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This study revealed that 41.9% of wild-born Japanese captive dolphins (18 out of 43 dolphins) have neutralizing antibodies specific to cetacean morbillivirus (CeMV). This finding indicates a widespread yet undetected CeMV infection among wild dolphins in the waters around Japan, occurring without notable epidemic or mass mortality of dolphins., (© 2025 The Author(s). Microbiology and Immunology published by The Societies and John Wiley & Sons Australia, Ltd.)

Cetaceans have adapted to aquatic life by evolving various anatomic and physiologic traits, but biological defense mechanisms specific to aquatic mammals that protect against pathogenic microorganisms in the aquatic environment have not been elucidated. In this study, we investigated the migration of polymorphonuclear leukocytes in bottlenose dolphins in response to various chemotactic factors and compared the migration response with that of terrestrial animals such as cows and humans to characterize biological defense mechanisms unique to cetaceans. Bottlenose dolphin neutrophils showed strong chemotactic activity toward zymosan-activated serum and recombinant human interleukin-8 but no chemotaxis toward N-formyl-methionyl-leucyl-phenylalanine or leukotriene B 4 at any concentration examined. Bovine and human neutrophils showed the strongest chemotactic activity at 37°C, whereas chemotactic activity declined significantly at 15°C and 4°C. By contrast, bottlenose dolphin neutrophils exhibited relatively strong chemotactic activity even at 15°C. These results suggest that the mechanism by which bottlenose dolphin neutrophils detect chemoattractants differs from that of terrestrial mammals and that the immune system of cetaceans may be cold-adaptive, allowing the animals to exert robust host defense responses in aquatic habitats, which tend to be colder than the terrestrial environment., 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 © 2025 Elsevier B.V. All rights reserved.)

Objective: The optimal treatment strategy for large-vessel occlusion (LVO) related to intracranial atherosclerotic disease (ICAD), particularly for tandem lesions that complicate access and device delivery, remains unclear. We report a case in which angioplasty with a stent retriever (SR) and combined antithrombotic therapy was effective in treating re-occlusion associated with dissection of the residual stenosis after thrombectomy for acute atherosclerotic occlusion of the basilar artery (BA) with the left vertebral artery (VA) stenosis., Case Presentation: An 80-year-old woman was brought to our hospital with progressively worsening consciousness and tetra-paresis. MRA revealed occlusion of the middle to proximal portion of the BA. The patient underwent percutaneous transluminal angioplasty using a balloon catheter for severe stenosis at the origin of the left VA, followed by mechanical thrombectomy for the BA occlusion. While initial recanalization was achieved, residual stenosis in the proximal portion of the BA led to re-occlusion. An attempt at angioplasty with a balloon catheter failed to reach the stenotic segment due to stenosis and tortuosity of the left VA. Consequently, the SR was redeployed into the BA, and a loading dose of antiplatelet agents and intravenous anticoagulant were administered during prolonged deployment. Following the confirmation of BA patency, the SR was re-sheathed and removed. The patient achieved remarkable improvement in consciousness and tetra-paresis without postoperative re-occlusion of the BA., Conclusion: Angioplasty with a SR and combined antithrombotic therapy may be a useful treatment option for ICAD-related LVO, particularly in cases such as tandem lesions that hinder access and make distal balloon catheter navigation challenging., (©2025 The Japanese Society for Neuroendovascular Therapy.)

The immune system has garnered attention due to its association with disease progression in amyotrophic lateral sclerosis (ALS). However, the role of peripheral immune cells in this context remains controversial. Here, we conducted single-cell RNA-sequencing of peripheral blood mononuclear cells to comprehensively profile immune cells concerning the rate of disease progression in patients with ALS. Our analysis revealed increased frequencies of T helper 17 cells (Th17) relative to regulatory T cells, effector CD8 T cells relative to naïve CD8 T cells, and CD16 high CD56 low mature natural killer cells relative to CD16 low CD56 high naïve natural killer cells in patients with rapidly progressive ALS. Additionally, we employed serum proteomics through a proximity extension assay combined with next-generation sequencing to identify inflammation-related proteins associated with rapid disease progression. Among these proteins, interleukin-17 A correlated with the frequency of Th17, while killer cell lectin-like receptor D1 (CD94) correlated with the frequency of effector CD8 T cells. These findings further support the active roles played by these specific immune cell types in the progression of ALS., Competing Interests: Declarations. Ethics approval and consent to participate: All study protocols were approved by the Ethics Committee of Tokushima University Hospital under protocol #3682. All clinical information was collected after patients provided written informed consent. The investigations were conducted following the principles of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: TI, YO, DW, SM, and YK are employees of Takeda Pharmaceutical Company Limited., (© 2024. The Author(s).)

[Purpose] This study examined the feasibility of including physical therapists in the Health Services and Preventive Care program at community gatherings. [Participants and Methods] The participants were 56 older adults from five community gatherings who did not have a long-term care insurance service. As part of the Health Services and Preventive Care program, interventions by physical therapists were conducted for 90 minutes once a month for 6 months at five community gatherings, which involved exercises, and home-based exercises. The feasibility outcomes were dropout rate, number of times people participated in the program, and understanding of frailty. The effectiveness outcomes were frailty, grip strength, walking speed, and five-times-sit-to-stand test. [Results] The feasibility study results showed a dropout rate of 4.3%, 4.7 ± 0.4 times participation, and a 93.2% frailty understanding. Effectiveness outcomes revealed no increase in frailty. The physical indices showed that all participants statistically improved in the five-times-sit-to-stand test (Pre: 7.3 ± 2.3 times, Post: 6.5 ± 7.6 times). [Conclusion] The results of the feasibility study indicate that the program is feasible because of the high rates of completion and frailty prevention understanding., Competing Interests: None., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Cetacean-cultured cells are a promising tool for life science research. Most cells used in cetacean research are derived from the skin and kidneys. However, cell cultures from various organs are required for more flexible cetacean research. Primary cultures were prepared from kidney, intestinal, and lung tissues using a simple tissue fragment culture method from a striped dolphin (Stenella coeruleoalba). Kidney and intestinal cells were mostly epithelial-like, whereas lung cells were mostly fibroblast-like. The simple tissue fragment culture method presented in this study will be useful for expanding cetacean cell resources. Culturing allogeneic cell models is expected to introduce a flexible in vitro approach to cetacean research., (© 2024. The Society for In Vitro Biology.)

