Effectiveness of primary series, first, and second booster vaccination of monovalent mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections and severe diseases during the SARS-CoV-2 omicron BA.5 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: This study aimed to evaluate VE of primary, first, and second booster ancestral-strain monovalent mRNA COVID-19 vaccination against symptomatic infections and severe diseases in Japan. METHODS: We conducted a test-negative case-control study. We included medically attended episodes and hospitalizations involving individuals aged ≥16 with signs and symptoms from July to November 2022, when Omicron BA.5 was dominant nationwide. To evaluate VE, we calculated adjusted ORs of vaccination among test-positive versus test-negative individuals using a mixed-effects logistic regression. RESULTS: For VE against symptomatic infections among individuals aged 16 to 59, VE of primary vaccination at > 180 days was 26.1% (95% CI: 10.6-38.8%); VE of the first booster was 58.5% (48.4-66.7%) at ≤90 days, decreasing to 41.1% (29.5-50.8%) at 91 to 180 days. For individuals aged ≥60, VE of the first booster was 42.8% (1.7-66.7%) at ≤90 days, dropping to 15.4% (-25.9-43.2%) at 91 to 180 days, and then increasing to 44.0% (16.4-62.5%) after the second booster. For VE against severe diseases, VE of the first and second booster was 77.3% (61.2-86.7%) at ≤90 days and 55.9% (23.4-74.6%) afterward. CONCLUSION: mRNA booster vaccination provided moderate protection against symptomatic infections and high-level protection against severe diseases during the BA.5 epidemic in Japan.

Polypharmacy-Related Shock Symptoms and Complications Associated with Phenothiazine: A Case Report.

This report describes a case of shock symptoms in a 72-year-old woman with epilepsy who had been in a state of polypharmacy, taking multiple antipsychotic drugs. After receiving a normal dose of periciazine, she exhibited impaired consciousness, hypothermia, and hypotension and was admitted to hospital. Despite poor response to vasopressors, conservative treatment led to gradual improvement. Subsequent pharmacokinetic analysis showed non-toxic blood concentrations of periciazine, suggesting that even small doses of phenothiazines could result in toxic symptoms. This case highlights the importance of monitoring for adverse reactions when prescribing multiple antipsychotic drugs, particularly in older polypharmacy patients.

Transmission dynamics of seasonal influenza in a remote island population.

Seasonal influenza outbreaks remain an important public health concern, causing large numbers of hospitalizations and deaths among high-risk groups. Understanding the dynamics of individual transmission is crucial to design effective control measures and ultimately reduce the burden caused by influenza outbreaks. In this study, we analyzed surveillance data from Kamigoto Island, Japan, a semi-isolated island population, to identify the drivers of influenza transmission during outbreaks. We used rapid influenza diagnostic test (RDT)-confirmed surveillance data from Kamigoto island, Japan and estimated age-specific influenza relative illness ratios (RIRs) over eight epidemic seasons (2010/11 to 2017/18). We reconstructed the probabilistic transmission trees (i.e., a network of who-infected-whom) using Bayesian inference with Markov-chain Monte Carlo method and then performed a negative binomial regression on the inferred transmission trees to identify the factors associated with onwards transmission risk. Pre-school and school-aged children were most at risk of getting infected with influenza, with RIRs values consistently above one. The maximal RIR values were 5.99 (95% CI 5.23, 6.78) in the 7-12 aged-group and 5.68 (95%CI 4.59, 6.99) in the 4-6 aged-group in 2011/12. The transmission tree reconstruction suggested that the number of imported cases were consistently higher in the most populated and busy districts (Tainoura-go and Arikawa-go) ranged from 10-20 to 30-36 imported cases per season. The number of secondary cases generated by each case were also higher in these districts, which had the highest individual reproduction number (Reff: 1.2-1.7) across the seasons. Across all inferred transmission trees, the regression analysis showed that cases reported in districts with lower local vaccination coverage (incidence rate ratio IRR = 1.45 (95% CI 1.02, 2.05)) or higher number of inhabitants (IRR = 2.00 (95% CI 1.89, 2.12)) caused more secondary transmissions. Being younger than 18 years old (IRR = 1.38 (95%CI 1.21, 1.57) among 4-6 years old and 1.45 (95% CI 1.33, 1.59) 7-12 years old) and infection with influenza type A (type B IRR = 0.83 (95% CI 0.77, 0.90)) were also associated with higher numbers of onwards transmissions. However, conditional on being infected, we did not find any association between individual vaccination status and onwards transmissibility. Our study showed the importance of focusing public health efforts on achieving high vaccine coverage throughout the island, especially in more populated districts. The strong association between local vaccine coverage (including neighboring regions), and the risk of transmission indicate the importance of achieving homogeneously high vaccine coverage. The individual vaccine status may not prevent onwards transmission, though it may reduce the severity of infection.

