A Japanese Case of COVID-19 Caused by Omicron Strain with Y453F Substitution.

Frequent mutations of SARS-CoV-2 change the strain more transmissible, leading to the pandemic in worldwide. We detected Y453F substitution on Omicron strain, isolated from a Japanese patient in July 2022. While Y453F substitution was identified B1.1.298 lineage in Netherlands and Denmark in 2020, the substitution has not been reported in Omicron strain especially in Japan. Y453F substitution is associated with higher viral infectivity because it is sited in the receptor-binding domain (RBD), and Y453F substitution contributes to increase binding affinity to angiotensin converting enzyme 2 (ACE2). Additionally, Y453F substitution has been reported to escape human leukocyte antigen (HLA), which is known to recognize non-self-antigens in virus-infected cells as cellular immunity, so it should be closely monitored.

Point-of-purchase health information encourages customers to purchase vegetables: objective analysis by using a point-of-sales system.

OBJECTIVES: Point-of-purchase (POP) information at food stores could help promote healthy dietary habits. However, it has been difficult to evaluate the effects of such intervention on customers' behavior. We objectively evaluated the usefulness of POP health information for vegetables in the modification of customers' purchasing behavior by using the database of a point-of-sales (POS) system. METHODS: Two supermarket stores belonging to the same chain were assigned as the intervention store (store I) and control store (store C). POP health information for vegetables was presented in store I for 60 days. The percent increase in daily sales of vegetables over the sales on the same date of the previous year was compared between the stores by using the database of the POS system, adjusting for the change in monthly visitors from the previous year (adjusted ∆sales). RESULTS: The adjusted ∆sales significantly increased during the intervention period (Spearman's ρ = 0.258, P for trend = 0.006) at store I but did not increase at store C (ρ = -0.037, P for trend = 0.728). The growth of the mean adjusted ∆sales of total vegetables from 30 days before the intervention period through the latter half of the intervention period was estimated to be greater at store I than at store C by 18.7 percentage points (95% confidence interval 1.6-35.9). CONCLUSIONS: Health-related POP information for vegetables in supermarkets can encourage customers to purchase and, probably, consume vegetables.

Prolonged effects of participation in disaster relief operations after the Mid-Niigata earthquake on increased cardiovascular risk among local governmental staff.

OBJECTIVE: Major disasters can affect the health status of the victims. However, the effects on the health status of those involved in disaster relief operations are unclear. The aim of this study was to clarify how disaster-related administrative workloads affect the cardiovascular risk factors of local governmental staff. METHODS: A big earthquake struck the central area of Niigata Prefecture, Japan, in October 2004. Thereafter, the Niigata Prefectural Government was engaged in intensive disaster relief operations until March 2005. We compared the changes in the cardiovascular risk factor measurements of 4035 governmental staff members across this period in terms of their workloads due to the relief operations. RESULTS: Compared with the staff having the lowest workloads, those with the highest workloads showed significantly greater increases of BMI, systolic blood pressure (SPB) and serum total cholesterol for men as well as SBP and diastolic blood pressure for women even after cessation of the intensive operations. They had an approximately two-fold higher risk of SBP elevation by 10 mmHg than those with the lowest workloads; the age-adjusted odds ratio (95% confidence interval) was 2.02 (1.47-2.79) for men and 1.82 (1.21-2.75) for women. CONCLUSION: Workloads during disaster relief operations can cause prolonged worsening of blood pressure levels and some other cardiovascular risk factors among local governmental staff. Therefore, when a disaster occurs, health management should be considered not only for the victims, but also for the local governmental staff.

Quantification of mouse pulmonary cancer models by microcomputed tomography imaging.

The advances in preclinical cancer models, including orthotopic implantation models or genetically engineered mouse models of cancer, enable pursuing the molecular mechanism of cancer disease that might mimic genetic and biological processes in humans. Lung cancer is the major cause of cancer deaths; therefore, the treatment and prevention of lung cancer are expected to be improved by a better understanding of the complex mechanism of disease. In this study, we have examined the quantification of two distinct mouse lung cancer models by utilizing imaging modalities for monitoring tumor progression and drug efficacy evaluation. The utility of microcomputed tomography (micro-CT) for real-time/non-invasive monitoring of lung cancer progression has been confirmed by combining bioluminescent imaging and histopathological analyses. Further, we have developed a more clinically relevant lung cancer model by utilizing K-ras(LSL-G12D)/p53(LSL-R270H) mutant mice. Using micro-CT imaging, we monitored the development and progression of solitary lung tumor in K-ras(LSL-G12D)/p53(LSL-R270H) mutant mouse, and further demonstrated tumor growth inhibition by anticancer drug treatment. These results clearly indicate that imaging-guided evaluation of more clinically relevant tumor models would improve the process of new drug discovery and increase the probability of success in subsequent clinical studies.

Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide (FTIDC).

A highly potent and selective metabotropic glutamate receptor (mGluR) 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2, 3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide (FTIDC), is described. FTIDC inhibits, with equal potency, l-glutamate-induced intracellular Ca(2+) mobilization in Chinese hamster ovary cells expressing human, rat, or mouse mGluR1a. The IC(50) value of FTIDC is 5.8 nM for human mGluR1a and 6200 nM for human mGluR5. The maximal response in agonist concentration-response curves was reduced in the presence of higher concentrations of FTIDC, suggesting the inhibition in a noncompetitive manner. FTIDC at 10 microM showed no agonistic, antagonistic, or positive allosteric modulatory activity toward mGluR2, mGluR4, mGluR6, mGluR7, or mGluR8. FTIDC did not displace [(3)H]l-quisqualate binding to human mGluR1a, indicating FTIDC is an allosteric antagonist. Studies using chimeric and mutant receptors of mGluR1 showed that transmembrane (TM) domains 4 to 7, especially Phe801 in TM6 and Thr815 in TM7, play pivotal roles in the antagonism of FTIDC. FTIDC inhibited the constitutive activity of mGluR1a, suggesting that FTIDC acts as an inverse agonist of mGluR1a. Intraperitoneally administered FTIDC inhibited face-washing behavior elicited by a group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine in mice at doses that did not produce motor impairment. Oral administration of FTIDC also inhibited the face-washing behavior. FTIDC is a highly potent and selective allosteric mGluR1 antagonist and a compound having oral activity without species differences in its antagonistic activity on recombinant human, mouse, and rat mGluR1. FTIDC could therefore be a valuable tool for elucidating the functions of mGluR1 not only in rodents but also in humans.