Retraining retired racehorses for various purposes can help correct behavioral issues. However, ensuring efficiency and preventing accidents present global challenges. Based on the hypothesis that a simple personality assessment could help address these challenges, the present study aimed to identify genetic markers associated with personality. Eight genes were selected from 18 personality-related candidate genes that are orthologs of human personality genes, and their association with personality was verified based on actual behavior. A total of 169 Thoroughbred horses were assessed for their tractability (questionnaire concerning tractability in 14 types of situations and 3 types of impressions) during the training process. Personality factors were extracted from the data using principal component analysis and analyzed for their association with single nucleotide variants as non-synonymous substitutions in the target genes. Three genes, CDH13, SLC6A4, and MAOA, demonstrated significant associations based on simple linear regression, marking the identification of these genes for the first time as contributors to temperament in Thoroughbred horses. All these genes, as well as the previously identified HTR1A, are involved in the serotonin neurotransmitter system, suggesting that the tractability of horses may be correlated with their social personality. Assessing the genotypes of these genes before retraining is expected to prevent problems in the development of a racehorse's second career and shorten the training period through individual customization of training methods, thereby improving racehorse welfare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and fatigability. In particular, seronegative MG constitutes 10%-15% of MG cases and presents diagnostic challenges especially in early-onset female patients who often show severe disease and resistance to immunosuppressive therapy. Furthermore, the immunopathology of seronegative MG remains unclear. Thus, in this study, we aimed to elucidate the pathogenic mechanism of seronegative MG using scRNA-seq analysis and plasma proteome analysis; in particular, we investigated the relationship between immune dysregulation status and disease severity in refractory seronegative MG. Employing single-cell RNA-sequencing and plasma proteome analyses, we analyzed peripheral blood samples from 30 women divided into three groups: 10 healthy controls, 10 early-onset AChR-positive MG, and 10 refractory early-onset seronegative MG patients, both before and after intravenous immunoglobulin treatment. The disease severity was evaluated using the MG-Activities of Daily Living (ADL), MG composite (MGC), and revised 15-item MG-Quality of Life (QOL) scales. We observed numerical abnormalities in multiple immune cells, particularly B cells, in patients with refractory seronegative MG, correlating with disease activity. Notably, severe MG cases had fewer regulatory T cells without functional abnormalities. Memory B cells were found to be enriched in peripheral blood cells compared with naïve B cells. Moreover, plasma proteome analysis indicated significantly lower plasma protein levels of soluble CD22, expressed in the lineage of B-cell maturation (including mature B cells and memory B cells), in refractory seronegative MG patients than in healthy donors or patients with AChR-positive MG. Soluble CD22 levels were correlated with disease severity, B-cell frequency, and RNA expression levels of CD22. In summary, this study elucidates the immunopathology of refractory seronegative MG, highlighting immune disorders centered on B cells and diminished soluble CD22 levels. These insights pave the way for novel MG treatment strategies focused on B-cell biology., Competing Interests: YO, SM, TI, MS, MI, DW, and YK were employed by the company Takeda Pharmaceutical Company Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Okuzono, Miyakawa, Itou, Sagara, Iwata, Ishizuchi, Sekiguchi, Motegi, Oyama, Warude, Kikukawa and Suzuki.)

Cetaceans are specialized marine mammals with a unique respiratory system adapted for diving behavior. Furthermore, respiratory diseases are commonly observed in these mammals. Nevertheless, much of their respiratory physiology remains unknown due to the limited supply and poor quality of their biological samples for research. In this study, we established a novel lung cell line, dLu, derived from the common bottlenose dolphin (Tursiops truncatus), which can prove useful in cetacean research, including for understanding the pathogenesis of respiratory diseases in cetaceans. The cells were cultured in a simple medium consisting of Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. The morphology of the cells was fibroblast-like. dLu was produced by transfecting the simian virus 40 large T antigen into primary cultured cells. Although dLu exhibited approximately 80 cell divisions, it was unable to achieve complete immortalization, as the cells stopped proliferating beyond this number. dLu cells expressed toll-like receptor 3 but not toll-like receptor 4. Immunostimulation with poly(I:C) altered the gene expressions of interferon beta 1 and tumor necrosis factor alpha in dLu cells. In summary, dLu established in this study is a novel cetacean cell resource that can be easily cultured and is a useful in vitro tool in cetacean research, particularly for studying host immune responses in the lungs., (© 2023. The Society for In Vitro Biology.)

Ezin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a scaffold protein that interacts with several partner molecules including β-catenin. Here, we examined the crosstalk between EBP50 and nuclear catenin during colorectal carcinoma (CRC) progression. In clinical samples, there were no correlations between the subcellular location of EBP50 and any clinicopathological factors. However, EBP50 expression was significantly lower specifically in the outer areas of tumor lesions, in regions where tumor budding (BD) was observed. Low EBP50 expression was also significantly associated with several unfavorable prognostic factors, suggesting that EBP50 depletion rather than its overexpression or subcellular distribution plays an important role in CRC progression. In CRC cell lines, knockout of EBP50 induced epithelial-mesenchymal transition (EMT)-like features, decreased proliferation, accelerated migration capability, and stabilized nuclear β-catenin due to disruption of the interaction between EBP50 and β-catenin at the plasma membrane. In addition, Slug expression was significantly higher in outer lesions, particularly in BD areas, and was positively correlated with nuclear β-catenin status, consistent with β-catenin-driven transactivation of the Slug promoter. Together, our data suggest that EBP50 depletion releases β-catenin from the plasma membrane in outer tumor lesions, allowing β-catenin to accumulate and translocate to the nucleus, where it transactivates the Slug gene to promote EMT. This in turn triggers tumor budding and contributes to the progression of CRC to a more aggressive phase.

We report a young woman with ileocecal endometriosis who presented with repeated abdominal pain. Under hormonal effects, the endometrium may proliferate and cause bleeding in the bowel wall, leading to cyclical abdominal pain. When recurring abdominal pain is observed in reproductive-aged women, physicians should always be aware of gastrointestinal endometriosis., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

RNase H-dependent gapmer antisense oligonucleotides (ASOs) are a promising therapeutic approach via sequence-specific binding to and degrading target RNAs. However, the efficacy and mechanism of antiviral gapmer ASOs have remained unclear. Here, we investigated the inhibitory effects of gapmer ASOs containing locked nucleic acids (LNA gapmers) on proliferating a mosquito-borne flavivirus, Japanese encephalitis virus (JEV), with high mortality. We designed several LNA gapmers targeting the 3' untranslated region of JEV genomic RNAs. In vitro screening by plaque assay using Vero cells revealed that LNA gapmers targeting a stem-loop region effectively inhibit JEV proliferation. Cell-based and RNA cleavage assays using mismatched LNA gapmers exhibited an underlying mechanism where the inhibition of viral production results from JEV RNA degradation by LNA gapmers in a sequence- and modification-dependent manner. Encouragingly, LNA gapmers potently inhibited the proliferation of five JEV strains of predominant genotypes I and III in human neuroblastoma cells without apparent cytotoxicity. Database searching showed a low possibility of off-target binding of our LNA gapmers to human RNAs. The target viral RNA sequence conservation observed here highlighted their broad-spectrum antiviral potential against different JEV genotypes/strains. This work will facilitate the development of an antiviral LNA gapmer therapy for JEV and other flavivirus infections.

