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Yuichi Kasai,1 Takaya Kato,2 Tadashi Inaba,3 Sotaro Baba,3 Permsak Paholpak,1 Taweechok Wisanuyotin,1 Weerachai Kosuwon,1 Hirohito Hirata,4 Tadatsugu Morimoto4 1Department of Orthopaedics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 2Graduate School of Regional Innovation Studies, Tsu, Japan; 3Department of Mechanical Engineering, Graduate School of Engineering, Mie University, Tsu, Japan; 4Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, JapanCorrespondence: Yuichi Kasai, Email ykasai55@gmail.comIntroduction: Although kissing spine syndrome in the lumbar spinal region is a relatively common condition in older adults, no study examining its biomechanical characteristics has been reported. We hypothesized that kissing of the spinous processes during extension causes an increase in the flexural rigidity of the spine and significantly limits the deformation behavior of extension, which in turn might cause lower back pain.Methods: Three test models (human cadavers A, B, and C) were prepared by removing supraspinal/interspinous ligaments between L4 and L5. The dental resin was attached to the cephalocaudal spinous process so that the spinous processes between L4 and L5 were almost in contact with each other to simulate the condition of a kissing spine. The flexion-extension direction’s torque–range-of-motion (torque–ROM) curve was generated with a six-axis material tester for biomechanical measurements.Results: In all three models, the maximum ROMs at the time of extension were smaller than those at the time of flexion, and no sudden increase in torque was observed during extension.Conclusion: The results indicated no apparent biomechanical effects of kissing between the spinous processes, suggesting that the contact between the spinous processes has little involvement in the onset of lower back pain.Keywords: kissing spine syndrome, Baastrup’s disease, biomechanical study, low back pain, lumbar spine

Yoko Tanino,1,2,* Keisuke Nishioka,1,* Chie Yamamoto,2,* Yohei Watanabe,1,3 Tomo Daidoji,1,4 Masataka Kawamoto,5 Sayaka Uda,6 Shoko Kirito,1 Yuta Nakagawa,2 Yu Kasamatsu,2 Yoshiyuki Kawahara,7 Yuri Sakai,7 Shuji Nobori,8 Tohru Inaba,2 Bon Ota,9 Naohisa Fujita,7 Atsushi Hoshino,10 Yoko Nukui,2 Takaaki Nakaya1 1Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3JST, MIRAI, Tokyo, Japan; 4School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan; 5Department of Forensics Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 6Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 7Kyoto Prefectural Institute of Public Health and Environment, Kyoto, Japan; 8Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; 9Department of Emergency Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 10Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan*These authors contributed equally to this workCorrespondence: Takaaki Nakaya; Yohei Watanabe, Department of Infectious Diseases, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan, Tel +81-75-251-5325, Fax +81-75-251-5328, Email tnakaya@koto.kpu-m.ac.jp; nabe@koto.kpu-m.ac.jpIntroduction: Various therapeutic agents are being developed for the treatment of coronavirus disease 2019 (COVID-19). Therefore, it is crucial to accumulate information regarding the features of drug-resistant viruses to these antiviral drugs.Methods: We investigated the emergence of dual-drug resistance in a kidney transplant recipient who received sotrovimab (from day 0) and remdesivir (RDV) (from day 8 to day 17). We sequenced the whole viral genomes from nasopharyngeal swabs taken on day 0 and seven points after starting treatment (on days 12, 19, 23, 37, 43, 48, and 58). The genetic traits of the wild-type (day 0) and descendant viruses (after day 12) were determined by comparing the genomes with those of a Wuhan strain and the day 0 wild-type strain, respectively. Three viral isolates (from samples collected on days 0, 23, and 37) were investigated for their escape ability and growth kinetics in vitro.Results: The sotrovimab resistant mutation (S:E340K) and the RDV resistant mutation RdRp:V792I (nt: G15814A) emerged within 12 days (day 12) and 11 days (day 19) after the treatment, respectively. The day 23 isolate harboring S:E340K/RdRp:V791I was resistant to both sotrovimab and RDV, showing 364- and 2.73-fold higher resistance respectively, compared with the wild-type. Moreover, compared with the day 23 isolate, the day 37 isolate accumulated multiple additional mutations and had a higher level of resistance to both drugs.Conclusion: Drug-resistant variants with double mutations (S:E340K/RdRp:V791I) became dominant within 23 days after starting treatment, suggesting that even a combination therapy involving sotrovimab and RDV, dual-drug resistant viruses may emerge rapidly in immunocompromised patients. The dual-resistant variants had lower virus yields than those of the wild-type virus in vitro, suggesting that they paid a fitness cost.Keywords: SARS-CoV-2, sotrovimab, remdesivir, drug resistance, immunosuppression therapy

