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Understanding the habitat selection patterns of animals is important for developing land-use plans for species conservation. The death of endangered Amami rabbits (Pentalagus furnessi), which are found only on two islands in Japan, due to vehicle collisions is a serious problem. To reduce the incidence of road kill and conserve the population of Amami rabbits, factors that contribute to the species' proximity to roads need to be examined. We examined the habitat selection of Amami rabbits by counting their fecal pellet groups on roads on Tokuno-Shima Island, Japan. We obtained 101 presence observations, which revealed that Amami rabbits select areas close to natural forests, farmlands, and rivers and areas with steeper slopes. The selection by the species of natural forest and farmland is likely due to the availability of herbaceous and shrub plants at forest edges and crops and weeds in farmland for foraging. The high utilization of steep-sloping terrain could help Amami rabbits minimize predation risk from the native habu pit viper (Protobothrops flavoviridis). The frequent utilization of forest edges and farmland by Amami rabbits increases their risk of becoming road kill and the risk of crop damage, which are serious problems on the island. To prevent Amami rabbits from crossing roads and reduce crop damage, fences should be constructed particularly in high-rabbit-density areas, and should not facilitate population fragmentation of the species. [ABSTRACT FROM AUTHOR]

Purpose: Eimeria spp. are commonly found among rabbits (Mammalia: Lagomorpha) worldwide. Among the 11 Eimeria species, several are highly virulent, including E. intestinalis and E. flavescens, which cause intestinal coccidiosis, and E. stiedae, which causes hepatic coccidiosis. Unlike other countries, the occurrence of Eimeria infections in rabbits in Japan remains unknown, except for one reported case of natural infection. Methods: We surveyed Eimeria infections in clinically affected rabbits over the past approximately 10 years at Livestock Hygiene Centers in 42 prefectures. A total of 16 tissue samples (14 liver, 1 ileum, and 1 cecum) were collected from 15 rabbits in 6 prefectures. Results: Characteristic histopathologic findings were observed, especially around the bile ducts, depending on the developmental stages of the parasites. Eimeria stiedae and E. flavescens were successfully identified by PCR and sequencing analyses in 5 liver samples and 1 cecum sample, respectively. Conclusion: Our results could enhance understanding of infection with Eimeria spp. in rabbits in Japan and contribute to pathological or molecular diagnoses. [ABSTRACT FROM AUTHOR]

The Amami rabbit (Pentalagus furnessi) is found only on the two islands of Amami-Ōshima and Tokunoshima in southwest Japan. It has a primitive appearance and ecology, is an evolutionarily valuable animal and has been assigned to the International Union for Conservation of Nature Red List of Threatened Species. We describe a case with mild purulent wounds on the distal digital skin of both forelimbs and multiple nodular lesions in various organs, including the heart and kidney. Microscopically, the heart lesions were characterized by disruption of the mitral valve and multifocal myocardial necrosis and abscesses due to infection with gram-positive cocci. Similar bacterial infarctions were also found in other organs, including the kidneys. The bacteria were identified as Staphylococcus aureus by immunohistochemical and molecular biological examinations. This first report of infective endocarditis and systemic infarctions caused by S. aureus in an Amami rabbit indicates the importance of monitoring purulent injuries, even if mild, to prevent secondary infections in this species. [ABSTRACT FROM AUTHOR]

Among the 11 species of Eimeria in rabbits, some of which are known to be pathogenic and cause enteritis, E. stiedae induces severe liver lesions resulting in elevated mortality. Unlike in other countries, the incidence and prevalence of the parasites in rabbits have not been reported in Japan. In the present study, we histopathologically analyzed hepatic coccidiosis in a rabbit and attempted several primers to genetically identify the parasites and investigated the prevalence of Eimeria species at the same farm. In the liver of the affected rabbit, we observed fibrosis and edema around multiple bile ducts and epithelial cell hyperplasia of the bile ducts. Large numbers of developing parasites of Eimeria spp., mainly oocysts, were present in the bile ducts. PCR and sequencing analyses with the published primers for Cyclospora and Eimeria spp. were used to successfully identify the parasites in the liver as E. stiedae. The oocysts of Eimeria spp. were detected in 13 out of 20 fecal samples collected from other rabbits at the farm, and five Eimeria spp. (E. perforans, E. flavescens, E. exigua, E. magna, and E. vejdovskyi) were genetically confirmed. Our results provide the first indication that Eimeria spp., including highly pathogenic species, are present in Japan and the primer set used herein can be a useful tool for the identification of rabbit Eimeria spp. [ABSTRACT FROM AUTHOR]

Although intranasal oxytocin is expected to be a novel therapy for the core symptoms of autism spectrum disorder, which has currently no approved medication, the efficacy of repeated administrations was inconsistent, suggesting that the optimal dose for a single administration of oxytocin is not optimal for repeated administration. The current double-blind, placebo-controlled, multicentre, crossover trial (ClinicalTrials.gov Identifier: NCT03466671) was aimed to test the effect of TTA-121, a new formulation of intranasal oxytocin spray with an enhanced bioavailability (3.6 times higher than Syntocinon® spray, as assessed by area under the concentration-time curve in rabbit brains), which enabled us to test a wide range of multiple doses, on autism spectrum disorder core symptoms and to determine the dose-response relationship. Four-week administrations of TTA-121, at low dose once per day (3 U/day), low dose twice per day (6 U/day), high dose once per day (10 U/day), or high dose twice per day (20 U/day), and 4-week placebo were administered in a crossover manner. The primary outcome was the mean difference in the reciprocity score (range: 0-14, higher values represent worse outcomes) on the Autism Diagnostic Observation Schedule between the baseline and end point of each administration period. This trial with two administration periods and eight groups was conducted at seven university hospitals in Japan, enrolling adult males with high-functioning autism spectrum disorder. Enrolment began from June 2018 and ended December 2019. Follow-up ended March 2020. Of 109 males with high-functioning autism spectrum disorder who were randomized, 103 completed the trial. The smallest P-value, judged as the dose-response relationship, was the contrast with the peak at TTA-121 6 U/day, with inverted U-shape for both the full analysis set (P = 0.182) and per protocol set (P = 0.073). The Autism Diagnostic Observation Schedule reciprocity score, the primary outcome, was reduced in the TTA-121 6 U/day administration period compared with the placebo (full analysis set: P = 0.118, mean difference = -0.5; 95% CI: -1.1 to 0.1; per protocol set: P = 0.012, mean difference = -0.8; 95% CI: -1.3 to -0.2). The per protocol set was the analysis target population, consisting of all full analysis set participants except those who deviated from the protocol. Most dropouts from the full analysis set to the per protocol set occurred because of poor adherence to the test drug (9 of 12 in the first period and 8 of 15 in the second period). None of the secondary clinical and behavioural outcomes were significantly improved with the TTA-121 compared with the placebo in the full analysis set. A novel intranasal spray of oxytocin with enhanced bioavailability enabled us to test a wide range of multiple doses, revealing an inverted U-shape dose-response curve, with the peak at a dose that was lower than expected from previous studies. The efficacy of TTA-121 shown in the current exploratory study should be verified in a future large-scale, parallel-group trial. [ABSTRACT FROM AUTHOR]

