Attenuation of hepatitis A antibody after immunization with hepatitis A vaccine (Aimmugen) in people living with HIV.

AIM: Hepatitis A (HA) is a vaccine-preventable disease. In regions with good sanitation, men who have sex with men (MSM) are the key affected populations. During the 2018-2019 HA outbreak among MSM in Japan, we actively vaccinated MSM living with HIV (MSM-LWHIV) with Aimmugen. As previously reported, their antibody seroconversion rate due to vaccination was lower than that of healthy individuals. However, the durability of Aimmugen in people living with HIV has not yet been reported. We evaluated attenuation after the one-series vaccination (comprising three inoculations) and the factors associated with attenuation. METHODS: We retrospectively examined anti-HA immunoglobulin G (anti-HA-IgG) titers and other clinical data from our hospital's medical records. Patients with no history of vaccination or HA infection (i.e., negative HA-IgG titers) who received one series of Aimmugen, achieved seropositivity, and anti-HA-IgG antibodies were tested ≥2 years after three doses were included. Fisher's exact test and the Mann-Whitney U-test were performed. p < 0.05 was considered statistically significant. RESULTS: Fifty-one MSM-LWHIV were included. All were seropositive after the third dose with a median HA-IgG titer of 10.1 (interquartile range, 7.2-12.2) (sample/cut-off values [s/co]). In 45 (40-49) months, seropositivity decreased to 90% (46/51) and was attenuated to a median of 4.4 (2.3-6.5) s/co. Lower baseline B cell counts (p = 0.049), lower anti-HA-IgG levels after the second dose (p = 0.002), and lower anti-HA-IgG levels after the third dose (p = 0.003) were associated with seronegativity. CONCLUSIONS: Anti-HA-IgG titers of vaccinated MSM-LWHIV may be attenuated; thus, additional immunizations should be considered.

No association between inactivated influenza vaccination and influenza viral load at diagnosis among young Japanese children: An observational study of the 2013/2014 through 2017/2018 influenza seasons.

BACKGROUND: The association between inactivated influenza vaccination and viral load in young children remains unclear. METHODS: During the 2013/2014 to 2017/2018 influenza seasons in Japan, children under 6 years of age with pre-defined influenza-like illness and influenza-positive status by real-time RT-PCR were recruited at pediatric clinics for this observational study. Influenza viral load was measured for the most predominant subtype/lineage in each season. Using median dichotomized viral load as an outcome, a multilevel logistic regression model was applied to estimate the multivariable adjusted odds ratio (MOR) and 95% confidence interval (CI) for higher viral load. RESULTS: A total of 1,185 influenza-positive children were analyzed. The median log10 viral load copy number (copies per milliliter) was 5.5 (interquartile range, 4.6 to 6.1) and did not differ by vaccination status: 5.5 for unvaccinated, 5.7 for one dose, and 5.5 for two doses (p = 0.67). The MOR of vaccinated (one or two doses) versus unvaccinated children was 1.19 (95% CI: 0.86-1.64). Other factors showing significant associations with higher viral load were positive results for A(H1N1)pdm09 and A(H3N2) in comparison with B/Yamagata. The respective MORs were 3.25 (95% CI: 2.28-4.64) and 1.81 (95% CI: 1.32-2.49). Significantly elevated MORs against higher viral load were also observed for higher body temperature at influenza diagnosis and shorter duration from fever onset to specimen collection. CONCLUSION: No association was observed between inactivated-influenza vaccination and viral load at influenza-positive diagnosis. Influenza subtype/lineage, body temperature, and time elapsed since fever onset were significantly associated with viral load.

Cardiac Structure and Cardiorespiratory Fitness in Young Male Japanese Rugby Athletes.

