Unwillingness to cooperate with COVID-19 contact tracing in Japan.

OBJECTIVES: Contact tracing for COVID-19 relies heavily on the cooperation of individuals with authorities to provide information of contact persons. However, few studies have clarified willingness to cooperate and motivation to provide information for contact tracing. This study sought to describe willingness to cooperate and motivation to report contact persons for COVID-19 contact tracing among citizens in Japan, and to assess any associated sociodemographic factors. STUDY DESIGN: Cross-sectional study. METHODS: This was an online-based survey using quota sampling. Participants were asked about their willingness to cooperate in reporting contacts for COVID-19 contact tracing if they tested positive. Participants also responded to questions regarding their reasons for cooperating or not cooperating and provided sociodemographic data. Multiple logistic regression analysis was performed to clarify associations between sociodemographic factors and willingness to cooperate. RESULTS: This study included 2844 participants. The proportion of participants who were not willing to cooperate in reporting contacts was 27.6%, with their main reasons being concerns about causing trouble for the other person and being criticised for revealing their names. Willingness to cooperate was lower among men, young adults and those with an educational level less than a university degree. CONCLUSIONS: To improve the effectiveness of contact tracing, educational campaigns, such as reducing the fear and stigma associated with COVID-19, may be important. Furthermore, it is essential to understand that individuals may have contacts whom they do not wish to disclose to others and to be considerate when handling such situations.

Subjective Well-Being Is Associated with Food Behavior and Demographic Factors in Chronically Ill Older Japanese People Living Alone.

OBJECTIVES: This study aimed to examine the relationships among subjective well-being, food and health behaviors, socioeconomic factors, and geography in chronically ill older Japanese adults living alone. DESIGN: The design was a cross-sectional, multilevel survey. A questionnaire was distributed by post and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select a representative sample of older people living alone based on their proximity to a supermarket. Study recruitment was conducted with municipal assistance. MEASUREMENTS: To assess subjective well-being and food and health behaviors of respondents with disease, a logistic regression analysis was performed using stepwise variable analyses, adjusted for respondent age, socioeconomic status, and proximity to a supermarket. The dependent variable was good or poor subjective well-being. RESULTS: In total, 2,165 older people (744 men, 1,421 women) completed the questionnaire (63.5% response rate). Data from 737 men and 1,414 women were used in this study. Among people with a chronic disease, individuals with good subjective well-being had significantly higher rates than those with poor subjective well-being for satisfaction with meal quality and chewing ability, food diversity, food intake frequency, perception of shopping ease, having someone to help with food shopping, eating home-produced vegetables, preparing breakfast themselves, eating with other people, and high alcohol consumption. A stepwise logistic analysis showed that the factors strongly related to poor subjective well-being were shopping difficulty (men: odds ratio [OR] = 3.19, 95% confidence interval [CI], 1.94-5.23; P < 0.0001; women: OR = 2.20, 95% CI, 1.54-3.14; P < 0.0001), not having someone to help with food shopping (women: OR = 1.41, 95% CI, 1.01-1.97; P = 0.043), not preparing breakfast (women: OR = 2.36, 95% CI, 1.40-3.98; P = 0.001), and eating together less often (women: OR = 1.99, 95% CI, 1.32-3.00; P = 0.002). CONCLUSION: Subjective well-being of people with chronic diseases is associated with food intake and food behavior. The factors that affect poor subjective well-being in chronically ill older Japanese people living alone include food accessibility and social communication.

"Eating Together" Is Associated with Food Behaviors and Demographic Factors of Older Japanese People Who Live Alone.

OBJECTIVE: This study aimed to examine the relationships between eating together and subjective health, frailty, food behaviors, food accessibility, food production, meal preparation, alcohol intake, socioeconomic factors and geography among older Japanese people who live alone. DESIGN: A cross-sectional, multilevel survey was designed. The questionnaire was distributed by post and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select a representative sample of older people who lived alone based on their proximity to a supermarket. Recruitment for the study was conducted with municipal assistance. MEASUREMENTS: A logistic regression analysis was performed that adjusted for the respondent's age, socioeconomic status and proximity to a supermarket using stepwise variable analyses. The dependent variable was whether the respondent ate together more or less than once a month. RESULTS: In total, 2,196 older people (752 men and 1,444 women) completed the questionnaire (63.5% response rate). It was found that 47.1% of men and 23.9% of women ate together less than once a month. Those who ate together less than once a month had a significantly lower rate of subjective health, food diversity and food intake frequency than those who ate together more often. A stepwise logistic analysis showed that the factors most strongly related to eating together less than once a month were not having any food shopping assistance (men: OR = 3.06, women: OR = 2.71), not receiving any food from neighbors or relatives (men: OR = 1.74, women: OR = 1.82), daily alcohol intake (women: OR = 1.83), frailty (men: OR = 0.48) and income (men: OR = 2.16, women: OR = 1.32). CONCLUSION: Eating together is associated with subjective health and food intake. Factors that affect how often older Japanese people who live alone eat together include food accessibility, daily alcohol intake, frailty and a low income.