Oxidation and wear of 100-Mrad cross-linked polyethylene shelf-aged for 30 years.

Some previous studies suggest that aging influences wear and oxidatively degraded nonsterilized ultra-high-molecular-weight polyethylene (UHMWPE) exhibits decreased wear resistance. We therefore asked whether shelf-aging storage conditions influenced degradation and wear resistance of gamma-irradiated UHMWPE. We examined oxidation and wear of 100-Mrad gamma-irradiated UHMWPE (100-Mrad polyethylene) cups shelf-aged for 30 years without (n=2) or with (n=2) packages. The oxidation index of the unpackaged 100-Mrad polyethylene surface (4) was higher than that of the packaged one (2.7). The packaged 100-Mrad polyethylene cup exhibited a high wear resistance with a steady wear rate of 0.5 mg/10(6) cycles. In contrast, the unpackaged 100-Mrad polyethylene exhibited an extremely high initial wear rate of 187.9 mg/10(6) cycles over the first 0.25 x 10(6) cycles with a subsequently reduced wear rate of 5 mg/10(6) cycles after 5 x 10(6) cycles. Packaging over long periods inhibits surface oxidation and maintains the wear resistance of gamma-irradiated UHMWPE cups.

Dose effects of cross-linking polyethylene for total knee arthroplasty on wear performance and mechanical properties.

Wear performance and mechanical properties of cross-linking polyethylene (XLPE) tibial inserts were investigated using a knee simulator, scanning electron microscopy (SEM), and a small punch test (SPT). Ultrahigh molecular weight PE made from GUR1050 resin was irradiated at doses ranging from 0 to 200 kGy and then machined into tibial inserts followed by annealing. The knee simulator was run for up to four million cycles. As the radiation dose increased from 0 to 100 kGy, the wear rate decreased dramatically, yielding 95% wear reduction at 100 kGy. The microwear features observed by SEM supported the dose-dependent wear reduction. The SPT for XLPE after the simulation test showed that, as the radiation dose increased from 0 to 200 kGy, the ultimate displacement decreased dose-dependently, while the ultimate load increased from 0 to 75 kGy and decreased from 75 to 200 kGy. The resulting toughness of the PE increased to its maximum at a dose of 50 kGy and then decreased with higher doses up to 200 kGy. PE cross-linked with radiation doses from 25 to 75 kGy had greater toughness than virgin, nonirradiated PE. However, PE irradiated with 100 kGy or more had lower toughness than virgin PE. These data suggest that a certain amount of irradiation enhances both wear performance and toughness of PE tibial inserts. Although a certain amount of cross-linking would be effective for clinical application of PE tibial inserts, an optimal radiation dose should be much smaller than that used in current XLPE in total hip arthroplasty.

Subacute systemic toxicity assessment of beta-tricalcium phosphate/carboxymethyl-chitin composite implanted in rat femur.

