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Autoantibodies (aAbs) to type I interferons (IFNs) have been found in less than 1% of individuals under the age of 60 in the general population, with the prevalence increasing among those over 65. Neutralizing autoantibodies (naAbs) to type I IFNs have been found in at least 15% of patients with life-threatening COVID-19 pneumonia in several cohorts of primarily European descent. We aimed to evaluate the prevalence of aAbs and naAbs to IFN-α2 or IFN-ω in Japanese patients who suffered from COVID-19 as well as in the general population.Patients who suffered from COVID-19 (n = 622, aged 0-104) and an uninfected healthy control population (n = 3,456, aged 20-91) were enrolled in this study. The severities of the COVID-19 patients were as follows: critical (n = 170), severe (n = 235), moderate (n = 112), and mild (n = 105). ELISA and ISRE reporter assays were used to detect aAbs and naAbs to IFN-α2 and IFN-ω using E. coli-produced IFNs.In an uninfected general Japanese population aged 20-91, aAbs to IFNs were detected in 0.087% of individuals. By contrast, naAbs to type I IFNs (IFN-α2 and/or IFN-ω, 100 pg/mL) were detected in 10.6% of patients with critical infections, 2.6% of patients with severe infections, and 1% of patients with mild infections. The presence of naAbs to IFNs was significantly associated with critical disease (P = 0.0012), age over 50 (P = 0.0002), and male sex (P = 0.137). A significant but not strong correlation between aAbs and naAbs to IFN-α2 existed (r = - 0.307, p value 0.0001) reinforced the importance of measuring naAbs in COVID-19 patients, including those of Japanese ancestry.In this study, we revealed that patients with pre-existing naAbs have a much higher risk of life-threatening COVID-19 pneumonia in Japanese population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load dynamics in respiratory samples have been studied, but knowledge about changes in serial serum samples of infected patients in relation to their immunological response is lacking. We investigated the dynamics of SARS-CoV-2 viral load and antibody response in sequential serum of coronavirus disease 2019 (COVID-19) patients and attempted to culture the virus in the serum. A total of 81 sequential serum samples from 10 confirmed COVID-19 patients (5 with mild and 5 with moderate symptoms) were analyzed. Samples were collected during hospitalization and after discharge (median follow-up of 35 days). SARS-CoV-2 ribonucleic acid in the serum was detected by real-time polymerase chain reaction. Total antibody and IgG to SARS-CoV-2 Spike protein were analyzed by Chemiluminescent Immunoassays, and neutralizing antibodies were detected using a Surrogate Virus Neutralization Test. Viremia was observed in all cases at admission, and viral copy gradually dropped to undetectable levels in patients with mild symptoms but fluctuated and remained persistent in moderate cases. The viral culture of samples with the highest viral load for each patient did not show any cytopathic change. The antibody response was faster and higher in moderate cases. This study provides a basic clue for infectious severity-dependent immune response, viremia, and antibody acquisition pattern.

Several factors related to anti-spike(S) IgG antibody titers after mRNA COVID-19 vaccination have been elucidated, but the magnitude of the effects of each factor has not been fully understood. This cross-sectional study assessed anti-S and anti-nucleocapsid (N) antibody titers on 3744 healthy volunteers (median age, 36 years; IQR, 24–49 years; females, 59.0%) who received two doses of mRNA-1273 or BNT162b2 vaccine and completed a survey questionnaire. Multiple regression was conducted to identify factors associated with antibody titers. All but one participant tested positive for anti-S antibodies (99.97%). The following factors were independently and significantly associated with high antibody titer

Introduction The BNT162b2 and mRNA-1273 COVID-19 vaccines are the main vaccines that have been used for mass vaccination in Japan. Information on adverse reactions to COVID-19 vaccines in the Japanese population is limited. Methods We conducted an online survey on self-reported adverse reactions in individuals who had received two doses of the BNT162b2 or mRNA-1273 vaccine. The incidence of adverse events after each dose of vaccine was investigated. Propensity score matching was used to compare the incidence of adverse reactions after the second dose of the BNT162b2 and mRNA-1273 vaccines. Results After the first and second doses of the BNT162b2 vaccine, and the first and second doses of the mRNA-1273 vaccine, 890, 853, 6401, and 3965 individuals, respectively, provided complete responses. Systemic reactions, including fever, fatigue, headache, muscle/joint pain, and nausea were significantly more common in females, individuals aged