Association between Satisfaction with State of Health and Meals, Physical Condition and Food Diversity, Health Behavior, and Perceptions of Shopping Difficulty among Older People Living Alone in Japan.

OBJECTIVE: This study aimed to examine perceptions of shopping difficulty, and the relationships with satisfaction with state of health and meals, physical condition, food diversity and health behavior in older people living alone in Japan. DESIGN: A cross-sectional, multilevel survey was designed. The questionnaire was distributed by mail and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select the sample of older people living alone, by proximity to a supermarket. In total, 2,346 older people (827 men and 1,519 women) completed the questionnaire. MEASUREMENTS: The dependent variable was whether shopping was easy or difficult. A logistic regression analysis was performed, adjusting for age, socioeconomic status and proximity of residence to a supermarket using stepwise variable analyses. RESULTS: The response rate was 67.8%. Overall, 14.5% of men and 21.7% of women considered shopping difficult. The stepwise logistic analysis showed that the factors most strongly related to shopping difficulty were a subjective feeling of poor health (men: OR = 3.01, women: OR = 2.16) and lack of satisfaction with meals (men: OR = 2.82, women: OR = 3.69). Other related physical condition and dietary factors were requiring nursing care (men: OR = 3.69, women: OR = 1.54), a high level of frailty, measured using the frailty index score (women: OR = 0.36) and low food diversity score (men: OR = 1.84, women: OR = 1.36). CONCLUSION: The study found that older people's assessment of their shopping difficulty was related to satisfaction aspects, including a subjective feeling of poor health, and lack of satisfaction with meals, as well as physical condition. These have a greater influence on shopping difficulty than income in both sexes, and proximity to a supermarket in women.

Food Accessibility and Perceptions of Shopping Difficulty among Elderly People Living Alone in Japan.

OBJECTIVES: This aim of this study was to describe the association between shopping difficulty and food accessibility for elderly people living alone in Japan. DESIGN: A cross-sectoral, multilevel survey was designed to measure shopping difficulty from a food accessibility perspective. The questionnaire was distributed by mail. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select the sample: it identified the proximity of elderly people living alone to a supermarket. In total, 2,028 elderly people (725 men and 1,303 women) responded to the questionnaire. MEASUREMENTS: The binary dependent variables were shopping is easy/shopping is difficult. A logistic regression analysis adjusting for age and area of residence and using stepwise variable analyses was performed. RESULTS: The response rate was 58.6%. Overall, 14.6% of elderly men and 21.7% of elderly women consider shopping difficult. The stepwise logistic analysis showed that the food accessibility factors strongly related to shopping difficulty are infrequent car use (women: OR = 6.97), walking difficulties (men: OR = 2.81, women: OR = 3.48), poor eyesight (men: OR = 2.26, women: OR = 1.75), not cooking lunch by oneself (men: OR = 1.63, women: OR = 1.72), not having anyone to help with food shopping (women: OR = 1.45) and living over 1 km away from a supermarket (men: OR = 2.30, women: OR = 2.97). CONCLUSION: The study concludes that elderly people's assessment of shopping difficulty is related to their food accessibility. Important food accessibility aspects include car or motorbike ownership, walking continuously for 1 km, poor eyesight, and having cooking skills and having someone to help with shopping. These physical activity restrictions have a greater influence on shopping difficulty than do either income or proximity to a supermarket.

Long-term detection of seasonal influenza RNA in faeces and intestine.

Some cases of seasonal influenza virus (human influenza A virus (IAV)/human influenza B virus (IBV)) are associated with abdominal symptoms. Although virus RNA has been detected in faeces, intestinal infection has not been clearly demonstrated. We aimed to provide evidence that IAV/IBV infects the human intestine. This prospective observational study measured virus RNA in faecal and sputum samples from 22 patients infected with IAV/IBV (19 IAV positive and three IBV positive). Nineteen patients were included in the analysis and were assigned to faecal IAV-positive and -negative groups. Virus kinetics were examined in faecal samples from an IAV-infected patient (patient 1) and an IBV-infected patient (patient 2). Finally, intestinal tissue from an IAV-diagnosed patient who developed haemorrhagic colitis and underwent colonoscopy was examined for the presence of replicating IAV (patient 3). Virus RNA was detected in faecal samples from 8/22 IAV/IBV-infected patients (36.4%). Diarrhoea occurred significantly more often in the faecal IAV-positive group (p 0.002). In patients 1 and 2, virus RNA became undetectable in sputum on days 7 and 10 after infection, respectively, but was detected in faeces for a further 2 weeks. Virus mRNA and antigens were detected in intestinal tissues (mucosal epithelium of the sigmoid colon) from patient 3. These findings suggest that IAV/IBV infects within the intestinal tract; thus, the human intestine may be an additional target organ for IAV/IBV infection.

Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide.

The host components and commensal microorganisms of the intestinal microenvironment play roles in the development and maintenance of the host defence. Recent observations have suggested that toll-like receptors (TLRs) are involved in the recognition of innate immunity against intestinal microbes. However, little is known regarding the role of TLR in the maintenance of systemic host defence by intestinal microorganisms. We studied the expression and function of TLR4 and TLR2 on alveolar and peritoneal macrophages in mice after 3 weeks of oral administration of streptomycin and cefotaxime. After active treatment, the intestinal microorganisms were nearly completely eradicated, and the surface expression of TLR4 and TLR2 on the peritoneal macrophages was prominently downregulated. When the actively treated mice were challenged with lipopolysaccharide (LPS), a TLR4 ligand, the host response was markedly impaired. Our results suggest that the oral administration of antimicrobials downregulates the expression of surface TLR on the peritoneal macrophages and modulates the host immune responses against LPS by modifying the intestinal environment.

Geographically weighted Poisson regression for disease association mapping.

This paper describes geographically weighted Poisson regression (GWPR) and its semi-parametric variant as a new statistical tool for analysing disease maps arising from spatially non-stationary processes. The method is a type of conditional kernel regression which uses a spatial weighting function to estimate spatial variations in Poisson regression parameters. It enables us to draw surfaces of local parameter estimates which depict spatial variations in the relationships between disease rates and socio-economic characteristics. The method therefore can be used to test the general assumption made, often without question, in the global modelling of spatial data that the processes being modelled are stationary over space. Equally, it can be used to identify parts of the study region in which 'interesting' relationships might be occurring and where further investigation might be warranted. Such exceptions can easily be missed in traditional global modelling and therefore GWPR provides disease analysts with an important new set of statistical tools. We demonstrate the GWPR approach applied to a data set of working-age deaths in the Tokyo metropolitan area, Japan. The results indicate that there are significant spatial variations (that is, variation beyond that expected from random sampling) in the relationships between working-age mortality and occupational segregation and between working-age mortality and unemployment throughout the Tokyo metropolitan area and that, consequently, the application of traditional 'global' models would yield misleading results.

Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice.

Intravascular plasmid DNA (pDNA) vaccine encoding herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) effectively induces prophylactic immunity against lethal HSV-1 infection in mice. We investigated whether the vaccine potency is further improved by coadministration of cytokine genes together with a low dose of genetic vaccine. pDNA encoding IL-12, IL-15, IL-18 or IL-21 was capable of elevating survival rates of HSV-1-infected mice when coinjected with 1 microg of gB pDNA, while IL-10 gene delivery failed to affect the effectiveness of the genetic immunization. Although only 17% of mice survived acute HSV infection after the gB pDNA vaccination at a dose of 1 microg, all mice coadministered with 1 microg each of gB and IL-12 pDNAs not only survived the acute infection but also escaped latent infection. In these animals, the neutralizing antibody against HSV-1 was abundantly produced, and CTL activity against the gB antigen was augmented. Coadministration of the gB and IL-12 genes also elevated the serum level of interferon-gamma. Adaptive transfer experiments indicated that soluble factors contributed to preventive immunity, while cell components alone were not capable of protecting mice from fatal viral infection. These results strongly suggest potential usefulness of Th1 cytokine genes as effective molecular adjuvants that facilitate specific humoral as well as cellular immune responses elicited by intravascular molecular vaccination.

Intravascular naked DNA vaccine encoding glycoprotein B induces protective humoral and cellular immunity against herpes simplex virus type 1 infection in mice.

