Evaluation of protein requirements using the indicator amino acid oxidation method: a scoping review.

BACKGROUND: The indicator amino acid oxidation (IAAO) method has been accepted as an approach to evaluate habitual protein requirements under free-living conditions. OBJECTIVES: This scoping review reports on literature that evaluated protein requirements in humans using the IAAO methods. METHODS: Three databases (PubMed/Medline, Web of Science, and ProQuest) were systematically searched to identify studies that evaluated protein requirements using the IAAO method published in English until 5 June, 2023. We evaluated the study quality using previously developed criteria. We extracted the characteristics of the study design and the results of protein requirements. Two reviewers conducted both reviews and quality assessments independently; any differences among them were resolved by consensus or agreement of all team members. RESULTS: We extracted 16 articles targeting children, young adults (including pregnant women, resistance training athletes, endurance-training athletes, and team sports), and older adults. In quality assessment, 14 studies were evaluated "strong," but the remaining 2 were "moderate." These studies were conducted in only 3 countries and did not include all sexes or life stages. The range of the estimated average protein requirements of each life stage was 1.30 g/kg body weight/d for children, 0.87 to 2.10 (0.87-0.93 for general young adults, 1.22-1.52 for pregnant women, 1.49-2.00 for resistance-trained athletes, 1.65-2.10 for endurance athletes, and 1.20-1.41 for team sports athletes) g/kg body weight/d for young adults, and 0.85 to 0.96 g/kg body weight/d for older adults. CONCLUSIONS: Protein requirements in 14 studies were higher than the current reference for each sex, life stage, and physical activity that are related to protein requirements. In the future, protein requirements of various populations including sex and life stage could be assessed using the IAAO methods worldwide.

Risk of Stroke in Atrial Fibrillation According to Sex in Patients Aged Younger Than 75 Years: A Large-Scale, Observational Study Using Real-World Data.

BACKGROUND: It is unclear whether women have a higher risk of stroke than men. This study aimed to clarify the effects of a sex difference on the risk of ischaemic stroke in patients with atrial fibrillation (AF). METHODS: Health check and insurance claims data were used of people who were aged <75 years from 2005 to 2017 in Japan. Patients with AF who were not on anticoagulation therapy were identified. After excluding patients with artificial valves (n=28), haematological disease (n=1,124), aged ≤20 years (n=207), and taking anticoagulant therapy (n=11,848), 9,733 remained for inclusion into the study. The primary outcome was hospital admission due to ischaemic stroke. RESULTS: Of the 9,733 participants, 7,079 (72.7%) were men. The mean age of women (54.4 years) was significantly higher than that of men (53.2 years). During a mean 2.5-year follow-up period, 143 ischaemic stroke events occurred. Female sex was not associated with ischaemic stroke (adjusted hazard ratio [95% confidence interval]: 1.13 [0.78-1.66]). When stratified using the CHA2DS2-VASc score, the annual incidence of ischaemic stroke was similarly low among women with a CHA2DS2-VASc score of 1 (0.8%) and men with a score of 0 (0.7%). The incidence of ischaemic stroke increased with a CHA2DS2-VASc score of 2 in women and 1 in men. CONCLUSIONS: In this large-scale, real-world study of patients with AF, the risk of ischaemic stroke among those aged <75 years was comparable between women and men. These findings are consistent with the current guidelines, which do not recommend anticoagulant therapy for women with no other risk factors (CHA2DS2-VASc score of 1).

Increased Incident Ischemic Stroke Risk in Advanced Kidney Disease: A Large-Scale Real-World Data Study.

