Incidence of sodium-glucose cotransporter-2 inhibitor-associated perioperative ketoacidosis in surgical patients: a prospective cohort study.

PURPOSE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are commonly prescribed anti-diabetic medications with various beneficial effects; however, they have also been associated with ketoacidosis. The aim of this study was to determine the incidence of SGLT2i-associated perioperative ketoacidosis (SAPKA) in surgical patients. METHODS: We conducted a multicenter, prospective cohort study across 16 centers in Japan, enrolling surgical patients with diabetes who were prescribed SGLT2is between January 2021 and August 2022. Patients were monitored until the third postoperative day to screen for SAPKA, defined as urine ketone positivity with a blood pH of < 7.30 and HCO3 level ≤ 18.0 mEq/L, excluding cases of respiratory acidosis. RESULTS: In total, 759 of the 762 evaluated patients were included in the final analysis. Among these, three patients (0.40%) had urine ketones with a blood pH of < 7.30; however, blood gas analysis revealed respiratory acidosis in all three, and none of them was considered to have SAPKA. The estimated incidence of SGLT2i-associated postoperative ketoacidosis was 0% (95% confidence interval, 0%-0.4%). CONCLUSIONS: The observed incidence of SAPKA in our general surgical population was lower than expected. However, given that the study was observational in nature, interpretation of study results warrants careful considerations for biases.

For making a declaration of countermeasures against the falling birth rate from the Japanese Society for Hygiene: summary of discussion in the working group on academic research strategy against an aging society with low birth rate.

In 1952, the Japanese Society for Hygiene had once passed a resolution at its 22nd symposium on population control, recommending the suppression of population growth based on the idea of cultivating a healthier population in the area of eugenics. Over half a century has now passed since this recommendation; Japan is witnessing an aging of the population (it is estimated that over 65-year-olds made up 27.7% of the population in 2017) and a decline in the birth rate (total fertility rate 1.43 births per woman in 2017) at a rate that is unparalleled in the world; Japan is faced with a "super-aging" society with low birth rate. In 2017, the Society passed a resolution to encourage all scientists to engage in academic researches to address the issue of the declining birth rate that Japan is currently facing. In this commentary, the Society hereby declares that the entire text of the 1952 proposal is revoked and the ideas relating to eugenics is rejected. Since the Society has set up a working group on the issue in 2016, there have been three symposiums, and working group committee members began publishing a series of articles in the Society's Japanese language journal. This commentary primarily provides an overview of the findings from the published articles, which will form the scientific basis for the Society's declaration. The areas we covered here included the following: (1) improving the social and work environment to balance between the personal and professional life; (2) proactive education on reproductive health; (3) children's health begins with nutritional management in women of reproductive age; (4) workplace environment and occupational health; (5) workplace measures to counter the declining birth rate; (6) research into the effect of environmental chemicals on sexual maturity, reproductive function, and the children of next generation; and (7) comprehensive research into the relationship among contemporary society, parental stress, and healthy child-rearing. Based on the seven topics, we will set out a declaration to address Japan's aging society with low birth rate.

Association of blood pressure and body mass index with intraocular pressure in middle-aged and older Japanese residents: a cross-sectional and longitudinal study.

To clarify whether high blood pressure (BP) and high body mass index (BMI) are associated with elevated intraocular pressure (IOP), a cross-sectional and longitudinal study was conducted. This epidemiological study analyzed health examination data obtained between 2001 and 2005 from 896 Japanese individuals (aged 32-79 years) who had not undergone any ocular surgery or medical treatment for hypertension, ocular hypertension, or glaucoma. Multiple-regression analysis of our cross-sectional data showed that systolic and diastolic BP (SBP and DBP) and BMI had significant and near-significant positive associations with IOP in men (p＜0.05) and women (p＜0.1). Our longitudinal study from analyses of covariance found that the adjusted mean level of changes in IOP tended to increase with increased levels of SBP, DBP, and BMI in men (p＜0.1). In women also, changes in SBP and BMI tended to be positively related with that of IOP (p＜0.1). The results of this study suggested that BP and BMI were positively associated with IOP in middle-aged and older Japanese. Therefore, management of BP and improvement of obesity might be especially important to Japanese patients with open-angle glaucoma or ocular hypertension as they have a higher incidence of normal-tension glaucoma than Europeans and Americans.

Difference in concentration trends of airborne particulate matter during rush hour on weekdays and Sundays in Tokyo, Japan.

