Regular dental check-up status and related factors among Thai residents in Japan.

The objectives of this online study were to determine the status of regular dental check-ups among Thai nationals living in Japan and to identify barriers to regular dental check-ups by comparing them with general health check-ups. We conducted the online survey twice, in 2021 and 2022, among Thai nationals aged 18 years and older living in Japan via social networking services by an organization that supports Thai nationals living in Japan. Respondents between the ages of 30 and 59 were included in this study. Independent factors included gender, age, length of stay in Japan, family economic status, confidence in Japanese and stay for work purposes. Dependent factors were regular dental check-ups and general health check-ups in the past year. Chi-square tests and multiple logistic regression analyses were used for analysis. 56.6% of respondents had regular dental check-ups. The adjusted odds ratio for the proportion of people with regular dental check-ups was significantly higher for those with high economic status, 2.15 (1.06-4.33), compared with those with low economic status. It was also significantly higher 1.88 (1.10-3.21) for those with confidence in the Japanese language compared with those without. The study suggested the need for Japanese language support in addition to financial support for dental health prevention programs for foreigners living in Japan.

Association Between Dietary Potassium Intake Estimated From Multiple 24-Hour Urine Collections and Serum Potassium in Patients With CKD.

Introduction: Limited and inconclusive evidence for the association of dietary potassium intake with serum potassium in chronic kidney disease (CKD) patients have been shown, though restricting dietary potassium has been recommended for CKD patients to prevent hyperkalemia. Multiple 24-hour urine collections are necessary to adequately assess potassium intake. We investigated associations of 24-hour urinary potassium excretion (UKV) with serum potassium in CKD outpatients based on multiple 24-hour urine collections. Methods: This retrospective cohort study was based on outpatients with CKD stages G3 to G5, median age of 72.0 years; and median follow-up of 3.9 months and 8.9 months, respectively, for analyses using 3-time measurement (N = 290 and 870 observations) and 7-time measurements (N = 220 and 1540 observations). The outcome was serum potassium. Results: Multivariable-adjusted mean difference in serum potassium (mEq/l) and odds ratio of hyperkalemia per 10 mEq/d increase in UKV were, respectively, 0.12 (95% confidence interval [CI]: 0.09-0.15) and 2.15 (1.70-2.73) in generalized estimating equations (GEEs) with 3-time measurements. The mean difference became more pronounced as CKD stages progressed: 0.08 (0.05-0.12), 0.12 (0.08-0.16), and 0.16 (0.12-0.20) for CKD G3, G4, and G5. Similar results were obtained from analyses using 7-time measurements and hierarchical Bayesian measurement error models treating measurement error of UKV adequately. Conclusion: We suggest significant but weak associations (R2: 0.08, 0.14, and 0.18 for CKD G3, G4, and G5) between serum potassium and dietary potassium intake estimated by multiple 24-hour urine collections in CKD patients. Further studies are needed to validate nutritional and clinical aspects of the associations.

A multiple 24-hour urine collection study indicates that kidney function decline is related to urinary sodium and potassium excretion in patients with chronic kidney disease.

Multiple 24-hour urine collections are necessary to adequately assess sodium and potassium intake. Here, we assessed kidney function decline for four years after baseline in relation to seven-time averaged 24-hour urinary sodium and potassium excretion (UNaV, UKV), their UNaV/UKV ratio, and their categorical combination in outpatients with chronic kidney disease (CKD). This retrospective cohort study was based on 240 outpatients with baseline CKD stages 3-5, baseline age 20 years or more (median age 72.0 years), and a median follow-up (with interquartile range) of 2.9 (1.4-4.0) years. Outcome was the percentage change in annual slope of estimated glomerular filtration rate (delta eGFR per year). In linear mixed models, percentage changes in delta eGFR per year were -3.26% (95% confidence interval -5.85 to -0.60), +5.20% (2.34 to 8.14), and -5.20% (-7.64 to -2.69), respectively, per one standard deviation increase in the seven-time averaged UNaV and UKV, and their UNaV/UKV ratio. Additionally, percentage changes per year in delta eGFR per year were -16.27% (-23.57 to -8.27) in the middle-to-high UNaV and low UKV group, compared with the low UNaV and middle-to high UKV group. Thus, our study reinforces the observation of opposite associations between GFR decline and urinary excretion rates of sodium (positive) and potassium (negative), respectively. Whether changes in dietary sodium and potassium intake slow GFR decline still requires further study.