Background: This study aimed to evaluate whether "visiting restrictions" implemented due to the coronavirus disease 2019 (COVID-19) pandemic are a risk factor for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS)., Methods: This case-control study participants who gave birth during the spread of COVID-19 (COVID-19 study group) and before the spread of COVID-19 (control group). Participants completed the EPDS at 2 weeks and 1 month after childbirth., Results: A total of 400 cases (200 in each group) were included in this study. The EPDS positivity rate was significantly lower with visiting restrictions than without (8.5% vs.18.5%, p = 0.002). Multivariate analysis of positive EPDS screening at the 1st month checkup as the objective variable revealed that visiting restrictions (odds ratio (OR): 0.35, 95% confidence interval (CI): 0.18-0.68), neonatal hospitalization (OR: 2.17, 95% CI: 1.08-4.35), and prolonged delivery (OR: 2.87, 95% CI: 1.20-6.85) were factors associated with an increased risk of positive EPDS screening., Conclusion: Visiting restrictions on family during the hospitalization period for delivery during the spread of COVID-19 pandemic did not worsen EPDS screening scores 1 month postpartum, but stabilized the mental state of some mothers., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Common bottlenose dolphin (Tursiops truncatus) is a well-known cetacean species that inhabits temperate and tropical seas worldwide. Limited supply and poor quality of samples hinder the investigation of the effects of various pathogens and environmental pollutants on this cetacean species. Cultured cells are useful for experimental studies; however, no cell lines derived from cetaceans are generally available. Therefore, in this study, we established a novel kidney cell line, TK-ST, derived from T. truncatus. Primary cells exhibited the morphological characteristics of epithelial and fibroblast cells, but their immortalization and passaging resulted in a predominantly epithelial cell morphology. TK-ST was immortalized using the large T SV40 antigen and human telomerase reverse transcriptase and exhibited long-term stable cell growth. TK-ST cells are generally cultured in Dulbecco's modified Eagle's medium with 10% fetal bovine serum at 37°C and 5% CO 2 but can also be cultured in 5-20% fetal bovine serum and several other classical media commonly used for common animal cell culture. TK-ST cells were found to be susceptible to several viruses, including the dolphin morbillivirus (most important virus in cetaceans), and exhibited cytopathic effects, facilitating the replication of the dolphin morbillivirus. Furthermore, mRNA expression levels of cytokine genes were increased in TK-ST cells after stimulation with lipopolysaccharides and poly(I:C). Therefore, the novel TK-ST cell line derived in this study can potentially be used for further in vitro studies on cetaceans., (© 2023. The Society for In Vitro Biology.)

Background: A characteristic of modern medical care is the reduction in the length of hospital stay, and several facilities across Japan are working towards this goal. The presence of postoperative pain is correlated with the number of days to hospital discharge. Therefore, this study investigated the relationship between the analgesic methods used in clinical practice and the initial ambulation of postoperative laparotomy patients with severe postoperative worked incisional pain to enable better analgesic management in the future., Methods: This retrospective study collected information from the medical records of 117 patients who underwent laparotomy between December 1, 2019, and October 13, 2020, at the Department of Gastroenterology of the International University of Health and Welfare Mita Hospital. Based on the failure or success of the ambulation process, the patients were divided into the delayed and successful groups, respectively., Results: In the delayed group, patient-controlled epidural analgesia (PCEA) was used in 32 patients, intravenous patient-controlled analgesia (IV-PCA) was used in two patients, continuous worked incisional infiltration anesthesia was used in one patient, and transvenous acetaminophen was used in one patient for postoperative analgesia. In the successful group, PCEA was used in 66 patients, IV-PCA was used in 11 patients, continuous worked incisional infiltration anesthesia was used in three patients, and acetaminophen administered intravenously at patient's request was used in one patient (P = 0.094)., Conclusions: No significant differences were observed between different postoperative analgesia methods, suggesting that there may be no association between postoperative ambulation and the postoperative analgesia method., Competing Interests: The authors declare that they have no conflict of interest., (Copyright 2023, Mitobe et al.)

Allograft inflammatory factor-1 (AIF-1) is expressed in microglia. Unilateral common carotid artery occlusion (UCCAO) was conducted to elucidate mechanisms that regulate AIF-1 expression in C57BL/6 male mice. Immunohistochemical reactivity of microglia against anti-AIF-1 antibody was increased significantly in the brain of this model. The increased AIF-1 production was further confirmed by ELISA using brain homogenate. Real-time PCR demonstrated that the increased AIF-1 production was regulated at the transcriptional level. Serum AIF-1 levels were further examined by ELISA and marked increase was observed on Day 1 of UCCAO. To examine the influence of AIF-1, immunohistochemical staining was performed and revealed that the immunoreactivity against anti-Iba-1 antibody was significantly increased in various organs. Among them, the accumulation of Iba-1 + cells were observed prominently in the spleen. Intraperitoneal injection of minocycline, a potent microglia inhibitor, reduced the number of Iba-1 + cells suggesting microglia activation-dependent accumulation. Based on these results, AIF-1 expression was further examined in the murine microglia cell line MG6. AIF-1 mRNA expression and secretion were up-regulated when the cells were cultured under hypoxic condition. Importantly, stimulation of the cells with recombinant AIF-1 induced the expression of AIF-1 mRNA. These results may suggest that increased AIF-1 production by microglia in cerebral ischemia regulate the AIF-1 mRNA expression at least in part by an autocrine manner., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Indwelling bladder catheters are routinely used in clinical practice. Patients may experience postoperative indwelling catheter-related bladder discomfort (CRBD). This study aimed to perform a literature review to identify predictors of postoperative CRBD., Methods: We searched PubMed for relevant articles published between 2000 and 2020 using the search items "CRBD", "catheter-related bladder discomfort", and "prediction". Additionally, we searched for articles that matched the research objectives from the references of the extracted articles. We included only prospective observational studies involving human participants and excluded interventional studies, observational studies that did not report sample sizes, or observational studies that did not research on predictors of CRBD. We narrowed our search to the keyword "prediction" and found five references. We selected five studies that met the objectives of the study as the target literature., Results: Using the keywords "CRBD" and "catheter-related bladder discomfort", we identified 69 published articles. The results were narrowed down by the keyword "prediction", and five studies that recruited 1,147 patients remained. The predictors of CRBD can be divided into four factors: 1) patient factors; 2) surgical factors; 3) anesthesia factors; and 4) device and insertion technique factors., Conclusion: Our study suggests that patients with predictors of CRBD should be closely monitored to reduce postoperative patient suffering, and their quality of life should be improved after anesthesia., Competing Interests: The authors declare no conflict of interest., (Copyright 2023, Mitobe et al.)

This study aimed to investigate whether phosphate contributes to the pathogenesis of chronic kidney disease (CKD) in dolphins. Renal necropsy tissue of an aged captive dolphin was analyzed and in vitro experiments using cultured immortalized dolphin proximal tubular (DolKT-1) cells were performed. An older dolphin in captivity died of myocarditis, but its renal function was within the normal range until shortly before death. In renal necropsy tissue, obvious glomerular and tubulointerstitial changes were not observed except for renal infarction resulting from myocarditis. However, a computed tomography scan showed medullary calcification in reniculi. Micro area X-ray diffractometry and infrared absorption spectrometry showed that the calcified areas were primarily composed of hydroxyapatite. In vitro experiments showed that treatment with both phosphate and calciprotein particles (CPPs) resulted in cell viability loss and lactate dehydrogenase release in DolKT-1 cells. However, treatment with magnesium markedly attenuated this cellular injury induced by phosphate, but not by CPPs. Magnesium dose-dependently decreased CPP formation. These data support the hypothesis that continuous exposure to high phosphate contributes to the progression of CKD in captive-aged dolphins. Our data also suggest that phosphate-induced renal injury is mediated by CPP formation in dolphins, and it is attenuated by magnesium administration., (© 2023. The Author(s).)

Considering the personality traits of racehorses (e.g., flightiness, anxiety, and affability) is considered essential to improve training efficiency and decrease accident frequency, especially when retraining for a second career that may involve contact with inexperienced personnel after retiring from racing. Studies on human personality-related genes are frequently conducted; however, such studies are rare in horses because a consistent methodology for personality evaluation is lacking. Using the recently published whole genome variant database of 101 Thoroughbred horses, we compared horse genes orthologous to human genes related to the Big Five personality traits, and identified 18 personality-related candidate genes in horses. These genes include 55 variants that involve non-synonymous substitutions that highly impact the encoded protein. Moreover, we evaluated the allele frequencies and functional impact on the proteins in terms of the difference in molecular weights and hydrophobicity levels between reference and altered amino acids. We identified 15 newly discovered genes that may affect equine personality, but their associations with personality are still unclear. Although more studies are required to compare genetic and behavioral information to validate this approach, it may be useful under limited conditions for personality evaluation.