Limited data are available on athlete's heart for rugby athletes. This study aimed to investigate cardiac structure and its relationship with cardiorespiratory fitness in young Japanese rugby athletes. A prospective cross-sectional study using echocardiography and cardiopulmonary exercise testing (CPET) was conducted on 114 male collegiate rugby players. There was a higher prevalence of increased left ventricular (LV), atrial, and aortic dimensions in the young athletes than that in previously published reports, whereas the wall thickness was within the normal range. Anthropometry and CPET analyses indicated that the forwards and backs presented muscular and endurance phenotypes, respectively. Indexed LV and aortic dimensions were significantly larger in the backs than in the forwards, and the dimensions significantly correlated with oxygen uptake measured by CPET. On the four-tiered classification for LV hypertrophy, abnormal LV geometry was found in 16% of the athletes. Notably, the resting systolic blood pressure was significantly higher in athletes with concentric abnormal geometry than in the other geometry groups, regardless of their field positions. Japanese young athletes may exhibit unique phenotypes of cardiac remodeling in association with their fitness characteristics. The four-tiered LV geometry classification potentially offers information regarding the subclinical cardiovascular risks of young athletes.

Survey of pediatricians concerning the human papillomavirus vaccine in Japan: Positive attitudes toward vaccination during the period of proactive recommendation being withheld.

In 2013, the human papillomavirus (HPV) vaccine was introduced as a national immunization program in Japan. However, because of a wide range of symptoms after vaccination, the Japanese Ministry of Health, Labor and Welfare decided to withhold proactive recommendations, a situation that has continued for more than eight years. During the withholding, absent any scientific or epidemiological evidence to support a relationship between HPV vaccines and symptoms, we surveyed pediatricians at Osaka Pediatric Association and analyzed the changing of attitudes in 2020 (n = 200) and 2021 (n = 190). A total of 44.5% respondents in 2020 and 67.9% in 2021 offered HPV vaccination to targets at the time the questionnaire was administered, indicating that the rate of pediatricians providing vaccines had increased significantly (p < .001). A total of 74.0% of respondents in 2020 and 77.9% in 2021 had a positive opinion of HPV vaccination (p = .369), and 64.3% in 2020 and 78.3% in 2021 were "not at all concerned or had almost no concern" about HPV vaccination (p = .002). These results suggest that, in general, most physicians who are primarily responsible for HPV vaccination in a given field had a positive attitude toward vaccination during the proactive recommendation having been withheld.

Predictors associated with a better response to the Japanese aluminum-free hepatitis A vaccine, Aimmugen® , for people living with HIV.

AIM: After the hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) around 2018, the importance of HAV vaccination was emphasized, especially for MSM-living with human immunodeficiency virus (MSM-LWHIV). Aimmugen® is licensed and distributed exclusively in Japan. While administration of three doses is recommended, 85% of recipients in the general population were reported to acquire seroprotection after the second dose. In this study, we evaluated the efficacy of two or three vaccine doses along with predictors associated with the response to Aimmugen® in MSM-LWHIV. METHODS: We retrospectively examined anti-HA-IgG titers of MSM-LWHIV vaccinated with Aimmugen® in our hospital. Patients' data were collected from medical records. RESULTS: Between January 2018 and October 2019, 141 subjects whose median age was 46 years old, were examined. All the subjects were on antiretroviral therapy (ART) and the median CD4 count was 615/µL. The acquisition rate of protectable anti-HA-IgG titers after the second and third dose was 71.1% and 98.6%, respectively. In 114 subjects whose anti-HA-IgG titers were tested after the second-dose, factors significantly associated with better response were prolonged ART duration and higher CD4 count. The titers of anti-HA-IgG after the third dose were higher in those who became seropositive after the second-dose than those who did not. CONCLUSIONS: Three-dose of Aimmugen® for MSM-LWHIV was effective while two-dose was less effective compared to non-HIV-infected people. People-LWHIV with shorter duration of ART and lesser CD4 cell count achieved lower titers of anti-HA-IgG and might require an additional vaccination.

Influence of Prior Influenza Vaccination on Current Influenza Vaccine Effectiveness in Children Aged 1 to 5 Years.

