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Internal conversion electrons from the decay of 148Ce and 148mPr have been measured with a Si(Li) detector. The radioactive sources were produced by the thermal neutron-induced fission of 235U, followed by an on-line mass separation. K- and L-conversion electrons of the isomeric transition from 148mPr were newly observed at 34.6 and 70.8 keV, respectively. The M3 multipolarity was assigned to this transition from the experimental conversion coefficients, and, consequently, the 76.8 keV isomeric level was found to be a 4- state. Parities of some excited levels in 148Pr were also deduced. [ABSTRACT FROM AUTHOR]

Background: Dialysis patients are susceptible to developing severe coronavirus disease 2019 (COVID-19) due to hypoimmunity. Antibody titers against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) after the primary vaccinations are lower in hemodialysis (HD) patients than in healthy individuals. This study aimed to evaluate the effect of a SARS-CoV-2 booster vaccination in HD and peritoneal dialysis (PD) patients based on antibody titers and cellular and humoral immunity., Methods: Participants of the control, HD, and PD groups were recruited from 12 facilities. SARS-CoV-2 antigen-specific cytokine and IgG-antibody levels were measured. Regulatory T cells and memory B cells were counted using flow cytometry at 6 months after primary vaccination with BNT162b2 and 3 weeks after the booster vaccination in HD and PD patients and compared with those of a control group., Results: Booster vaccination significantly enhanced the levels of antibodies, cytokines, and memory B cells in three groups. The HD group showed significantly higher levels of IgG-antibodies, IL-1β, IL-2, IL-4, IL-17, and memory B cells than those in the control group at 3 weeks after the booster dose. The PD group tended to show similar trends to HD patients but had similar levels of IgG-antibodies, cytokines, and memory B cells to the control group., Conclusions: HD patients had significantly stronger cellular and humoral immune responses than the control 3 weeks after the booster dose. Our findings will help in developing better COVID-19 vaccination strategies for HD and PD patients., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Coronavirus disease 2019 (COVID-19) following primary immunization (breakthrough infection) has been reported in hemodialysis patients; however, their post-infection immune status remains unclear. We evaluated the humoral and cellular immunity of hemodialysis patients after breakthrough infection. Hemodialysis patients who had received primary immunization against COVID-19 at least six months prior to the study but developed mild/moderate COVID-19 before a booster dose (breakthrough infection group) and hemodialysis patients who were not infected with COVID-19 but received a booster dose (booster immunization group) were recruited. In both groups, SARS-CoV-2 antigen-specific cytokines and IgG levels were measured three weeks after infection or three weeks after receiving a booster dose. Memory T and B cells were also counted in the breakthrough infection group using flow cytometry three weeks after infection. Significantly higher SARS-CoV-2 antigen-specific IgG, IFN-γ, IL-5, TNF-α, and IL-6 levels occurred in the breakthrough infection group compared to the booster immunization group ( p = 0.013, 0.039, 0.024, 0.017, and 0.039, respectively). The SARS-CoV-2 antigen-specific IgG and cytokine levels were not significantly different between the two groups. The breakthrough infection group had significantly higher percentages of central and effector memory T cells and regulatory T cells than the comparison group ( p = 0.008, 0.031, and 0.026, respectively). Breakthrough infections may induce stronger cellular and humoral immune responses than booster immunizations in hemodialysis patients.

A COVID-19 patient surge in Japan from July to September 2021 caused a mismatch between patient severity and bed types because hospital beds were fully occupied and patient referrals between hospitals stagnated. Japan's predominantly private healthcare system lacks effective mechanisms to coordinate healthcare providers to address the mismatch. To address the surge, in August 2021, Tokyo Saiseikai Central Hospital started a scheme to exchange patients with other hospitals to mitigate the mismatch. In this article, we outline a retrospective observational study using medical records from a tertiary care medical center that treated severe COVID-19 cases. We describe daily patient admissions to our hospital's COVID-19 beds from July to September 2021, and compared the moving average of daily admissions before and after the exchange scheme was introduced. Bed occupancy reached nearly 100% in late July when the patient surge began and continued to exceed 100% in August when the surge peaked. However, the average daily admission did not decrease in August compared with July: the median daily admission (25th to 75th percentile) during each period was 2 (1 to 2.5) in late July and 3 (2 to 4) in August. The number of patients referred in from secondary care hospitals and the number of patients referred out was balanced in August. During the patient surge, the exchange scheme enabled the hospital to maintain and even increase the number of new admissions despite the bed shortage. Coordinating patient referrals in both directions simultaneously, rather than the usual 1-way transfer, can mitigate such mismatches.

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT ® .COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.