Suspended particulate matter (SPM) and fine particulate matter (less than or equal to 2.5 microm: PM2.5) have generally been decreasing for the last decade in Tokyo, Japan. To elucidate the major cause of this decrease, the authors investigated the different trends of airborne particulates (both SPM and PM2.5 concentrations) by evaluating comparisons based on the location of the monitoring stations (roadside vs. ambient), days of the week (weekdays vs. Sundays), and daily fluctuation patterns (2002 vs. 2010). Hourly mean SPM and PM2.5 concentrations were obtained at four monitoring stations (two roadside stations, two ambient stations) in Tokyo, Japan. Annual mean concentrations of each day of the week and of each hour of the day from 2002 to 2010 were calculated. The results showed that (1) the daily differences in annual mean concentration decreased only at the two roadside monitoring stations; (2) the high hourly mean concentrations observed on weekdays during the daily rush hour at the two roadside monitoring stations observed in 2002 diminished in 2010; (3) the SPM concentration that decreased the most since 2002 was the PM2.5 concentration; and (4) the fluctuation of hourly concentrations during weekdays at the two roadside monitoring stations decreased. A decreasing trend of airborne particulates during the daily rush hour in Tokyo, Japan, was observed at the roadside monitoring stations on weekdays since 2002. The decreasing PM2.5 concentration resulted in this decreasing trend of airborne particulate concentrations during the daily rush hours on weekdays, which indicates fewer emissions were produced by diesel vehicles. Implications: The authors compared the trends of SPM and PM2.5 in Tokyo by location (roadside vs. ambient), days of the week (weekdays vs. Sundays), and daily fluctuation patterns (2002 vs. 2010). The high hourly mean concentrations observed at the roadside location during rush hour on weekdays in 2002 diminished in 2010. The SPM concentration that decreased during rush hour the most was the PM2.5 concentration. This significant decrease in the PM2.5 concentration resulted in the general decreasing trend of SPM concentrations during the rush hours on weekdays, which indicates fewer emissions were produced from diesel vehicles.

Association of smoking with intraocular pressure in middle-aged and older Japanese residents.

OBJECTIVES: To clarify whether smoking was associated with elevated intraocular pressure (IOP) and to evaluate the interrelationship among IOP, blood viscosity, and smoking. METHODS: This cross-sectional study analyzed health examination data obtained between 2001 and 2004 from 1113 individuals (829 men and 284 women), ranging in age from 28 to 79 years, who had not undergone any ocular surgery or medical treatment for hypertension, ocular hypertension, and glaucoma. RESULTS: Multiple-regression analysis showed that systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and number of cigarettes smoked per day had a significantly positive association with IOP in men (P < 0.05). In women also, SBP, DBP, and BMI were positively related to IOP (P < 0.05). On the contrary, age had a significant negative association with IOP in both sexes (P < 0.01). Analysis of covariance and multiple logistic regression analyses showed that the adjusted mean IOP and the multivariate odds ratios for IOP increased with increasing cigarette consumption in men (P for trend = 0.01 and 0.06, respectively). Analysis of covariance found that smoking was significantly associated with both high IOP and high hematocrit in men (P for trend <0.05); however, the adjusted mean IOP values were higher in smokers than in nonsmokers, regardless of the hematocrit level. CONCLUSIONS: The results of this study suggested that the IOP level may be substantially affected by smoking habit in middle-aged and older Japanese men.

Unexpected combined effects of NADH dehydrogenase subunit-2 237 Leu/Met polymorphism and green tea consumption on renal function in male Japanese health check-up examinees: a cross-sectional study.

BACKGROUND: NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in Japanese. A previous study has shown that ND2-237 Leu/Met polymorphism modulates the effects of green tea consumption on risk of hypertension. For men with ND2-237Leu, habitual green tea consumption may reduce the risk of hypertension. Moreover, there is a combined effect of ND2-237 Leu/Met polymorphism and alcohol consumption on risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m2). Several beneficial effects of green tea on the kidney have been reported. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of green tea consumption on risk of mildly decreased eGFR in male Japanese health check-up examinees. RESULTS: For ND2-237Leu genotypic men, after adjustment for confounding factors, green tea consumption may increase the risk of mildly decreased eGFR (P for trend = 0.016). The adjusted odds ratio (OR) for mildly decreased eGFR was significantly higher in subjects with ND2-237Leu who consume ≥6 cups of green tea per day than those who consume ≤1 cup of green tea per day (adjusted OR = 5.647, 95% confidence interval: 1.528-20.88, P = 0.009). On the other hand, for ND2-237Met genotypic men, green tea consumption does not appear to determine the risk of mildly decreased eGFR. CONCLUSION: The present results suggest that ND2-237 Leu/Met polymorphism unexpectedly modifies the effects of green tea consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.