Objective: We report a case of near-occlusion of the common carotid bifurcation caused by a giant free-floating thrombus (FFT) successfully treated with mechanical thrombectomy using a large dual-layer stent retriever., Case Presentation: A 51-year-old man presented to our hospital with dysarthria, right hemiparalysis, and paresthesia. MRI revealed an acute infarction of the left cortical watershed zone, and MRA revealed decreased signals in the left common carotid bifurcation. Carotid ultrasonography demonstrated a giant FFT in the left common carotid bifurcation. Angiography revealed a giant thrombus extending from the left common carotid artery (CCA) to the internal carotid artery (ICA) and the external carotid artery. As direct aspiration from both a balloon-guided catheter (BGC) and an aspiration catheter (AC) was ineffective, we deployed a large dual-layer stent retriever from the ICA to the CCA with an AC-connected aspiration pump and retrieved it under manual aspiration through the BGC. The giant thrombus was successfully removed, and complete recanalization was achieved without distal embolisms., Conclusion: Although there is no established treatment for giant thrombi in the carotid artery, mechanical thrombectomy using a large dual-layer stent retriever may be an effective treatment option., Competing Interests: The authors declare no conflict of interest., (©2023 The Japanese Society for Neuroendovascular Therapy.)

We investigated the prevalence of Bartonella in 123 northern bats (Eptesicus nilssonii) and their ectoparasites from Hokkaido, Japan. A total of 174 bat fleas (Ischnopsyllus needhami) and two bat bugs (Cimex japonicus) were collected from the bats. Bartonella bacteria were isolated from 32 (26.0%) of 123 bats. Though Bartonella DNA was detected in 79 (45.4%) of the bat fleas, the bacterium was isolated from only one bat flea (0.6%). The gltA sequences of the isolates were categorized into genotypes I, II, and III, which were found in both bats and their fleas. The gltA sequences of genotypes I and II showed 97.6% similarity with Bartonella strains from a Finnish E. nilssonii and a bat flea from a E. serotinus in the Netherlands. The rpoB sequences of the genotypes showed 98.9% similarity with Bartonella strain 44722 from E. serotinus in Republic of Georgia. The gltA and rpoB sequences of genotype III showed 95.9% and 96.7% similarity with Bartonella strains detected in shrews in Kenya and France, respectively. Phylogenetic analysis revealed that Bartonella isolates of genotypes I and II clustered with Bartonella strains from Eptesicus bats in Republic of Georgia and Finland, Myotis bats in Romania and the UK, and a bat flea from an Eptesicus bat in Finland. In contrast, genotype III formed a clade with B. florencae, B. acomydis, and B. birtlesii. These data suggest that northern bats in Japan harbor two Bartonella species and the bat flea serves as a potential vector of Bartonella transmission among the bats., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In a previous study, we observed that the hair color of Japanese females darkens with age and that the causes of this are the increase in melanosome size, the amount of melanin, and the mol% of 5,6-dihydroxyindole (DHI) which has a high absorbance. In this study, we extended the same analyses to male hair to examine the sex differences in hair color, melanin composition, and melanosome morphology. Male hair also tended to darken with age, but it was darker than female hair in those of younger ages. Although there was no age dependence of DHI mol% in male hair, as with female hair, the melanosomes' sizes enlarged with age, the total melanin amount increased, and these findings were correlated with hair color. The analyses, considering age dependence, revealed that there were significant sex differences in the ratio of absorbance of dissolved melanin at the wavelength of 650 nm to 500 nm, in pheomelanin mol%, and in melanosome morphology parameters such as the minor axis. This may be the cause of the sex differences in hair color. Furthermore, the factors related to hair color were analyzed using all the data of the male and female hairs. The results suggested that total melanin amount, pheomelanin mol%, and DHI mol% correlated with hair color.

Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd)., Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database., Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia., Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All authors received research funding from Ono Pharma. and Celgene (Current Bristol Myers Squibb). JKa, SF, TI, HT, HS, SY, KS, KO, MH, CS, and JKu received speaker’s bureau from Ono Pharma. JKa, SF, TI, HT, HS, SY, SK, KO, IM, MH, CS, AT-K, and JKu received speaker’s bureau from Celgene (Current Bristol Myers Squibb). SF, TI, TH, HS, SY, SK, KO, IM, MH, CS, and JKu received speaker’s bureau from Janssen. JKa, SF, TI, HT, HS, SY, SK, KO, IM, MH, CS, and JKu received speaker’s bureau from Takeda Pharma. JKa, SF, TI, HT, HS, SY, SK, MH, CS, and JKu received speaker’s bureau from Sanofi. JKa, TI, HT, HS, SY, SK, KO, IM, MH, AT-K, and JKu received speaker’s bureau from Novartis. SK and JKu received speaker’s bureau from Fujimoto Pharma. TI, HS, MH, and JKu received research funding from Celgene (Current Bristol Myers Squibb). HS received research funding from Janssen. IM and JKu received research funding from Takeda Pharma. HS, IM, and JKu received research funding from Sanofi. HS and MH received research funding from Novartis. JKu received research funding from Fujimoto Pharma. JKa received consulting fees from Janssen and Takeda Pharma. MH received scholarship donations from Takeda Pharma. and Ono Pharma. AT-K received scholarship donations from Takeda Pharma. and Sanofi., (© The Author(s), 2022.)

Postoperative sore throat can occur as a complication in patients who have undergone surgery under general anesthesia. The incidence of postoperative sore throat ranges from 12.1% to 70%, and its effects include damage to the epithelium and mucosal cells caused by airway securement, damage to the vocal cords, congestion, blood clots, and factors such as an inappropriately large tube, cuff shape, cuff pressure, and airway securement. Notably, there are individual differences in pain thresholds, and the sensation of pain is affected by mental states, such as anxiety, and varies from person to person. Therefore, we conducted a literature review using PubMed to clarify patient factors related to the development of postoperative sore throat. The extracted keywords were "postoperative sore throat," "anesthesia," and "patient factors." We found 16 articles that met our search criteria. We expanded the search period and retrieved 19 cases from 1990 to 2020. We also included references that were judged to be closely related to the list of citations of the retrieved references. The study designs included were randomized controlled trials, clinical trials, meta-analyses, reviews, and systematic reviews. The results showed that female sex, smoking, and age were the most common patient factors. However, we could not find any literature that studied the relationship between postoperative sore throat and mental states such as anxiety., Competing Interests: The authors declare no conflict of interest., (Copyright 2022, Mitobe et al.)