The efficacy of a composite of beta-tricalcium phosphate particles and carboxymethyl-chitin (beta-TCP/CM-chitin) for bone repair has already been established in animal experiments. In the present study, subacute systemic toxicity was evaluated to further assess the biological safety of the implanted composite. beta-TCP/CM-chitin (approximately 4 mg/kg and 7 mg/kg in male and female rats, respectively) was implanted for 28 days into penetrating defects (2 mm diameter) made artificially in the shaft of the right femur of rats. Sham operation groups with the defect only were prepared as controls. Haematology, blood chemistry, urinalysis, and the histopathology of 44 organs and tissues were investigated. Body weight measurements and clinical observations were performed daily throughout the study. No subacute systemic toxicity possibly caused by the implantation of beta-TCP/CM-chitin was detected. These findings indicate that beta-TCP/CM-chitin composite is a highly biocompatible bone substitute, at least with an implantation dosage of < 4-7 mg/kg.

Biological roles of carboxymethyl-chitin associated for the growth factor production.

Many techniques to restore cartilage defection have been tried. However, the development is still under way because of problems, including loosening of artificial joint, degenerative change of compensated tissue, risk of viral transmission via allograft/autograft, and cost of therapeutic materials for repair. In the previous research, we found that complementing cartilage defective part with carboxymethyl-chitin (CM-chitin)/beta-tricalcium phosphate composite induced regeneration of cartilage in rabbits in vivo, and it is presumable that CM-chitin plays a key role in chondrogenesis causing the regeneration of cartilage. However, the induction mechanism of chondrogenesis with CM-chitin is still unclear. In this study, we investigated the cell responses to CM-chitin by using peritoneal exudate cell (PEC) in mice and found that CM-chitin induced the expression of inflammatory cytokines and growth factors, both of which are both considered to correlate with chondrogenesis. After intraperitoneal injection CM-chitin showed enhanced expressions of mRNA of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), keratinocyte-derived chemokine, tumor necrosis factor-alpha, and transforming growth factor-beta1 (TGF-beta1) in PEC as observed by reverse transcriptase polymerase chain reaction. Productions of TGF-beta1 protein were confirmed by enzyme linked immunosorbant assay. It was also shown that mononuclear cells in PEC were responsible for the TGF-beta1 production. These results suggest that CM-chitin is an inductor of inflammatory cytokines and growth factors and may contribute to regeneration of cartilage.

A gridified protein structure prediction system "Rokky-G" and its implementation issues.

In recent years, simulation using computer systems has been of increasing importance in the life sciences. We have developed a system called "Rokky-G" that facilitates a protein structure prediction strategy called "Rokky" on Grid systems. Rokky-G provides the framework of protein structure prediction on the Grid. In this paper we discuss the architecture of Rokky-G and implementation issues identified in order to obtain highly reliable results.

Repair of 20-mm long rabbit radial bone defects using BMP-derived peptide combined with an alpha-tricalcium phosphate scaffold.

In previous studies, we have reported that the BMP-2-derived peptide KIPKASSVPTELSAISTLYL, corresponding to BMP-2 residues 73-92, binds to a BMP-2-specific receptor, and elevates both alkaline phosphatase activity and osteocalcin mRNA in the murine mesenchymal cell line, C3H10T1/2. This 73-92 peptide conjugated to a covalently crosslinked alginate gel induced ectopic bone formation in rat calf muscle, and activated osteoblasts to promote the repair of rat tibial bone defects. Here, we report repair of 20-mm long rabbit radial bone defects using the 73-92 peptide combined with a porous alpha-tricalcium phosphate (TCP) scaffold. In vitro, the 73-92 peptide was released from the porous alpha-TCP scaffold over more than one week. In vivo, radiomorphometric analysis showed that the 73-92 peptide combined with the porous alpha-TCP scaffold promoted calcification in the implanted area in a dose-dependent manner, and that 5 mg of the 73-92 peptide induced connection of 20-mm long defects, defects of critical size, 12 weeks after implantation. Histological examination revealed newly formed bone and a marrow cavity in the implanted area. The area of bone denser than 690 mg/cm(3) induced by the 73-92 peptide was nearly equal to that of the contralateral radius.

Change in UHMWPE properties of retrieved ceramic total knee prosthesis in clinical use for 23 years.