INTRODUCTION: Evidence using real-world data is sparse regarding the effects of oral anticoagulants (OACs) among patients with kidney disease. The aim of this study was to investigate the effects of kidney disease on ischemic stroke (IS) or systemic embolism (SE) among patients taking OAC, using large-scale real-world data in Japan. METHODS: This was a retrospective cohort study using claims data and health checkup data from health insurance associations in Japan, from January 2005 to June 2017. We enrolled 21,581 patients diagnosed with atrial fibrillation (AF). Of the total population, 11,848 (54.9%) patients were taking OAC. A Cox proportional hazards model was used to examine the effect of kidney disease on IS/SE with or without OAC. RESULTS: During follow-up, 208 participants who were not taking OAC (mean follow-up 2.6 years) and 200 who were taking OAC (mean follow-up 3.0 years) experienced IS/SE. The % IS/SE incidence rates with and without kidney disease were 2.42/person-year and 0.63/person-year in the total population, 3.66/person-year and 0.76/person-year in the group without OAC use, and 1.52/person-year and 0.55/person-year in patients with OAC use, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) of kidney disease for IS/SE were high, irrespective of OAC, even after adjustment: adjusted HR 2.62 (95% CI: 1.72-3.99) without OAC and adjusted HR 2.03 (95% CI: 1.20-3.44) with OAC; p = 0.193 for interaction between no OAC and OAC. Although bleeding risk was also high for kidney disease irrespective of OAC use (HR 2.93 [95% CI: 2.27-3.77] in the total population, HR 3.08 [95% CI: 2.15-4.43] in the group without OAC, and HR 2.73 [95% CI: 1.90-3.91] in the group with OAC use), net clinical benefit indicated that the benefit of OAC use exceeded the risk of bleeding: HR 4.50 (95% CI: 0.76-8.23) among those with kidney disease and HR 0.35 (95% CI: 0.04-0.66) among those without kidney disease. CONCLUSION: Although we found that OAC use was effective and recommended for patients with AF, advanced kidney disease is still an independent risk factor for IS/SE, even in patients taking OAC. Physicians should be aware of this risk and strictly control modifiable risk factors, regardless of OAC use.

The Babesia divergens Asia Lineage Is Maintained through Enzootic Cycles between Ixodes persulcatus and Sika Deer in Hokkaido, Japan.

Parasites of the Babesiadivergens Asia lineage, which are closely related to B. divergens in Europe and Babesia sp. strain MO1 in the United States, were recently reported in sika deer (Cervus nippon) in eastern Japan. To identify the tick vector(s) for this parasite, we conducted a field survey in Hokkaido, Japan, where the infection rate in sika deer is the highest in the country. A specific PCR system which detects and discriminates between lineages within B. divergens and between those lineages and Babesia venatorum showed that Ixodes persulcatus (11/822), but not sympatric Ixodes ovatus (0/595) or Haemaphysalis sp. (0/163) ticks, carried B. divergens Asia lineage. Genomic DNA was archived from salivary glands of partially engorged I. persulcatus females and three isolates of B. divergens Asia lineage were newly described. The 18S rRNA gene sequence of the isolates formed the Asia lineage cluster with those previously described in sika deer isolates. One salivary gland also contained parasites of Babesia microti U.S. lineage, which were subsequently isolated in a hamster in vivoB. venatorum (strain Etb5) was also detected in one I. persulcatus tick. The 18S rRNA sequence of Etb5 was 99.7% identical to that of B. venatorum (AY046575) and was phylogenetically positioned in a taxon composed of B. venatorum isolates from Europe, China, and Russia. The geographical distribution of I. persulcatus is consistent with that of B. divergens in sika deer in Japan. These results suggest that I. persulcatus is a principal vector for B. divergens in Japan and Eurasia, where I. persulcatus is predominantly distributed.IMPORTANCE The Babesiadivergens Asia lineage of parasites closely related to B. divergens in Europe and Babesia sp. MO1 in the United States was recently reported in Cervus nippon in eastern Japan. In this study, specific PCR for the Asia lineage identified 11 positives in 822 host-seeking Ixodes persulcatus ticks, a principal vector for many tick-borne disease agents. Gene sequences of three isolates obtained from DNA in salivary glands of female ticks were identical to each other and to those in C. nippon We also demonstrate the coinfection of B. divergens Asia lineage with Babesia microti U.S. lineage in a tick salivary gland and, furthermore, isolated the latter in a hamster. These results suggest that I. persulcatus is the principal vector for B. divergens as well as for B. microti, and both parasites may be occasionally cotransmitted by I. persulcatus This report will be important for public health, since infection may occur through transfusion.