Importin α1/KPNA1 is a member of the Importin α family widely present in the mammalian brain and has been characterized as a regulator of neuronal differentiation, synaptic functionality, and anxiety-like behavior. In humans, a de novo mutation of the KPNA1 (human Importin α5) gene has been linked with schizophrenia; however, the precise roles of KPNA1 in disorder-related behaviors are still unknown. Moreover, as recent studies have highlighted the importance of gene-environment interactions in the development of psychiatric disorders, we investigated the effects of Kpna1 deletion and social isolation stress, a paradigm that models social stress factors found in human patients, on psychiatric disorder-related behaviors in mice. Through assessment in a behavioral battery, we found that Kpna1 knockout resulted in the following behavioral phenotype: (1) decreased anxiety-like behavior in an elevated plus maze test, (2) short term memory deficits in novel object recognition test (3) impaired sensorimotor gating in a prepulse inhibition test. Importantly, exposure to social isolation stress resulted in additional behavioral abnormalities where isolated Kpna1 knockout mice exhibited: (1) impaired aversive learning and/or memory in the inhibitory avoidance test, as well as (2) increased depression-like behavior in the forced swim test. Furthermore, we investigated whether mice showed alterations in plasma levels of stress-associated signal molecules (corticosterone, cytokines, hormones, receptors), and found that Kpna1 knockout significantly altered levels of corticosterone and LIX (CXCL5). Moreover, significant decreases in the level of prolactin were found in all groups except for group-housed wild type mice. Our findings demonstrate that Kpna1 deletion can trigger widespread behavioral abnormalities associated with psychiatric disorders, some of which were further exacerbated by exposure to adolescent social isolation. The use of Kpna1 knockout mice as a model for psychiatric disorders may show promise for further investigation of gene-environment interactions involved in the pathogenesis of psychiatric disorders., Competing Interests: The authors have declared that no competing interests exist.

Parasite resistance traits in aquaculture species often have moderate heritability, indicating the potential for genetic improvements by selective breeding. However, parasite resistance is often synonymous with an undesirable negative correlation with body size. In this study, we first tested the feasibility of genomic selection (GS) on resistance to heterobothriosis, caused by the monogenean parasite Heterobothrium okamotoi, which leads to huge economic losses in aquaculture of the tiger pufferfish Takifugu rubripes. Then, using a simulation study, we tested the possibility of simultaneous improvement of parasite resistance, assessed by parasite counts on host fish (HC), and standard length (SL). Each trait showed moderate heritability (square-root transformed HC: h 2  = 0.308 ± 0.123, S.E.; SL: h 2  = 0.405 ± 0.131). The predictive abilities of genomic prediction among 12 models, including genomic Best Linear Unbiased Predictor (GBLUP), Bayesian regressions, and machine learning procedures, were also moderate for both transformed HC (0.248‒0.344) and SL (0.340‒0.481). These results confirmed the feasibility of GS for this trait. Although an undesirable genetic correlation was suggested between transformed HC and SL (r g  = 0.228), the simulation study suggested the desired gains index can help achieve simultaneous genetic improvements in both traits.

Objectives: To evaluate improved protein extraction and two-dimensional electrophoresis (2DE) separation methods with Japanese reference human hair (JRH); to determine whether fibre curvature is related to protein composition in curly and straight Japanese women's human hair (JHH) samples; and to identify proteins from JRH 2DE maps and expression differences between curly and straight JHH., Methods: Hair keratin and keratin-associated proteins (KAPs) were extracted intact with dithiothreitol or tris(2-carboxyethyl) phosphine from JRH or from curved or straight JHH. Extracted proteins were isoelectric-focused on first-dimensional pH gradient gel strips, then separated by molecular weight on laboratory-made, second-dimension, large format gels. The software compared protein abundance between duplicate 2DE gels of curved and straight JHH. Thirty-eight proteins from a JRH 2DE gel were enzyme-cleaved for MALDI-TOF-MS analysis to determine peptide composition, and where possible, de novo sequencing gave peptide sequence data. An in-house human hair protein database incorporating ninety-eight annotated protein sequences assisted MS analysis., Results: 2DE gels of tris(2-carboxyethyl) phosphine-extracted JRH improved keratin and KAP resolution and number compared to those of dithiothreitol-extracted JRH and published commercially made second-dimensional gels. Silver-stained 2DE gels of the straight or curved JHH sets were remarkably similar. Over-staining to reveal basic proteins caused poor resolution of the major acidic protein classes. Software comparisons of fifty-nine resolved proteins revealed two were significantly different in abundance between curved and straight hairs but in insufficient amounts for MS analysis. MS identified twelve proteins from a JRH CBBG-stained 2DE gel: six type II keratins, three type I keratins and three high sulphur proteins. A further eight were potential conformational isoforms and isoelectric variants of the identified proteins bringing the total to twenty identified or partially identified proteins., Conclusion: Root-end human hair extraction with tris(2-carboxyethyl) phosphine improves protein resolution and visualizes more proteins on large format 2DE gels. The two minor protein differences between duplicate straight or curved JHH 2DE gels were unlikely to change fibre structure from straight to curved hair. MS results confirmed that multiple isoforms exist of various hair proteins. Low sequence coverage prevented distinction between members in rows of homologous protein spots of similar molecular weight., (© 2020 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Novel multistage redox tetrathiafulvalenes (TTFs) bearing 6-aryl-1,4-dithiafulvene moieties were synthesized by palladium-catalyzed direct C-H arylation. In the presence of a catalytic amount of Pd(OAc) 2 , P( t -Bu 3 )·HBF 4 , and an excess of Cs 2 CO 3 , the C-H arylation of TTF with several aryl bromides bearing 1,3-dithiol-2-ylidenes took place efficiently to produce the corresponding π-conjugated molecules. We also succeeded in the estimation of the oxidation potentials and number of electrons involved in each oxidation step of the obtained compounds by digital simulations., (Copyright © 2020, Yoshimura et al.; licensee Beilstein-Institut.)

Solid-state physics and soft-matter physics have been developed independently, with little mutual exchange of the underlying physical concepts. However, after many studies of correlated electron systems, it has been recognized that correlated electrons (especially in Mott-transition systems) in solid matter sometimes show behavior similar to "structured fluids" in soft matter; that is, the electrons exhibit long-length self-organization (but without long-range order) and slow dynamics, which is inevitable for the long-length structures. The essential question is this: what condition causes such behavior in solid matter? We focused on an organic Mott-transition system and demonstrated that the electrons of this system fluctuate very slowly only when the following two factors are met simultaneously: (i) the electronic system is on the metal and Mott-insulator boundary and (ii) the system is subject to quenched disorder. This electronic state with slow dynamics under this condition can be explained by the concept of the "(electronic) Griffiths phase." This concept will potentially be a key in connecting solid-state physics with soft-matter physics.

There is no established treatment for appendiceal mucinous adenocarcinoma. When this condition is complicated by pseudomyxoma peritonei(PMP), multidisciplinary treatment is often administered. A 40-year-old woman was diagnosed with right ovarian cancer for which laparotomy was performed. At the time of laparotomy, we considered the tumor to be an appendiceal carcinoma infiltrating the right ovary and performed ileocecal resection with lymph node dissection(D3)and right salpingo-oophorectomy. The pathological diagnosis was stage pT3, pN0, pM0, pStage Ⅱ mucinous adenocarcinoma of the appendix. Fourteen months later, the patient underwent abdominal total hysterectomy and left salpingo-oophorectomy because a CT scan suggested recurrence in the uterus, left fallopian tube, and ovary. Seventeen months after the second operation, despite adjuvant chemotherapy, CT revealed a peritoneal nodule in the pelvic cavity. Therefore, we administered chemotherapy comprising 5 lines for 32 months, which resulted in failure. CT showed an enlarged tumor and ascites and the patient became terminally ill. We repeatedly performed cytoreduction surgery and intraperitoneal chemotherapy, which improved her QOL. One year after discharge, abdominal CT showing an abdominal wall and intraperitoneal mass. We performed again cytoreduction surgery and intraperitoneal chemotherapy. Her postoperative course is good and she is currently an outpatient.