Combined effect of mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on estimated glomerular filtration rate in male Japanese health check-up examinees: a cross-sectional study.

BACKGROUND: Prevention of chronic kidney disease (CKD) is a major public health issue. Although several studies have been performed on the association between alcohol consumption and CKD or renal function, it remains controversial. Numerous genetic polymorphisms have been reported to be associated with CKD and kidney function. Mitochondrial DNA cytosine/adenine (Mt5178 C/A) polymorphism is associated with longevity in Japanese. This polymorphism modifies the effects of alcohol consumption on blood pressure, risk of hypertension, serum triglyceride levels, risk of hyper-LDL cholesterolemia and serum uric acid levels. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of alcohol consumption on renal function in male Japanese health check-up examinees. METHODS: A total of 394 male subjects aged 29-76 years were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effects of Mt5178 C/A polymorphism and habitual drinking on the risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m(2)) was conducted. RESULTS: For Mt5178A genotypic men, habitual drinking may increase eGFR (P for trend = 0.003) or reduce the risk of mildly decreased eGFR (P for trend = 0.003). Daily drinkers had a significantly higher eGFR than non-drinkers (P = 0.005). The crude odds ratio for decreased eGFR was significantly lower in daily drinkers than in non-drinkers (odds ratio = 0.092, 95% confidence interval: 0.012-0.727, P = 0.024). On the other hand, for Mt5178C genotypic men, habitual drinking does not appear to affect eGFR. CONCLUSION: The present results suggest a joint effect of Mt5178 C/A polymorphism and alcohol consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.

Decreasing trends of suspended particulate matter and PM2.5 concentrations in Tokyo, 1990-2010.

In Tokyo, the annual average suspended particulate matter (SPM) and PM2.5 concentrations have decreased in the past two decades. The present study quantitatively evaluated these decreasing trends using data from air-pollution monitoring stations. Annual SPM and PM2.5 levels at 83 monitoring stations and hourly SPM and PM2.5 levels at four monitoring stations in Tokyo, operated by the Tokyo Metropolitan Government, were used for analysis, together with levels of co-pollutants and meteorological conditions. Traffic volume in Tokyo was calculated from the total traveling distance of vehicles as reported by the Ministry of Land, Infrastructure, Transport, and Tourism. High positive correlations between SPM levels and nitrogen oxide levels, sulfur dioxide levels, and traffic volume were determined. The annual average SPM concentration declined by 62.6%from 59.4 microg/m3 in 1994 to 22.2 microg/m3 in 2010, and PM2.5 concentration also declined by 49.8% from 29.3 microg/m3 in 2001 to 14.7 microg/m3 in 2010. Likewise, the frequencies of hourly average SPM and PM2.5 concentrations exceeding the daily guideline values have significantly decreased since 2001 and the hourly average SPM or PM2.5 concentrations per traffic volume for each time period have also significantly decreased since 2001. However SPM and PM2.5 concentrations increased at some monitoring stations between 2004 and 2006 and from 2009 despite strengthened environmental regulations and improvements in vehicle engine performance. The annual average SPM and PM2.5 concentrations were positively correlated with traffic volumes and in particular with the volume of diesel trucks. These results suggest that the decreasing levels of SPM and PM2.5 in Tokyo may be attributable to decreased traffic volumes, along with the effects of stricter governmental regulation and improvements to vehicle engine performance, including the fitting of devices for exhaust emission reduction.

A rad50 germline mutation induces tumorigenesis and ataxia-telangiectasia phenotype in a transparent medaka model.

The MRE11A-RAD50-NBS1 complex activates the ataxia-telangiectasia mutated (ATM) pathway and plays a central role in genome homeostasis. The association of RAD50 mutations with disease remains unclear; hence, we adopted a medaka rad50 mutant to demonstrate the significance of RAD50 mutation in pathogenesis using the medaka as an experimental animal. A 2-base pair deletion in the rad50 gene was introduced into transparent STIII medaka using the CRISPR/Cas9 system. The mutant was analyzed histologically for tumorigenicity and hindbrain quality, as well as for swimming behavior, to compare with existing ATM-, MRE11A-, and NBS1-mutation-related pathology. Our results revealed that the medaka rad50 mutation concurrently reproduced tumorigenesis (8 out of 10 rad50Δ2/+ medaka), had a decrease in median survival time (65.7 ± 1.1 weeks in control vs. 54.2 ± 2.6 weeks in rad50Δ2/+ medaka, p = 0.001, Welch's t-test), exhibited semi-lethality in rad50Δ2/Δ2 medaka and most of the major ataxia-telangiectasia phenotypes, including ataxia (rheotaxis ability was lower in rad50Δ2/+ medaka than in the control, Mann-Whitney U test, p < 0.05), and telangiectasia (6 out of 10 rad50Δ2/+ medaka). The fish model may aid in further understanding the tumorigenesis and phenotype of ataxia-telangiectasia-related RAD50 germline mutations and in developing novel therapeutic strategies against RAD50 molecular disorders.