Socioeconomic Status and Knowledge of Cardiovascular Risk Factors: NIPPON DATA2010.

BACKGROUND: The relationship between socioeconomic status (SES) and knowledge of cardiovascular risk factors remains unknown in a general Japanese population. METHODS: Of 8,815 participants from 300 randomly selected areas throughout Japan, 2,467 participants who were free of cardiovascular disease and who provided information on SES in the National Health and Nutrition Survey of Japan 2010 were enrolled in this cross-sectional analysis. SES was classified according to the employment status, length of education, marital and living statuses, and equivalent household expenditure (EHE). Outcomes were ignorance of each cardiovascular risk factor (hypertension, diabetes, hypercholesterolemia, low high-density lipoprotein [HDL] cholesterol, arrhythmia, and smoking) and insufficient knowledge (number of correct answers <4 out of 6). RESULTS: A short education and low EHE were significantly associated with a greater ignorance of most cardiovascular risk factors. A short education (<10 years) was also associated with insufficient knowledge of overall cardiovascular risk factors: age- and sex-adjusted odds ratios (OR) were 1.92 (95% confidence interval [CI], 1.51-2.45) relative to participants with ≥13 years of education. Low EHE was also associated with insufficient knowledge (age- and sex-adjusted OR 1.24; 95% CI, 1.01-1.51 for the lowest quintile vs the upper 4 quintiles). These relationships remained significant, even after further adjustments for regular exercise, smoking, weekly alcohol consumption, body mass index, hypertension, diabetes mellitus, hypercholesterolemia, and low HDL cholesterol. CONCLUSION: Participants with a short education and low EHE were more likely to have less knowledge of cardiovascular risk factors.

Reducing radiation exposure using commonly available objects.

OBJECTIVES: One and a half years have passed since the Fukushima Daiichi nuclear power plant disaster. The environmental radiation dose rate was not critical, but an existing exposure situation has been identified in a large part of Fukushima Prefecture. Although people continue to live and work in the contaminated area, they are not provided with sufficient information to reduce their exposure to radiation by themselves. In this study, we attempt to evaluate the efficiency of radiation shielding by using everyday items widely available to people. METHODS: NaI scintillation and Geiger-Müller survey meters were used to measure the radiation dose of (1) contaminated soil and (2) soil covered with commonly available items. RESULTS: In the soil at a depth of 10 cm from the surface, the radiation dose rate decreased from 3.36 to 0.65 µSv/h, and the count rate decreased from 3,120 to 352 cpm. Both the radiation dose rate and count rate reduced when the soil was covered with everyday items, such as a magazine more than 20 mm thick, a polystyrene foam board, and a wooden board of the same thickness. CONCLUSIONS: To protect residents from unnecessary radiation exposure in the existing exposure situation, covering contaminated soil with a wooden board or a magazine, either of them 20 mm thick, is useful to reduce the radiation dose.

Association between serum ALT levels and incidence of new-onset diabetes in general population of Japanese: a longitudinal observational study (ISSA-CKD).