Background: Although various reconstruction techniques are available for anterior cruciate ligament (ACL) injuries, a long recovery time is required before patients return to sports activities, as the reconstructed ACL requires time to regain strength. To date, several studies have reported use of mesenchymal stem cells in orthopaedic surgery; however, no studies have used adipose-derived stem cell (ADSC) sheets in ACL reconstruction (ACLR). Hypothesis: ADSC sheet transplantation can improve biomechanical strength of the autograft used in ACLR. Study Design: Controlled laboratory study. Methods: A total of 68 healthy Japanese white rabbits underwent unilateral ACLR with a semitendinosus tendon autograft after random enrollment into a control group (no sheet; n = 34) and a sheet group (ADSC sheet; n = 34). At 2, 4, 8, 16, and 24 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing using histological staining, micro–computed tomography, and biomechanical testing. At 24 weeks, scanning transmission electron microscopy of the graft midsubstance was performed. Results: The ultimate failure load for the control and sheet groups, respectively, was as follows: 17.2 ± 5.5 versus 37.3 ± 10.3 (P =.01) at 2 weeks, 28.6 ± 1.9 versus 47.4 ± 10.4 (P =.003) at 4 weeks, 53.0 ± 14.3 versus 48.1 ± 9.3 (P =.59) at 8 weeks, 66.2 ± 9.3 versus 95.2 ± 43.1 (P =.24) at 16 weeks, and 66.7 ± 27.3 versus 85.3 ± 29.5 (P =.39) at 24 weeks. The histological score was also significantly higher in the sheet group compared with the control group at early stages up to 8 weeks. On micro–computed tomography, relative to the control group, the bone tunnel area was significantly narrower in the sheet group at 4 weeks, and the bone volume/tissue volume of the tendon-bone interface was significantly greater at 24 weeks. Scanning transmission electron microscopy at 24 weeks indicated that the mean collagen fiber diameter in the midsubstance was significantly greater, as was the occupation ratio of collagen fibers per field of view, in the sheet group. Conclusion: ADSC sheets improved biomechanical strength, prevented bone tunnel enlargement, and promoted tendon-bone interface healing and graft midsubstance healing in an in vivo rabbit model. Clinical Relevance: ADSC sheets may be useful for early tendon-bone healing and graft maturation in ACLR. [ABSTRACT FROM AUTHOR]

Objective: Hangeshashinto is a Japanese Kampo medicine applied for the treatment of oral mucositis and gastroenteritis. Hangeshashinto exhibits broad-spectrum antibacterial activity and suppresses prostaglandin (PG)E2 production in the mucosa and has the ability to improve the inflammatory condition. In addition to these effects, because cAMP, a composition of Hangeshashinto, facilitates ciliary beat, Hangeshashinto could also improve the physiological function of the nasal mucosa, consist of ciliated epithelium, but details were unknown.Methods: This study was aimed to investigate the effects of Hangeshashinto on the nasal mucosa. Healthy nasal mucosal sections were collected from the nasal septum of ten Japanese white rabbits, placed in a collagen dish for tissue culture, and rinsed with two different concentrations of Hangeshashinto solution (1.0%, n = 10 and 2.5%, n = 10) and cAMP solution (50µM, n=10 and 100 µM, n=10) or saline (control, n = 10). Ciliary beat frequency (CBF) as a physiological function of the nasal mucosa was recorded at 1, 3 and 7 days after rinsing, and histological evaluation of epithelial damage was performed at 7 days after rinsing.Results: CBF in the 1.0% but not in the 2.5% Hangeshashinto group, increased at 3 and 7 days compared with that in the control group (p < 0.05). This trend was also observed in the CBF in the 100 µM cAMP group, significant difference was not observed between the CBF of the 1.0% Hangeshashinto group and the 100 µM cAMP group at 1, 3 and 7 days after rinsing (p > 0.05). Histological score only in the 2.5% Hangeshashinto group was lower than that in the control group (p < 0.05), while a significant decline was not observed in the other groups compared to that in the control group (p > 0.05).Conclusion: Our results suggest that 1.0% Hangeshashinto solution facilitates the physiological function of the nasal mucosa by promoting ciliary functions without histological damage of cilia epithelium. When applied with the appropriate concentration, Hangeshashinto could have ability to improve the physiological functions of the nasal mucosal epithelium. [ABSTRACT FROM AUTHOR]

Background/context: Disc degeneration (DD) is a significant driver of low back pain and few treatments exist to treat the pain and disability associated with the disease.Purpose: Our group has developed a method to generate therapeutic discogenic cells as a potential treatment for symptomatic DD. These cells are derived and modified from adult nucleus pulposus cells. In this study, we evaluated the characteristics, mode of action, and in vivo efficacy and safety of these cells prior to human clinical testing.Study Design: Privately funded in vitro studies and in vivo preclinical models were used in this study.Methods: Discogenic cells generated from different adult human donors were evaluated for surface marker expression profile, matrix deposition and tumorigenic potential. Discogenic cells were then injected subcutaneously into nude mice to assess cell survival and possible extracellular matrix production in vivo. Finally, a rabbit model of DD was used to evaluate the therapeutic potential of discogenic cells after disc injury.Results: We found that discogenic cells have a consistent surface marker profile, are multipotent for mesenchymal lineages, and produce extracellular matrix consisting of aggrecan, collagen 1 and collagen 2. Cells did not show abnormal karyotype after culturing and did not form tumor-like aggregates in soft agar. After subcutaneous implantation in a nude mouse model, the human discogenic cells were found to have generated regions rich with extracellular matrix over the course of 4 months, with no signs of tumorigenicity. Intradiscal injection of human discogenic cells in a rabbit model of DD caused an increase in disc height and improvement of tissue architecture relative to control discs or injection of vehicle alone (no cells) with no signs of toxicity.Conclusions: This study demonstrates that intradiscal injection of discogenic cells may be a viable treatment for human degenerative disc disease. The cells produce extracellular matrix that may rebuild the depleting tissue within degenerating discs. Also, the cells do not pose any significant safety concerns.Clinical Significance: Human clinical testing of discogenic cells combined with a sodium hyaluronate carrier is ongoing in multiple randomized, controlled, double-blinded studies in the United States (clinicaltrials.gov identifier NCT03347708) and Japan (clinicaltrials.gov identifier NCT03955315). [ABSTRACT FROM AUTHOR]

Clinical presentation of systemic amyloidosis differs among subtypes, and accurate subtype classification is important for choosing the treatment. Amyloid transthyretin (ATTR) amyloidosis was the predominant among the recently consulted amyloidosis cases in Japan. To reveal the latest subtype frequency of systemic amyloidosis among autopsy cases in Japan. We analyzed systemic amyloidosis cases autopsied from January 2017 to December 2018, that were listed in the Annuals of the Pathological Autopsy Cases in Japan, Volumes 60 and 61. When the subtype was unclear, we performed a questionnaire survey, immunohistochemistry with in-house rabbit polyclonal anti-κ 116 - 133 , anti-λ 118 -microglobulin were 9.3% (n = 37) and 6.0% (n = 24), respectively. Double deposition of amyloid was identified in 1.6% (n = 6). In 168 cases (42.1%), systemic amyloidosis was the main cause of death. Of these cases, AL was the most common subtype (47.6%, n = 80), followed by ATTR (41.1%, n = 69). ATTR is the most predominant subtype among the current autopsy cases in Japan.-134 , and anti-transthyretin 115 -124 antibodies, and proteomic analysis. Out of 481 systemic amyloidosis cases listed in the Annuals, 411 cases were available for analysis (85.4%). We classified 399 of these systemic amyloidosis cases. ATTR was the most common subtype (44.4%, n = 177), followed by amyloid immunoglobulin light chain (AL) (38.8%, n = 155). Amyloid A and amyloid β 2 -microglobulin were 9.3% (n = 37) and 6.0% (n = 24), respectively. Double deposition of amyloid was identified in 1.6% (n = 6). In 168 cases (42.1%), systemic amyloidosis was the main cause of death. Of these cases, AL was the most common subtype (47.6%, n = 80), followed by ATTR (41.1%, n = 69). ATTR is the most predominant subtype among the current autopsy cases in Japan., (© 2023 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