BACKGROUND: Although annual influenza vaccination is an important strategy used to prevent influenza-related morbidity and mortality, some studies have reported the negative influence of prior vaccination on vaccine effectiveness (VE) for current seasons. Currently, the influence of prior vaccination is not conclusive, especially in children. METHODS: We evaluated the association between current-season VE and prior season vaccination using a test-negative design in children aged 1-5 years presenting at nine outpatient clinics in Japan during the 2016/17 and 2017/18 influenza seasons. Children with influenza-like illness were enrolled prospectively and tested for influenza using real-time RT-PCR. Their recent vaccination history was categorized into six groups according to current vaccination doses (0/1/2) and prior vaccination status (unvaccinated = 0 doses/vaccinated = 1 dose or 2 doses): (1) 0 doses in the current season and unvaccinated in prior seasons (reference group); (2) 0 doses in the current season and vaccinated in a prior season; (3) 1 dose in the current season and unvaccinated in a prior season; (4) 1 dose in the current season and vaccinated in a prior season; (5) 2 doses in the current season and unvaccinated in a prior season, and (6) 2 doses in the current season and vaccinated in a prior season. RESULTS: A total of 799 cases and 1196 controls were analyzed. The median age of the subjects was 3 years, and the proportion of males was 54%. Overall, the vaccination rates (any vaccination in the current season) in the cases and controls were 36% and 53%, respectively. The VEs of the groups were: (2) 29% (95% confidence interval: -25% to 59%); (3) 53% (6% to 76%); (4) 70% (45% to 83%); (5) 56% (32% to 72%), and (6) 61% (42% to 73%). The one- and two-dose VEs of the current season were significant regardless of prior vaccination status. The results did not differ when stratified by influenza subtype/lineage. CONCLUSION: Prior vaccination did not attenuate the current-season VE in children aged 1 to 5 years, supporting the annual vaccination strategy.

Changes in survival and causes of death among people living with HIV: Three decades of surveys from Tokyo, one of the Asian metropolitan cities.

INTRODUCTION: Survival among people living with HIV (PLWH) has dramatically improved in the antiretroviral therapy (ART) era. This is the first study in Asia to describe three decades of surveys on survival and causes of death among PLWH. METHODS: We included 1121 HIV-infected patients, categorized into three period groups according to date of first visit: 1986-1996 (Pre-ART); 1997-2007 (Early-ART); and 2008-2018 (Late-ART). RESULTS: Ten-year all-cause mortality has reduced from Pre-ART (49.6/1000 person-years) to Late-ART (6.3/1000 person-years). Mortality for AIDS-defining illnesses (ADIs) has also reduced from Pre-ART (34.4/1000 person-years) to Late-ART (2.9/1000 person-years), and mortality for non-ADIs has reduced from Pre-ART (11.7/1000 person-years) to Late-ART (2.9/1000 person-years). In the ART-era, deaths from non-AIDS-defining malignancies and unnatural events including suicide represented the majority of non-ADI-related deaths and mortality rates of non-AIDS defining malignancies and unnatural cause event were not different between each group (3.4, 1.9 and 2.5/1000 person-years). Crude cumulative survival improved over the study period, and 10-year survival ratios of HIV-infected patients to the general Japanese population approached 1.00, from Pre-ART (0.66) to Late-ART (0.99). Even in the Late-ART period, survival remained lower in patients with a history of ADIs than in those without, but the difference in 5-year mortality between these groups has shrunk in the Late-ART compared to the Pre-ART. CONCLUSIONS: Mortality for ADIs and non-ADIs in PLWH has reduced in the Early-ART and Late-ART. To improve survival for PLWH further, early HIV detection and treatment and good management of non-AIDS-defining malignancies and mental disorders are needed. (248/250).

Lactobacillus reuteri DSM 17938 and Magnesium Oxide in Children with Functional Chronic Constipation: A Double-Blind and Randomized Clinical Trial.