Combined effect of longevity-associated mitochondrial DNA 5178 c/a polymorphism and green tea consumption on risk of hypertension in middle-aged Japanese men.

Mitochondrial DNA 5178 cytosine/adenine (Mt5178C/A) polymorphism is reported to be associated with longevity and to modify the effects of alcohol consumption or coffee consumption on the risk of hypertension in the Japanese population. The objective of this study was to investigate whether Mt5178C/A polymorphism modifies the effects of green tea consumption on blood pressure or risk of hypertension in middle-aged Japanese men. A total of 394 male subjects (age, 53.9±7.9 years; mean±SD) was selected among individuals visiting the hospital for regular medical check-ups. Hypertension was defined as systolic blood pressure (SBP)≥140 mmHg, diastolic blood pressure (DBP)≥90 mmHg, and/or undergoing antihypertensive drug treatment. After adjustment, irrespective of antihypertensive drug treatment, the association between Mt5178C genotype and hypertension was dependent on green tea consumption (P for trend=0.043 and P for trend=0.011, respectively). In particular, among subjects≥50 years old with Mt5178C, excluding those taking antihypertensive drugs, a significant association between green tea consumption and risk of hypertension was observed (P for trend=0.019), and the odds ratio for hypertension was significantly lower in those who consumed≥6 cups of green tea per day than in those who consumed≤1 cup per day (odds ratio=0.167, 95% confidence interval: 0.033-0.832). On the other hand, the association between Mt5178A genotype and hypertension did not depend on green tea consumption. No consistent association between green tea consumption and blood pressure was observed in either genotype. The present results suggest a joint effect for Mt5178C/A polymorphism and green tea consumption on the risk of hypertension in middle-aged Japanese men.

Mitochondrial DNA 5178 C/A polymorphism influences the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men.

BACKGROUND: Several genetic polymorphisms have been reported to modify the effects of smoking on serum lipid levels. The objective of this study was to investigate whether longevity-associated mitochondrial DNA 5178 (Mt5178) C/A polymorphism modifies the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese subjects. METHODS: A total of 394 male subjects (age, 53.9 ± 7.9 years; mean ± SD) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effect of Mt5178 C/A polymorphism and cigarette smoking on the risk of hypo-high-density lipoprotein (HDL) cholesterolemia, hyper-low-density lipoprotein (LDL) cholesterolemia or hypertriglyceridemia was conducted. RESULTS: For subjects with Mt5178C, the risk of hypo-HDL cholesterolemia increased with the number of cigarettes smoked daily (P for trend = 0.001). On the other hand, the association between Mt5178A genotype and the risk of hypo-HDL cholesterolemia did not appear to depend on the number of cigarettes smoked daily. For those with Mt5178A, the risk of hyper-LDL cholesterolemia or hypertriglyceridemia increased with cigarettes smoked daily (P for trend = 0.017 and P for trend = 0.002, respectively). However, the association between Mt5178C genotype and the risk of hyper-LDL cholesterolemia or hypertriglyceridemia did not depend on the number of cigarettes smoked daily. CONCLUSIONS: The present results suggest that Mt5178 C/A polymorphism modulates the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men.

Influence of mitochondrial DNA 5178 C/A polymorphism on serum cholesterol changes: a short-term follow-up in middle-aged Japanese men.

OBJECTIVE: The mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is reportedly associated with longevity in the Japanese population, and the Mt5178A genotype may exert anti-atherogenic effects. The aim of this study was to determine whether there were longitudinal differences in serum lipid levels between carriers of the Mt5178C genotype and those of the Mt5178A genotype and to assess the impact of these genotypes on serum cholesterol levels. METHODS: The serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) were measured and the Mt5178 C/A genotypes determined in 110 Japanese men aged 41-66 (mean 52.3) years who had received medical checkups twice in the period 1999-2005. The longitudinal changes of TC, HDLC, and LDLC were calculated according to genotype. RESULTS: The serum levels of TC at baseline and follow-up were significantly different, whereas those of HDLC and LDLC were not. The changes in HDLC differed significantly between the two Mt5178 C/A genotype groups, with the changes in HDLC level being significantly greater in the Mt5178A genotype group than in the Mt5178C group (p = 0.015). CONCLUSIONS: The Mt5178 C/A genotype may modify longitudinal changes in serum TC and HDLC levels in middle-aged Japanese men.