OBJECTIVE: We aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population. SETTING: Population-based retrospective cohort study using annual health check-up data for residents of Iki City, Nagasaki Prefecture, Japan. PARTICIPANTS: A total of 5330 Japanese individuals (≥30 years old) without diabetes at baseline were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Serum ALT levels were determined using an enzymatic method and were classified into gender-specific quartile groups as follows: group 1 (3-16 U/L in men and 3-13 U/L in women), group 2 (17-21 U/L in men and 14-16 U/L in women), group 3 (22-29 U/L in men and 17-22 U/L in women) and group 4 (30-428 U/L in men and 23-268 U/L in women). The study outcome was the incidence of diabetes (fasting glucose ≥7.0 mmol/L, non-fasting glucose ≥11.1 mmol/L, glycated haemoglobin ≥6.5% or use of glucose-lowering therapies). RESULTS: After an average follow-up period of 5.0 years, 279 individuals developed diabetes. The incidence rate of diabetes increased with elevation of serum ALT levels (0.7% per 100 person-years in group 1, 0.9% in group 2, 0.9% in group 3 and 1.7% in group 4) (p<0.001 for trend). This association was significant after adjustment for other risk factors including age, sex, obesity, hypertension, dyslipidaemia, smoking, current daily alcohol intake and regular exercise (p<0.001 for trend). Comparable associations were observed between men and women (p=0.459 for interaction). CONCLUSION: Serum ALT levels were associated with future development of diabetes in the general Japanese population.

Detection of two zoonotic Babesia microti lineages, the Hobetsu and U.S. lineages, in two sympatric tick species, ixodes ovatus and Ixodes persulcatus, respectively, in Japan.

The species Babesia microti, commonly found in rodents, demonstrates a high degree of genetic diversity. Three lineages, U.S., Kobe, and Hobetsu, are known to have zoonotic potential, but their tick vector(s) in Japan remains to be elucidated. We conducted a field investigation at Nemuro on Hokkaido Island and at Sumoto on Awaji Island, where up to two of the three lineages occur with similar frequencies in reservoirs. By flagging vegetation at these spots and surrounding areas, 4,010 ticks, comprising six species, were collected. A nested PCR that detects the 18S rRNA gene of Babesia species revealed that Ixodes ovatus and I. persulcatus alone were positive. Lineage-specific PCR for rRNA-positive samples demonstrated that I. ovatus and I. persulcatus carried, respectively, the Hobetsu and U.S. parasites. No Kobe-specific DNA was detected. Infected I. ovatus ticks were found at multiple sites, including Nemuro and Sumoto, with minimum infection rates (MIR) of ∼12.3%. However, all I. persulcatus ticks collected within the same regions, a total of 535, were negative for the Hobetsu lineage, indicating that I. ovatus, but not I. persulcatus, was the vector for the lineage. At Nemuro, U.S. lineage was detected in 2 of 139 adult I. persulcatus ticks (MIR, 1.4%), for the first time, while 48 of I. ovatus ticks were negative for that lineage. Laboratory experiments confirmed the transmission of Hobetsu and U.S. parasites to hamsters via I. ovatus and I. persulcatus, respectively. Differences in vector capacity shown by MIRs at Nemuro, where the two species were equally likely to acquire either lineage of parasite, may explain the difference in distribution of Hobetsu throughout Japan and U.S. taxa in Nemuro. These findings are of importance in the assessment of the regional risk for babesiosis in humans.

Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese.

OBJECTIVE: It is well known that manganese (Mn) exposure is involved in parkinsonism. The aim of our study was to test the hypotheses that Mn affects nicotinamide N-methyltransferase (NNMT) activity, increases the metabolism of nicotinamide (NA) to 1-methylnicotinamide (MNA), and leads to neurocytotoxicity. METHODS: Following demonstration of the effects of Mn concentrations on the survival rate of Mouse CD1 brain striatum neuronal cells (MS cells), the effect of Mn on NNMT activity was investigated by comparing the difference in the amount of MNA produced after various Mn concentrations were added to mouse brain cytosol fractions as an enzyme solution. Toxicity induced by MNA and its precursor NA on MS cells was measured. RESULTS: The survival rate of MS cells decreased significantly with increasing concentrations of Mn in the culture medium. With respect to the influence of Mn on NNMT activity, NNMT activity increased significantly at Mn concentrations of 1 µmol/mg protein. MNA and NA neurotoxicity were compared by comparing cell survival rate. Cell survival rate dropped significantly when the cells were cultivated with 10 mM of MNA. There was also a tendency for the survival rate to fall following the addition of 10 mM NA; however, the difference with the control was not significant. CONCLUSIONS: Our study suggests the possibility that Mn causes increased NNMT activity, thereby increasing MNA levels in the brain and bringing about neuron death. Daily absorption of Mn and NA may thus contribute to idiopathic Parkinson's disease.