OBJECTIVE: Chronic functional constipation is a frequent condition. The aim of the study was to evaluate the efficacy of the probiotic Lactobacillus (L.) reuteri DSM 17938 and magnesium oxide (MgO) for relieving chronic functional constipation in children. STUDY DESIGN: A prospective, double-blind, placebo-controlled, randomized, and parallel-group trial was conducted in five pediatric outpatient clinics in Japan. Sixty patients who were more than six months old and under six years of age with a diagnosis of functional constipation according to Rome IV criteria were randomly divided into three groups: group A (n = 20) received L. reuteri DSM 17938 and lactose hydrate as a placebo of MgO; group B (n = 19) received L. reuteri DSM 17938 and MgO; and group C (n = 21) received a placebo of L. reuteri DSM 17938 and MgO. RESULTS: All three groups exhibited significant improvement in defecation frequency in the fourth week compared with the baseline condition (group A: p < 0.05; group B: p < 0.05; group C: p < 0.05). The MgO group and combination group showed a significant decrease in stool consistency, but the L. reuteri DSM 17938 group did not (group A: p = 0.079; group B: p < 0.05; group C: p < 0.05). MgO significantly suppressed the presence of the genus Dialister. Defecation frequency negatively correlated with the frequency of Clostridiales-belonging bacteria among the gut microbiome. CONCLUSIONS: L. rueteri DSM 17938 and MgO were both effective in the management of functional constipation in young children. MgO caused an imbalance in the gastrointestinal microbiome, which was not the case in the probiotic group.

Association Between Cerebral Small Vessel Disease and Central Motor Conduction Time in Patients with Vascular Risk.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is related to motor function disturbance. It includes several types: lacunar infarction, white matter hyperintensity, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). Transcranial magnetic stimulation (TMS) has been successfully used to evaluate the function of the pyramidal tract. Central motor conduction time (CMCT) is one of the indicators of pyramidal tract dysfunction in motor evoked potential (MEP). The aim of this study was to investigate the association between each type of CSVD and CMCT. METHODS: We enrolled 350 patients with vascular risk factors or a history of cerebrovascular events, who showed signs of CSVD in magnetic resonance imaging in the prospective registry. Among them, 138 patients agreed to the evaluation of MEP. CMCT, resting motor threshold (RMT), and silent period are indicators of the function of motor pathways in MEP. A total of 276 hemispheres were divided into 45 symptomatic hemispheres with a history of pyramidal tract dysfunction and 231 without it. Correlation between each type of CSVD and CMCT were examined in total, symptomatic, and asymptomatic hemispheres. RESULTS: The mean age was 70.5 ± 10.3 (mean ± SD) years, and 89 (65%) were men. In the symptomatic hemisphere, CMCT and RMT were significantly higher than in the asymptomatic hemisphere. In the symptomatic hemisphere, significant association was observed between the number of EPVS in the white matter and CMCT (R2 = 0.201, p < .01). CONCLUSIONS: In the symptomatic hemispheres, CMCT was associated with the number of EPVS in the white matter. The EPVS in the white matter may be involved in the motor disturbance due to CSVD.

[Milk, Daily products and Bone health.Effect of milks and daily products on bone health.]

In Japan, nutrition education programs to prevent osteoporosis and osteoporotic fractures have focused primarily on increasing dietary calcium intake and recommended the consumption of milk and dairy products. However, the effect of milk and dairy product consumption on bone density loss or fracture incidence in Japanese has rarely been evaluated in randomized controlled studies. In the present study, we reviewed the literature investigating the consumption of milk and dairy products in relation to bone density and fracture risk. The results showed that milk and dairy product consumption had only a modest effect in the prevention of midlife bone loss and subsequent fractures. However, given that infrequent(once weekly or less)consumption of milk may be associated with an increased risk of femoral neck fracture, and that Japanese generally have a lower calcium intake, it is still necessary to encourage elderly and younger adults to increase their consumption of milk and dairy products to promote bone health.

Characterization of iron-responsive promoters in the marine diatom Phaeodactylum tricornutum.

It is well established that iron is one of the major constraints of primary productivity of marine diatoms in world oceans. In the present study, changes in the transcript levels of the 20 iron related genes were profiled in the marine diatom Phaeodactylum tricornutum during an early stage of acclimation from iron replete to iron-limited conditions. The results clearly showed that the profiles differ depending on genes, suggesting the occurrence of several modes of iron-responsive regulation at the transcriptional level. Upstream DNA sequences of iron starvation induced protein1 (Isi1), ferrichrome binding protein1 (FBP1), and flavodoxin (Fld) genes were isolated, fused with the GUS reporter gene, uidA, and transformed into P. tricornutum. Obtained transformants were subjected to the GUS reporter assay and the result clearly revealed that the GUS activity of all transformants was significantly increased upon iron limitation. Iron responsive Cis-elements in each promoter region were determined by the promoter truncation technique, demonstrating the occurrence of the critical iron-responsive regulatory regions of about 30bp in the promoter regions of three genes, Isi1, FBP1, and Fld. Interestingly, these sequences were similar with each other revealing two conserved motifs, A; A(A/C)G(G/C)C(G/-)C(A/G)TG; and B; CACGTG(T/C)C, which are homologous to the iron responsive Cis-element in the green alga, Chlamydomonas reinhardtii. The impairment of the motif B in the Isi1 promoter resulted in the loss of iron response and the core regulatory region of the FBP1 promoter conferred an iron response on the constitutive cytomegalovirus promoter, PCMV, indicating that these conserved promoter sequences are iron-responsive elements. Finally, the inductive regulation of these promoters under iron-limited conditions was dissipated specifically by 5% CO2, strongly suggesting the participation of CO2 in the transcriptional regulation of the iron-related gene promoters.