I. Watanabe et al. isolated approximately 30 strains of RNA phages from various parts of Japan. To isolate RNA phages, they assessed the infection specificity of male Escherichia coli and RNase sensitivity. They found that the isolated strains of RNA phages could be serologically separated into three groups. Furthermore, most of them were serologically related, and the antiphage rabbit serum prepared by one of these phages neutralized most of the other phages. The only serologically unrelated phage was the RNA phage Qβ, which was isolated at the Institute for Virus Research, Kyoto University, in 1961.

Introduction: Brimonidine bioavailability in the aqueous humor depends on the solution pH following topical administration. The purpose of this study was to investigate the effect of solution pH on brimonidine distribution in the posterior ocular tissues in pigmented rabbits. Methods: The anterior retina/choroid, posterior retina/choroid, and vitreous body of pigmented rabbits were collected 0.67, 1.5, 3, 6, 12, 24, 168, and 360 h after the administration of a single topical dose of 0.2% brimonidine tartrate ophthalmic solution, pH 6.4 (Alphagan®; Allergan Inc., Irvine, CA, USA). Brimonidine concentrations in these tissues were quantified using liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were determined using noncompartmental analysis, and the results were compared with tissues from eyes administered 0.1% brimonidine tartrate ophthalmic solution, pH 7.3 (Aiphagan®; Senju Pharmaceutical Co., Ltd., Osaka, Japan) in our previous study conducted using the same procedure. Results: Topically applied brimonidine was distributed rapidly into the posterior tissues of the eye after a single ophthalmic administration of the 0.2% ophthalmic solution. The areas under the curve from time 0 to 360 h following dosing with the 0.2% ophthalmic solution were 500,000, 14,300, and 28.7 ng h/g in the anterior and posterior retina/choroid, and vitreous body, respectively. Conclusion: The differences in the areas under the curve between two ophthalmic solutions were less than the difference in drug concentrations between these two products in any tissues. This finding indicates that the change in the solution pH from 6.4 to 7.3 increases brimonidine bioavailability into the posterior ocular tissues similarly as into the aqueous humor. Funding: Senju Pharmaceutical Co., Ltd. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed efficacy and safety of therapy with rabbit antithymocyte globulin (rATG) in combination with cyclosporine A (CsA) in 30 Japanese adult patients with acquired aplastic anemia (AA) in the Kyoto Clinical Hematology Study Group. The median observation period was 31 months and the median age of the patients was 54 years. The objective response rates (ORRs) to rATG plus CsA increased over time until 18 months after the start of treatment; the rate of achievement of better than partial response at 18 months was 66.7%. The 2-year overall survival (OS) rate was 79% in all patients. In eight patients aged ≥ 75 years old, the ORR was 62.5% and the 2-year OS rate of 50% was not significantly inferior to that in patients aged ≤ 74 years old. The overall mortality rate was 16.7% in our cohort, while the mortality rate in patients aged ≥ 75 years old was 37.5%, which was higher than that in patients aged ≤ 74 years old (9.1%), although the difference was not statistically significant. Collectively, rATG combined with CsA is an effective and feasible treatment for AA, while patients should be appropriately selected. [ABSTRACT FROM AUTHOR]

Background: In 2019, 2020 and 2022, the Japanese Government approved the use of tafamidis and two technetium-scintigraphies for transthyretin amyloid (ATTR) cardiomyopathy, and announced the patient criteria for tafamidis therapy. In 2018, we had started a nation-wide pathology consultation of amyloidosis., Objective: To reveal the impact of approval of tafamidis and technetium-scintigraphy on the diagnosis of ATTR cardiomyopathy., Methods: Ten institutes participated in this study on the pathology consultation of amyloidosis and shared rabbit polyclonal anti-κ 116-133 , anti-λ 118-134 , and anti-transthyretin 115-124 antibodies. Proteomic analysis was performed when the typing diagnosis by immunohistochemistry was unavailable., Results: Out of 5400 consultation cases received from April 2018 to July 2022, the type of amyloidosis by immunohistochemistry was determined in 4119 of the 4420 Congo-red positive cases. The incidences of AA, ALκ, ALλ, ATTR, Aβ2M and others were 3.2, 11.3, 28.3, 54.9, 0.6 and 1.8%, respectively. Out of 2208 cardiac biopsy cases received, 1503 cases were ATTR positive. There were 4.0 and 4.9 times more total cases and ATTR-positive cases, respectively, in the last 12 months as compared to the first 12 months., Conclusions: The approval of tafamidis and technetium-scintigraphy raised the awareness of ATTR cardiomyopathy, leading to an upsurge in ATTR-positive cardiac biopsy cases.

Background: Although osteochondral autograft transplantation (OAT) provides satisfactory outcomes for osteochondral defects, for large defects OAT is often inadequate because of graft availability. Osteochondral allograft transplantation is an alternative treatment for large defects, but this approach is limited by graft storage constraints and carries disease transmission risks. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate, and its positive effect on articular cartilage has been reported. However, the effect of PRF with OAT of osteochondral defects is unknown. Purpose: To compare the effects of OAT with platelet-rich plasma (PRP) and PRF on osteochondral defects in a rabbit model. Study Design: Controlled laboratory study. Methods: Forty-two juvenile rabbits were divided into control, PRP, and PRF groups. In the control and PRP groups, a cylindrical osteochondral defect (5 mm in diameter and 2 mm in depth) was created on the patellar groove, and an osteochondral graft (3.5 mm in diameter and 5 mm in length) harvested from the contralateral side was inserted into the distal portion of the defect. After wound closure, either normal saline or PRP was injected in the knee. In the PRF group, a PRF clot was placed in the defect before grafting. The surgical site was macroscopically and histologically assessed after 3 and 12 weeks. Results: At 3 weeks, the PRF group (n = 8) was macroscopically healed compared with the other 2 groups (control, n = 7; PRP, n = 6) (P < .005). Histologically, osteochondral graft cartilage of the PRF group had normal cellularity and higher amounts of safranin O staining relative to the other 2 groups (P < .005). At 12 weeks, all 3 groups (n = 8 per group) were macroscopically healed with normal or nearly normal cartilage, and osteochondral graft cartilage was histologically hyaline cartilage. In contrast, the PRF group healed with hyaline-like cartilage at nongrafted defects, whereas the other 2 groups healed with fibrocartilage (P < .001). Conclusion: OAT with PRF maintained hyaline cartilage, and the nongrafted defect healed with hyaline-like cartilage. Clinical Relevance: PRF has the potential to improve clinical outcomes of OAT used to treat osteochondral lesions. [ABSTRACT FROM AUTHOR]