We experienced a case of low-grade appendiceal mucinous neoplasm complicated by pseudomyxoma peritonei that was successfully treated with cytoreductive surgery and early postoperative intraperitoneal chemotherapy. The patient was a 26- year-old man with massive ascites and a swollen appendix on the computed tomography(CT). The appendix was a cystic mass of 5 cm in size. The entire parietal peritoneum, omentum, stomach, spleen, gall bladder, and entire colon were covered with numerous mucous nodules. Total colectomy, total gastrectomy, splenectomy, cholecystectomy, total omentectomy, parietal peritonectomy, ileostomy, and intraperitoneal irrigation were performed. The pathological diagnosis was low-grade appendiceal mucinous neoplasm. Postoperative intraperitoneal chemotherapy with cisplatin and mitomycin C was performed. A residual tumor was found on the dorsal side of the hepatoduodenal ligament 3 months postoperation on the CT. The residual tumor was successfully excised via a concomitant resection of the hepatic caudate lobe. Postoperative intraperitoneal chemotherapy was then performed. No recurrence was found at 8 months postoperation. The addition of early postoperative intraperitoneal chemotherapy improved the patient's quality of life in a short period. This could be one of the treatment options.

In a previous study, we showed that the size of melanosomes isolated from Japanese female hairs enlarges with age, and this affects the hair color. In this study, we analyzed the age-dependent changes in hair melanin in order to further explore the factors related to hair color changing by aging. A significant positive correlation with age was found in the total melanin amount (TM) and the mol% of 5,6-dihydroxyindole (DHI) units, while no correlation was found in pheomelanin mol%. TM showed significant correlations with hair color parameters and the melanosome volume, suggesting that hair color darkening by aging is caused by the increase in TM due to the enlargement of the size of melanosome. From the measurement of absorbance spectra on synthetic eumelanins with different ratios of DHI and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), we found that the increase in DHI mol% also contributes to the darkening of hair color by aging. In addition, the level of pyrrole-2,3-dicarboxylic acid (PDCA), a marker of DHI melanin, showed a significant negative correlation with the aspect ratio of melanosome, suggesting a contribution of DHI melanin to the change in melanosome morphology by aging.

Objective: According to oral traditions of horse caretakers and trainers, the differences in the position and number of facial hair whorls may be associated with temperamental traits. Elucidating genetic background of facial hair whorls and its relationship to temperamental traits may promote more efficient breeding and maintenance of racehorses. In this study, we estimated heritabilities of the position and number of facial hair whorls in Japanese Thoroughbred horses., Results: The number of facial hair whorls varied from one to four and heritability estimate in 4024 Thoroughbred horses was low (h 2 = 0.160). The positions of facial hair whorls were categorized into high, medium, and low, based on their locations. This trait was estimated to have high heritability (h 2 = 0.643) in 3782 Thoroughbred horses. These results indicated that a larger proportion of the variation in the studied population was due to genetic factors for facial hair whorls position. Because a similar result was also observed in another horse breed, Polish Konik horses, high heritability of facial hair whorl position may be characteristic of multiple horse breeds. We expect that these results will stimulate future studies to elucidate the relationship among temperamental traits and facial hair whorls in all horse breeds.

Studies using genome-wide single nucleotide polymorphisms (SNPs) have become commonplace in genetics and genomics, due to advances in high-throughput sequencing technologies. Since the numbers of required SNPs and samples vary depending on each research goal, genotyping technologies with high flexibility in the number of SNPs/samples and high repeatability have been intensively investigated. For example, the ultrahigh-multiplexed amplicon sequencing, Ion AmpliSeq, has been used as a high-throughput genotyping method mainly for diagnostic purposes. Here, we designed a custom panel targeting 3,187 genome-wide SNPs of fugu, Takifugu rubripes, and applied it for genotyping farmed fugu to test its feasibility in aquaculture studies. We sequenced two libraries consisting of different pools of individuals (n = 326 each) on the Illumina MiSeq sequencer. Consequently, over 99% target regions (3,178 SNPs) were amplified and 2,655 SNPs were available after filtering steps. Strong correlation was observed in the mean depth of coverage of each SNP between duplicate runs (r = 0.993). Genetic analysis using these genotype data successfully detected the known population structure and the sex determining locus of fugu. These results show the method is superior in repeatability and flexibility, and suits genetic studies including molecular breeding, such as marker assisted and genomic selection.

Objective: A new hair-care process has been specifically developed for the straightening of curved Japanese woman's hair . The process included sodium 2-naphthalene sulfonate (SNS) in the reduction and oxidation steps of a conventional perming process. Our objective was to develop an understanding of how this process caused hair straightening by measuring the changes to morphology and ultrastructure between untreated, conventionally permed and SNS permed hair. Untreated and SNS permed Merino wool fibres were used to confirm structural changes., Methods: Japanese hair samples were measured for single-fibre curvature before and after perming treatments. A silver staining method was developed to stain hair fibres without changing fibre curvature so that transmission electron microscopy could be used to measure changes in the lateral dimensions of all structural components from the cellular to protein filament level. Electron tomography determined intermediate filament slopes and slope changes after SNS perming relative to the central longitudinal axis of the fibre., Results: SNS perming was found to cause greater lateral swelling than conventional perming of: the paracortical cells of wool; the cuticle, the cuticular cell membrane complex and the macrofibrillar centre-to-centre distance of hair; and of the intermediate filaments in wool and hair. In curved hair, SNS perming caused the intermediate filaments of the helical macrofibrils to simultaneously swell and to tilt further, resulting in the slight longitudinal contraction of the macrofibrils. The overall swelling and tilting was greatest in the helical macrofibrils of Type B cortical cells predominately located in the convex fibre half. The presence of a higher percentage of helical macrofibrils in the convex fibre half than in the concave fibre half caused a contraction differential between the two halves leading to straighten of the curved fibre. A mechanical model was proposed to explain how SNS perming straightened curly hair., Conclusion: The effects of conventional and SNS perming on the morphological and ultrastructural components of curved Japanese hair and high-curl Merino wool fibres have given clear insights into understanding the mechanism of fibre curvature change., (© 2019 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

An endogenous viral element derived from adeno-associated virus containing a nearly intact open reading frame (ORF) of the rep gene (enAAV-rep) has been identified in the genomes of various mammals including degu and African elephant. Particularly, in degu, mRNA expression of enAAV-rep has been observed specifically in the liver. Here we newly identified enAAV-rep in Asian elephant and rock hyrax, both of which are afrotherians. The enAAV-rep of African and Asian elephants appeared to be orthologous and originated from an integration event of the entire genome of AAV into the ancestral genome of elephants more than 6 million years ago, whereas that of rock hyrax appeared to have originated independently. Negative selection operating at the amino acid sequence level was detected for the ORF of enAAV-rep in elephants. As in degu, mRNA expression of enAAV-rep was specifically observed in the liver in Asian elephant. Integrations of enAAV-rep appeared to have occurred independently on the evolutionary lineages of elephants and degu, suggesting that the AAV Rep protein has been co-opted repeatedly in the mammalian liver., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: This study was conducted to assess the presence and extent of differences in the gut microbiota of common bottlenose dolphins depending on rearing facilities., Methods and Results: Faecal samples were collected from 16 common bottlenose dolphins at three aquaria in Japan. After extracting DNA from the faeces, the V3-V4 region of bacterial 16S rRNA was amplified and sequenced using Illumina MiSeq platform. The constituent phyla of the gut microbiota were similar among aquaria; however, the most dominant phylum differed depending on the facility, and the compositions of microbiota were remarkably varied at the family level among aquaria. The alpha diversity indices tended to differ among aquaria. Some bacterial families observed in terrestrial mammalian carnivores or carnivorous fish were detected, as well as several bacterial species suspected of being pathogenic in dolphins., Conclusion: Our findings indicate that captive environmental conditions including prey and housing types may contribute to differences in the gut microbiota of the dolphins., Significance and Impact of the Study: This is the first study revealing the differences in gut microbiota of captive dolphins among facilities. Our findings will provide valuable information for improving the health management of dolphins., (© 2018 The Society for Applied Microbiology.)

