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Background: Prenatal exposure to metallic elements may adversely affect early childhood health. However, more evidence is needed as population-based cohort studies are currently limited., Objectives: We aimed to examine the associations between prenatal metallic (mercury, selenium, and manganese) exposure and the risk of allergic diseases in early childhood until three years of age., Methods: The data from 94,794 mother-infant pairs, who participated in the Japan Environment and Children's study, were used in this study. Prenatal metallic element exposure was measured in maternal blood collected during mid-pregnancy. The incidence of atopic dermatitis, food allergies, asthma, and allergic rhinitis during the first three years of life was prospectively investigated using self-reports of physician-diagnosed allergies. A multivariable modified Poisson regression model was used to estimate the cumulative incidence ratio and their 95% confidence intervals of allergic diseases associated with prenatal exposure to mercury, selenium, and manganese. We further evaluated the interaction between mercury and selenium exposures in this association., Results: We confirmed 26,238 cases of childhood allergic diseases: atopic dermatitis, food allergies, asthma, and allergic rhinitis in 9,715 (10.3%), 10,897 (11.5%), and 9,857 (10.4%), 4,630 (4.9%), respectively. No association was found between prenatal mercury or manganese exposure and the risk of allergic diseases. Prenatal selenium exposure was inversely associated with atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases, but not with asthma. These inverse associations were more pronounced for lower mercury exposures than for higher exposures., Conclusions: Our findings suggest that prenatal exposure to selenium may be beneficial for reducing the risk of atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases in early childhood, especially with lower prenatal mercury exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mycobacterium leprae (M. leprae) is the etiological agent of leprosy, and the skin lesions of lepromatous leprosy are filled with numerous foamy or xanthomatous histiocytes that are parasitized by M. leprae. Lipids are an important nutrient for the intracellular survival of M. leprae. In this study, we attempted to determine the intracellular lipid composition and underlying mechanisms for changes in host cell lipid metabolism induced by M. leprae infection. Using high-performance thin-layer chromatography (HPTLC), we demonstrated specific induction of triacylglycerol (TAG) production in human macrophage THP-1 cells following M. leprae infection. We then used [14C] stearic acid tracing to show incorporation of this newly synthesized host cell TAG into M. leprae. In parallel with TAG accumulation, expression of host glycerol-3-phosphate acyltransferase 3 (GPAT3), a key enzyme in de novo TAG synthesis, was significantly increased in M. leprae-infected cells. CRISPR/Cas9 genome editing of GPAT3 in THP-1 cells (GPAT3 KO) dramatically reduced accumulation of TAG following M. leprae infection, intracellular mycobacterial load, and bacteria viability. These results together suggest that M. leprae induces host GPAT3 expression to facilitate TAG accumulation within macrophages to maintain a suitable environment that is crucial for intracellular survival of these bacilli., Competing Interests: The authors have declared that no competing interests exist.

Standards and guidelines for preparedness and response in the case of a nuclear accident cover radiation protection, health management and communication with affected populations. Decision makers use these recommendations to decide on measures that protect people residing around a nuclear power plant that suffers an accident from radiation exposure; for example, sheltering, evacuation and relocation. While technological and radiological criteria exist for these protective measures, studies on past radiological and nuclear emergencies have shown that evacuation and relocation result in serious health effects; this needs to be considered in accident preparedness and responses in the future. Within the framework of the Nuclear Emergency Situations Improvement of Medical and Health Surveillance (SHAMISEN) (Ohba et al., 2020), a critical review of recommendations and experiences of previous major nuclear accidents was conducted, and the current paper focuses on the lessons learned about evacuation and relocation. We reviewed the contents of official documents and literature relating to the evacuation and relocation of residents, and to the evacuation of medical and other facilities in the three largest nuclear accidents to date: the Three Mile Island accident, Chernobyl accident, and Fukushima accident. We developed recommendations classified into the preparedness phase, early and intermediate phases, and recovery phase after an accident. In the cases of Three Mile Island and Fukushima, the evacuation area was set at 8-10 km from the nuclear power plant in the disaster prevention plan, and emergency responses, such as information provision and evacuation, had been developed only in this area. When the Fukushima accident occurred, evacuation beyond this area was urgently planned or instructed, resulting in marked confusion, such as forced multiple evacuations and relocations for long periods. Furthermore, information was lacking, and personal protective measures such as respiratory protection and iodine prophylaxis were not applied to evacuees. In hospital and facility evacuation, it became more difficult to implement evacuation owing to a lack of advance planning and support in the event of the accident. In Fukushima, more than 60 people in hospitals and nursing care facilities died during or soon after evacuation. In long-term relocation, in addition to continuing adverse mental effects, there were health effects relating to relocation, such as lifestyle-related disease. The return of residents to the evacuation area required many issues, such as a delayed recovery of the living environment, to be overcome in addition to measures to reduce the effects of radiation. Recommendations for evacuation in the SHAMISEN framework were developed (SHAMISEN Consortium, 2017; Liutsko et al., 2020) from these lessons of previous accidents., (Copyright © 2021. Published by Elsevier Ltd.)