[Nutrition and bone health. Soybean and soy foods, and bone health].

Soybean and various types of soy products, such as natto, tofu, miso, and soy sauce, have long been consumed in Japan. Soybean, a rich source of plant proteins, contains a relatively high amount of calcium as well as being an important source of isoflavones, a group of substances whose chemical structure is similar to that of estrogen. Natto, fermented soybeans, contains vitamin K, which is involved in the activation of osteocalcin. For bone health and osteoporosis prevention in Japanese, it is thus beneficial to consume adequate amounts of soybean and soy products on a daily basis.

[Calcium in aging, health, and anti-aging. Significance of calcium supplement for anti-aging].

For prevention of osteoporosis and debilitating bone fractures, poor calcium intake has long been a major public health problem in Japan. However, few randomized controlled studies have been conducted to clarify the relationship between calcium intake and bone mineral density, and the effect of the prevention of bone fractures. Therefore we reviewed the articles about the evidence for calcium intake and bone fracture incidence in European, American and Asian. We get the results that many articles supported the basis of current health guidelines for the prevention of osteoporosis that recommended increasing calcium intake to the recommended age-related daily allowance levels.

[Allowance of optimal calcium intake for the prevention of osteoporosis and osteoporotic fractures].

One of the main focuses of lifestyle modification for the prevention of osteoporosis and osteoporotic fractures in Japan is improvement in dietary calcium intake. However, virtually no randomized controlled trial to assess the preventive effects of administration of calcium on the risk of fractures has been conducted in Japan. In this study, we reviewed all the scientific papers currently available from medical literature databases to propose evidence-based recommendations on the preventive procedures for osteoporosis. The evidence also supports the current health policy guiding the elderly to increase their dietary calcium intake in daily life.

[Optimization of calcium intake for the prevention of osteoporosis and osteoporotic fractures: a review of the evidence].

One of the main focuses of lifestyle modification for the prevention of osteoporosis and osteoporotic fractures in Japan is improvement in dietary calcium intake. However, virtually no randomized controlled trial to assess the preventive effects of administration of calcium on the risk of fractures has been conducted in Japan. In this study, we reviewed all the scientific papers currently available from medical literature databases to propose evidence-based recommendations on the preventive procedures for osteoporosis. The result of the present systematic review gives the evidence showing that calcium supplementation or optimal dietary calcium intake increases bone density in childhood and adolescence and reduces the risk of fracture due to osteoporosis in the elderly people regardless of the gender. The evidence also supports the current health policy guiding the elderly to increase their dietary calcium intake in daily life.

A mutation in the flavin-containing monooxygenase 3 gene and its effects on catalytic activity for N-oxidation of trimethylamine in vitro.

To clarify the mutation of the flavin-containing monooxygenase (FMO) 3 gene causing fish-odor syndrome, we analyzed the FMO3 gene of a Thai subject who possibly suffered from fish-odor syndrome. A novel mutation, a single-base substitution from G to A at the position of 265 (G265A), was identified in exon 3. The mutation caused an amino acid substitution from valine to isoleucine at residue 58 (V58I). The mutated FMO3 protein with V58I exhibited the reduced trimethylamine N-oxidase activity when it was expressed in E. coli. The V(max)/K(m) value for the activity of the mutant-type FMO3 was about 5 times lower than that for the wild-type FMO3.