Lipid-modifying efficacy and tolerability of anacetrapib added to ongoing statin therapy in Japanese patients with dyslipidemia.

BACKGROUND AND AIMS: We aimed to assess the effects of cholesteryl ester transfer protein inhibitor anacetrapib added to statin ± other lipid-modifying therapies (LMT) in Japanese patients with dyslipidemia who were not at their LDL-C goal. METHODS: Patients on a stable dose of statin ± other LMT with LDL-C ≥100 mg/dL to <145 mg/dL, ≥120 mg/dL to <165 mg/dL, ≥140 mg/dL or ≥160 mg/dL for patients with a history of coronary heart disease (CHD), high-, moderate- and low-risk patients respectively, were randomized 2:1, stratified by background therapy, to double-blind anacetrapib 100 mg (n = 204) or placebo (n = 103) for 24 weeks, followed by a 28-week open-label extension phase (anacetrapib 100 mg) and a 12-week off-drug safety follow-up phase. The primary endpoint was percent change from baseline in LDL-C (beta-quantification method), as well as the safety profile of anacetrapib at Week 24; HDL-C was a key secondary endpoint. RESULTS: Anacetrapib 100 mg further reduced LDL-C (38.0%), non-HDL-C (35.1%), ApoB (28.7%), and Lp(a) (48.3%) and increased HDL-C (148.9%) and ApoAI (50.7%) versus placebo (p < 0.001 for all). There were no meaningful differences between the groups in the proportion of patients with liver enzymes elevations (2.0% vs. 0%), creatine kinase elevations overall (0.5% vs. 0%) or with muscle symptoms (0.5% vs. 0%), blood pressure, electrolytes or adjudicated cardiovascular events (0.5% vs. 0%). In the open-label period, sustained effects on lipid parameters were observed with anacetrapib and the treatment was generally well tolerated. CONCLUSIONS: Long-term treatment with anacetrapib 100 mg substantially reduced LDL-C, increased HDL-C and was well tolerated in Japanese patients with dyslipidemia (ClinicalTrials.gov number NCT01760460).

[Mortality rates of foreign national residents in Japan: comparison with the Japanese population and a possible healthy migrant effect].

Objectives　This study clarified the health status of foreign nationals residing in Japan by comparing their current mortality rates with those of the Japanese population.Methods　We focused on foreign national residents and used official statistical data from 2010. Due to the possible overestimation of published death rates (PDRs), we computed calculated death rates (CDRs) for foreign national residents, using the number of registered foreign national residents as the denominator. We obtained this number from the Statistics on Foreign National Residents provided by the Ministry of Justice.Results　The all-cause age-adjusted mortality rates (per 100,000 population) of foreign national residents were 571.5 for men and 316.1 for women. The ratios with reference to the mortality rates of the Japanese population were 1.1 and 1.0 for men and women, respectively, indicating that the age-adjusted mortality rates for foreign national residents were similar to those of the Japanese population. However, the rate ratios by age group were 0.3-0.5 for those aged 20-34 years, 0.6-1.0 for those aged 35-59 years, and 1.0-1.4 for those aged ≥60 years, suggesting that the mortality rate of foreign national residents increases with age when compared to that of the Japanese population. Although the foreign population are thought to be disadvantaged in many ways, the mortality rates of the young and middle-aged groups were lower than those of the Japanese population. A similar tendency was observed in the cause-specific mortality rates of the young and middle-aged groups of foreign national residents, except the rates of mortality due to accidents and suicide in the middle-aged group, which were higher than those of the Japanese population. In those aged ≥60 years, the mortality rates were higher than those of the Japanese population overall, especially the mortality rates due to suicide.Conclusion　These results suggest that young and middle-aged foreign national residents are relatively healthy and that a healthy migrant effect exists in Japan. Because this health advantage may either decrease or converge with that of the native population after long-term residence as a previous research reported; without intervention, these lower mortality rates in the young and middle-aged foreign national residents may eventually increase or even exceed those of the Japanese population. More attention should be paid to middle-aged foreign national residents who have higher rates of mortality due to accidents and suicide as well as foreign national residents aged ≥60 years, who have an extremely high mortality rates due to suicide. Although overestimations and underestimations are still possible, CDRs are considered more appropriate than PDRs, since the impact is smaller. Future investigations should focus on the healthy migrant effect in Japan in order to address current and upcoming health issues among foreign national residents.

Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib in Japanese patients with heterozygous familial hypercholesterolemia.

BACKGROUND AND AIMS: This multicenter, randomized, double-blind, placebo-controlled study assessed the lipid-modifying efficacy/safety profile of anacetrapib 100 mg added to ongoing statin ± other lipid-modifying therapies (LMT) in Japanese patients with heterozygous familial hypercholesterolemia (HeFH). METHODS: Patients 18-80 years with a genotype-confirmed/clinical diagnosis of HeFH who were on a stable dose of statin ± other LMT for ≥6 weeks and with an LDL-C concentration ≥100 mg/dL were randomized to anacetrapib 100 mg (n = 34) or placebo (n = 34) for 12 weeks, followed by a 12-week off-drug reversal phase. The primary endpoints were percent change from baseline in LDL-C (beta-quantification method [BQ]) and safety/tolerability. RESULTS: At Week 12, treatment with anacetrapib reduced LDL-C (BQ) compared to placebo and resulting in a between-group difference of 29.8% (95% CI: -38.6 to -21.0; p < 0.001) favoring anacetrapib. Anacetrapib also reduced non-HDL-C (23. 6%; p < 0.001), ApoB (14.1%; p < 0.001) and Lp(a) (48.7%; p < 0.001), and increased HDL-C (110.0%; p < 0.001) and ApoA1 (48.2%; p < 0.001) versus placebo. Anacetrapib 100 mg added to ongoing therapy with statin ± other LMT for 12 weeks was generally well-tolerated. There were no differences between the groups in the proportion of patients who discontinued drug due to an adverse event or abnormalities in liver enzymes, creatinine kinase, blood pressure, electrolytes or adjudicated cardiovascular events. CONCLUSIONS: In Japanese patients with HeFH, treatment with anacetrapib 100 mg for 12 weeks resulted in substantial reductions in LDL-C and increases in HDL-C and was well tolerated. (ClinicalTrials.govNCT01824238).

Association of non-synonymous variants in WIPF3 and LIPA genes with abdominal aortic aneurysm: an autopsy study.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a multifactorial disease with strong genetic components. Various genetic loci have been associated with clinical AAA, but few studies have investigated pathological AAA, an intermediate phenotype of the disease. METHODS: We examined 2263 consecutive autopsies of older Japanese subjects from a study on geriatric diseases in Japanese individuals (The JG-SNP study). The presence of AAA was determined with a pathological diagnosis during autopsy. Single nucleotide variants (SNVs) associated with AAA were determined with an Illumina HumanExome Beadchip array. Logistic regression analyses were performed to determine genetic associations. Age, gender, and other risk factors of AAA were analyzed as covariates. RESULTS: 118 subjects with AAA and 2145 subjects without AAA were analyzed in a case-control setting. No variants reached significance after applying the Bonferroni correction (P < 2.05×10-6). The strongest associations were found with rs3750092 (p.E321G, OR: 0.36, 95% CI: 0.24-0.56, P = 6.09 × 10-6), a variant in the WAS/WASL interacting protein family 3 (WIPF3), and with rs1051338 (p.T16P, OR: 2.50, 95% CI: 1.70-3.66, P = 2.79 × 10-6) and rs2246942 (intronic, OR: 2.32, 95% CI: 1.58-3.41, P = 1.61 × 10-5), variants in the lysosomal acid lipase A (LIPA). LIPA is essential for macrophage cholesterol metabolism. Immunohistological analyses of WIPF3 protein in AAA samples from three subjects revealed that WIPF3 was expressed in macrophages of atheromatous plaques. CONCLUSIONS: This study suggests that WIPF3 and LIPA, both of which are expressed in the macrophages are involved in pathological AAA. These results should be regarded as hypothesis-generating; thus, replication study is warranted.

Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism.

We recently showed that prenatal exposure to valproic acid (VPA) in mice causes autism-like behavioral abnormalities, including social interaction deficits, anxiety-like behavior and spatial learning disability, in male offspring. In the present study, we examined the effect of prenatal VPA on cognitive function and whether the effect is improved by chronic treatment with VPA and sodium butyrate, histone deacetylase inhibitors. In addition, we examined whether the cognitive dysfunction is associated with hippocampal dendritic morphological changes. Mice given prenatal exposure to VPA exhibited novel object recognition deficits at 9 weeks of age, and that the impairment was blocked by chronic (5-week) treatment with VPA (30 mg/kg/d, i.p.) or sodium butyrate (1.2g/kg/d, i.p.) starting at 4 weeks of age. In agreement with the behavioral findings, the mice prenatally exposed to VPA showed a decrease in dendritic spine density in the hippocampal CA1 region, and the spine loss was attenuated by chronic treatment with sodium butyrate or VPA. Furthermore, acute treatment with sodium butyrate, but not VPA, significantly increased acetylation of histone H3 in the hippocampus at 30 min, suggesting the difference in the mechanism for the effects of chronic VPA and sodium butyrate. These findings suggest that prenatal VPA-induced cognitive dysfunction is associated with changes in hippocampal dendritic spine morphology.

An enriched environment ameliorates memory impairments in PACAP-deficient mice.

We previously found that juvenile pituitary adenylate cyclase-activating polypeptide (PACAP)-knockout (PACAP(-/-)) mice reared in an enriched environment (EE) for 4 weeks showed attenuated hyperactivity, jumping behavior, impairments in social interaction, and depression-like behavior. The present study examined the effects of EE on memory function and memory-related protein levels in PACAP(-/-) mice. Eight-week-old PACAP(-/-) mice displayed fear memory dysfunction in a contextual fear conditioning test and cognitive impairments in a novel object recognition test. Rearing of 4-week-old PACAP(-/-) mice in an EE for 4 weeks ameliorated these memory impairments. The beneficial effects of EE were also observed 2 weeks after a return to housing in a standard environment (SE). This suggests that the effects of EE on impaired memory are long-lasting. In both wild-type and PACAP(-/-) mice, EE increased the protein levels of the NMDA receptor NR2B subunit, phospho-ERK, phospho-CaMKII, and brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased neurotrophin-3 levels, whereas it did not affect nerve growth factor and glial cell-derived neurotrophic factor levels. Increased levels of NR2B, phospho-ERK, phospho-CaMKII and BDNF were not observed 2 weeks after a return to housing in a SE. These findings suggest that living in an EE engenders long-lasting reductions in memory impairments in PACAP(-/-) mice. The present study also implies that increases in hippocampal memory-related protein and BDNF levels are responsible for the beneficial effects of an EE, but not for the maintenance of these effects.

Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid.