Naked plasmid DNA (pDNA) vaccine expressing herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) was tested for protective activity against acute HSV-1 infection in mice. The pDNA was intravenously injected into Balb/c mice via their tail vein under high pressure, and the vaccination was performed two times at an interval of 7 days. The gB gene vaccination significantly protected the mice from subsequent intraperitoneal challenge with a lethal dose of HSV-1, which killed all the animals given control plasmid or saline. The protective activity was correlated with the dose of the plasmid inoculated, the survival rate reaching 83% in mice vaccinated with 5 microg of pDNA. The vaccinated mice were also protected from latent HSV infection. The immunized mice showed significant elevation in neutralizing antibody against HSV-1 as well as serum levels of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma). When mice were immunized with 5 microg of an Epstein-Barr virus (EBV)-based plasmid vector harboring the gB, the cytotoxic T lymphocytes (CTLs) activity and proliferative response for HSV-1 were also induced. The results strongly suggest that intravenous immunization of naked pDNA may induce humoral and cellular immune responses against the virus, leading to a significant prophylactic outcome against HSV-1 infection in mice.

Recombinant paramyxovirus type 1-avian influenza-H7 virus as a vaccine for protection of chickens against influenza and Newcastle disease.

Current vaccines to prevent avian influenza rely upon labor-intensive parenteral injection. A more advantageous vaccine would be capable of administration by mass immunization methods such as spray or water vaccination. A recombinant vaccine (rNDV-AIV-H7) was constructed by using a lentogenic paramyxovirus type 1 vector (Newcastle disease virus [NDV] B1 strain) with insertion of the hemagglutinin (HA) gene from avian influenza virus (AIV) A/chicken/NY/13142-5/94 (H7N2). The recombinant virus had stable insertion and expression of the H7 AIV HA gene as evident by detection of HA expression via immunofluorescence in infected Vero cells. The rNDV-AIV-H7 replicated in 9-10 day embryonating chicken eggs and exhibited hemagglutinating activity from both NDV and AI proteins that was inhibited by antisera against both NDV and AIV H7. Groups of 2-week-old white Leghorn chickens were vaccinated with transfectant NDV vector (tNDV), rNDV-AIV-H7, or sterile allantoic fluid and were challenged 2 weeks later with viscerotropic velogenic NDV (vvNDV) or highly pathogenic (HP) AIV. The sham-vaccinated birds were not protected from vvNDV or HP AIV challenge. The transfectant NDV vaccine provided 70% protection for NDV challenge but did not protect against AIV challenge. The rNDV-AIV-H7 vaccine provided partial protection (40%) from vvNDV and HP AIV challenge. The serologic response was examined in chickens that received one or two immunizations of the rNDV-AIV-H7 vaccine. Based on hemagglutination inhibition and enzyme-linked immunosorbent assay (ELISA) tests, chickens that received a vaccine boost seroconverted to AIV H7, but the serologic response was weak in birds that received only one vaccination. This demonstrates the potential for NDV for use as a vaccine vector in expressing AIV proteins.

Superior antitumour activity of S-1 in tumours with a high dihydropyrimidine dehydrogenase activity.

To elucidate the mechanism of the enhanced antitumour activity of S-1 (1 M tegafur, 0.4 M 5-chloro-2, 4-dihydroxypyridine, and 1 M potassium oxonate) in terms of the phosphorylation and degradation pathways of 5-fluorouracil (5-FU) metabolism, we investigated tumoral thymidylate synthase (TS) content, dihydropyrimidine dehydrogenase (DPD) activity, the TS inhibition rate (TS-IR), and 5-FU incorporated into RNA (F-RNA) in four human gastric cancer xenografts (MKN-28, MKN-74, GCIY and GT3TKB) and compared the results obtained with S-1 with those obtained with 5-FU and UFT (1 M tegafur, 4 M uracil). 5-FU was administered intraperitoneally (i.p.) to mice at a dose of 50 mg/kg, three times, on days 0, 4 and 8. S-1 and UFT were administered orally at doses of 10 and 24 mg/kg, respectively, once a day, for 9 consecutive days. Antitumour activity was evaluated as the maximum inhibition of tumour growth in each animal. S-1 showed a better antitumour activity than 5-FU and UFT in tumours with a high DPD activity (GCIY and GT3TKB). There were inverse correlations between the antitumour activity and both TS content and DPD activity in the 5-FU and UFT groups. However, no such correlations were observed in the S-1 group. In GCIY and GT3TKB xenografts, TS-IR was significantly higher in the S-1 group than in the 5-FU or UFT groups. In GT3TKB xenografts, the F-RNA level was significantly higher in the S-1 group than in the 5-FU or UFT groups. The superior cytotoxicity of S-1 appears to be attributable to both an increased inhibition of DNA synthesis and an enhanced blockade of RNA function against tumours with a high DPD activity.

Role of thymidine phosphorylase and dihydropyrimidine dehydrogenase in tumour progression and sensitivity to doxifluridine in gastric cancer patients.