The alumina-ceramic total knee prosthesis developed by Kyocera Corp. was implanted in 1979, and was in clinical use for 23 years until total knee arthroplasty revision surgery in January 2002. It is believed that this is the longest clinical period of a ceramic total knee prosthesis reported to date in the world. In the present study, we gave consideration to the long-term clinical stability of the alumina-ceramic femoral component as well as the mechanism of in vivo degradation of ultrahigh molecular weight polyethylene (UHMWPE) based on the evaluated wear, oxidation, and fracture toughness of the retrieved UHMWPE. We concluded that the degradation of UHMWPE by progressive oxidation is an issue to be solved in the future. To moderate stress concentration, use of a thin UHMWPE insert should be avoided. The low wear rate and the mild wear pattern observed this time suggest the possibility of reduced wear of the UHMWPE against the alumina-ceramic femoral component, and the usefulness of the alumina-ceramic total knee prosthesis component was recognized even after long clinical use.

In vitro cytocompatibility assessment of beta-tricalcium phosphate/carboxymethyl-chitin composite.

A novel bioabsorbable bone substitute composed of a beta-tricalcium phosphate (beta-TCP) and a carboxymethyl-chitin (CM-chitin) sodium has been developed. Rabbit tibia defects (4 mm in diameter) were repaired after 4 weeks more effectively by the composite compared with a sham-operation group. To further investigate the biological safety of the components, genotoxicity and carcinogenicity of an extract prepared from the composite were determined using four different in vitro assays. The main extract component was identified as CM-chitin sodium [average molecular weight (Mw) approximately 230 kDa] as determined by Fourier transform infrared spectroscopy and gel permeation chromatography analysis. The concentrations of P and Ca possibly derived from beta-TCP were 17.7 and 37.1 microg/g, respectively, as determined by inductively coupled plasma mass spectroscopy. Both the metabolic activation and nonactivation (-S9) systems of the rat microsome S9 fraction were used to perform a genotoxicity evaluation using the Ames test and chromosome aberration assay on Chinese hamster lung fibroblast cells treated with the extract. In these assays, no genotoxicity was detected with doses < or =5 mg/mL (maximum concentration). The cell transformation assay using BALB/c 3T3 cells and the metabolic cooperation assay with V79 cells both showed negative results for any tumor-promoting activity caused by the extract (approximately 5 mg/mL). These results indicate that the bioabsorbable beta-TCP/CM-chitin composite is a highly biocompatible bone substitute.

Assessment of wear in extensively irradiated UHMWPE cups in simulator studies.

Higher levels of UHMWPE crosslinking currently are being advocated for improved wear resistance of acetabular cups. Pioneering Japanese studies, begun in 1971, have achieved good clinical results with UHMWPE irradiated to 1000 kGy for use with a cemented-cup design. The objective of our study was to use contemporary simulator techniques to determine the in vitro wear performance of such high-dose irradiated cups. Extruded UHMWPE cups were processed with 500, 1000, and 1500 kGy of gamma-radiation doses under vacuum, annealed, and machined to shape. The cups were mated with 26-mm alumina heads and run in a multidirectional simulator with bovine serum. Over a 6-million cycle (Mc) study, the weight loss of the nonirradiated control cups averaged 52.8 mg/Mc + 1.4% (wear = 57.2 mm(3)/Mc). In contrast, the irradiated wear cups had a consistent weight gain. Thus cups with irradiation of 500-1500 kGy had no detectable wear in this study. The original machining marks still were partially evident in the wear zones, along with some macrofissures in the 1000- and 1500-kGy cups. Areas adjacent to the fissures showed delaminating plaques of 100-300 microm in size. It also was noted that the wear cups systematically gained more weight than their corresponding soak controls. Each 200-kGy radiation gain increased the fluid sorption ratio by 10%. The increased fluid sorption and evidence of some surface deterioration may indicate that such high-dose irradiated cups are more susceptible to mechanical damage. This indicates that we should take care to ensure that our desire to reduce the wear debris to a zero amount does not result in a modified UHMWPE that lacks the necessary mechanical properties for contemporary metal-backed cup designs.