Rabbit haemorrhagic disease (RHD) is a highly contagious and fatal disease in rabbits caused by the rabbit haemorrhagic disease virus (RHDV), which includes two genotypes, RHDV-GI.1 and RHDV2-GI.2. RHDVs tend to recombine among different strains, resulting in significant genetic evolution. This study evaluated the genetics of Japanese RHDV strains associated with six outbreaks between 2000 and 2020 using whole-genome sequencing, genomic recombination and phylogenetic analyses. Genomic recombination analysis using near-complete genomic sequences revealed that two Japanese strains detected in 2000 and 2002 were non-recombinant GI.1 (variant RHDVa-GI.1a) strains of different origins, most closely related to strains identified in PR China in 1997 and the USA in 2001, respectively. In contrast, four recent Japanese GI.2 strains detected between 2019 and 2020 were recombinant viruses harbouring structural protein (SP) genes from GI.2 strains and non-SP (NSP) genes from a benign rabbit calicivirus (RCV) strain of genotype RCV-E1-GI.3 (GI.3P-GI.2) or an RHDV G1-GI.1b variant (GI.1bP-GI.2). Phylogenetic analysis based on SP and NSP regions revealed that the GI.1bP-GI.2 recombinant virus detected in Ehime prefecture and the GI.3P-GI.2 recombinant viruses detected in Ibaraki, Tochigi and Chiba prefectures were most closely related to recombinant viruses identified in Australia in 2017 and Germany in 2017, respectively. These results suggested that past RHD outbreaks in Japan did not result from the evolution of domestic RHDVs but rather represented incursions of foreign RHDV strains, implying that Japan is constantly at risk of RHDV incursion from other countries.

To investigate the antigenic changes in parechovirus 1 (PeVA1), seroepidemiological analyses were performed against the Harris strain (Harris), isolated in 1956, and PeVA1/Yamagata.JPN/2021-4785, isolated in 2021, using immune sera and 207 and 237 human serum specimens collected in 2021 and 1976, respectively. Although rabbit immune sera showed the highest neutralization antibody (NT-Ab) titers against the immunized viruses at 1:12 800-1:102 400, they were cross-reactive at 1:400-1:800. All 62 Yamagata isolates obtained between 2001 and 2021 (Yamagata strains), belonging to phylogenetic lineage 1B, reacted more strongly (mostly 4-64 times) to antiserum against PeVA1/Yamagata.JPN/2021-4785 than to antiserum against Harris, belonging to phylogenetic lineage 1 A. Human serum specimens obtained in 2021 showed higher NT-Ab titers against PeVA1/Yamagata.JPN/2021-4785, whereas those obtained in 1976 had similar NT-Ab titers against both strains. These findings suggested that Yamagata strains and Harris were antigenically cross-reactive, although there were differences. There are still high NT-Abs titers present against Harris in 2021 in particular, indicating that PeVA1 has been in circulation with high immunity in the population. In conclusion, this study suggested that PeVA1 has been endemically perpetuated with only minor antigenic changes as well as with high immunity over several decades in the community., (© 2023 Wiley Periodicals LLC.)

Escherichia albertii has recently been recognized as a zoonotic enteropathogen associated with food poisoning. The reservoirs and transmission routes of this bacterium to humans are still unclear. In this study, we performed a survey of E. albertii in fecal specimens of wild and safeguarded animals in Okayama Prefecture and its prefectural borders, Japan to understand its reservoir in the environment. Forty-two E. albertii were isolated from 10 and 31 droppings of 59 crows and 125 starlings, respectively. Fifty-two E. albertii were isolated from 906 mammal droppings, and out of 52 isolates, origin of 33, 6 and 1 isolates were from martens, foxes, and rabbit, respectively, however, origin of 12 isolates remained unknown. Three E. albertii were isolated from two and one feces of 159 dogs and 76 cats, respectively. Pulsed-filed gel electrophoresis analysis grouped 97 E. albertii strains into 66 pulsotypes including 36 and 30 pulsotypes of isolates from mammals and birds, respectively. E. albertii strains isolated in this study were genetically diverse. Although clonal relationship was not observed between mammal and bird isolates, there were intra- and inter-species relationship in mammalian isolates. All E. albertii strains were positive for eae and Eacdt virulence genes. Furthermore, 20 and 7 strains also carried Eccdt-I and stx2f genes, respectively. Taken together, the results indicate that genetically diverse and potentially virulent E. albertii are distributed among various wild and safeguarded animals in Okayama Prefecture, and the animals could also be reservoirs of E. albertii.

Background: Rotator cuff regeneration using tissue engineering techniques is a challenging treatment in elderly patients with irreparable rotator cuff tears.Hypothesis: A polyglycolic acid sheet scaffold with seeded mesenchymal stem cells (MSCs) may enhance the expression of type I collagen products and increase the mechanical strength of the regenerated tendon in vivo.Study Design: Controlled laboratory study.Methods: A surgically created defect of infraspinatus tendons of rabbits was reconstructed with 2 different materials, a polyglycolic acid (PGA) sheet alone (PGA group) (n = 34) and a PGA sheet seeded with autologously cultured MSCs (MSC group) (n = 34). The authors created a tendon defect model without embedding any graft as the control model (control group) (n = 34). The rabbits were sacrificed at 4, 8, and 16 weeks after the operation and then were histologically evaluated. The rabbits were also biomechanically evaluated by measuring the ultimate failure loads and Young’s modulus at 4 and 16 weeks following implantation.Results: In the MSC group, the fibrocartilage layers and Sharpey fibers were found regularly in the insertion site at 8 weeks compared with the PGA group. In control group, thin membranes with many fibroblasts arranged in an irregular pattern linked the end of the torn cuff to the bone without any Sharpey fibers and type I collagen. A large volume of type I collagen was found in comparison with type III collagen at 16 weeks in the MSC group, whereas type III collagen was more prevalent than type I in the PGA group. The tendon maturing score in the MSC group had higher values than the PGA and control groups at 8 and 16 weeks (mean values were 21.0 ± 0.89, 24.0 ± 2.53 in the MSC group; 16.7 ± 2.25, 21.3 ± 2.42 in the PGA group; and 10.2 ± 0.98, 12.2 ± 1.72 in the control group, respectively) (P < .05). The results of the mechanical analysis revealed that the regenerated tendons in the MSC group had better tensile strength than in the PGA and control groups at 16 weeks (mean values were 3.04 ± 0.54 in the MSC group, 2.38 ± 0.63 in the PGA group, and 1.58 ± 0.13 in the control group) (P < .05).Conclusion: Bone marrow–derived MSCs were able to regenerate tendon-bone insertions and the tendon belly, including the production of type I collagen, and increased the mechanical strength of the regenerated rotator cuff tendon.Clinical Relevance: Rotator cuff regeneration using MSCs is a promising treatment for massive rotator cuff defects. [ABSTRACT FROM PUBLISHER]