Maternal use of valproic acid (VPA) during pregnancy has been implicated in the aetiology of autism spectrum disorders in children, and rodents prenatally exposed to VPA showed behavioural alterations similar to those observed in humans with autism. However, the exact mechanism for VPA-induced behavioural alterations is not known. To study this point, we examined the effects of prenatal exposure to VPA and valpromide, a VPA analog lacking histone deacetylase inhibition activity, on behaviours, cortical pathology and histone acetylation levels in mice. Mice exposed to VPA at embryonic day 12.5 (E12.5), but not at E9 and E14.5, displayed social interaction deficits, anxiety-like behaviour and memory deficits at age 4-8 wk. In contrast to male mice, the social interaction deficits (a decrease in sniffing behaviour) were not observed in female mice at age 8 wk. The exposure to VPA at E12.5 decreased the number of Nissl-positive cells in the middle and lower layers of the prefrontal cortex and in the lower layers of the somatosensory cortex at age 8 wk. Furthermore, VPA exposure caused a transient increase in acetylated histone levels in the embryonic brain, followed by an increase in apoptotic cell death in the neocortex and a decrease in cell proliferation in the ganglionic eminence. In contrast, prenatal exposure to valpromide at E12.5 did not affect the behavioural, biochemical and histological parameters. Furthermore, these findings suggest that VPA-induced histone hyperacetylation plays a key role in cortical pathology and abnormal autism-like behaviours in mice.

Multiple-type dynamic culture of highly oriented fiber scaffold for ligament regeneration.

The ruptured anterior cruciate ligament does not heal spontaneously as it has a low capacity for healing. Therefore, the development of new healing techniques employing tissue engineering is vital. As a potentially new approach for ligament regeneration, this study used a highly oriented fiber scaffold made of elastin and collagen (the mean diameters were 1.7 ± 0.4 µm and 0.5 ± 1.4 µm, respectively), which comprise the extracellular matrix of the ligament. In addition, a multiple-type dynamic culture consisting of a combination of pressure and twist stimulation was performed to examine the influence of mechanical force on the functional maintenance of ligament cells and on the differentiation of ligament cells to osteoblast-like cells. Our results show that a pressure stimulation and elastin A upregulated the expression of alkaline phosphatase (ALP) (a marker of osteogenic differentiation) and promoted the osteogenic differentiation of ligament cells. In addition, the twist stimulation upregulated the expression of type III collagen (the main component of ligament tissue). Furthermore, the combination of pressure and twist stimulation promoted the expression of type III collagen and ALP protein depending on the portion of scaffold.

Extraction of Noble and Rare-Earth Metals from Aqueous Solutions by DNA Cross-Linked Hydrogels.

Invited for this month's cover is the group of Prof. Shizuaki Murata and Dr. Anatoly Zinchenko from Nagoya University and the group of Prof. Vladimir Sergeyev from Moscow State University. The cover picture shows the accumulation of noble and rare-earth metals by DNA cross-linked hydrogel. Read the full text of the article on page 619 ff..

Extraction of Noble and Rare-Earth Metals from Aqueous Solutions by DNA Cross-Linked Hydrogels.

Treasure trove: A method for the extraction of noble and rare-earth metals by a DNA cross-linked hydrogel, based on high DNA affinity to these elements, is described. The hydrogel is promising in applications for metal accumulation and recycling.

Effect of prenatal valproic acid exposure on cortical morphology in female mice.

We have recently shown that prenatal valproic acid (VPA) exposure causes autism spectrum disorders-like behavioral abnormalities and Nissl-positive cell loss in both prefrontal and somatosensory cortices in male mice. We have also found that VPA-induced social interaction deficits are observed in male but not female offspring. This study demonstrated that the exposure to VPA at embryonic day 12.5 significantly decreased Nissl-positive cell numbers in the prefrontal cortex, but not in the somatosensory cortex, in female offspring. These findings suggest that VPA-induced morphological abnormalities in the somatosensory cortex may be involved in the sex-dependent social interaction deficits.

Chiral diene-phosphine tridentate ligands for rhodium-catalyzed asymmetric cycloisomerization of 1,6-enynes.