In April 2019, baobab (Adansonia digitata L.) seedlings from Thailand, exhibiting galls on the roots, were intercepted during an import plant quarantine inspection at Chubu Centrair International Airport, Japan. Root-knot nematodes (RKNs) were extracted from the galled roots of baobab seedlings and identified by morphological, morphometrical and molecular methods as the guava root-knot nematode, Meloidogyne enterolobii Yang & Eisenback. The morphology and morphometrics of the intercepted population were similar to those of the original and subsequent descriptions of M. enterolobii. The sequences of D2–D3 of 28S rRNA, mtDNA intergenic COII-16S rRNA and COI genes obtained in this study matched well (99–100% similarity) with each of the gene sequences of M. enterolobii deposited in GenBank. Phylogenetic analysis of these genes revealed that the intercepted population clustered with M. enterolobii and clearly differed from other RKN species. To the best of our knowledge, this is the first report of M. enterolobii from baobab.

Akio Onishi,1 Yayoi Matsumura-Kimoto,1,2 Shinsuke Mizutani,1 Taku Tsukamoto,1 Takahiro Fujino,1 Akihiro Miyashita,1,3 Daichi Nishiyama,4 Kazuho Shimura,5 Hiroto Kaneko,5 Eri Kawata,6 Ryoichi Takahashi,7 Tsutomu Kobayashi,1,8 Hitoji Uchiyama,8 Nobuhiko Uoshima,3 Yoko Nukui,9 Yuji Shimura,1 Tohru Inaba,9 Junya Kuroda1 1Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Hematology, Japan Community Health Care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Japan; 3Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan; 4Department of Hematology, Fukuchiyama City Hospital, Fukuchiyama, Japan; 5Department of Hematology, Aiseikai Yamashina Hospital, Kyoto, Japan; 6Department of Hematology, Matsushita Memorial Hospital, Moriguchi, Japan; 7Department of Hematology, Omihachiman Community Medical Center, Omihachiman, Japan; 8Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan; 9Division of Infection Control & Molecular Laboratory Medicine, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, JapanCorrespondence: Junya Kuroda, Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan, Tel +81-75-251-5740, Fax +81-75-251-5743, Email junkuro@koto.kpu-m.ac.jpBackground and Purpose: Anti-CD20 monoclonal antibodies (MoAbs), rituximab (RIT), and obinutuzumab (OBZ) are the central components of immunochemotherapy for B-cell lymphoma (BCL). However, these agents potentially cause B-cell depletion, resulting in the impairment of antibody (Ab) production. During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the optimal prediction of Ab response against anti–SARS-CoV-2 vaccination is critically important in patients with BCL treated by B-cell depletion therapeutics to prevent coronavirus disease 2019 (COVID-19).Patients and Methods: We investigated the effect of using RIT and/or OBZ on the Ab response in 131 patients with various types of BCL who received the second SARS-CoV-2 mRNA vaccine either after, during, or before immunochemotherapy containing B-cell–depleting moiety between June and November 2021 at seven institutes belonging to the Kyoto Clinical Hematology Study Group. The SARS-Cov-2 neutralizing Ab (nAb) was measured from 14 to 207 days after the second vaccination dose using the iFlash3000 automatic analyzer and the iFlash-2019-nCoV Nab kit.Results: Among 86 patients who received the vaccine within 12 months after B-cell depletion therapy, 8 (9.3%) were seropositive. In 30 patients who received the vaccine after 12 months from B-cell depletion therapy, 22 (73%) were seropositive. In 15 patients who were subjected to B-cell depletion therapy after vaccination, 2 (13%) were seropositive. The multivariate analysis indicated that an interval of 12 months between B-cell depletion therapy and the subsequent vaccination was significantly associated with effective Ab production. Receiver operating characteristic curve analysis identified the optimal threshold period after anti-CD20 MoAb treatment, which determines the seropositivity against SARS-CoV-2, to be 342 days.Conclusion: The use of anti-CD20 MoAb within 12 months before vaccination is a critical risk for poor Ab response against anti–SARS-CoV-2 vaccination in patients with BCL.Keywords: COVID-19, vaccine, B-cell lymphoma, anti-CD20 monoclonal antibody

