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Yoshiyuki Morishita1, Minami Watanabe1, Shiho Hanawa1, Osamu Iimura2, Sadao Tsunematsu3, Kenichi Ishibashi4, Eiji Kusano11Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan; 2Kumakura Clinic, Tochigi, Japan; 3Yuki Clinic, Ibaragi, Japan; 4Department of Medical Physiology, Meiji Pharmaceutical University, Tokyo, JapanObjective: The long-term effects of aliskiren in hypertensive hemodialysis patients remain to be elucidated.Design: In this post hoc analysis, we followed up 25 hypertensive hemodialysis patients who completed 8-week aliskiren treatment in a previous study for 20 months to investigate the blood pressure-lowering effect and inhibitory effect on the renin-angiotensin-aldosterone system.Results: Among the 25 patients, eleven patients continued with aliskiren treatment. Blood pressure (± standard deviation) decreased from 175 ± 18/80 ± 11 mmHg at baseline to 156 ± 20/76 ± 9 mmHg at month 20. Plasma renin activity, angiotensin I, and angiotensin II decreased from baseline to month 20 (plasma renin activity (ng/mL/h): 2.3 ± 2.6 to 0.3 ± 0.4 (P < 0.05), angiotensin I (pg/mL): 909.1 ± 902.5 to 41.5 ± 14.8 (P < 0.05), angiotensin II (pg/mL): 41.5 ± 45.8 to 11.0 ± 4.9 (P < 0.05).Conclusion: Long-term treatment with aliskiren provides effective blood pressure lowering and inhibition of the renin-angiotensin-aldosterone system, which are sustained over 20 months in hypertensive hemodialysis patients.Keywords: aliskiren, blood pressure, renin, angiotensin, aldosterone, hemodialysis patients, long-term effects

Dry-wound superconducting solenoid offers a good manufacturability of high current density magnet but occasionally suffers from premature quenches triggered by small heat generated within the magnet. Principal source of heat is thought to be conductor motion induced frictional heating and/or filler material fracture released energy in windings. This paper describes stress analysis, training performance and their relation for both the large bore and the small bore magnets constructed and tested to establish stability of the dry-wound superconducting solenoid. The results suggested that conductor motion took place even though radial stress in the magnet was still compressive and a conductor was expected in its original position. They also suggested that same stress condition in both large and small bore magnets triggered premature quenches even though they have difference in major specification.

We applied a new solid state bonding technique to the joints of the forced-cooled superconducting poloidal coils for LHD. The NbTi/Cu wires of the cable-in-conduit(CIC) conductors were joined superconductively by this technique to realize the low electrical resistance and compactness. We make several joint samples and study the joint condition among the NbTi filaments. By the Scanning Electron Microscope (SEM) we make sure that the filaments are joined with very narrow gaps. We measure the magnetization of the joint using Superconducting Quantum Interference Device and estimate the effective diameter of the filaments to be about 90[[micro]meter]. This value shows that the joint is magnetically stable by the adiabatic theory.

Stability margin of the Cable-in-Conduit Conductor used under the pulse field is greatly influenced by inter-strand coupling losses and current unbalance with coupling current among strands. The large transverse resistance trades sufficient current transfer among strands for low AC losses. The large stability margin is brought by sufficient current transfer, low AC losses and uniform current distribution. Then we should decide the reasonable value of transverse resistance corresponding to the pulse condition. In this paper, the stability is estimated by the simplified distributed constant circuits simulating unbalanced current, that is transient coupling current, and transfer current among strands. In the non-insulated strands, the inductive voltage occurred during charging in a twisted area of half pitch must be enough lower than normal voltage of local quench at the limiting current. This paper also shows that the short twisted pitch and long cables about 1000m give not only low AC losses hut also uniform current distribution during charging for insulated strands.

A single cooldown test of an Inner Vertical (IV) field coil for the Large Helical Device (LHD) was started on February 1 of 1995, and the superconducting transition of the coil was confirmed on February 23. The coil is a forced-flow type using a cable-in-conduit (CIC) conductor and weighing about 16 tons. The total cooldown time was about 250 hours, not including suspended time. Pressure drop characteristics were measured during the cooldown, and the same results were obtained as the R&D coil previously tested. The cooldown time could be reduced by indirect cooling using stainless steel sleeves with cooling pipes. The indirect cooling is effective for the CIC conductor which has no subchannel because otherwise an adequate mass flow cannot be obtained due to a high pressure drop in the high temperature region. The temperature distribution in the vertical direction was also examined during the indirect cooling.