Objective. To investigate the effects of an anti-platelet drug (clopidogrel) on the prevention of steroid-induced osteonecrosis (ON) in rabbits.Methods. Adult male Japanese white rabbits were divided into two groups and treated as follows: one group received daily clopidogrel mixed in normal saline (AP; n = 35), the other received only normal saline (NS; n = 30). One week after the administration, all rabbits were injected once intramuscularly with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. Three weeks after, both the femora and humeri were examined histopathologically for the presence of ON. The platelet aggregation assay and hematological examinations were performed before and after the steroid injection.Results. The incidence of ON in the AP group (48.5%) was significantly lower than that observed in the NS group (73.3%). The platelet aggregations in the AP group were significantly inhibited by the administration of clopidogrel. The levels of total cholesterol and triglycerides showed no significant differences between the AP and NS group.Conclusion. The present experimental study demonstrated that the administration of an anti-platelet drug prevented steroid-induced ON in rabbits and that platelet aggregation seems to be one of the possible factors involved in the pathogenesis of steroid-induced ON. [ABSTRACT FROM PUBLISHER]

The article discusses economic ideas and policies in Japan in the late nineteenth century, focusing on a boom in rabbit trading in the 1870s and laissez-faire economics. It examines the rise in rabbits' popularity and prices. The author comments on government intervention following the growth in crime and social disorder related to rabbit trading, which included banning organizations known as rabbit associations, or usagi kai, as well as taxing the trade. He also comments on the idea that rabbits were involved in a cholera epidemic that hit Japan in 1877.

The Japan Materials Testing Reactor (JMTR) is now under refurbishment, and the operation of the new JMTR will start in FY 2011. The new JMTR has a plan to produce ^99Mo, which is the parent nuclide of ^99mTc, and two ^99Mo production technologies have been developed: one is a solid irradiation method, and the other is a solution irradiation method. In the solid irradiation method, it was found that JMTR can provide about 20% of the ^99Mo imported into Japan. In the solution irradiation method, the fundamental characteristics of the aqueous molybdate solutions selected as candidates for the irradiation target were cleared by the gamma-ray irradiation test. Aiming at the domestic production of ^99Mo in Japan, the development of ^99Mo production technologies in JMTR is kept going. [ABSTRACT FROM AUTHOR]

Background: A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N′-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo.Purpose: To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel.Study Design: Controlled laboratory study.Methods: A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O’Driscoll et al.Results: The DN gel–implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel–implanted defects compared with the untreated control at each period (P < .0001). The mean relative values of type 2 collagen mRNAs in the regenerated tissue were obviously higher in the DN gel–implanted defect than in the untreated control at each period. The mean surface roughness of the untreated control was significantly higher than the normal cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel–implanted and normal knees.Conclusion: This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds.Clinical Relevance: This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery. [ABSTRACT FROM AUTHOR]

• Rabbit hepatitis E virus (HEV) circulates among feral rabbits in Japan. • Persistent HEV infection was observed in a rabbit experimentally infected with the HEV isolate JP-59. • Further studies are required to determine the zoonotic risk of rabbit HEV. Rabbit hepatitis E virus (HEV) has been detected among rabbits and recently isolated from immunocompromised patients, suggesting zoonotic transmission. In this study, HEV infection among feral rabbits (Oryctolagus cuniculus) was assessed by detection of anti-HEV antibodies and HEV RNA. The prevalence of anti-HEV antibodies in sera was of 33 % (20/60) and HEV RNA was detected from only one of fecal swabs (1.7 %, 1/58). Furthermore, one naïve rabbit was intravenously inoculated with the suspension of the HEV-positive fecal specimen, exhibiting persistent HEV shedding in feces, intermittent viremia, seroconversion to anti-HEV IgM and IgG, and high alanine aminotransferase (ALT) values, indicating persistent HEV infection. The isolate JP-59 had a length of 7,282 bp excluding a poly (A) tail and possessed the characteristic 93 bp-insertion in ORF1. Phylogenetic analysis indicated that JP-59 formed a cluster with other rabbit HEV isolates from rabbits and human origin. The JP-59 shared the nucleotide sequence identities less than 87 % with other rabbit HEVs, suggesting that a novel rabbit HEV strain was circulating in Japan. [ABSTRACT FROM AUTHOR]

Purpose: To introduce a new procedure for evaluating posterior capsule opacification (PCO) in rabbit eyes and to perform a comparative study of the single-piece and 3-piece acrylic intraocular lenses (IOLs) on PCO using the new evaluation method. Setting: Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan. Methods: A single-piece or 3-piece acrylic IOL was implanted in 1 eye and the other in the contralateral eye of 5 rabbits. Three weeks after surgery, PCO was scored by Evaluation of Posterior Capsule Opacification (EPCO) in posterior view. Before the posterior view was photographed, the anterior capsule was removed from the whole optic area to eliminate disturbing anterior capsule opacification (ACO) for the PCO evaluation. Results: Posterior capsule opacification could be well observed and viewed in the posterior view so that it could be scored by EPCO without confusion with ACO. The mean PCO score of the single-piece and 3-piece acrylic IOLs was 3.12 ± 0.19 and 2.41 ± 0.70, respectively (P<.05 and P = .03, respectively). Conclusion: The removal of ACO allowed scoring of PCO by EPCO in rabbit eyes. The single-piece acrylic IOL showed singnificantly more PCO than the 3-piece acrylic IOL at least 3 weeks after surgery in rabbits. [Copyright &y& Elsevier]

Studies the effects of rate earth ions on bone resorbing function of osteoclasts by culturing Japanese white rabbit osteoclasts on bone slices. Measurement of the number and surface areas of lacunae; Calcium concentration in the supernatant; Osteoclastic bone resorbing function.

The Amami rabbit Pentalagus furnessi is a rare forest-dwelling form endemic to the Amami and Tokuno Islands in Japan. In order to estimate the distribution and abundance of the Amami rabbit we counted their faecal pellets along forest roads and streams as well as within the forests on Amami and Tokuno Islands during January 1993–March 1995. The number of pellets/km along a stream gave a practical index for measuring relative abundance. The rabbit was estimated to be distributed over about 370 sq km on Amami Island and 33 sq km on Tokuno Island. There was a large variance in faecal abundance among the survey routes. Some populations were completely isolated and thought to be very small. The size of a local population was positively correlated with those of neighbouring populations and the amount of mature forest relative to other seral stages. We compared the results of this survey with those of previous surveys to find that the total population of this species appears to be declining. Some conservation measures are proposed for forest habitat management, designed to avert the decline of the Amami rabbit and to ensure its preservation. [ABSTRACT FROM AUTHOR]

We reconstructed April mean temperatures in Kyoto since the fifteenth century by investigating historical documents such as diaries and chronicles and compiling phenological data series of the full bloom date for herbaceous peony. In order to fill gaps in phenological data series, we used the full bloom date of rabbit-ear iris, an herbaceous plant that flowers at about the same time of the year as an herbaceous peony. We obtained floral phenological data covering a total of 278 years. Calibration using modern temperature data showed herbaceous peony phenology to be the preferred data source for April temperature estimation. Variations in the reconstructed April temperatures in Kyoto were synchronous with changes in the solar cycle. In particular, April temperatures were about 2 ℃ lower than at present around the ends of the Spoerer and Maunder grand solar minima, from 1550 to 1590 and from 1690 to 1730, respectively. In addition, the reconstructed April temperatures suggested a time lag in the climate response to solar activity changes that was about 10 years longer than the previously estimated lags in the responses of wintertime and March temperatures. However, further research is needed to accurately quantify this time lag., (© 2022. The Author(s) under exclusive licence to International Society of Biometeorology.)

