Search

Background: Although the effectiveness of coronavirus disease 2019 (COVID-19) vaccines is a crucial public health concern, evidence from Western Pacific countries is limited, including Japan. This study aimed to estimate the COVID-19 vaccines effectiveness (VE) against infection during the Delta variant predominance (July-September 2021) in Japan., Methods: We performed a test-negative study using COVID-19 test data of ≥20-year-old residents in four municipalities who were tested in medical institutions between July 1 and September 30, 2021. We extracted COVID-19 test data from healthcare claims data, and the vaccination status at the testing date was ascertained using the Vaccination Record System data. Confirmed positive cases were identified using data from the national system for COVID-19, Health Center Real-time Information-sharing System on COVID-19. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. VE was calculated as (1 - odds ratio) × 100%., Results: This study included 530 positive and 15,650 negative results. Adjusted manufacturer-unspecified VE was 4.1% (95% confidence interval [CI], -36.5-32.6) at 0-13 days after the first dose, 45.2% (95% CI, 13.4-65.3) at ≥14 days after the first dose, 85.2% (95% CI, 69.9-92.7) at 0-13 days after the second dose, and 79.6% (95% CI, 72.6-84.8) at ≥14 days after the second dose. In addition, the VE after the second dose was highest at 14-34 days after the dose (VE, 89.1%; 95% CI, 80.5-93.9)., Conclusions: High real-world effectiveness of COVID-19 vaccines, especially two doses, against infection during the Delta variant predominance in Japan was confirmed., 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 © 2023 Elsevier Ltd. All rights reserved.)

Obesity is a risk factor associated with several lifestyle-related diseases, for example, diabetes, high blood pressure, hyperlipidemia and cancer. Caffeic acid 2-phenylethyl ester (CAPE, 1), a naturally-occurring compound found in various plants and propolis, which exhibits anti-inflammatory, immunomodulatory and cytotoxic activities and inhibits 3T3-L1 differentiation to adipocytes. As part of our efforts to moderate lifestyle-related diseases, we synthesized analogs of 1 and studied their effects on pancreatic lipase activities, lipid absorption, and 3T3-L1 differentiation. We found that catechols 1-4 show inhibitory activities against pancreatic lipase in a dose-dependent manner in vitro. Compounds 1-3 proved to be more potent inhibitors of pancreatic lipase than 5, 6, 8, and 9, which have one hydroxyl group, respectively. Compound 7 has three aromatic hydroxyl groups and restrains greater lipase inhibitory activity than the other compounds. In addition, 7 and 3 significantly suppress a rise in blood triglyceride (TG) levels in mice given corn oil orally. Furthermore, 2 and 3 are more potent at preventing 3T3-L1 differentiation (lipid accumulation) than 1, while 7 is more potent than 3, 8, and 9 in these assays. Compounds 2, 3, and 7 inhibit lipid absorption and accumulation, with new compound 7 being the most potent. These results indicate that 7 may have potential benefits as a health agent with anti-obesity properties., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: A theoretical model, based on fluid dynamics, was developed to measure impression pressure. The purpose of this study was to evaluate the validity of this theoretical model by comparing its theoretical analysis against actual pressure measurements conducted using an impression tray and edentulous oral mucosa analog embedded with pressure sensors., Methods: In the theoretical model, a hollow tube was mounted onto an impression tray by penetrating through the tray. When force was applied to the tray, pressure was produced which then caused the impression material to flow into the hollow tube. Length of impression material which flowed into tube was denoted as l. In the calculation formula for theoretical model, pressure impulse I was expressed as a function of impression flow length l. For actual pressure measurements, four electric pressure sensors were embedded in an experimental edentulous arch. To visually observe and measure length of impression material flow, four transparent silicon tubes were mounted vertically at different positions on tray. During tray seating, impression material flowed into tubes and pressure which caused material flow movement was measured by the embedded sensor at each tube's position., Results: Based on actual pressure measurements under one experimental condition, regression analysis of pressure data acquired from electric sensors yielded the formula, Y=0.056X²+0.124X. Based on theoretical analysis using a particular viscosity value, the numerical formula yielded was Y=0.057X², which resembled that of the regression formula., Significance: Theoretical model presented in this paper augured well for clinical application as an easy and economical means to examine magnitude and distribution of impression pressure by measuring lengths of impression material flow in tubes fixed to impression tray., (Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Initial chondrocyte-silk fibroin interactions are implicated in chondrogenesis when using fibroin as a scaffold for chondrocytes. Here, we focused on integrin-mediated cell-scaffold adhesion and prepared cell adhesive fibroin in which a tandem repeat of the Arg-Gly-Asp-Ser (RGDS) sequence was genetically interfused in the fibroin light chain (L-chain) (L-RGDSx2 fibroin). We investigated the effects of the sequence on chondrocyte adhesion and cartilage synthesis, in comparison to the effects of fibronectin. As the physicochemical surface properties (e.g., wettability and zeta potential) of the fibroin substrate were not affected by the modification, specific cell adhesion to the RGDS predominately changed the chondrocyte adhesive state. This suggestion was also supported by the competitive inhibition of chondrocyte attachment to the L-RGDSx2 fibroin substrate with soluble RGD peptides in the medium. Unlike fibronectin, the expression of RGDS in the fibroin L-chain had no effect on chondrocyte spreading area but enhanced mRNA expression levels of integrins alpha5 and beta1, and aggrecan at 12 h after seeding. Although both the sequence and fibronectin increased cell adhesive force, chondrocytes grown on the fibroin substrate exhibited a peak in the force with time in culture. These results suggested that moderate chondrocyte adhesion to fibroin induced by the RGDS sequence was able to maintain the chondrogenic phenotype and, from the histology findings, the sequence could facilitate chondrogenesis., (2010 Elsevier Ltd. All rights reserved.)