A solid-state bonding method for fabricating cable-in-conduit conductor joints has been developed with respect to the specifications of the poloidal coil of the Large Helical Device. The technique, which has been applied to niobium-tin filaments, reduces the quench current in a joint to one-third of the conductor critical current. It also reduces the space requirement and magnetic field errors.

The stability and limiting current of a NbTi forced-cooled superconducting coil have been investigated experimentally and analytically at the subcooled condition below 4.5 K. The test coil was wound in a one layer solenoid from a cable-in-conduit type conductor of critical current of 5.1 kA at 4.2 K and 6.5 T, whose total length was 10 m. It was installed in the bore of a back-up superconducting magnet that provided field 8 T at the test coil. The stability margin of the coil as a function of normalized current (transport current/critical current) were measured. The results are compared with the formula proposed by Dresner and reported to predictions of stability margin and limiting current at subcooled condition below 4.5 K.

This study compared the associations among motor competence, health-related fitness, and physical activity measured by gold standard and field-based methods in children. A total of 248 first-grade children (153 boys) aged 6-7 years participated in the study. Motor competence was assessed using the Test of Gross Motor Development, Second Edition (TGMD -2). Gold standard measures were percent body fat using dual-energy X-ray absorptiometry, peak oxygen uptake per weight using a gas analyser, and moderate-to-vigorous physical activity using accelerometers. Field-based measures were body mass index, maximum speed during progressive running on a treadmill, and a physical activity questionnaire. Multiple regression analysis adjusted for age and sex was used to examine the associations of motor competence with one of the health-related variables and compared differences by measurement method. The results indicated that field-based measures models showed lower associations (R 2  = 0.02-0.17) than the gold standard (R 2  = 0.21-0.27) and lower standardised regression coefficients for sex and motor competence, except for maximum speed. In conclusion, gold standard measures resulted in stronger associations between motor competence, and health-related fitness and physical activity in children. Examining the contribution of motor competence in children's health using field-based tests can underestimate it.

Syncytiotrophoblasts, which are formed by the fusion of villous cytotrophoblasts, play an essential role in maintaining a successful pregnancy. Secreted protein acidic and rich in cysteine (SPARC) is a non-structural Ca 2+ -binding extracellular matrix glycoprotein involved in tissue remodeling and cell proliferation, differentiation, and migration. Previous studies have revealed that SPARC is expressed in villous and extravillous cytotrophoblasts in the first trimester and that RNA interference targeted at SPARC significantly inhibited invasion of human extravillous trophoblast HTR8/SVneo cells. However, the involvement of SPARC in cytotrophoblast fusion remains unknown. This study aimed to investigate the role of SPARC in cytotrophoblast fusion, using the BeWo choriocarcinoma cell line as a model of villous cytotrophoblasts. Immunohistochemical analysis was conducted to assess SPARC expression in normal human placentas using placental tissues obtained during the first and third trimesters of pregnancy. We investigated the effects of SPARC knockdown on trophoblast differentiation markers and cell fusion in BeWo cells using small interfering RNA. Immunohistochemical analysis revealed that SPARC expression was high in the early gestational chorionic villi and low in the late gestational chorionic villi. SPARC knockdown increased the expressions of human chorionic gonadotropin and Ovo-like transcriptional repressor 1; however, glial cells missing transcription factor 1, syncytin-1, and syncytin-2 showed no significant changes. The assessment revealed that SPARC knockdown significantly enhanced cell fusion compared to the non-silencing control. Our data suggest that SPARC plays a vital role in regulating trophoblast fusion and differentiation during placental development., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