The nonlinearity of internal exposure to 8 pesticides was investigated in toxicity studies using kinetics to identify nonlinearity visually and to investigate the influence of nonlinearity on toxicological evaluation. Data were obtained from risk assessment reports published by the Food Safety Commission (FSCJ). Nonlinearity was defined using 2 indicators: the lowest visual inflection point (LVIP) and the second lowest visual inflection point (SVIP) of kinetics by drawing a linear distribution chart. The area under the curve and 24-h urine concentrations were stable parameters used to identify the LVIP/SVIP. The sampling timing affected the blood concentrations, and the LVIP/SVIP was detected for 6 pesticides using the parent compounds or their metabolites as analytes. The subproportional nonlinearity was significant for these pesticides. The LVIP/SVIP values were consistent in the same species up to a 1-year period, but the values showed species-specific differences in several compounds. In all compounds found to be nonlinear, apical outcomes were observed at the SVIP or above. The presence of nonlinearity was recognized by the FSCJ. The recognition influenced their judgment of no-observed-adverse-effect levels (NOAELs) for carcinogenicity or health-based guidance values, indicating the importance of appropriate kinetics to identify the nonlinearity for toxicological evaluation of pesticide residue., (Copyright © 2021 Elsevier Inc. All rights reserved.)

One of the clonal strains of Karenia mikimotoi NGU04 isolated from Kyushu Island in Japan, showed the most potent fish-killing activity in preliminary experiments. To evaluate shellfish toxicity, two species of juvenile abalone were exposed to the NGU04, and the toxicities were compared with those of two other K. mikimotoi strains. Of the two abalone species tested, N. gigantea showed a higher sensitivity to NGU04 than the hybrid abalone (N. discus hannai male × N. gigantea female) did. In comparative studies using N. gigantea , the NGU04 exhibited stronger toxicity on abalone than other strains. The cell-free culture supernatant and the ruptured cell suspension of the NGU04 showed no significant lethal effects on N. gigantea. The NGU04 showed a stronger haemolytic activity on rabbit erythrocytes than did the other two strains. Furthermore, the haemolytic activities of the NGU04 strain towards erythrocytes of four fish species were also stronger than those of other strains. • The NGU04 strain of K. mikimotoi showed a potent lethal effect on abalone. • The NGU04 strain showed much stronger haemolytic activity than the other two strains. • Bluefin tuna erythrocytes showed the highest susceptibility to the NGU04 strain-induced haemolysis. • The direct attack by live cells is essential for the toxicity of the NGU04 strain on abalones. • Live cell-mediated haemolytic activity is mainly responsible for the toxicity of the NGU04 strain on abalones. [ABSTRACT FROM AUTHOR]

Twenty-three of 42 European rabbits (Oryctolagus cuniculus), belonging to the same rabbit colony, died in March 2020 (55% mortality) in Chiba prefecture, Japan. The disease course was extremely acute without indicators of death or hemorrhage. Necropsy revealed liver swelling, discoloration, cloudiness and fragility, and pulmonary edema. Histologically, severe hepatocellular necrosis (mainly peripheral) and intra-glomerular capillary hyalin thrombi were observed. On molecular-biological examination, reverse transcription polymerase chain reaction analysis of RNA from tissues detected a rabbit hemorrhagic disease virus, confirmed as a RHDV-2 VP60 fragment, which shared 99.42% nucleotide identity with the homologous fragment of RHDV-2 German isolate by nucleotide sequence analysis. This report shows the outbreak of rabbit hemorrhagic disease caused by RHDV-2, an emerging infectious disease, in Japan.

Leptospirosis is a worldwide zoonosis caused by the pathogenic Leptospira spp. Canine and human leptospirosis sometimes occur on Amami Oshima Island, located in the Nansei Archipelago, southwestern Japan; however, information on the causative Leptospira spp. on this island is quite limited. This study aimed to investigate the molecular and serological characteristics of Leptospira spp. isolated from wild animals and a dog in Amami Oshima Island. We obtained seven Leptospira strains by culturing kidney tissues of wild animals, such as black rats (2), wild boars (3), and rabbit (1) as well as blood from a symptomatic dog. Using flaB sequencing and microscopic agglutination test with antisera for 18 serovars, the isolates were identified as Leptospira borgpetersenii serogroups Javanica (black rat), L. interrogans serogroup Australis (black rat and dog), and L. interrogans serogroup Hebdomadis (wild boar and rabbit). The sequence type (ST) of L. borgpetersenii serogroup Javanica was determined to be ST143 via multilocus sequence typing (MLST) using seven housekeeping genes. For L. interrogans, MLST and multiple-locus variable-tandem repeat analysis (MLVA) revealed identical ST and MLVA types in rat and canine isolates, whereas two STs and MLVA types were identified in wild boar isolates. The STs and MLVA types of rabbit and one of the wild boars were identical. Bacterial culture and flaB-nested polymerase chain reaction demonstrated a high rate of Leptospira infection in wild boars (58.3%, 7/12), whereas Leptospira spp. were detected in 4.8% of black rats (2/42). This study revealed diverse Leptospira genotype and serotype maintenance in wild mammals on Amami Oshima Island. MLST and MLVA indicated that black rats were a source of canine infection. Wild boars carry L. interrogans and are considered an important maintenance host because antibodies against serogroup Hebdomadis were detected in human and canine leptospirosis patients on this island., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to compare changes in tissue blood flow and tissue oxygen tension in the masseter muscle and mandibular bone marrow induced by remifentanil under desflurane or sevoflurane anesthesia. Eleven male tracheotomized Japan White rabbits were anesthetized with desflurane or sevoflurane under mechanical ventilation. The order of the inhalation of desflurane or sevoflurane was randomized. Desflurane or sevoflurane was administered at 1.0 minimum alveolar concentration and remifentanil was infused at 0.4 µg/kg/min. Observed variables included heart rate (HR), blood pressure (BP), common carotid artery blood flow (CCBF), mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), mandibular bone marrow tissue oxygen tension (PbO 2 ), and masseter muscle tissue oxygen tension (PmO 2 ). Two way repeated measures ANOVA showed no interaction between volatile anesthetics and remifentanil infusion except for MBF. There were significant differences in HR, SBP, DBP, MAP and CCBF between desflurane and sevoflurane groups. There were also significant differences in HR, SBP, DBP, MAP, CCBF, BBF and PbO 2 before, during and after remifentanil infusion. Desflurane reduced tissue blood flow in the masseter muscle and mandibular bone marrow while better maintained HR and BP than sevoflurane. Under remifentanil infusion, although both anesthetics reduced tissue blood flow, tissue oxygen tension was maintained in masseter muscle and mandibular bone marrow.