Chika Maekura,1 Ayako Muramatsu,1 Hiroaki Nagata,1 Haruya Okamoto,1 Akio Onishi,1 Daishi Kato,1 Reiko Isa,1 Takahiro Fujino,1 Taku Tsukamoto,1 Shinsuke Mizutani,1 Yuji Shimura,1,2 Tsutomu Kobayashi,1 Keita Okumura,3 Tohru Inaba,4 Yoko Nukui,4 Junya Kuroda1 1Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Blood Transfusion, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Faculty of Clinical Laboratory, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan; 4Department of Infection Control & Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, JapanCorrespondence: Junya Kuroda, Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan, Tel +81 75 251 5740, Fax +81 75 251 5743, Email junkuro@koto.kpu-m.ac.jpAbstract: Previous studies have demonstrated that the appropriate production of serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) neutralizing antibody (nAb) plays a critical role in the recovery from coronavirus disease 2019 (COVID-19); however, the role of nAb production in the recovery from a flare-up of chronic immune thrombocytopenia (ITP) has been unknown. We here report the first retrospectively investigated case of serum anti-SARS-Cov-2 nAb production during chronic ITP flare-up triggered by COVID-19. A 79-year-old woman with a history of corticosteroid-refractory ITP visited our hospital complaining of fever, cough, and sore throat for 4 days. Although chronic ITP was controlled by 12.5 mg of eltrombopag (EPAG) every other day, laboratory tests showed a decreased peripheral blood platelet count of 15.0 × 109/L, which indicated worsening thrombocytopenia. Meanwhile, PCR testing of a nasopharyngeal swab revealed that the patient was positive for SARS-Cov-2, and a computed tomography scan revealed bilateral pneumonia. On the basis of the flare-up of chronic ITP associated with COVID-19 pneumonia which was determined as a moderately severe status according to the WHO clinical progression scale, intravenous immunoglobulin therapy for 5 days (days 0– 4) and antiviral therapy were added on top of EPAG, which only resulted in a transient increase in the platelet count for several days. After decreasing to 8.0 × 109/L on day 13, the platelet count increased from day 16, coinciding with a positive detection for serum nAb against SARS-Cov-2. Although the increased dose up to 50 mg/day of EPAG was challenged during the clinical course, rapid dose reduction did not cause another relapse. In addition, no thrombotic or bleeding event was seen. These collectively suggest the vital role of the production of anti-SARS-Cov-2 nAb and improvement of clinical symptoms for recovery from a flare-up of chronic ITP in our case.Keywords: chronic immune thrombocytopenia, COVID-19, flare, neutralizing antibody

We developed a growth technique that improves the crystallinity and optical properties (photoluminescence intensity and lifetime) of Er-doped Gd2O3 (Er:Gd2O3) on a Si(111) substrate. Deposition of thin (7.5 Å thick) Gd metal on the SiOx-covered surface of the Si(111) substrate prior to the growth of Er:Gd2O3, and the successive, thermally-induced redox reaction gives rise to the solid-phase epitaxy of GdOx on Si, which protects Si from unintentional oxidation and fosters the epitaxial growth of Er:Gd2O3 on it; i.e., GdOx serves as a protection and seed (bifunctional) layer. This technique is promising for developing high-performance optical devices using high-quality rare-earth oxide films grown on Si substrates. [ABSTRACT FROM AUTHOR]

Shinsaku Imashuku1, Ikuyo Ueda2, Tohru Inaba3 1Divisions of Pediatrics and Hematology, Takasago-seibu Hospital, Takasago, Japan; 2Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan Abstract: We report the treatment course of a 29-year-old man who has had unique oscillating FIP1L1-PDGFRA fusion gene-negative hypereosinophilic syndrome (HES) for nearly 6 years. His periodic oscillating pattern of eosinophilia associated with angioedematous soft tissue swelling has shown two to three seasonal peaks (>15,000/µL absolute eosinophil counts [AEC]) a year. Initially, the patient, who was thought to have distinct HES not compatible with previously described cases, did not respond to treatment except for a temporary response to imatinib mesylate. For 6 years, from 2005 to 2010, he was treated with a combination of oral cyclosporine A, suplatast tosilate, and a small dose of prednisolone, which significantly reduced the peak heights of AEC as well as blunting the oscillating patterns. Keywords: hypereosinophilic syndrome, eosinophilia, angioedema, IgM, sIL-2R, treatment, cyclosporin A, suplatast tosilate

The frequent occurrence of glomerular lesions in schistosomiasis patients has been reported, although appropriate animal models for the study of schistosomal glomerulonephritis have not been developed. To analyze the relationship between glomerulonephritis and Schistosoma mansoni infection, gerbils, Meriones unguiculatus, were infected with different number of cercariae and sacrificed at different weeks of post infection. Fifty cercariae were the optimum dose to produce the disease, glomerulonephritis, without early death of the animal. Infected gerbils showed heterogeneous types of glomerular lesions with increased serum creatinine level. Immune complex deposition was not detected at glomeruli of infected gerbils even by means of immunuofluorescence and also by transmission electron microscopy. However, infiltration of mononuclear cells in and around some of the altered glomeruli was observed. Immunohistochemical staining, using monoclonal antibody (HUSM-M.g. 15) specific to gerbils T-cells, revealed significant infiltration of T-cells. These findings suggest that T-cells might be involved in the development of glomerulonephritis. Gerbil could be a useful model to clarify the role of T-cells in the development of glomerulonephritis of schistosomiasis