The risk of dysphagia and/or aspiration is determined using screening tests, such as the repeated saliva swallowing test and modified water swallowing test, which evaluate cued swallowing. However, humans masticate and swallow foods with various consistencies, forms, and amounts, without conscious awareness. Therefore, this study aimed to examine the difference in the behavior of masticatory and swallowing muscles during spontaneous versus cued swallowing through a series of mastication and swallowing processes by evaluating surface electromyogram (sEMG) signals. The effect of the consistency and amount of food on the behavior of these muscles was also investigated. The sEMG recordings of the masseter muscles and anterior belly of the digastric muscle for 12 subjects, and genioglossus muscle for 5 subjects were obtained. The genioglossus activity was recorded using custom-made ball electrodes. The test foods were cookies and tofu, in amounts of 2 g and 4 g. The normalized muscle activity (integrated EMG), duration of the muscle activity, initial activation timepoint of each muscle, and total duration of swallowing were compared among four conditions. The activity of each muscle was significantly higher during the swallowing of cookies than tofu, for 4 g vs 2 g, and for cued versus spontaneous swallowing. The duration of each muscle activity, initial activation timepoint, and total duration of swallowing were significantly longer for cookies versus tofu, for 4 g vs 2 g, and for spontaneous versus cued swallowing. These results suggest that the behavior of the masticatory and swallowing muscles is affected by cued swallowing and by the consistency and amount of food., (© 2023. The Author(s).)

Background: Expression of programmed death ligand-1 (PD-L1) is related to the prognosis of many solid malignancies, including oral squamous cell carcinoma (OSCC), but the mechanism of PD-L1 induction remains obscure. In this study, we examined the expression of PD-L1 and partial epithelial-mesenchymal transition (pEMT) induced by bacterial lipopolysaccharide (LPS) in OSCC., Methods: The expression of Toll-like receptor 4 (TLR4) recognizing LPS in OSCC cell lines was analyzed. Moreover, the induction of PD-L1 expression by Porphyromonas gingivalis ( P.g ) or Escherichia coli ( E. coli ) LPS and EMT was analyzed by western blotting and RT-PCR. Morphology, proliferation, migration, and invasion capacities were examined upon addition of LPS. PD-L1 within EXOs was examined., Results: PD-L1 expression and pEMT induced by LPS of P.g or E. coli in TLR4-expressing OSCC cell lines were observed. Addition of LPS did not change migration, proliferation, or cell morphology, but increased invasive ability. Moreover, higher expression of PD-L1 was observed in OSCC EXOs with LPS., Conclusion: Oral bacterial LPS is involved in enhanced invasive potential in OSCC cells, causing PD-L1 expression and induction of pEMT. The enhancement of PD-L1 expression after addition of LPS may be mediated by EXOs.

Background: Antiviral and antibody therapies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being recommended for high-risk patients, but the potential for the development of multidrug-resistant mutations in immunocompromised patients is unclear., Methods: To investigate the treatment course in cases of prolonged viral shedding in an immunocompromised patient with SARS-CoV-2 infection, we conducted longitudinal measurements of laboratory tests, chest computed tomography (CT) image evaluations, antibody titers, and antigen levels in nasopharyngeal swabs. Furthermore, we performed whole-genome sequencing and digital PCR analysis to examine the mechanisms of drug resistance., Findings: We present a case of a 65-year-old man with a history of malignant lymphoma who was treated with multiple antiviral and antibody therapies, including sotrovimab, remdesivir, paxlovid (nirmatrelvir/ritonavir), and molnupiravir. Initially, viral antigen levels decreased after treatments. However, after the virus rebounded, the patient showed no virologic response. The viral genome analysis revealed a single Omicron subvariant (BA.1.1), which evolved within the host during the disease progression. The viruses had acquired multiple resistance mutations to nirmatrelvir (3 chymotrypsin-like protease [3CLpro] E166 A/V), sotrovimab (spike P337L and E340K), and remdesivir (RNA-dependent RNA polymerase [RdRp] V166L)., Conclusions: Our results indicate that viruses with multidrug-resistant mutations and survival fitness persist in the infected subpopulation after drug selection pressure., Funding: This study was supported by the JSPS KAKENHI Early-Career Scientists 18K16292 (Y.H.), Grant-in-Aid for Scientific Research (B) 20H03668 and 23H02955 (Y.H.), the YASUDA Medical Foundation (Y.H.), the Uehara Memorial Foundation (Y.H.), the Takeda Science Foundation (Y.H.), and Kato Memorial Bioscience Foundation (Y.H.)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)