Minesapride is a novel 5-hydroxytryptamine 4 (5-HT 4 ) receptor partial agonist that is expected to show efficacy in patients with irritable bowel syndrome with predominant constipation and functional constipation. An open-label study was conducted to evaluate pharmacokinetics (PK) and safety of minesapride. Japanese subjects, 12 elderly and 12 young, received a single oral dose of minesapride 40 mg/day in the fasted state. Metabolite profiles were also investigated in this clinical study and in an in vitro study using cryopreserved hepatocytes. Clinical results showed that minesapride was rapidly absorbed (C max : 2302.1 ng/mL in the elderly group, 2117.5 ng/mL in the young group), and the plasma concentration then decreased with half-life of approximately 7 h. There were no notable PK differences between elderly and young groups. No serious adverse events (AEs) were observed. The only AE that occurred in 2 or more subjects was diarrhea. Metabolite profiles in plasma and urine were similar between elderly and young groups. No major metabolites exceeded 10% of unchanged minesapride, and results of the in vitro study suggested that there were no human-specific metabolites. From the viewpoints of PK and metabolite profiling, no dose adjustment of minesapride is warranted in elderly population without renal or hepatic impairment., Competing Interests: Declaration of competing interest Both studies (clinical study and in vitro study) were founded by Sumitomo Dainippon Pharma Co., Ltd. T. Hamatani, Y. Shibue, N. Sawada, T. Takagaki, M. Hashimoto, Y. Nakada and H. Kakuyama are employees of Sumitomo Dainippon Pharma Co., Ltd., (Copyright © 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

The Amami rabbit (Pentagulus furnessi) is a dark brown-furred rabbit classified as an endangered species and only found in the Amami Islands of Japan. They are often called living fossils because they retain primitive characteristics of ancient rabbits that lived approximately 1 million years ago, such as short feet and hind legs and small ears. Although the ancient rabbit has disappeared due to the competition with European rabbit (Oryctolagus cuniculus) in the most of the Asian area, Amami rabbit survived since Amami Islands has isolated from Japan and Taiwan. Although Amari rabbit is one of the protected animals, their population decreases each year due to human activities, such as deforestation and roadkill. In this study, we collected roadkill samples of Amami rabbits and established primary and immortalized fibroblast cell lines. Combined expression of human-derived mutant Cyclin-dependent kinase 4, Cyclin D1, and hTERT allowed us to immortalize fibroblasts successfully in three individuals of Amami rabbits. The immortalized fibroblasts dramatically extended the cell culture period, when it was compared with the cell culture period of wild type cells. Furthermore, the immortalized cells maintained their normal chromosomal pattern (2n = 46). Our results suggest that cellular senescence which mainly regulated by p16-RB signaling pathway is conserved in animal evolution at least from 1 million years ago., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To characterise the genotypic profiles of methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates from companion animals and to investigate their association with those from humans in Japan., Methods: Non-duplicated MRSA clinical isolates recovered between July 2016 and January 2018 were analysed. The MRSA isolates were typed by polymerase chain reaction (PCR)-based open reading frame (ORF) typing (POT) scores, SCCmec types, multilocus sequence typing, and virulence gene profiles. Phylogenetic comparison of those isolates with previously described human isolates was performed., Results: Among 56 MRSA isolates (33 cats, 20 dogs and three rabbits), 26 isolates with a POT1 score of 93, SCCmec type II mostly belonged to CC5, including ST5. Twenty-six isolates with a POT1 score of 106, SCCmec type IV showed diversity of STs: 15 isolates belonged to CC8, mainly including ST8, and 11 isolates belonged to CC1, including ST1 and newly identified STs 4768, 4775, and 4779. Two cat isolates were ST8-SCCmec type IV possessing pvl/ACME-arcA, presumed to be the hypervirulent community-associated MRSA (CA-MRSA) clone USA300. Notably, all three rabbit isolates belonged to ST4768. The POT1 score 106 CA-MRSA isolates from animals and humans were divided into two large clusters of CC1 and CC8, where host species-specific sub-clusters were not identified within each cluster. A large cluster of POT1 score 93 healthcare-associated MRSA (HA-MRSA) isolates from animals and humans consisted of sub-clusters formed exclusively by the vast majority of human isolates and those formed by animal and human isolates., Conclusion: Companion animals could be potential reservoirs and vehicles for the transmission of CA-MRSA to humans, and could transmit companion animal-adaptive HA-MRSA lineages to humans as their second reservoirs., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Animal cafés-businesses in which customers pay by the hour to have a drink and relax in a space filled with cats, rabbits or other animals-began to appear in Japan in 2004, as a part of the iyashi healing boom. The iyashi boom, in goods and experiences that offer emotional and physical healing, was a response to problems of economic and social precarity triggered by the end of the Japanese bubble and the changing economic situation, particularly among younger Japanese facing the loss of earlier forms of social support and community. Animal cafés offer iyashi to their customers by providing them a refuge from the stress of their everyday lives, where they can relax through engagement with companion animals, rather than returning to tiny, empty apartments. The focus of these businesses is to offer the opportunity to develop positive affective relationships with the animals, who offer stress relief, physical affection, and a listening ear to the visitors who come to spend time with them.This research explores the way that affective relationships with animals in these cafés are being used as a method to maintain emotional well-being and control stress levels. Based on 18 months of anthropological fieldwork in Tokyo, Japan, this paper draws on the narratives of café visitors to argue that the popularity of these businesses is indicative of a shift towards the commodification of care relationships, and that visitors are using animals to reduce their stress in order to further productivity, by investigating how affective connections with non-human animals helps them feel 'healed"', and to explore how this relates to larger social considerations about healing and wellness in modern Japan., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Although coxsackievirus A6 (CV-A6) is generally recognized as a causative agent of herpangina in children, CV-A6 infections globally emerged as a new and major cause of epidemic hand-foot-and-mouth-diseases (HFMDs) around 2008. To clarify the longitudinal epidemiology of CV-A6, we carried out sequence and phylogenetic analyses for the VP1 and partially for the VP4-3D regions as well as antigenic analysis using 115 CV-A6 isolates and 105 human sera in Yamagata, Japan between 2001 and 2017. Phylogenetic analysis revealed that CV-A6 isolates were clearly divided into two clusters; strains in circulation between 2001 and 2008 and those between 2010 and 2017. Neutralizing antibody titers of two rabbit antisera, which were immunized with Yamagata isolates in 2001 and 2015, respectively, against 28 Yamagata representative strains as well as the prototype Gdula strain were 1:2560-1:5120 and 1:160-1:640, respectively. The neutralizing antibody titers among residents in Yamagata against the above two strains were similar. Our analyses revealed that there were cross-antigenicities among all analyzed CV-A6 strains, although the newly emerged strains were introduced into Yamagata around 2010 and replaced the previous ones. With regard to control measures, these findings suggest that we can prevent CV-A6 infections through the development of a vaccine that effectively induces neutralizing antibodies against CV-A6, irrespective of genetic cluster., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

After George McCoy accidentally discovered a new infection in 1911 while investigating bubonic plague in squirrels, he transmitted the disease to experimental animals and isolated the causative organism. He called it Bacterium tularense, after Tulare County, California. In 1919, Edward Francis determined that an infection called "deer-fly fever" was the same disease, naming it "tularemia." He demonstrated that it occurred in wild rabbits and inadvertently showed that it was highly infectious, for he and all his laboratory assistants contracted the illness. This characteristic led to studies of its potential as a biological weapon, including involuntary human experimentation by Japan among civilian, political and military prisoners, and its probable use in warfare during World War II. Later, in the United States, voluntary human experimentation occurred in the 1950s-1960s with penitentiary inmates and non-combatant soldiers. Soviet Union scientists allegedly developed a vaccine-resistant strain, which they tested as a biological weapon in 1982-1983., (Published by Elsevier Inc.)