Various changes appear in hair by aging, and graying is the most remarkable one. Changes in melanocytes have been well studied as the cause; however, little is known about the change in melanosomes which have a role of carrying melanin pigments into hair shafts. Using pigmented hairs of Japanese females from their age of 4-75, I isolated melanosomes and observed them. As a result, I found a significant change in the morphology of hair melanosomes with age. They were ellipsoidal on the whole and there was no age dependence in the major axis, while the minor axis significantly increased and its frequency distribution broadened with age. The anticipated volume of the melanosome of the oldest person hairs was about twice larger than that of child hairs. This enlargement of melanosome seems to be a cause of the age-related color change in pigmented hairs from brown to black., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The appearance of edematous lesions in the subacute phase is a rare complication following neuroendovascular therapy. Effective management of these lesions remains unclear. In this report, a case with progressive edematous lesions in the subacute phase after neuroendovascular therapy was described, and the clinical features and therapeutic strategies were discussed., Case Description: A 54-year-old female with a large, right cavernous internal carotid artery aneurysm was treated with a flow diverter. Left hemiparesis developed 15 days after the procedure, and multiple edematous lesions in areas of prior catheter procedures were revealed on radiological findings. Steroid pulse therapy was employed, and the lesions were gradually reduced without any additional neurological deficits. No recurrence was recognized in the follow-up study., Conclusion: In some reports, pathological findings indicate that these lesions result from the presence of foreign bodies, and emboli could be caused by cotton fibers or hydrophilic polymers used as surface coatings on endovascular catheters. In this case, the edematous lesions were most likely caused by hydrophilic polymer emboli. Steroid pulse therapy had a beneficial effect on the lesions. It is important to effectively manage prescribed periods after the procedure to avoid such a rare complication., Competing Interests: There are no conflicts of interest.

We established a system for the recovery of a segmented recombinant rabies virus, the virus genome RNA of which was divided into two parts: segment 1 encoding the nucleoprotein, phosphoprotein, matrix protein, and glycoprotein genes, and segment 2 encoding the large RNA-dependent RNA polymerase gene. The morphology of the segmented recombinant rabies virus was bullet-like in shape with a length of approximately 130 nm, which is shorter than the 200-nm long non-segmented recombinant rabies virus. The segmented recombinant rabies virus was maintained for at least 18 passages. The virus multiplication rate of the segmented recombinant rabies virus was lower than that of the non-segmented recombinant rabies virus during the passages, and the relative amounts of virus genome RNAs for segment 1 and segment 2 differed in the supernatant of the segmented recombinant rabies virus infected cells. These results suggest that the segmented recombinant rabies virus packages either segment 1 or segment 2 into each virus particle. Thus, co-infection with segmented recombinant rabies virus particles packaging segment 1 or segment 2 may be necessary for the production of progeny virus., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The patient was a 66-year-old woman who was examined by a local physician for the chief complaint of a mass palpable in the left lower abdomen. Abdominal plain computed tomography (CT) indicated a subcutaneous mass extending continuously from the apex of the bladder to the retropubic space, and she was referred to our medical department. Tumor markers were normal, and cystoscopic examination indicated no clear findings. Abdominal contrast-enhanced CT and plain abdominal magnetic resonance imaging results led to suspicion of actinomycosis. An open biopsy was performed on the subcutaneous mass, and subsequent histopathological testing led to a definitive diagnosis of actinomycosis. After 2 weeks of antibiotic therapy, the mass had diminished on CT. There has been no relapse approximately 24 weeks after discontinuation of the antibiotic therapy.

Hair curvature underpins structural diversity and function in mammalian coats, but what causes curl in keratin hair fibres? To obtain structural data to determine one aspect of this question, we used confocal microscopy to provide in situ measurements of the two cell types that make up the cortex of merino wool fibres, which was chosen as a well-characterised model system representative of narrow diameter hairs, such as underhairs. We measured orthocortical and paracortical cross-sectional areas, and cortical cell lengths, within individual fibre snippets of defined uniplanar curvature. This allowed a direct test of two long-standing theories of the mechanism of curvature in hairs. We found evidence contradicting the theory that curvature results from there being more cells on the side of the fibre closest to the outside, or convex edge, of curvature. In all cases, the orthocortical cells close to the outside of curvature were longer than paracortical cells close to the inside of the curvature, which supports the theory that curvature is underpinned by differences in cell type length. However, the latter theory also implies that, for all fibres, curvature should correlate with the proportions of orthocortical and paracortical cells, and we found no evidence for this. In merino wool, it appears that the absolute length of cells of each type and proportion of cells varies from fibre to fibre, and only the difference between the length of the two cell types is important. Implications for curvature in higher diameter hairs, such as guard hairs and those on the human scalp, are discussed., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert their antidiabetic effects by promoting urinary glucose excretion. Nutrition therapy is obviously important, but little is known about the interactions between SGLT2i agents and carbohydrate restriction. Therefore, we studied these interactions using an obese diabetic animal model. KK-A y mice were pair-fed normal chow [NC; carbohydrate: fat: protein = 65:15:20], low carbohydrate [LC; 43:42:15] or severely carbohydrate restricted diets [SR; 12:45:43] for 12 weeks. Tofogliflozin (Tofo) was administered as the SGLT2i in the NC and LC diet groups. Blood glucose levels were significantly increased in the SR group. Tofo reduced blood glucose levels significantly in the NC group during the experiment and in the LC group at 2-6 weeks. Plasma triglycerides were markedly elevated in the SR group without Tofo, but decreased in response to Tofo administration. Hepatic triglyceride contents were not changed by the LC or the SR diet alone. However, Tofo ameliorated hepatosteatosis in NC-fed animals. Consistent with the downregulation of stearoyl-CoA desaturase 1, the ratio of plasma monounsaturated to saturated fatty acids was significantly reduced in the LC with Tofo and in the SR alone groups, but was not altered in the NC with Tofo group. In summary, metabolism of glucose and lipids was improved by Tofo but not by the SR diet. Furthermore, Tofo improved these parameters more effectively in the NC than in the LC diet group. These data suggest that the effects of SGLT2i are distinct from those of carbohydrate restriction and that a nonrestricted dietary carbohydrate composition is essential for SGLT2i treatment to be effective., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The high affinity K⁺ transporter 1;4 (HKT1;4) in rice ( Oryza sativa ), which shows Na⁺ selective transport with little K⁺ transport activity, has been suggested to be involved in reducing Na in leaves and stems under salt stress. However, detailed physiological roles of OsHKT1;4 remain unknown. Here, we have characterized a transfer DNA (T-DNA) insertion mutant line of rice, which overexpresses OsHKT1 ; 4 , owing to enhancer elements in the T-DNA, to gain an insight into the impact of OsHKT1;4 on salt tolerance of rice. The homozygous mutant (the O/E line) accumulated significantly lower concentrations of Na in young leaves, stems, and seeds than the sibling WT line under salt stress. Interestingly, however, the mutation rendered the O/E plants more salt sensitive than WT plants. Together with the evaluation of biomass of rice lines, rhizosphere acidification assays using a pH indicator bromocresol purple and 22 NaCl tracer experiments have led to an assumption that roots of O/E plants suffered heavier damages from Na which excessively accumulated in the root due to increased activity of Na⁺ uptake and Na⁺ exclusion in the vasculature. Implications toward the application of the HKT1-mediated Na⁺ exclusion system to the breeding of salt tolerant crop cultivars will be discussed., Competing Interests: The authors declare no conflict of interest.