In tissue engineering for cartilage repair using scaffold, initial chondrocyte-material interactions are significantly important for the following cell behaviors such as phenotypic expression and matrix synthesis. Silk fibroin scaffold is considered to be one of the useful materials in/on which chondrocytes can proliferate without dedifferentiating into fibroblast-like cells and can organize a hyaline-like tissue. For the purpose of seeking some useful aspects for designing scaffold, initial adhesive force of chondrocytes to the surface of fibroin substrate was measured by using a lab-made apparatus applying the cantilever beam method. It was found that the adhesive force per unit spreading area of chondrocytes on fibroin substrate had a clear peak between 6 and 12h after seeding. From the results of immunofluorescence staining for actin and vinculin during this period, it could be thought that an immature formation of actin fibers which was uniquely observed at the periphery of cells attaching to fibroin substrate did not contribute to the increase of adhesive force. Results in this study suggested that surface of the fibroin substrate was gradually covered with some substances which inhibit the adhesion during this period. These cell-material interactions have a possibility to be useful information for designing the adhesive performance of scaffold surface in cartilage regeneration.

Background: Our recent study suggested involvement of calpain-induced proteolysis in retinal degeneration and dysfunction in acute ocular hypertensive rats. The purpose of the present study was to determine if an orally available form of calpain inhibitor, ((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), ameliorated retinal degeneration induced by acute hypertension in rats. To help extrapolate the effect of SNJ-1945 from the rat model to the human glaucomatous patient, in vitro inhibition of calpain-induced proteolysis by SNJ-1945 in monkey and human retinal proteins was compared with proteolysis in rat proteins., Methods: Intraocular pressure (IOP) in rats was elevated to 110 mm Hg for 50 min. SNJ-1945 was administrated i.p. or orally before ocular hypertension. Retinal degeneration was evaluated by hematoxylin and eosin (H&E) staining and cell counting. Transcripts for calpains and calpastatin in rat, monkey, and human retinas were measured by quantitative RT-PCR. Calpain activities were determined by casein zymography. Soluble retinal proteins from rat, monkey, and humans were incubated with calcium to activate calpains, with or without SNJ-1945. Proteolysis of calpain substrate alpha-spectrin was analyzed by immunoblotting., Results: Elevated IOP caused retinal degeneration and proteolysis of alpha-spectrin. Both i.p. and oral administration of SNJ-1945 inhibited proteolysis of alpha-spectrin and ameliorated retinal degeneration. Transcript levels for calpain 1 and calpastatin were similar in rat, monkey, and human retinas. Calpain 2 transcript levels were higher in rats compared with monkey and human. Appreciable caseinolytic activities due to calpains were observed in monkey and human retinas. Incubation of retinal soluble proteins with calcium led to proteolysis of alpha-spectrin due to calpains in rat, monkey, and human samples. SNJ-1945 similarly inhibited proteolysis in all species., Conclusion: Our results suggested that orally available calpain inhibitor SNJ-1945 might be a possible candidate drug for testing in preventing progression of glaucomatous retinal degeneration.

Although tribological function is the most important mechanical property of articular cartilage, few studies have examined this function in tissue-engineered cartilage. We investigated changes in the frictional properties of cartilage regenerated from the inoculation of rabbit chondrocytes into fibroin sponge. A reciprocating friction-testing apparatus was used to measure the friction coefficient of the regenerated cartilage under a small load. The specimen was slid against a stainless steel plate in a water vessel filled with physiological saline. The applied load was 0.03 N, the stroke length was 20 mm, and the mean sliding velocity was 0.8 mm/s. The friction coefficient of the regenerated cartilage decreased with increasing cultivation time, because a hydrophilic layer of synthesized extracellular matrix was formed on the fibroin sponge surface. The friction coefficient of the regenerated cartilage was as low as that of natural cartilage in the early stages of the sliding tests, but it increased with increasing duration of sliding owing to exudation of interstitial water from the surface layer.