An assessment of radiation doses at an educational institution 57.8 km away from the Fukushima Daiichi nuclear power plant 1 month after the nuclear accident.

OBJECTIVES: On 11 March 2011, the Great East Japan Earthquake occurred. Due to this earthquake and subsequent tsunami, malfunctions occurred at the Fukushima Daiichi nuclear power plant. Radioactive material even reached the investigated educational institution despite being 57.8 km away from the power station. With the goal of ensuring the safety of our students, we decided to carry out a risk assessment of the premises of this educational institution by measuring radiation doses at certain locations, making it possible to calculate estimated radiation accumulation. METHODS: Systematic sampling was carried out at measurement points spaced at regular intervals for a total of 24 indoor and outdoor areas, with 137 measurements at heights of 1 cm and 100 cm above the ground surface. Radiation survey meters were used to measure environmental radiation doses. RESULTS: Radiation dose rates and count rates were higher outdoors than indoors, and higher 1 cm above the ground surface than at 100 cm. Radiation doses 1 cm above the ground surface were higher on grass and moss than on asphalt and soil. The estimated radiation exposure for a student spending an average of 11 h on site at this educational institution was 9.80 µSv. CONCLUSIONS: Environmental radiation doses at our educational institution 57.8 km away from the Fukushima Daiichi nuclear power plant 1 month after the accident were lower than the national regulation dose for schools (3.8 µSv/h) at most points. Differences in radiation doses depending on outdoor surface properties are important to note for risk reduction.

Determination of Optimal Daily Magnesium Intake among Physically Active People: A Scoping Review.

Little is known about the optimal daily magnesium (Mg) intake for individuals with high levels of physical activity. The aim of this study was to clarify the optimal dietary Mg intake for people with high levels of physical activity in a scoping review. In this review, we searched MEDLINE and Japan Medical Abstracts Society for studies published up to May 31, 2020. We conducted two searches, one for studies using gold standard measurement methods such as the balance method and factorial calculation (Search 1), and the other for studies using estimation from daily food intake (Search 2). We also performed a meta-analysis of studies that compared the Mg intake among physically active people with the Mg intake among controls. After the primary and secondary screening, 31 studies were included in the final review. All of the included studies examined professional or recreational athletes. We found no studies that examined the optimal intake of Mg using gold standard measurement methods. The Mg intake among physically active individuals was below the recommended dietary allowance in most studies. In five studies that conducted meta-analyses, physically active individuals had significantly higher intakes of Mg than controls, although these levels were still below the recommended dietary allowance. The present review revealed that evidence regarding the optimal daily magnesium intake is currently scarce, and further studies are needed.

Residual risks of ischaemic stroke and systemic embolism among atrial fibrillation patients with anticoagulation: large-scale real-world data (F-CREATE project).