Background: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has recently been utilized to accurately detect the amyloid proteins of renal amyloidosis. The present study investigated the optimal procedures for analyzing samples by LCMS/MS, and the advantage of using this technique to diagnosis renal amyloidosis., Methods: To detect amyloid proteins, laser microdissected glomeruli from AL (n = 13) or AA (n = 10) renal amyloidosis patients were digested and analyzed by LCMS/MS. To determine the best procedures for analyzing samples by LCMS/MS, we examined the suitability of tissue samples, frozen or formalin-fixed paraffin-embedded (FFPE), the number of dissected glomeruli required for analysis (2, 10, or 50 glomeruli), and the amount of trypsin with or without dithiothreitol (DTT). We additionally compared the detection of amyloid proteins between immunostaining and LCMS/MS., Results: Examining 10 dissected glomeruli from FFPE sections digested with trypsin 3 µL (0.1 mg/mL) without DDT made it possible to detect amyloid protein in all 10 AA and in 10 out of 12 AL amyloidosis cases. All AA amyloidosis cases were diagnosed using immunohistochemistry for amyloid A. With immunostaining, however, there were several inconclusive immunoglobulin and/or their light chain staining noted in the AA or AL amyloidosis cases. Even so, LCMS/MS was able to accurately detect amyloid protein in renal amyloidosis., Conclusion: The use of 10 laser microdissected glomeruli (170,000-220,000 µm 2 ) with amyloid deposition from FFPE sections digested with trypsin 3 µL (0.1 mg/mL) allowed the accurate detection of amyloid protein in AA and AL amyloidosis.

Neuropathic pain has a substantial effect on quality of life (QOL). The Japanese Society of Pain Clinicians (JSPC) has developed clinical guidelines of pharmacotherapy for neuropathic pain. These guidelines offer clarity on recommendations based on both the most recent scientific evidence and expert opinions. Understanding the concept, disease entity, and burden of neuropathic pain, as well as its screening and diagnosis are important steps before starting pharmacotherapy. As well as other guidelines, the guidelines propose several lines of pharmacotherapies in a step-wise manner. To name a few different points, our guidelines propose an extract from inflamed cutaneous tissue of rabbits inoculated with vaccinia virus, which has been found to be effective for post-herpetic neuralgia in Japan, as one of the second-line drugs. When prescribing opioid analgesics, proposed as the third-line drugs, for neuropathic pain, the guidelines recommend physicians continue evaluations on either abuse or addiction. The guidelines do not recommend concomitant use of nonsteroidal anti-inflammatory drugs and acetaminophen because of lack of clinical evidence of their efficacy. If patients do not respond well to pharmacotherapy, which is prescribed in a step-wise manner, other treatment strategies should be considered to improve patients' activities of daily living and QOL.

Human parechovirus 3 (HPeV3), a member of the Picornavirus family, is frequently detected worldwide. However, the observed seropositivity rates for HPeV3 neutralizing antibodies (nAbs) vary from high in Japan to low in the Netherlands and Finland. To study if this can be explained by technical differences or antigenic diversity among HPeV3 strains included in the serological studies, we determined the neutralizing activity of Japanese and Dutch intravenous immunoglobulin batches (IVIG), a rabbit HPeV3 hyperimmune polyclonal serum, and a human HPeV3-specific monoclonal antibody (mAb) AT12-015, against the HPeV3 A308/99 prototype strain and clinical isolates from Japan, the Netherlands and Australia, collected between 1989 and 2015. The rabbit antiserum neutralized all HPeV3 isolates whereas the neutralization capacity of the IVIG batches varied, and the mAb exclusively neutralized the A308/99 strain. Mapping of the amino acid variation among a subset of the HPeV3 strains on an HPeV3 capsid structure revealed that the majority of the surface-exposed amino acid variation was located in the VP1. Furthermore, amino acid mutations in a mAb AT12-015-resistant HPeV3 A308/99 variant indicated the location for potential antigenic determinants. Virus aggregation and the observed antigenic diversity in HPeV3 can explain the varying levels of nAb seropositivity reported in previous studies.

Anti-human T-lymphocyte immunoglobulin, rabbit (ATG, Zetbulin(®) intravenous infusion liquid), is an immunosuppressive agent that is indicated for aplastic anemia in Japan. The "prevention of graft-versus-host disease (GVHD) for allogeneic hematopoietic stem cell transplantation in adults" indication has been added to ATG in 32 countries worldwide, but has not yet been approved for GVHD prevention in Japan. The pharmacokinetics of ATG in Japanese people has not yet been assessed. In this study, to assess ATG pharmacokinetics, ATG (2 mg/kg/day from day-4 to day-1) as a pretransplant treatment was administered to six patients who had received transplantation of HLA-haploidentical stem cells. The ATG concentration was measured using an ELISA kit for rabbit IgG. The serum ATG concentration increased with administration for 4 consecutive days, peaking at a concentration of 66.0 μg/ml (±8.8 SD). Subsequently, it gradually decreased with an elimination half-life of 21.9 days (±20.4 SD) but was still detectable in serum even a few weeks after allogeneic hematopoietic stem cell transplantation. We found the pharmacokinetics of ATG in this study to be comparable to those described in previous reports from Europe.

Trichophyton mentagrophytes were isolated from 19 of 20 guinea pigs in a children’s corner of a zoo. The nucleotide sequence identity of the internal transcribed spacer region among 19 guinea pig isolates was 99%, including the reference strain of animal type 3 of T. mentagrophytes. The genomic DNA of all isolates were investigated for the mating (MAT) gene by specific polymerase chain reaction. The alpha-box gene was detected in all 19 isolates, while the high-mobility-group (HMG) gene was detected in only one of 19 isolates. Therefore, the guinea pig population harbored at least 2 MAT types of Arthroderma vanbreuseghemii. The T. mentagrophytes that was prevalent in this population may constitute a constant source of infection for persons coming into contact with guinea pigs.

The potential contamination of Toxoplasma gondii and Neospora caninum oocysts in the human environment is a concern from the public health viewpoint. However, estimation of their seroprevalences in humans cannot be performed in a manner that distinguishes between oocysts and tissue cysts as a source of infection. Rabbits are considered popular pet animals in Japan that can acquire natural infections by the aforementioned parasites only through the ingestion of oocysts. Therefore, this study was conducted to estimate the seroprevalences of T. gondii and N. caninum in pet rabbits in Japan as an indicator of the possible oocyst contamination in the environment surrounding human beings. Serum samples of 337 rabbits were examined by different serological methods. Enzyme-linked immunosorbent assays were performed to measure the titer of IgG and IgM antibodies. Samples revealed to be seropositive by ELISA were further analyzed by a latex agglutination test, Western blotting and an indirect immunofluorescence assay. The rates of seropositivity for T. gondii were 0.89% (3/337) and 0.29% (1/337) in IgG and IgM ELISA, respectively. SAG1 and SAG2 were detected as major antigens by the positive rabbit sera in Western blotting associated with strong staining observed by IFA in T. gondii tachyzoites. Regarding N. caninum, none of the serum samples showed a specific reaction in both Western blotting and the IFA. The results of this study indicate low seroprevalences of toxoplasmosis and neosporosis in pet rabbits in Japan, suggesting low oocyst contamination in the human environment.