Silk fibroin (Bombyx mori) was sulfated using chlorosulfonic acid in pyridine. FT-IR spectra showed introduction of sulfate group by this reaction; NMR spectra indicated that sulfation occurred mainly at tyrosine and serine residues. Molecular size decreased and dispersed with sulfation. The molecular weight was estimated in around 20,000 by GPC using protein standards. Amino acid composition suggested that sulfated fibroin came from H-chain of fibroin; the crystal region of fibroin molecule remained in sulfated fibroin. The amount of sulfate groups increased with overall reaction time. The maximum amount was estimated in 1.0 mmol/g by acidimetric titration. Sulfation efficiency was calculated as 66.7%. Blood coagulation was prevented by 0.5 mg of sulfated fibroin in 1 ml of blood, while original fibroin did not show any effect. Anticoagulant activity of sulfated fibroin strongly depends on the amount of sulfate groups introduced. These results indicate that sulfate group introduction results in addition of anticoagulant function to silk fibroin. Sulfated fibroin is a new type of anticoagulant material having a protein backbone.

The influence of sulfonated polyisoprene (SPIP) on coagulation factors and human blood cells was investigated to elucidate and compare its anticoagulant mechanism with that of heparin. While the number of red cells was unaffected, the number of platelets decreased dramatically in the presence of SPIP due to aggregation. Using a synthetic peptide substrate to assay thrombin activity in the presence of its natural inhibitor, antithrombin (AT), we observed no stimulation by SPIP of AT-mediated inhibition. Nevertheless, thrombin cleavage of its natural substrate fibrinogen to fibrin peptide A was slightly inhibited. SPIP altered the electrophoretic mobility of fibrinogen and completely inhibited fibrinogen from clotting. We detected no significant influence of SPIP on factors II, VII, IX, and X, while factor XI and factors V and VIII were only slightly affected. Therefore, the main mechanism of SPIP's anticoagulant activity appears to be a strong interaction with fibrinogen and fibrin monomer, first, to prevent proteolytic conversion of the former to the latter and second, to inhibit polymerization of the fibrin monomer, once formed.

2-Methacryloyloxyethyl phosphorylcholine (MPC) was grafted onto silk fabric in a two-step heterogeneous system through the vinyl bonds of 2-methacryloyloxyethyl isocyanate (MOI) modified on the fabric. First, habutae silk fabric was modified with the MOI monomer in anhydrous dimethyl sulfoxide using di-n-butyltin (IV) dilaurate and hydroquinone at 35 degrees C. The saturated weight gain of modified MOI monomer on the fabric was 7.3 wt% versus the original silk. Second, graft polymerization with MPC onto the MOI modified silk was conducted using 2,2'-azo bis[2-(2-imidazolin-2-yl)propane dihydrochloride] (VA-044) as an azo polymerization initiator. The weight of the grafted MPC eventually gained was about 26.0 wt%. The MOI-modified and MPC-grafted silk fabrics were analyzed by Fourier transform infrared (FT-IR) spectroscopy. To confirm the improved biocompatibility of the silk fabric, platelet adhesion was preliminarily tested measuring lactate dehydrogenase. The number of platelets adhering to polyMPC-grafted silk fabric decreased by about one tenth compared to original and MOI-modified silk after 60 min of contact with human platelet-rich plasma (1.0 x 10(6) platelets cm(-2)).

Arginine vasopressin peptide and messenger RNA expression were examined at the cellular level in the magnocellular and parvocellular neurons in the rat paraventricular nucleus after dehydration and rehydration, employing immunocytochemistry and in situ hybridization histochemistry on the same tissue sections. Most magnocellular vasopressinergic neurons of control animals expressed both vasopressin-like immunoreactivity and messenger RNA. However, neurons negative for vasopressin-like immunoreactivity but expressing messenger RNA were also detected, and their number increased during dehydration. In contrast, almost all of the parvocellular vasopressinergic neurons of dehydrated animals expressed vasopressin messenger RNA alone, with continued increase in their number after rehydration, despite return of the number of magnocellular vasopressinergic neurons to the control level. Vasopressin messenger RNA and corticotropin releasing factor-like immunoreactivity were co-localized in the same parvocellular neurons, and vasopressin-immunoreactive nerve terminals were detected in the external zone of the median eminence. These findings suggest that magno- and parvocellular vasopressinergic neurons are differentially activated during dehydration/rehydration. Osmotic stimuli activate all magnocellular vasopressinergic neurons, but the effect is not simultaneous in all of these neurons. Parvocellular vasopressinergic neurons are also activated by the stress of dehydration which effect appears to last longer than in the magnocellular system.