Aim As our society ages, the number of people living with dementia also steadily increases. Some work has focused on masticatory behaviour as a form of daily health care that could help prevent cognitive impairment and dementia. However, it is not yet clear how masticatory behaviour influences various cognitive functions. Therefore, the purpose of this study was to examine the effect of masticatory behaviour on the decline of generalized attention, an important cognitive function. Methods Participants were 35 healthy, dentulous individuals without stomatognathic abnormalities (24 men, 11 women; mean age: 56.8 ± 4.8 years). All participants completed three interventions: mastication, foot-stepping, and none (control). Pre- and post-intervention measures of generalized attention were measured by using neuropsychological tests to examine general attention; the results were then compared. Simultaneously, during the generalized attention task, the functional activity of the prefrontal cortex was observed on functional near-infrared spectroscopy. Results Response time of generalized attention improved in both the masticatory and foot-stepping interventions. There was a transient increase in oxyhaemoglobin activity in the right and left prefrontal cortices in the masticatory intervention. Conclusions Masticatory behaviour may be involved in a partial improvement of generalized attention and may induce prefrontal cortex activity in middle-aged and older adults.

Objective The fecal occult blood (FOB) test is commonly used for colorectal cancer screening; however, it is uncertain if further diagnostic interventions, such as a colonoscopy, should be performed based on its results. Method To better understand patient behavior following the FOB test, 6,414 patients (3,807 men and 2,607 women) who underwent colonoscopy between August 2015 and March 2016 at any of the 26 medical institutions throughout Hiroshima Prefecture were invited to participate in the study. All patients provided their written consent, after which they completed a questionnaire, and their colonoscopy results were obtained. These datasets were analyzed in a blinded manner, and the unique codes linking the records were revealed at the end of the analysis. Results Of the total study population, 4,749 patients (74.0%) had previously undergone FOB testing. After classification of common behavioral responses that the patients displayed following their FOB test, the group who had undergone the test several times, who had not had positive test results in the past, and whose latest FOB test results were positive had a significantly higher diagnosis rate of both early- and advanced-stage cancer than the other groups. Furthermore, patients in whom several previous FOB test results had been negative whose previous colonoscopy was positive were associated with a higher diagnosis rate of early-stage cancer than other groups. Conclusion These results suggested that colonoscopy should be performed immediately for patients with positive FOB test results due to their association with colorectal cancer and the possible detection of cancer at an early stage.

This study determined the prevalence of total hepatitis A antibody (anti-HAV) among 5–7 years old children and their mothers in the whole Cambodia, using a nationwide study, and examined the differences between the two cohorts. A total of 4535 dried blood spot-driven (DBS) samples (2021 mothers and their 2514 children of 5–7 years old) and the concomitant 922 whole blood samples (subset of the whole participants) were collected using a multistage random sampling strategy throughout Cambodia in 2017. Total anti-HAV was detected using the chemiluminescence enzyme immunoassay method. Compared to gold standard whole blood samples, the sensitivity and specificity of DBS mediated anti-HAV detection were 94.8% and 98%, respectively. Total anti-HAV prevalence among mothers was 91.2% (95%CI: 90.0–92.5%), and that of their children was 31.5% (95%CI: 29.7–33.3%). In our study, the low prevalence of total anti-HAV among children indicates the country’s improvement of safe water and food supply, hygiene and sanitation. If the hygiene and sanitation are consistently improved in Cambodia, the prevalence might be no longer increased when the children become adults.

Monoclonal gammopathy (M-proteinemia) is a premalignant plasma cell disorder. The prevalence of M-proteinemia increases with age and is affected by genetic or environmental factors. Atomic bomb (A-bomb) survivors in Hiroshima are in an age range when they are susceptible to M-proteinemia. The prevalence and incidence of M-proteinemia in Hiroshima A-bomb survivors were investigated for 30 years (1989-2018) to examine the influence of radiation exposure. The overall prevalence of M-proteinemia among 38,602 A-bomb survivors was 2.4%. M-proteinemia prevalence at age 70 years and monoclonal gammopathy of undetermined significance (MGUS) incidence were not associated with radiation exposure category. Males had a 2.30-fold higher prevalence and a 2.08-fold higher incidence than females. The risk of incidence for MGUS was 4.32-fold higher in persons aged 10 years at the time of the A-bombing and 2.56-fold higher in those aged 10-19 years compared with those aged over 30 years. IgG type M-proteinemia was common and the IgM type developed 5-8 years later than other immunoglobulin types. Exposure to radiation was not clearly associated with the prevalence of M-proteinemia or incidence of MGUS in Hiroshima A-bomb survivors. However, males and those aged 20 years at A-bombing had higher susceptibility to MGUS.

