while considering the present state of forensic nursing education.

This study aims to elucidate the level of achievement and the challenges in a basic nursing practicum for second-year nursing students through the association method. Analysis revealed various descriptions of learning through the practicum training experiences in terms of understanding the healthcare environment, planning and implementing daily life assistance, and involvement in building a supportive relationship with a care recipient. In this sense, we can assume that the goal of the practicum was achieved. The students' attitude toward learning showed an emphasis on knowledge, basics, reasoning, and acquisition of knowledge through experience. At the same time, however, we did not observe descriptions of developing the healthcare environment, understanding the methods of developing healthcare plans, or respect for privacy, thus not indicating whether the goal was achieved. In the future, it is necessary to additionally examine specific details of students' learning through analyzing their reports.

What counter-measures can medical professionals take against violent and abusive patients in Japan? The aim of this article is to consider the role of law for protecting medical professionals from such patients in Japan, comparing it with its role in the UK. Medical professionals need to have legal knowledge for avoiding trouble after using such measures as "verbal defense" or "negotiation". When they use their body or objects for defense, they must use them within the limits of the law. Patients sometimes have violent and abusive behavior because of disease or depression from their condition or the environment. If a medical professional fights back against such a patient, is (s)he legally or morally responsible? This is a very important problem. Professional discretion is concerned with balancing patient healthcare and the safety of medical professionals.

Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop hypertension. In addition, some polymorphisms of the alcohol metabolism genes have been reported to exert significant impacts on the risk of alcoholism. We investigate the relevance of genetic susceptibility to drinking behavior and its influence on the sensitivity to pressor effects of alcohol in the Japanese general population. We initially screened SNPs in four candidate genes by resequencing. From 35 SNPs thus identified, 10 tag SNPs were selected and used for large-scale association analysis in a total of 5724 subjects. Among the SNPs tested, significant association (P<0.001) with drinking behavior was observed for ADH1B Arg47His (rs1229984) and ALDH2 Glu487Lys (rs671) polymorphisms. All subjects with Lys homozygote (AA genotype) of rs671 turned out to be nondrinkers and the combination of two SNP genotypes appeared to substantially influence people's drinking behavior in a synergistic manner. rs671 was significantly associated with blood pressure (P=0.0001-0.0491) in subgroups of drinkers. In the context of gene-environment interaction, our data clearly show the genetic impacts of two SNPs on drinking behavior and of one SNP on the sensitivity to the pressor effects of alcohol in the Japanese general population.

Essential hypertension is one of the most common, complex diseases, of which considerable efforts have been made to unravel the pathophysiological mechanisms. Over the last decade, multiple genome-wide linkage analyses have been conducted using 300-900 microsatellite markers but no single study has yielded definitive evidence for 'principal' hypertension susceptibility gene(s). Here, we performed a three-tiered, high-density association study of hypertension, which has been recently made possible. For tier 1, we genotyped 80 795 SNPs distributed throughout the genome in 188 male hypertensive subjects and two general population control groups (752 subjects per group). For tier 2 (752 hypertensive and 752 normotensive subjects), we genotyped a panel of 2676 SNPs selected (odds ratio >or= 1.4 and P

To systematically evaluate genetic susceptibility to type 2 diabetes (T2D) in "candidate" regions on chromosomes 1q, 3q and 12q, we examined disease association by using a total of 2,083 SNPs in two-step screening; a screening panel comprised 473 cases and 285 controls and an extended (or combined) panel involved 658 cases and 474 controls. For the total interval screened (40.9 Mb), suggestive evidence of association was provided for several annotated gene loci. For example, in the MCF2L2 gene on 3q, a significant association (a nominal P value of 0.00009) was observed when logistic regression analysis was performed for three associated SNPs (rs684846, rs35069869 and rs35368790) that belonged to different LD groups. Also, in the SLC15A4 gene on 12q, rs3765108 showed a marginally significant association with an overall estimated odds ratio of 0.79 (P=0.001). No significant association was found for known candidate gene loci on 3q, such as ADIPOQ and IGF2BP2. Using the available samples, we have observed disease associations of SNPs derived from two novel gene loci in the Japanese population through high-density searches of diabetes susceptibility in three chromosomal regions. Independent replication will clarify the etiological relevance of these genomic loci to T2D.