This paper explores how health concerns of populations living in contaminated areas following radiological accidents can be considered in developing health surveillance. The research was performed in the framework of the SHAMISEN project, and aimed at identifying the impacts on, and challenges associated with, living and social conditions of affected populations. These objectives were achieved through the analysis of specific Case Studies in different situations observed after the Chernobyl accident (Belarus and Norway) and the activities carried out after the Fukushima accident. It incorporates an analysis of testimonies of medical experts and local stakeholders from contaminated territories in Japan within two Case Studies as well as through a dedicated workshop jointly organised with Fukushima Medical University in Japan in March 2016. The analysis addresses the following topics:Thus, this paper outlines key lessons learned from each of these topics, by providing tangibles examples from the analysis of the various Case Studies., (Copyright © 2020. Published by Elsevier Ltd.)

The experiences of the Chernobyl and Fukushima nuclear accidents showed that dosimetry was the essential tool in the emergency situation for decision making processes, such as evacuation and application of protective measures. However, at the consequent post-accidental phases, it was crucial also for medical health surveillance and in further adaptation to changed conditions with regards to radiation protection of the affected populations. This review provides an analysis of the experiences related to the role of dosimetry (dose measurements, assessment and reconstruction) regarding health preventive measures in the post-accidental periods on the examples of the major past nuclear accidents such as Chernobyl and Fukushima. Recommendations derived from the review are called to improve individual dose assessment in case of a radiological accident/incident and should be considered in advance as guidelines to follow for having better information. They are given as conclusions., (Copyright © 2020. Published by Elsevier Ltd.)

Experience suggests that current nuclear accident response planning in European countries mostly has a technical focus, with less attention paid to social, psychological and ethical issues. Information provided tends to be directed towards decisions made by experts, rather than for the support of affected populations. The SHAMISEN (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) consortium, composed of close to 50 experts from 10 countries, performed a critical review of current recommendations and experiences regarding dose assessment and reconstruction, evacuation decisions, long-term health surveillance programmes and epidemiological studies. The review included case studies and lessons drawn from the living conditions and health status of populations affected by the Chernobyl and Fukushima accidents, taking an integrative approach to health and well-being. Based on this work, SHAMISEN developed a series of comprehensive recommendations aimed at improving the preparedness, response, long-term surveillance and living conditions of populations affected by past or future radiation accidents, in a manner responding to their needs, while minimising unnecessary anxiety., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Nabe-kaburi is a unique burial method, the purpose of which is shrouded in mystery. The burials were performed during the 15(th) to 18(th) centuries in eastern Japan, and involved covering the heads of the deceased with iron pots or mortars. The identification of leprosy-specific osteological lesions among some of the excavated remains has led to the suggestion that Nabe-kaburi burials were a reflection of the social stigma against certain infectious diseases, such as leprosy, tuberculosis or syphilis. However, molecular evidence for the presence of disease has been lacking. The goal of this study was to detect Mycobacterium leprae (M. leprae) DNA in archaeological human skeletal remains from Nabe-kaburi burials. The paleopathological data from three Nabe-kaburi burials were re-evaluated before small samples were taken from affected and control areas. DNA was extracted and used as a template to target the M. leprae-specific DNA using a combination of whole genome amplification, PCR analysis and DNA sequencing. M. leprae DNA fragments were detected in the two sets of skeletal remains that had also shown paleopathological evidence of leprosy. These findings provide definitive evidence that some of the Nabe-kaburi burials were performed for people affected by leprosy. Demonstration of the presence of M. leprae DNA, combined with archeological and anthropological examinations, will aid in solving the mystery of why Nabe-kaburi burials were performed in medieval Japan.

Despite the reported complete β-selectivity in glycosylation with 2,4-di-O-benzyl-3,6-O-(o-xylylene)glucopyranosyl fluoride, its preparation has been inefficient. This paper describes an improved route for the donor, including the formation of the 3,6-bridge on 1,2,4-orthoacetylglucose, the preparation of which was also refined, along with a discovered feature that the 3,6-bridged glucose prefers the furanose form. Although this feature made the synthesis of the desired glucopyranosyl donor difficult, application of thermal glycosylation solved the problem. With a modifiable intermediate, the improved availability of the donor would expand the applications.

This paper describes a total synthesis of (-)-strictinin, an ellagitannin that is 1-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl (HHDP)-β-D-glucose. In the study, total efficiency of the synthesis was improved to produce a 78% overall yield in 13 steps from D-glucose. In the synthesis, formation of the 4,6-(S)-HHDP bridge including the 11-membered bislactone ring was a key step, in which intramolecular aryl-aryl coupling was adopted. The coupling was oxidatively induced by CuCl2-n-BuNH2 with perfect control of the axial chirality, and the reaction conditions of this coupling were optimized thoroughly to achieve the quantitative formation of the bridge.