OBJECTIVE: Among patients with atrial fibrillation, the risks of ischaemic stroke and systemic embolism (IS/SE) are high even with effective anticoagulation. Using large-scale, real-world data from Japan, this study aims to clarify residual risks of IS/SE attributable to modifiable risk factors among patients with atrial fibrillation who are taking oral anticoagulants. METHODS: The study design we employed was a retrospective cohort. Health check-ups and insurance claims data of Japanese health insurance companies were accumulated from January 2005 to June 2017. We identified 11 848 participants with atrial fibrillation who were on oral anticoagulants during the study period. We set the modifiable risk factors as hypertension, diabetes and dyslipidaemia. A Cox proportional hazards model was used to obtain the effects of the risk factors for IS/SE. RESULTS: During an average of 3 years' follow-up, 200 cases of IS/SE occurred (incidence rate 0.57 per 100 person-years). In multivariable analyses, older age (65-74 vs <65 years; adjusted HR 2.02 (95% CI 1.49 to 2.73)), hypertension (adjusted HR 1.41 (1.04 to 1.92)) and dyslipidaemia (adjusted HR 1.46 (1.07 to 1.98)) were significantly associated with increased risk of IS/SE. Percentage of IS/SE risk attributable to modifiable risk factors (hypertension, diabetes and dyslipidaemia) was 30.0% (16.1% to 41.6%). CONCLUSION: Among patients with atrial fibrillation on anticoagulant therapy, approximately one-third of the residual risks were estimated to be attributable to modifiable risk factors such as hypertension, diabetes and dyslipidaemia.

Effect of chronic kidney disease on the association between hyperuricemia and new-onset hypertension in the general Japanese population: ISSA-CKD study.

We aimed to investigate the association between serum uric acid (SUA) level and development of hypertension as well as the interaction effect of chronic kidney disease (CKD) on this relationship in the general Japanese population. We included 7895 participants aged ≥30 years from the ISSA-CKD study, a population-based retrospective cohort study that used annual health check-up data of residents from Iki Island, Japan. After the exclusion of 1881 with l < 1-year follow-up, 2812 with hypertension at baseline, and 165 with missing information on SUA, a total of 3037 participants were enrolled in this analysis. Participants were divided into four groups according to the quartiles of SUA level at baseline, and multivariable-adjusted hazard ratios for new-onset hypertension were calculated. Stratified analyses were performed for each subgroup (defined by sex, age, alcohol intake, and CKD) to assess the interaction effects. During a mean follow-up period of 4.4 years, 943 participants developed hypertension. The first quartile group was set as the reference group, and the multivariable-adjusted hazard ratios (95% confidence interval) for new-onset hypertension were 1.11 (0.90-1.36) in the second quartile, 1.25 (1.02-1.54) in the third quartile, and 1.35 (1.07-1.70) in the fourth quartile compared with those in the reference group (p = .007 for trend). The stratified analyses showed that the association between SUA and hypertension was significantly stronger in participants with CKD than in those without CKD (p = .035 for interaction). SUA level is an independent risk factor for new-onset hypertension. This tendency was significantly stronger in participants with CKD.

Association between pulse pressure and progression of chronic kidney disease.

The aim of this study was to investigate the association between pulse pressure (PP) and chronic kidney disease (CKD) progression among the general population in Japan. We conducted a population-based cohort study of the residents of Iki Island, Nagasaki, Japan, from 2008 to 2018. We identified 1042 participants who had CKD (estimated glomerular filtration rate(eGFR) < 60 mL/min/1.73 m2 or the presence of proteinuria) at baseline. Cox's proportional hazard model was used to evaluate the association between PP and progression of CKD. During a 4.66-year mean follow-up, there were 241 cases of CKD progression (incident rate: 49.8 per 1000 person-years). A significant increase existed in CKD progression per 10 mmHg of PP elevation, even when adjusted for confounding factors [adjusted hazard ratio 1.17 (1.06-1.29) p < 0.001]. Similar results were obtained even after dividing PP into quartiles [Q2: 1.14 (0.74-1.76), Q3: 1.35 (0.88-2.06), Q4: 1.87 (1.23-2.83) p = 0.003 for trend]. This trend did not change significantly irrespective of baseline systolic or diastolic blood pressures. PP remained a potential predictive marker, especially for eGFR decline. In conclusion, we found a significant association between PP and CKD progression. PP might be a potential predictive marker for CKD progression.

Higher toxicity of dibutyltin and poly-L-lactide with a large amount of tin but lower toxicity of poly-L-lactide of synthetic artificial dura mater exhibited on murine astrocyte cell line.