This study was designed to investigate the role of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) on tumour progression and sensitivity to 5'-deoxy-5-fluorouridine (5'-DFUR). Tumour tissue was obtained from surgically resected samples from 93 patients with primary gastric cancer. Tumour TP and DPD expression levels were determined by the enzyme-linked immunosorbent assay (ELISA) system and compared with several clinicopathological factors and in vitro sensitivity to 5'-DFUR. DPD showed no correlation with any clinicopathological factors. However, the TP level was significantly correlated with the depth of tumour, lymphatic invasion and venous invasion. In comparison with 5'-DFUR sensitivity, there was a weak inverse correlation between the DPD level and the sensitivity to 5'-DFUR (r(s)=-0.361). Furthermore, the TP/DPD ratio showed a significant correlation with 5'-DFUR sensitivity (r(s)=0.634). In a subgroup of patients with postoperative 5'-DFUR administration, the survival rate was significantly better in patients with a high TP/DPD ratio (n=8) than in those with low TP/DPD ratio (n=14) (P=0.0140). These results suggest that sensitivity to 5'-DFUR is predictable by measurement of both TP and DPD levels.

Search for the KL-->pi 0 pi 0 e+e- decay in the KTeV experiment.

The recent discovery of a large CP violating asymmetry in KL-->pi+pi-e+e- mode has prompted us to seach for the associated KL-->pi 0 pi 0 e+e- decay mode in the KTeV-E799 experiment at Fermilab. In 2.7 x 10(11) K(L) decays, one candidate event has been observed with an expected background of 0.3 event, resulting in an upper limit for the KL-->pi 0 pi 0 e+e- branching ratio of 6.6 x 10(-9) at the 90% C.L.

Radiative decay width measurements of neutral kaon excitations using the primakoff effect.

We use K(L)'s in the 100-200 GeV energy range to produce 147 candidate events of the axial vector pair K1(1270)-K1(1400) in the nuclear Coulomb field of a Pb target and determine the radiative widths Gamma(K1(1400)-->K0+gamma)=280.8+/-23.2(stat)+/-40.4(syst) keV and Gamma(K1(1270)-->K0+gamma)=73.2+/-6.1(stat)+/-28.3(syst) keV. These first measurements appear to be lower than the quark-model predictions. We also place upper limits on the radiative widths for K(*)(1410) and K(*)(2)(1430) and find that the latter is vanishingly small in accord with SU(3) invariance in the naive quark model.

Measurement of the K(L) charge asymmetry.

We present a measurement of the charge asymmetry delta(L) in the mode K(L)-->pi(+/-)e(-/+)nu based on 298 x 10(6) analyzed decays. We measure a value of delta(L) = [3322+/-58(stat)+/-47(syst)]x10(-6), in good agreement with previous measurements and 2.4 times more precise than the current best published result. The result is used to place more stringent limits on CPT and DeltaS = DeltaQ violation in the neutral kaon system.

Roles of thymidylate synthase and dihydropyrimidine dehydrogenase in tumor progression and sensitivity to 5-fluorouracil in human gastric cancer.

BACKGROUND: The role of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) enzyme activities in tumor progression and sensitivity to 5-fluorouracil (5-FU) were evaluated. MATERIALS AND METHODS: TS and DPD activities were measured in 81 clinical samples of gastric cancer. TS and DPD activities were determined by 5-fluorodeoxyuridine monophosphate binding assay and by radioenzymatic assay, respectively. Sensitivity to 5-FU was determined by in vitro ATP assay. RESULTS: There was no correlation between TS activity and sensitivity to 5-FU. However, a weak correlation was found between DPD activity and sensitivity to 5-FU. In a subgroup of patients who did not receive adjuvant chemotherapy, overall survival was poorer in patients with high TS activity (p=0.0265). Conversely, in a subgroup of patients who received 5-FU-based adjuvant chemotherapy, overall survival was poorer in patients with high DPD activity (p=0.0465). CONCLUSION: These results suggest that TS has an important role in tumor progression and DPD may be the dominant predictor of 5-FU sensitivity in gastric cancer.

Recombinant Newcastle disease virus as a vaccine vector.

A complete cDNA clone of the Newcastle disease virus (NDV) vaccine strain Hitchner B1 was constructed, and infectious recombinant virus expressing an influenza virus hemagglutinin was generated by reverse genetics. The rescued virus induces a strong humoral antibody response against influenza virus and provides complete protection against a lethal dose of influenza virus challenge in mice, demonstrating the potential of recombinant NDV as a vaccine vector.