Leprosy is a chronic infectious disorder caused by Mycobacterium leprae, which mainly affects skin and peripheral nerves. It is classified as either paucibacillary or multibacillary based upon clinical manifestations and slit-skin smear results. It is speculated that leprosy develops after a long latency period following M. leprae infection. However, the actual time of infection and the duration of latency have never been proven in human patients. To date, four cases of spontaneous leprosy have been reported in chimpanzees who were caught in West Africa in infancy and used for medical research in the USA and Japan. One of these chimpanzees was extensively studied in Japan, and single-nucleotide polymorphism analysis for the M. leprae genome was conducted. This analysis revealed that the chimpanzee was infected with M. leprae during infancy in West Africa and the pathognomonic signs of leprosy appeared after at least 30 years of incubation. Analysis of leprosy in chimpanzees can contribute not only to medical research but also to the understanding of the pathoetiology of leprosy.

Background: Identification of pathogen DNA from archaeological human remains is a powerful tool in demonstrating that the infectious disease existed in the past. However, it is very difficult to detect trace amounts of DNA remnants attached to the human skeleton, especially from those buried in a humid atmosphere with a relatively high environmental temperature such as in Asia., Methodology/principal Findings: Here we demonstrate Mycobacterium leprae DNA from archaeological skeletal remains in Japan by polymerase chain reaction, DNA sequencing and single nucleotide polymorphism (SNP) analysis. In addition, we have established a highly sensitive method of detecting DNA using a combination of whole genome amplification and polymerase chain reaction, or WGA-PCR, which provides superior sensitivity and specificity in detecting DNA from trace amounts of skeletal materials., Conclusion/significance: We have detected M. leprae DNA in archaeological skeletal remains for the first time in the Far East. Its SNP genotype corresponded to type 1; the first detected case worldwide of ancient M. leprae DNA. We also developed a highly sensitive method to detect ancient DNA by utilizing whole genome amplification.

Mangiferin (MF) isolated from Anemarrhena asphodeloides Bunge rhizome, was tested for antidiabetic activity in KK-Ay mice, an animal model of type-2 diabetes. MF lowered the blood glucose level of KK-Ay mice 3 weeks after oral administration (p < 0.01). However, no effect on the blood glucose level in normal mice was seen, indicating that MF could be useful in treating type-2 diabetes. In addition, MF improved hyperinsulinemia and, on insulin tolerance test, reduced blood glucose levels of KK-Ay mice. From these findings, it seems likely that MF exerts its antidiabetic activity by decreasing insulin resistance.

The molecular basis of the uroporphyrinogen III synthase (UROIIIS) deficiency was investigated in two members of a Japanese family. This defect in heme biosynthesis is responsible for a rare autosomal recessive disease: congenital erythropoietic porphyria (CEP) or Gnther's disease. The first patient was homoallelic for a novel missense mutation: a T to C transition of nucleotide 634 that predicted a serine to proline substitution at residue 212 (S212P). The second patient appeared heteroallelic, carrying the same missense mutation and a nonsense mutation: a C to T change at nucleotide 745, resulting in a premature stop at codon 249, instead of a glutamine (Q249X). The corresponding mutated proteins were expressed in Escherichia coli and no residual activity was observed. A family study was also performed to determine the carrier status.

Glycogen storage disease (GSD) type 1a (von Gierke disease) is an autosomal recessive disorder caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase). We have identified a novel mutation in the G6Pase gene of a individual with GSD type 1a. The cDNA from the patient's liver revealed a 91-nt deletion in exon 5. The genomic DNA from the patient's white blood cells revealed no deletion or mutation at the splicing junction of intron 4 and exon 5. The 3' splicing occurred 91 bp from the 5' site of exon 5 (at position 732 in the coding region), causing a substitution of a single nucleotide (G to T) at position 727 in the coding region. Further confirmation of the missplicing was obtained by transient expression of allelic minigene constructs into animal cells. Another eight unrelated families of nine Japanese patients were all found to have this mutation. This mutation is a new type of splicing mutation in the G6Pase gene, and 91% of patients and carriers suffering from GSD1a in Japan are detectable with this splicing mutation.

Endoscopic polypectomy using high frequency voltage is contraindicated in patients with cardiac pacemakers. Recently, highly advanced pacemakers have enabled us to perform endoscopic polypectomy on these patients by taking appropriate cautions. We successfully removed 10 colonic polyps and one gastric polyp in patients with pacemakers by endoscopic polypectomy. No complication and dysfunction of the pacemaker occurred before, during or after the polypectomy.

Although foreign bodies of the gastrointestinal tract are common in children, they are rare in the adult. Complications of the foreign bodies are well recognized to be a cause of obstruction, bleeding and perforation of the intestine, or furthermore, they sometimes lead to death unfortunately. On the other hand, it is very difficult to diagnose and treat foreign bodies in the handicapped because of disability of complaining the symptoms. This paper reports a 31-year-old severe handicapped man suffering from foreign bodies in the esophagus and the small intestine, and was successful removed by endoscope.