Neurotoxicities of dibutyltin (DBT), tin(II) octylate (OT), poly-L-lactides (PLLA, molecular weight [MW]=5000, PLLA 5000), PLLA without tin (MW=3000, PLLA 3000), PLLA with a large amount (590 ppm) of tin (S3), poly(glycolic acid-co-epsilon-caprolactone) oligomer (MW=6200, PGC oligomer), and poly(L-lactic acid-co-glycolic acid-co-epsilon-caprolactone) oligomer (MW=6400, PLGC oligomer) related to artificial dura mater were examined using the murine astrocyte cell line, CRL-2534. The indices were cell viability, glutamate concentration in the cell supernatant, and cell proliferation. Lower cell viability was observed among cells exposed to 0.5 microM DBT or 10 microg/ml of S3. There were no differences in cell viability of astrocytes exposed to OT, PLLA 5000, PLLA 3000, PGC oligomer, or PLGC oligomer. Mean glutamate concentration in the supernatant of cells exposed to 0.25 muM DBT was higher than that of the control after 2 h incubation. Lower mean concentration of glutamate in the supernatant of cells exposed to 5 microg/ml of S3 was observed after 2 h incubation. Cells exposed to 50 microg/ml of PGC oligomer had a higher mean concentration of glutamate in the supernatant. OT only inhibited cell proliferation at 100 microM. Proliferation of cells exposed to 0.25 microM or 0.5 microM DBT was inhibited, as was that of cells exposed to 100 microM OT, 50 microg/ml PLLA 5000, 50 microg/ml PLLA 3000, and 5 microg/ml S3, 5 d and 7 d after exposure. Although DBT does not reach levels that induced neurotoxicity in artificial dura mater, these results suggest that DBT is neurotoxic and PLLA toxicity increases with the increase in tin concentration.

Risks of Bleeding and Stroke Based on CHA2DS2-VASc Scores in Japanese Patients With Atrial Fibrillation: A Large-Scale Observational Study Using Real-World Data.

Background This large-scale observational study on negative events in a real-world setting investigated Japanese patients with atrial fibrillation who were not on anticoagulants. This study aims to evaluate the incidence of ischemic stroke and bleeding events (intracranial hemorrhage, gastrointestinal bleeding, others) based on CHA2DS2-VASc scores in Japanese patients with atrial fibrillation who were not anticoagulated. Methods and Results We used health checkups and insurance claim data from a Japanese insurance organization. Altogether, 9733 atrial fibrillation patients were not prescribed anticoagulation during their follow-up periods. Patients' risk levels were defined by their CHA2DS2-VASc scores (range 0-≥3): Men with scores of 0, 1, or ≥2 and women with scores of 1, 2, or ≥3 were considered at low, intermediate, or high risk, respectively. Cox proportional hazards model was used to assess the association between the CHA2DS2-VASc-determined risk and the incidence of ischemic stroke and intracranial, gastrointestinal, and other bleeding. The mean 2.5-year follow-up revealed 143 ischemic strokes and 332 bleeding events. Annual event rates were 0.58% for ischemic stroke and 1.17% for total bleeding events. Annual incidence of ischemic stroke increased with elevated predicted risks based on CHA2DS2-VASc scores: 0.18% for low-risk, 0.44% intermediate-risk, and 1.29% high-risk groups (P<0.001 for trend). Annual incidences of total bleeding also increased with elevated predicted risks: 0.51% for low-risk, 1.28% intermediate-risk, and 2.02% high-risk groups (P<0.001 for trend). Conclusions Risks of ischemic stroke and bleeding events were high, particularly among those with high CHA2DS2-VASc scores.

Molecular evidence for the presence of new Babesia species in feral raccoons (Procyon lotor) in Hokkaido, Japan.