Highlights • This study proved of Cambodia achieving WHO 2017 target of, Background: Hepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children. Methods: A cross-sectional multi-stage cluster survey was conducted among children born during 2010–2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children’s failure to receive timely (within 24 h) vaccination were analysed by multivariate logistic analysis. Findings: A total of 2,520 children 5–7 years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered ≤ 24 h. Birth at home or “other” location were independent risk factors for children’s failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%–5.45%) among mothers and 0.56% (95%CI: 0.32%–0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%–14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%–18.11%). Interpretation: Having achieved the 2017 target of less than 1% HBsAg prevalence among 5 years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030. Funding: As per sources of funding.

Background Health care workers (HCWs) are at high risk of contracting blood-borne infections including hepatitis B virus (HBV) infection. In Japan, all HCWs are required to receive HB vaccination before beginning work. This study aimed to investigate the dynamics of the HB surface antibody (anti-HBs) titer after a three-dose HB vaccination in HCWs and to determine effective scheduling of HB vaccination for non-responders. Methods Subjects included 832 medical and dental students who had received a three-dose HB vaccination (Bimmugen® 0.5 ml/vial). Anti-HBs was measured three times (before the third dose and 1 and 5 months after the third dose) using the CLIA method. The cut-off value of anti-HBs acquisition was 10 mIU/mL. After booster doses (three maximum) were administered to non-responders, the anti-HBs titers were measured again. Results Out of 832 students, 491 were analyzed, of which 58.9% (289) were male. Anti-HBs-positive rates before the third dose and 1 and 5 months later were 47.9%, 95.9%, and 89.0%, respectively. The relationship between the antibody titer at one month (x) and 5 months (y) was estimated by log10y = log10x − 0.134 (P Conclusion Anti-HBs titer decreases by an average of 20% within 4 months between the 1st and 5th month after the third dose. Therefore, anti-HBs titer should be measured periodically after completing the three-dose vaccination. Additionally, results suggested that booster doses are effective if administered with the same schedule as primary vaccination.

Although hepatitis B (HBV) and C (HCV) virus infections are still global health issues, measuring sero-markers by standard venipuncture is challenging in areas limited with the adequate human resources and basic infrastructure. This study aimed to inform the usefulness of dried blood spot (DBS) sampling technique for epidemiological study of HBV and HCV in the resources limited areas. We compared specimen recovery rate expressed as analytical sensitivity ratio of HBsAg, HBcAb and anti-HCV between serum specimens and DBS samples (HemaSpot vs Whatman903). Sensitivity ratio was calculated as the ratio of the measured value from DBS to the measured value from serum. Then both the qualitative and quantitative comparisons of HBsAg detection by DBS were done using Cambodian samples. HBsAg, HBcAb and anti-HCV sensitivity ratios for the highest sample dilution (8-fold) were 31.2:1, 38.9:1 and 32.0:1 for Whatman903 card and 17.6:1, 23.5:1 and 26.3:1 for HemaSpot respectively. Detection efficacy of HemaSpot (80%) was not inferior to Whatman903 (60%) after 1 month storage, and no significant difference in any hepatitis virus sero-markers was observed in HemaSpot-spotted patient samples stored for 2 weeks at −25 °C and 29 °C. All reference HemaSpot -spotted 400 HBsAg sero-negative samples showed negative. Sensitivity and specificity of HBsAg in HemaSpot were 92.3% and 100%. The recovery expressed as analytical sensitivity ratio of HBsAg, HBcAb and anti-HCV of HemaSpot specimen were not inferior to Whatman903. Therefore, DBS with its usefulness proved as an acceptable tool for large epidemiological study of HBV and HCV in resources limited remote area.

Approximately 75% of hepatocellular carcinomas (HCC) occur in Asia; core promoter mutations are associated with HCC in HBV genotype C, the dominant genotype in Cambodia. We analyzed these mutations in Cambodian residents and compared them with HBV full genomes registered in GenBank. We investigated the characteristics of 26 full-length HBV genomes among 35 residents positive for hepatitis B surface antigen in Siem Reap province, Cambodia. Genotype C1 was dominant (92.3%, 24/26), with one case of B2 and B4 each. Multiple mutations were confirmed in 24 Cambodian C1 isolates, especially double mutation at A1762T/G1764A in 18 isolates (75.0%), and combination mutation at C1653T and/or T1753V and A1762T/G1764A in 14 isolates (58.3%). In phylogenetic analysis, 16 of 24 isolates were located in the cluster with Laos, Thailand, and Malaysia. In 340 GenBank-registered C1 strains, 113 (33.2%) had combination mutation amongst which 16.5%, 34.2%, and 95.2% were found in ASC, chronic hepatitis, and liver cirrhosis (LC)/HCC respectively (P