Prototheca zopfii is an achlorophyllic algae that causes bovine mastitis, resulting in a reduction in milk production and the secretion of thin, watery milk with white flakes. The aim of the present study was to evaluate the bacterial flora in the udder environment in protothecal mastitis. We used metagenomic next-generation sequencing (NGS) analysis to identify 16S rRNA genes from bacterial flora present in milk samples from protothecal mastitic dairy cows.Seven clinical strains of P. zopfii genotype 2 were isolated from 7 milk samples from 7 cases (Holstein cow) of protothecal mastitis; another 9 milk samples were obtained from 9 normal Holstein cows. The samples were collected in 2017 from cows in one dairy located in the Kushiro region in Hokkaido, Japan, which had a history of protothecal mastitis infection.The NGS produced 10,000 to 15,000 sequences in each DNA sample. To facilitate comparison, we grouped the sequencing results according to the culture-based protothecal mastitis diagnosis; sequences derived from the milk samples obtained from healthy cows were grouped separately.Sequences classified as Streptococcus spp., Pseudomonas spp. and Sphingomonas spp., Caulobacter segnis, Macrococcus caseolyticus, Methylobacterium tarhaniae, and Sphingomonas leidyi were the main sequences detected in the groups of samples from cows characterized by culture as having protothecal mastitis. Notably, Calothrix desertica (a cyanobacterium) sequences showed higher prevalence in these samples.To our knowledge, this is the first study to report that C. desertica sequences, effectively absent in the samples derived from healthy cows, are detected at high prevalence in samples from protothecal mastitic animals.

An 80-year-old man had a medical history of chronic hepatitis C and pancreatoduodenectomy. We detected recurrence of hepatocellular carcinoma, and performed transcatheter arterial chemoembolization, instead of radiofrequency ablation or surgery, because of the patient's medical history of bile duct reconstruction and liver dysfunction. On the second day, he was diagnosed with a gas-forming liver abscess and underwent liver abscess drainage. Clostridium perfringens and sordellii were detected by aspiration and the blood culture. Meropenem and Clindamycin were administered intravenously. He was treated shortly after the occurrence before the involvement of severe hemolysis and recovered from the acute phase.

The magnetoelectric effect in bulk matter is of growing interest both fundamentally and technologically. Since the beginning of the century, the magnetoelectric effect has been studied intensively in multiferroic materials. However, magnetoelectric phenomena in materials without any (anti-)ferroic order remain almost unexplored. Here we show the observation of a new class of bulk magnetoelectric effect, by revisiting elemental trigonal tellurium. We demonstrate that elemental tellurium, which is a nonmagnetic semiconductor, exhibits current-induced magnetization. This effect is attributed to spin splitting of the bulk band owing to the lack of inversion symmetry in trigonal tellurium. This finding highlights magnetoelectricity in bulk matter driven by moving electrons without any (anti-)ferroic order. Notably, current-induced magnetization generates a magnetic field that is not circular around but is parallel to the applied current; thus, this phenomenon opens a new area of magnetic field generation beyond Ampere's law that may lead to industrial applications.Electrical control of magnetic response in bulk material without electric or magnetic order is rare and potentially attractive for high efficient spintronics. Here, the authors report magnetization in elemental tellurium driven purely by current without any (anti-)ferroic order.

The purpose of this study was to evaluate in vivo supersaturation/precipitation/absorption behavior in the gastrointestinal (GI) tract based on the luminal concentration-time profiles after oral administration of pioglitazone (PG, a highly permeable lipophilic base) and its hydrochloride salt (PG-HCl) to rats. In the in vitro precipitation experiment in the classic closed system, while the supersaturation was stable in the simulated gastric condition, PG drastically precipitated in the simulated intestinal condition, particularly at a higher initial degree of supersaturation. Nonetheless, a drastic and moderate improvement in absorption was observed in vivo at a low and high dose of PG-HCl, respectively. Analysis based on the luminal concentration of PG after oral administration of PG-HCl at a low dose revealed that most of the dissolved PG emptied from the stomach was rapidly absorbed before its precipitation in the duodenum. At a high dose of PG-HCl, PG partly precipitated in the duodenum but was absorbed to some extent. Therefore, the extent of the absorption was mainly dependent on the duodenal precipitation behavior. Furthermore, a higher-than expected absorption after oral administration of PG-HCl from in vitro precipitation study may be due to the absorption process in the small intestine, which suppresses the precipitation by removal of the drug. This study successfully clarify the impact of the absorption process on the supersaturation/precipitation/absorption behavior and key absorption site for a salt formulation of a highly permeable lipophilic base based on the direct observation of in vivo luminal concentration. Our findings may be beneficial in developing an ideal physiologically based pharmacokinetic model and in vitro predictive dissolution tools and/or translating the in silico and in vitro data to the in vivo outcome., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The Mott transition-a metal-insulator transition caused by repulsive Coulomb interactions between electrons-is a central issue in condensed matter physics because it is the mother earth of various attractive phenomena. Outstanding examples are high- T c (critical temperature) cuprates and manganites exhibiting colossal magnetoresistance. Furthermore, spin liquid states, which are quantum-fluctuation-driven disordered ground states in antiferromagnets, have recently been found in magnetic systems very near the Mott transition. To date, intensive studies on the Mott transition have been conducted and appear to have established a nearly complete framework for understanding the Mott transition. We found an unknown type of Mott transition in an organic spin liquid material with a slightly disordered lattice. Around the Mott transition region of this material under pressure, nuclear magnetic resonance experiments capture the emergence of slow electronic fluctuations of the order of kilohertz or lower, which is not expected in the conventional Mott transition that appears as a clear first-order transition at low temperatures. We suggest that they are due to the unconventional metal-insulator fluctuations emerging around the disordered Mott transition in analogy to the slowly fluctuating spin phase, or Griffiths phase, realized in Ising spin systems with disordered lattices.

Purpose: In Japan, transabdominal preperitoneal (TAPP) inguinal hernia repair is performed by firmly pulling the peritoneum inwards to lift it from the underlying deep layer of subperitoneal fascia. It decreases the postoperative pain and discomfort in the inguinal area. The aim of this study was to evaluate the feasibility of the sandwich approach, which is a new technique for creating a preperitoneal space., Methods: The operation was performed via the sandwich approach. We made sure to protect the preperitoneal fascia areolar layer when making the preperitoneal space., Results: We performed TAPP in 745 patients (876 hernias) treated between October 2006 and April 2015 at Himeji Medical Center and Kurashiki Central Hospital. Before October 2010, we did not use the sandwich approach, and recurrence was observed in three patients. From October 2010, we always used the sandwich approach and never experienced any cases of recurrence. Clavien-Dindo classification Grade 3 or higher postoperative complications occurred in 6 patients (0.8%) between October 2006 and April 2015. Mesh-related ileus was the most frequently observed morbidity. There were no cases of vas differentia or spermatic vessel injury, postoperative chronic pain, or urinary retention., Conclusion: The sandwich approach is feasible as another standard dissective procedure for TAPP.