Introduction: Little research has examined the effects of anti-vascular endothelial growth factor therapy on subfoveal choroidal thickness (SCT), choroidal blood flow, aqueous flare, and humor levels of growth and inflammatory factors in patients with macular edema due to central retinal vein occlusion (CRVO)., Methods: In 58 patients with macular edema due to CRVO treated by intravitreal ranibizumab injection (IRI), we retrospectively assessed best-corrected visual acuity (BCVA, assessed as the logarithm of the minimum angle of resolution [logMAR]), 8 aqueous factors (by suspension array), mean blur rate (MBR; estimated by laser speckle flowgraphy as a measure of choroidal blood flow), aqueous flare (with a laser flare meter), and SCT and central macular thickness (CMT; by optical coherence tomography)., Results: After 4 weeks, IRI resulted in a significant improvement in BCVA and CMT and a significant reduction in SCT, choroidal MBR, and aqueous flare. SCT was significantly positively correlated with placental growth factor and significantly negatively correlated with platelet-derived growth factor-AA, and change in SCT was significantly negatively correlated with change in BCVA (logMAR). Aqueous flare was significantly negatively correlated with SCT., Conclusion: Growth and inflammatory factors may be associated with SCT, and changes in SCT may be associated with changes in BCVA after IRI to treat macular edema due to CRVO., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Dialysis patients are predisposed to severe disease and have a high mortality rate in coronavirus disease 2019 (COVID-19) due to their comorbidities and immunocompromised conditions. Therefore, dialysis patients should be prioritized for vaccination. This study aimed to examine how long the effects of the vaccine are maintained and what factors affect antibody titers., Methods: Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (Control group), receiving two doses of BNT162b2 vaccine, were recruited through the Japanese Society for Dialysis Therapy (JSDT) Web site in July 2021. Anti-SARS-CoV-2 immunoglobulin (IgG) (SARS-CoV-2 IgG titers) was measured before vaccination, 3 weeks after the first vaccination, 2 weeks after the second vaccination, and 3 months after the second vaccination, and was compared between Control group and HD group. Factors affecting SARS-CoV-2 IgG titers were also examined using multivariable regression analysis and stepwise regression analysis (least AIC). In addition, we compared adverse reactions in Control and HD groups and examined the relationship between adverse reactions and SARS-CoV-2 IgG titers., Results: Our study enrolled 123 participants in the Control group (62.6% men, median age 67.0 years) and 206 patients in the HD group (64.1% men, median age 66.4 years). HD group had significantly lower SARS-CoV-2 IgG titers at 3 weeks after the first vaccination ( p  < 0.0001), 2 weeks after second vaccination ( p  = 0.0002), and 3 months after the second vaccination ( p  = 0.045) than Control group. However, the reduction rate of SARS-CoV-2 IgG titers between 2 weeks and 3 months after the second vaccination was significantly smaller in HD group than in Control ( p  = 0.048). Stepwise regression analysis revealed that dialysis time was identified as the significant independent factors for SARS-CoV-2 IgG titers at 2 weeks after the second vaccination in HD group ( p  = 0.002) and longer dialysis time resulted in higher maximum antibody titers. The incidences of fever and nausea after the second vaccination were significantly higher in the HD group ( p  = 0.039 and p  = 0.020). Antibody titers in those with fever were significantly higher than those without fever in both groups (HD: p  = 0.0383, Control: p  = 0.0096)., Conclusion: HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

Elegantin and angustatin, which were isolated from the snake venoms of Protobothrops elegans and Dendroaspis angusticeps, markedly inhibit binding between platelet integrins and fibrinogen via the Arg-Gly-Asp (RGD) sequence. Angustatin, which is a three-finger toxin containing the RGD sequence, inhibits platelet aggregation almost ten times more strongly than disintegrin isolated from the venoms of Viperidae and Crotalidae. The RGD sequences of both polypeptides are located at the top of hairpin loops, and the composition of the RGD loop is very important for binding to integrin. We investigated the effects of synthetic RGD loop peptides from angustatin and elegantin on ADP- or collagen-induced platelet aggregation and αIIbβ3-fibrinogen binding. Synthetic angustatin (PRGDMP)-type peptides inhibited platelet aggregation more strongly than elegantin (ARGDDX)-type peptides. In particular, the cyclic angustatin peptide (CPRGDMPC) inhibited ADP- and collagen-induced platelet aggregation at least 10-50 times more strongly than the other peptides. The cyclic angustatin peptide (CPRGDMPC) was also the strongest inhibitor of binding between αIIbβ3 and fibrinogen, the IC 50 of this peptide was approximately 2.58μM. Regarding the inhibition of binding between αIIbβ3 and fibrinogen, CPRGDMPC demonstrated a stronger inhibitory and more stable effect in the presence of Mg 2+ than in the presence of Ca 2+ ., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Snake venom metalloproteinases (SVMP) are widely distributed among the venoms of Crotalinae and Viperidae, and are organized into three classes (P-I, P-II and P-III) according to their size and domain structure. P-I SVMP are the smallest SVMP, as they only have a metalloproteinase (M) domain. P-II SVMP contain a disintegrin-like (D) domain, which is connected by a short spacer region to the carboxyl terminus of the M domain. P-III SVMP contain a cysteine-rich (C) domain, which is attached to the carboxyl terminus of the D domain. Some SVMP exhibit hemorrhagic activity, whereas others do not. In addition, SVMP display fibrinolytic/fibrinogenolytic (FL) activity, and the physiological functions of SVMP are controlled by their structures. Furthermore, these proteinases also demonstrate fibrinogenolytic and proteolytic activity against synthetic substrates for matrix metalloproteinases and ADAM (a disintegrin and metalloproteinase). This article describes the structures and FL, hemorrhagic, and platelet aggregation-inhibiting activity of SVMP derived from Protobothrops snake venom that was collected in Japan.