Since the early 21st century, almost all developed countries have had a very low hepatitis A virus antibody (anti-HAV) sero-prevalence profile, as sanitation conditions and health care facilities have been optimized to a universal standard. There has not been a report on anti-HAV prevalence among a large scale population in Japan since 2003. Therefore, this study aimed to investigate the current HAV status among the general population in Hiroshima. From each age and sex specific group, a total of 1,200 samples were randomly selected from 7,682 stocked serum samples from residents’ and employees’ annual health check-ups during 2013–2015. Total anti-HAV was detected using Chemiluminescent Enzyme Immunoassay. The overall anti-HAV sero-prevalence was 16.8%. In both males and females, anti-HAV prevalence among individuals between 20–59 years of age was as low as 0.0–2.0%, whilst that among 70 s was as high as 70.0–71.0%. A large number of residents aged under 60 are now susceptible to HAV infection. The cohort reduction trend of anti-HAV in Japan exposes the high possibility of mass outbreak in the future. HAV vaccine especially to younger generation and high risk population may prevent outbreak in Japan.

Background In this study, we performed molecular characterization of SARS-CoV-2 strains in Hiroshima and its mutation pattern between the first and second waves of the outbreak. Method A total of 55 nasal swab samples from the first wave in Hiroshima and 13 from the second wave were examined quantitatively by RT-qPCR and qualitatively by nested PCR using specific primers. Four samples from each wave underwent next-generation sequencing and phylogenetic tree analysis including controls and all sequences retrieved in Japan from GISAID and GenBank. Subsequently, mutations were examined. Results Viral load ranged 7.85 × 101−1.42 × 108 copies/ml. Of 68 samples, one was Asian type-O, 65 were European type-GR, and 2 were undetectable. Phylogenetic tree analysis indicated that Japan was infected with various Asian strains (L, S, V, O) from January through April. By second week of March, European strains (G, GH, GR) had appeared, and GR strains became predominant after mid-March. The first case in Hiroshima was classified as Asian strain O, and the rest were GR strains. Then, second wave of GR strains appeared independently with 11–15 base mutations. Comparing the first- and second-wave GR strains, mutation rate was 1.17–1.36 × 10−3 base substitutions per site per year; in addition, amino acid changes occurred at S1361P and P3371S in ORF1a, A314V in ORF1b, and P151L in N. All seven GR strains were D614G variants with R202K and G203R mutations in N. A single-nucleotide insertion in ORF8 that causes a defect in ORF8 protein was found in one isolate (S66) from the second wave. Conclusion Our findings reveal the evolutionary hierarchy of SARS-CoV-2 in Japan. The predominant D614G variants and a new form of ORF8 deletion in Hiroshima provide the clue for role of viral factor in local outbreaks of SARS-CoV-2.

Although mortality rates of colorectal cancer (CRC) have been increasing in Japan, its screening rates remain stagnant at 19.2% among Japanese population aged 40 years in 2014. To evaluate the importance of CRC screening by fecal occult blood test (FOBT), this study estimated the incidence of FOBT-positivity and CRC by sex-age stratification and clarified the risk factors for CRC.Between 2007 and 2014, 56 324 residents (21 517 men and 34 807 women) were enrolled in this study. The sex-age-stratified incidence rates of FOBT-positivity and CRC were estimated by records from health checkups and colonoscopy. Regarding CRC incidence rate in particular, positive predictive value was adopted to adjust bias of FOBT-positivity that did not undergo colonoscopy by person-year method. To investigate the risks of CRC onset, a nested case-control study with 1:10 person-matching on sex and age was performed.Incidence rates of FOBT-positivity and CRC are 4183/100 000 person-year (100 Kpy) and 141.3/100 Kpy, respectively. In both cases, men has higher incidence rate than women (1.3 times for FOBT; 4977 vs 3718/100 Kpy and 2.3 times for CRC; 217.0 vs 96.4/100 Kpy).The records from health checkups were useful to estimate incidence rates of CRC with this procedure. The age-stratified incidence rate indicated the importance of CRC screening by FOBT, especially for men and those aged 50 years. Additionally, it is strongly recommended to do further investigation if positive for initial FOBT screening especially for those who are 70 years.