Asymmetric cycloisomerization of nitrogen-bridged 1,6-enynes proceeded in the presence of a cationic rhodium complex coordinated with a chiral diene/phosphine tridentate ligand to give high yields of chiral 3-azabicyclo[4.1.0]heptenes with high enantioselectivity.

Catalytic enantioselective 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines with alpha,beta-unsaturated aldehydes.

A yet-unexploited class of azomethine imines, C,N-cyclic azomethine imines, could be successfully employed in highly enantioselective 1,3-dipolar cycloaddition with enals catalyzed by titanium-BINOLate to give pharmaceutically attractive tetrahydroisoquinoline and piperidine motifs.

Reliability of evaluation for communication competency in pharmaceutical objective structured clinical examination (OSCE).

In the objective structured clinical examination (OSCE), which for pharmaceutical students training, adequate methods should be used for evaluating a student's skill and aptitude for good communication in a medical interview. However, the reliability of the evaluation methods used in the pharmaceutical OSCE has not been investigated sufficiently. In this study, we reviewed the evaluation scores and video recordings obtained in a pharmaceutical OSCE trial, and examined the reasons for disagreement in the scores between two raters. We had two experienced raters in medical communication re-evaluate the students using the vide images, and compared their scores with those on the examination day. The ratio of disagreement was 14.5% (87/600 items in 30 students), and the reason for disagreement could not be identified for 63 items that evaluated communication skills such as 'actively listen' and 'empathy'. A comparison of the scores on examination day and those on re-evaluation revealed a possible reason for the disagreement; the use of a checklist, i.e. binary scores, with criteria that differed between the raters. We suggest that the items used for a detailed performance evaluation be selected carefully and that rating scales be used in order to perform an adequate evaluation, especially regarding communication skill and aptitude.

Regulation of leg size and shape by the Dachsous/Fat signalling pathway during regeneration.

An amputated cricket leg regenerates all missing parts with normal size and shape, indicating that regenerating blastemal cells are aware of both their position and the normal size of the leg. However, the molecular mechanisms regulating this process remain elusive. Here, we use a cricket model to show that the Dachsous/Fat (Ds/Ft) signalling pathway is essential for leg regeneration. We found that knockdown of ft or ds transcripts by regeneration-dependent RNA interference (rdRNAi) suppressed proliferation of the regenerating cells along the proximodistal (PD) axis concomitantly with remodelling of the pre-existing stump, making the regenerated legs shorter than normal. By contrast, knockdown of the expanded (ex) or Merlin (Mer) transcripts induced over-proliferation of the regenerating cells, making the regenerated legs longer. These results are consistent with those obtained using rdRNAi during intercalary regeneration induced by leg transplantation. We present a model to explain our results in which the steepness of the Ds/Ft gradient controls growth along the PD axis of the regenerating leg.

Methamphetamine use and correlates in two villages of the highland ethnic Karen minority in northern Thailand: a cross sectional study.

BACKGROUND: The prevalence of methamphetamine use and human immunodeficiency virus (HIV) incidence are high in lowland Thai society. Despite increasing social and cultural mixing among residents of highland and lowland Thai societies, however, little is known about methamphetamine use among ethnic minority villagers in the highlands. METHODS: A cross-sectional survey examined Karen villagers from a developed and a less-developed village on February 24 and March 26, 2003 to evaluate the prevalence and social correlates of methamphetamine use in northern Thailand. Data were collected in face-to-face interviews using a structured questionnaire. RESULTS: The response rate was 79.3% (n = 548). In all, 9.9% (males 17.6%, females 1.7%) of villagers reported methamphetamine use in the previous year. Methamphetamine was used mostly by males and was significantly related to primary or lower education; to ever having worked in town; to having used opium, marijuana, or heroin in the past year; and to ever having been diagnosed with a sexually transmitted infection (STI). CONCLUSION: Since labor migration to towns is increasingly common among ethnic minorities, the prevention of methamphetamine use and of HIV/STI infection among methamphetamine users should be prioritized to prevent HIV in this minority population in Thailand.