Single nucleotide polymorphisms (SNPs) have been proposed to be grouped into haplotype blocks harboring a limited number of haplotypes. Within each block, the portion of haplotypes is expected to be tagged by a selected subset of SNPs; however, none of the proposed selection algorithms have been definitive. To address this issue, we developed a tag SNP selection algorithm based on grouping of SNPs by the linkage disequilibrium (LD) coefficient r(2) and examined five genes in three ethnic populations--the Japanese, African Americans, and Caucasians. Additionally, we investigated ethnic diversity by characterizing 979 SNPs distributed throughout the genome. Our algorithm could spare 60% of SNPs required for genotyping and limit the imprecision in allele-frequency estimation of nontag SNPs to 2% on average. We discovered the presence of a mosaic pattern of LD plots within a conventionally inferred haplotype block. This emerged because multiple groups of SNPs with strong intragroup LD were mingled in their physical positions. The pattern of LD plots showed some similarity, but the details of tag SNPs were not entirely concordant among three populations. Consequently, our algorithm utilizing LD grouping allows selection of a more faithful set of tag SNPs than do previous algorithms utilizing haplotype blocks.

We have developed a method for obtaining the cumulated activities in organs from radionuclides, which are injected into the patient in nuclear medicine procedures, by external exposure measurement with thermoluminescent dosimeters (TLDs) which are attached to the patient's body surface close to source organs to obtain information on body-surface doses. As the surface dose is connected to the cumulated activities in source organs through radiation transmission in the human body which can be estimated with the aid of a mathematical phantom, the organ cumulated activities can be obtained by the inverse transform method. The accuracy of this method was investigated by using a water phantom in which several gamma-ray volume sources of known activity were placed to simulate source organs. We then estimated by external measurements the organ cumulated activities and absorbed doses in subjects to whom the radiopharmaceuticals 11C-labelled Doxepin, 11C-labelled YM09151-2 and 11C-labelled Benzotropin were administered in clinical nuclear medicine procedures. The cumulated activities in the brain obtained with TLDs for Doxepin and YM09151-2 are 63.6 +/- 6.2 and 32.1 +/- 12.0 kBq h MBq-1 respectively, which are compared with the respective values of 33.3 +/- 9.9 and 23.9 +/- 6.2 kBq h MBq-1 with direct PET (positron emission tomography) measurements. The agreement between the two methods is within a factor of two. The effective doses of Doxepin, YM09151-2 and Benzotropin are determined as 6.92 x 10(-3), 7.08 x 10(-3) and 7.65 x 10(-3) mSv MBq-1 respectively with the TLD method. This method has great advantages, in that cumulated activities in several organs can be obtained easily with a single procedure, and the measurements of body surface doses are performed simultaneously with the nuclear medicine procedure, as TLDs are too small to interfere with other medical measurements.

Background/purpose: To identify recent trends in the diagnosis and treatment of total colonic aganglionosis with or without small bowel involvement (TCSA), the authors analyzed the findings in 107 patients who had TCSA seen between 1988 and 1992 at 147 medical institutions throughout Japan and compared the results with those of a previous survey conducted between 1978 and 1982., Results: The estimated incidence of total colonic aganglionosis was 1 in 58,084 live births, the male to female ratio was 1.5:1, and the incidence of associated anomalies was 15%. These findings were all very similar to those of the previous survey. Ten years ago, 83.6% of all patients underwent Martin's procedure. In the recent survey, this rate had fallen to 52.1%, and a right colon patch method has also been developed as a new procedure. A marked decrease in the overall mortality rate from 40.9% to 21.5% was observed. However, a high mortality rate persists in those cases with small bowel involvement (33.3%); most such cases are complicated with enterocolitis., Conclusions: Although the general features of TCSA were similar to those in the previous survey, a substantial improvement in the treatment results for TCSA has occurred. However, further efforts are still required both to prevent and more effectively to treat enterocolitis, especially in cases involving any aganglionosis extending into small bowel.

We describe an insert mutation in the prion protein (PrP) gene in a Japanese family line that encodes six octapeptide repeats. This is the second report to date of an inherited prion disease with a 144-base pair insertion, although the order of the repeat sequences differ from that reported for the disease in an English family line. The clinical features, like those of the English patients, were characterized by a slowly progressive generalized dementia with some neurological signs and cortical focal symptoms. Postmortem examination disclosed diffuse atrophy of cerebral gray matter and the cerebellar cortex; histologically, there were marked patchy and regional neuronal loss with astrocytosis in the frontal cortex, amygdala and hippocampus and PrP-immunoreactive plaques in the molecular layer of the cerebellum. These plaques were different from typical kuru plaques. The prion disease in the present Japanese family line is compared with that in the English family line.