Sulphonated polyisoprenes (SPIPs) having various molecular weights and sulphonate group contents were synthesized and their anticoagulant activities investigated. Prolongation of blood clotting time, prothrombin time and activated partial thromboplastin time were observed in the presence of SPIPs. The anticoagulant activity in blood was affected mainly by total sulphonate group concentration; however, the molecular weight of SPIPs also had an influence. Since thrombin time was prolonged by SPIPs for a condition which supplied enough thrombin to the assay system, interactions between fibrinogen and SPIPs may be one of the anticoagulant mechanisms of SPIPs.

The morphological interactions between astroglial and neuronal elements were elucidated in the rat suprachiasmatic nucleus (SCN) by light and electron microscopic immunocytochemistry using antibodies against glial fibrillary acidic protein (GFAP), vasoactive intestinal peptide (VIP) and arginine-vasopressin (AVP). Throughout the SCN, particularly in its ventral portion, GFAP-like-immunoreactive (GFAP-LI) astroglial elements were found. These astrocytes displaying GFAP-like immunoreactivity occasionally contained fairly well-developed organelles. Some of these astrocytes were found as satellite cells in close contact with non-immunoreactive neuronal perikarya and processes. Around the neurons, GFAP-LI astroglial processes were also observed to cover some portions of presynaptic and postsynaptic elements. In addition, these astroglial elements were seen between two neuronal somata and pericytes of blood capillaries as glial endfeet. By double labeling immunoelectron microscopy using antibodies against GFAP/VIP and GFAP/AVP, some portions of VIP-like-immunoreactive or AVP-like-immunoreactive neuronal somata and processes were found to be engulfed by GFAP-LI astroglial processes. The possible functional roles of the morphological interactions between astroglial and neuronal elements are discussed.

A method is proposed for counting the number of adhered platelets based on the determination of lactate dehydrogenase activity in bulk after lysis of adhered platelets. This method was compared with the widely used radioisotope labelling technique. It was concluded that the present lactate dehydrogenase method is effective in counting the adhered platelets, as no significant difference was found between the readings of two methods when commercial polymers and glass were used as samples.

The midline of the rostral ventral medulla (RVM) is the portion in which many serotonin (5-HT) neurons of the nucleus raphe magnus and the rostral nucleus raphe pallidus are located and where dense catecholaminergic (CA) fibers are distributed. In this study, we investigated the connection between spinally projecting 5-HT neurons and CA fibers in the rat RVM by light and electron microscopic immunocytochemistry. First, light microscopic immunocytochemistry using a triple labeling method revealed that the 5-HT-immunoreactive (IR) neuron containing retrograde tracer from the cervical cord was intimately surrounded by tyrosine hydroxylase (TH)-IR fibers. Second, silver-gold intensified TH-IR axon terminals were found to make synaptic contacts with 5-HT-IR neuronal perikarya and dendrites by double labeling immunoelectron microscopy. These morphological findings suggest that spinally projecting 5-HT neurons, presumed to be involved in pain modulation or sympathetic autonomic control, are directly regulated by CA neurons at the level of the RVM.

Following exposure to corona discharge, a polyethylene film was graft polymerized with different water-soluble monomers such as acrylamide (non-ionic), acrylic acid (anionic), 2-acrylamide-2-methyl propane sulphonic acid (anionic), styrene sulphonic acid sodium salt (anionic) and N,N-dimethylaminopropyl acrylamide (cationic). Attachment and proliferation of HeLa S3 cells were studied for grafted surfaces with different zeta potentials and contact angles. The polyethylene surface graft polymerized with styrene sulphonic acid sodium salt exhibited high cell attachment and protein adsorption, whereas the cells did not adhere to the 2-acrylamide-2-methyl propane sulphonic acid graft-polymerized surface, although both surfaces had high negative zeta potentials. Graft polymerization of acrylamide reduced the zeta potential of surface close to zero and rejected the cell attachment. The polyethylene surface became highly cell-adhesive through graft polymerization of the cationic N,N-dimethylaminopropyl acrylamide monomer, but too much grafting killed the attaching cells. Once the cells attached to a surface without being killed, they could proliferate at the same growth rate, whatever their surface zeta potential.

A bilayer artificial skin composed of an outer layer of silicone polymer and an inner sponge layer of collagen containing chondroitin 6-sulphate was developed by modifying the technique proposed by Yannas et al. The artificial skin was placed on the skin defects on the backs of rats. Histological observation indicated that fibroblasts and capillaries infiltrated into the pores and filled in lattice spaces, resulting in synthesis of the connective tissue matrix and absorption of the original network of collagen and chondroitin 6-sulphate. Epidermal cells migrated from the edge of the wound between the two layers. Post-operative contracture in the wound with the artificial skin was significantly less than in the control.