We recently reported that feral raccoons (Procyon lotor) with splenomegaly native to Japan were carriers of a Babesia microti-like parasite identical to that found in the United States, which was likely introduced to Japan from North America via raccoons imported as pets. Thus, we attempted extensive molecular survey for piroplasma infections of feral raccoon with normal spleen in Hokkaido, Japan using nested PCR that target broadly to 18S ribosomal RNA gene (SSU-rDNA) of all the parasites in the genus Babesia, Theileria, Cytauxzoon and B. microti group. Of the 348 raccoon samples analyzed, 9 gave positive signals. Cloning and phylogenetic analysis on SSU-rDNA sequences revealed that six of nine positives were found to be infected with Babesia and the remaining three with previously unreported Sarcocystis. Babesia sequences were further separated into two distantly related groups, those that reside in a novel phylogenetic group were consisted solely of four parasites found in this study, while those which included one identical sequence found in the three of our specimens were assembled together with both Babesia parasites of tick's in Japan and of raccoon's in U.S. These results may indicate that not only a B. microti-like parasite but also at least two yet undescribed Babesia species are being established in their new life cycles in the feral raccoon populations in Japan.

Babesia microti-group parasites compared phylogenetically by complete sequencing of the CCTeta gene in 36 isolates.

Babesia microti, the erythroparasitic cause of human babesiosis, has long been taken to be a single species because classification by parasite morphology and host spectrum blurred distinctions between the parasites. Phylogenetic analyses of the 18S ribosomal RNA gene (18S rDNA) and, more recently, the beta-tubulin gene have suggested inter-group heterogeneity. Intra-group relationships, however, remain unknown. This study was conducted to clarify the intra- and inter-group phylogenetic features of the B. microti-group parasites with the eta subunit of the chaperonin-containing t-complex polypeptide l (CCTeta) gene as a candidate genetic marker for defining the B. microti group. We prepared complete sequences of the CCTeta gene from 36 piroplasms and compared the phylogenetic trees. The B. microti-group parasites clustered in a monophyletic assemblage separate from the Babesia sensu stricto and Theileria genera and subdivided predominantly into 4 clades (U.S., Kobe, Hobetsu, Munich) with highly significant evolutionary distances between the clades. B. rodhaini branched at the base of the B. microti-group parasites. In addition, a unique intron presence/absence matrix not observable in 18S rDNA or beta-tubulin set the B. microti group entirely apart from either Babesia sensu stricto or Theileria. These results have strong implications for public health, suggesting that the B. microti-group parasites are a full-fledged genus comprising, for now, four core species, i.e., U.S., Kobe, Hobetsu, and Munich species nova. Furthermore, the CCTeta gene is an instructive and definitive genetic marker for analyzing B. microti and related parasites.

The frequency of cooking dinner at home and its association with nutrient intake adequacy among married young-to-middle-aged Japanese women: the POTATO Study.

Home cooking has been suggested as a key to healthy dietary intakes. However, little is known about the association between cooking behaviour and nutrient intake among young-to-middle-aged women. We aimed to investigate the association between home cooking frequency and nutrient intake adequacy among married Japanese women. Self-administered questionnaires were used to assess the weekly frequency of cooking dinner at home and habitual nutrient intake during the preceding month. We evaluated nutrient intake adequacy by comparing the self-reported intake with two indices of the dietary reference intakes for Japanese (2015): the estimated average requirement (EAR) of fourteen nutrients, and the 'tentative dietary goal for preventing lifestyle-related diseases' (DG) of seven nutrients. A total of 143 participants (25-44 years old) completed the questionnaires, with 32·9 % of participants reporting a weekly home cooking frequency of seven times/week. Women with a higher home cooking frequency (seven times/week) were more likely to have children (P = 0·001) than those with a lower home cooking frequency (0-6 times/week). Of the nutrients evaluated, there was no significant difference between the two groups in meeting EAR and DG. Our findings suggest that daily home cooking may not be necessary to achieve adequate nutrient intake, specifically among married, young-to-middle-aged Japanese women.