Arg-Gly-Asp (RGD) mimics were synthesized and their anti-platelet activity was evaluated. A concise method was developed for the synthesis of the target compounds from dehydroepiandrosterone and Wieland-Miescher and Hajos-Parrish ketones, which are suitable for readily available platform. Among the synthesized compounds, the perhydronaphthalene framework with a 3-(4-piperidinyl)propoxyl structure 3e possessed the highest anti-aggregative activity. The IC 50 values of 3e were 0.91 mM (ADP initiation) and 0.54 mM (collagen initiation).

We herein identified two high molecular mass metalloproteinases, named SV-PAD-2 and HR-Ele-1, in the venom of Protobothrops elegans. HR-Ele-1 appeared as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) regard under reducing and non-reducing conditions, and the molecular mass of this protease was approximately 60 kDa under reducing conditions. On the other hand, the molecular masses of SV-PAD-2 on SDS-PAGE were 110 kDa under the non-reducing condition and 52 kDa under the reducing condition. These SVMPs exhibited fibrinogenolytic and enzymatic activities against synthetic substrates for matrix metalloproteinases (MMPs) and the insulin B-chain, and were both inhibited by EDTA. SV-PAD-2 inhibited ADP- and collagen-induced platelet aggregation, with IC50 values of 240 nM and 185 nM, respectively. HR-Ele-1 exhibited hemorrhagic activity, and its minimum hemorrhagic dose (MHD) was 0.05 μg in the guinea pig., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Angustatin and H-toxin TA2 were purified from unfractionated Dendroaspis angusticeps venom (0.3 g) using S-Sepharose fast flow column chromatography, gelfiltration on a Sephadex G-50 column, and reverse-phase HPLC. The purified materials strongly inhibited ADP-induced platelet aggregation. The primary structure of angustatin was determined by the Edman degradation of peptides derived from digestions with endopeptidese Arg-C and α-chymotrypsin. Angustatin, which was composed of 59 amino acid residues and an RGD sequence, was identified as a short-length inhibitor similar to mambin, dendroaspin, echistatin, and eristicophin. Angustatin shared 83%, 17%, and 15% homologies with mambin, eristicophin, and echistatin, respectively. On the other hand, H-toxin TA2 did not conserve the RGD sequence in its structure; it was replaced for the Glu-Met-Leu sequence. Furthermore, the amino acid sequence of H-toxin TA2 corresponded to toxin TA2, excluding the amino acid residue of His28Arg., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A low molecular weight metalloproteinase, named PT-H₂ protease, with fibrinolytic activity, was purified from the venom of Protobothrops tokarensis (Tokara-habu) by gel-filtration using Sephadex G-100, and ion-exchange chromatographies using CM-Sepharose Fast Flow and Mono S HR 5/5. By this procedure, about 85 mg of purified protein were obtained from 1.0 g of P. tokarensis venom. The purified protein showed a single protein band with a molecular weight of about 22.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. The pI of purified protein showed a single band of 6.8. This proteinase showed a strong fibrinolytic activity. Further, this proteinase showed fibrinogenase activity and proteolytic activity against synthetic substrates for matrix metalloproteinase, ADAM-17, and TACE (tumor necrosis factor converting enzyme). These proteolytic activities were inhibited by metalloproteinase inhibitors such as EDTA. PT-H₂ protease consisted of 201 amino acid residues and had a calculated molecular weight of 22,994.7 Da. This protein showed conservation of the Zn²⁺-binding HEXXHXXGXXHD sequence. PT-H₂ protease showed high homology from 51.7 to 99.5% with amino acid sequences of other snake venom metalloproteinases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)