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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

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.

This study aimed to investigate the prevalence trend of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and their genotype distribution among hemodialysis patients, determining their long-term prognosis and the risk factors to the mortality. This cohort study used both the medical data and the blood samples of hemodialysis patients at nine dialysis centers in Hiroshima from 1999 to 2017. Hepatitis B surface antigen (HBsAg) and anti-HCV were screened and then amplification was done to positive sera by polymerase chain reaction for genotyping. Data were employed for multiple regressions to determine the associated risk factors. A total of 3968 patients were subdivided into three groups: who started hemodialysis before 1990, during 1991 to 2001, and after 2002. The periodic prevalence of HBsAg decreased from 2.8% to 1.3% and that of anti-HCV from 33.3% to 9.5% in the three groups. By multiple regressions, the adjusted hazard ratio of diabetes mellitus (DM) ranges from 1.59 to 2.12 and that of HCV RNA positivity ranges from 1.18 to 1.48 (P < .05). Heart failure is the primary cause of death in all groups. Genotype C2 is predominant for HBV and genotype 1b is predominant for HCV. The decreasing trend of both HBV and HCV was found in the cohort. DM and HCV RNA were the significant risk factors leading to poor prognosis among hemodialysis patients. The similar genotype distribution of both HBV and HCV was found as general population. This alarmed to provide early diagnosis, prompt, and adequate treatment to HCV infection among hemodialysis patients.

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.

Background This study aimed to detect Hepatitis B virus (HBV) genome sequences and their variants as of nationwide scale using dried blood spot (DBS) samples and to provide up-to-date reference data for infection control and surveillance in Cambodia. Method Among 2518 children age 5–7 years and their 2023 mothers participated in 2017 Cambodia nationwide sero-survey on hepatitis B surface antigen (HBsAg) prevalence using multistage random sampling strategy, 95 mothers and 13 children positive to HBsAg were included in this study. HBV DNA was extracted from DBS, then performed polymerase chain reaction. HBV genotypes and potential variants were examined by partial and full length genomic analysis. Results HBsAg positive rate was 4.7% (95/2023) in mothers and 0.52% (13/2518) in their children. Genotype C (80.49%) was abundantly found throughout the whole Cambodia whilst genotype B (19.51%) was exclusively found in regions bordering Vietnam. S gene mutants of HBV were found in 24.29% of mothers and 16.67% of children with HBV DNA positive sera. Full-length genome analysis revealed the homology of 99.62–100% in each mother-child pair. Genotype B was clarified to recombinant genotype B4/C2 and B2/C2. Double (48.39%) and combination mutation (32.26%) were observed in core promoter region of HBV C1 strains. Conclusions This study showed the capable of DBS for large-scale molecular epidemiological study of HBV in resource limited countries. Full-genome sequences yield the better understanding of sub-genotypes, their variants and the degree of homology between strains isolated from mother-child pairs calls for effective strategies on prevention, control and surveillance of mother-to-child HBV transmission in Cambodia.

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.

Background and Aim 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. Methods 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. Results 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). Conclusions 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.

Aim We aimed to estimate hepatitis B surface antigen (HBsAg) positivity among birth year-stratified pregnant women in Hiroshima, Japan, and compare prevalence rates between women born before and after implementation of a national immunoprophylactic vaccination program for babies born to hepatitis B virus (HBV) carrier mothers in Japan. Methods Pregnant women who gave birth at all delivery hospitals/clinics in Hiroshima prefecture between 1 April 2010 and 31 March 2011 were eligible. Lists collected from each institution included survey items such as age (pregnant woman's birth year) and HBsAg and hepatitis C virus (HCV) antibody (anti-HCV) test results, which were posted anonymously and non-consolidated from medical records. We calculated the HBsAg and anti-HCV prevalence in our cohort according to the mothers' birth year. Results In 41 of 58 hospitals/clinics, 15 233 and 15 035 pregnant women underwent HBsAg and anti-HCV testing, corresponding to 59.6% and 58.9% of 25 546 births in the 2010 fiscal year, respectively. The overall HBsAg positive rate was 0.51% (95% confidence interval [CI], 0.40–0.63%), and an extremely low prevalence (0.10%; 95% CI, 0.00–0.25%) was observed among pregnant women born after 1986. However, the prevalence in this study was slightly higher than the nationwide value (0.31%) and the Chugoku region-specific value (0.46%) among first-time blood donors at Japanese Red Cross blood centers between 2001 and 2006. No significant difference in anti-HCV positivity was observed. Conclusion Only two pregnant women born after the preventive program implementation were HBsAg-positive. Perinatal HBV transmission is estimated to be almost completely inhibited in the next generation.

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.

Countermeasures against hepatitis B and C virus (HBV, HCV) infection at work sites in Japan have not yet been implemented. This study aimed to determine the status of viral hepatitis infection among employees in Japan.We undertook a workplace-based cross-sectional study from 2011 to 2016 in Hiroshima, Japan. Hepatitis B virus and HCV markers were identified during a routine checkup of employees in 15 enterprises. The screening results were sent to employees directly and not to employers. A thorough examination of the participants who screened positive was encouraged by forwarding to them a referral letter by our research group to specialized medical institutions.Of the 3015 employees, 2420 (80.3%) underwent hepatitis virus screening. Of these, 13.8% had been screened for hepatitis virus before this survey. The prevalence of hepatitis B surface antigen was 0.95% (n = 23; 95% confidence interval, 0.6-1.3%). The prevalence of hepatitis B core antibody was as high as 31.5% at age 60-69 years, and 41.5% at age 70 years and over. The HCV carrier rate was 0.45% (n = 11; 0.2-0.7%) and 54.5% of them had genotype 2. Thirty-four carriers were detected, and 44.1% of them were detected for the first time; 53.3% of the newly detected carriers visited medical institutions with the referral, and underwent a periodic follow-up or treatment.Promoting hepatitis virus screening for employees may help detect carriers who are unaware of their infection and require treatment. Submitting the results to employees with a referral letter to medical institutions at the time of positive diagnosis may be effective.

This study aimed to survey the prevalence and incidence of hepatitis B (HBV) and hepatitis C virus (HCV) infection among elementary school students in Siem Reap province, Cambodia and to evaluate the effects of a national infant HBV vaccination program introduced in 2001.Students in 3rd grade during the 2011, 2012, and 2013 academic years were enrolled in this study; at the time of the second examination, in the 2014-2015 academic year, the students were in 5th or 6th grade. The incidence and prevalence rates of HBV and HCV infection were estimated and full HBV sequences were analyzed.Among 248 students (107 male and 141 female) born between 1999 and 2005, five students were HBV surface antigen (HBs-Ag) positive (2.02%), and all of them were infected with genotype C. Among them, subgenotype C1 was found in four students and, unexpectedly, complete genetic sequence identity of subgenotype C1 was found in two students from different families. The anti-HBV core (HBc) and anti-HBs prevalence rates were 10.89% and 16.13%, respectively. Twenty-five students were positive for anti-HBs and negative for both HBsAg and anti-HBc (10.08%; estimated serological vaccination rate); this rate increased significantly with the birth year (P = 0.0229). Prevalence of anti-HCV was 2.82%, and HCV RNA was not detected. The estimated incidence of HBV and HCV infection were both 0/1000 person-years (PY) (95% confidence interval, 0-20.61/1000 PY and 0-14.50/1000 PY, respectively).Hepatitis B virus full-genome sequencing and serological analysis revealed the possibility of horizontal transmission of HBV among Cambodian schoolchildren. However, the anti-HBc positivity rate decreased along with increasing age and estimated serological vaccination rates.