Excised human larynx in N-vinyl-2-pyrrolidone-embalmed cadavers can produce voiced sound by pliable vocal fold vibration.

Tissue-hardening effect and health-hazard issue of formaldehyde (FA) have long been a great disadvantage of this conventional fixative in anatomical research. We recently developed a FA-free embalming method for cadavers which utilizes N-vinyl-2-pyrrolidone (NVP) and enables assessment of motion kinetics by maintaining the softness of embalmed tissue. By assessing the feasibility of NVP-embalmed tissue to mimic vocalization, this study aimed to prove the potential of embalmed cadavers, which have previously been used only for the understanding of anatomical morphology, for the assessment of precise motion physiology in the human body. Ten cadavers embalmed in NVP (n = 6) and FA (n = 4) were incorporated in this study. Excised larynges underwent experimental phonation to mimic vocalization with fast and pliable vibration of vocal folds. High-speed digital imaging was utilized for the assessment of vocal fold vibration. Furthermore, acoustic analysis of the voiced sound, and reproducibility examination were also performed. Regular vocal fold vibrations successfully produced voiced sounds during experimental phonation using NVP-embalmed larynges. The vibratory frequency, vibration amplitude, and stretch rate of the vocal folds were comparable to those of living humans. Six months after the first experiment, the vocal parameters were reproduced, to suggest the long-term preservation potential of our NVP-embalming technique. On the other hand, neither voiced sound nor vocal fold vibration were observed in FA-embalmed larynges. This novel embalming technique could pioneer the next era to utilize embalmed cadavers for the examination of motion physiology in the human body.

Joint effect of longevity-associated mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on risk of hyper-LDL cholesterolemia in middle-aged Japanese men.

BACKGROUND: Combined effects between mitochondrial DNA 5178 (Mt5178) C/A polymorphism and alcohol consumption on the risk of hypertension or hyperuricemia have been reported. The objective of this study was to investigate whether Mt5178 C/A polymorphism modulates the effects of alcohol consumption on the risk of dyslipidemia. METHODS: A total of 394 male subjects were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effect of Mt5178 polymorphism and alcohol consumption on the risk of dyslipidemia was conducted. RESULTS: For men with Mt5178C, alcohol consumption was significantly and negatively associated with the risk of hyper-low-density lipoprotein (LDL) cholesterolemia (serum LDL cholesterol ≥ 140 mg/dl) (P for trend = 0.015). After adjustment for age, body mass index (BMI), habitual smoking, coffee consumption and use of antihypertensive medicine, the odds ratio (OR) for hyper-LDL cholesterolemia was significantly lower in daily drinkers with Mt5178C than non-drinkers with Mt5178C (OR = 0.360, 95% confidence intervals: 0.153-0.847). A significant and negative association between alcohol consumption and serum LDL cholesterol levels was also observed in Mt5178C genotypic men (P for trend < 0.01). On the other hand, the association between Mt5178A genotype and risk of hyper-LDL cholesterolemia does not appear to depend on alcohol consumption. CONCLUSIONS: For Mt5178C genotypic men, alcohol consumption may reduce the risk of hyper-LDL cholesterolemia.

Recent evidence from epidemiological studies on methylmercury toxicity.

More than fifty years have passed since the outbreak of Minamata disease, and large-scale methylmercury poisoning due to industrial effluents or methylmercury-containing fungicide intoxication has scarcely happened in developed countries. On the other hand, widespread environmental mercury contamination has occurred in gold and mercury mining areas of developing countries. In this article, we provided an overview of recent studies addressing human health effects of methylmercury, which we searched using the PubMed of the US National Library of Medicine. The following suggestions were obtained for low-level methylmercury exposure: (1) In recent years, the proportion of human studies addressing methylmercury has tended to decrease. (2) Prenatal exposure to methylmercury through fish intake, even at low levels, adversely affects child development after adjusting for polychlorinated biphenyls and maternal fish intake during pregnancy, whereas maternal seafood intake has some benefits. (3) Long-term methylmercury exposure through consumption of fish such as bigeye tuna and swordfish may pose a potential risk of cardiac events involving sympathovagal imbalance. (4) In measuring methylmercury levels in preserved umbilical cord collected from inhabitants born in Minamata areas between 1945 and 1989, the elevated concentrations (≥1 mg/g) were observed mainly in inhabitants born between 1947 and 1968, and the peak coincided with the peak of acetaldehyde production in Minamata. (5) Since some developing countries appear to be in similar situations to Japan in the past, attention should be directed toward early recognition of a risky agent and precautions should be taken against it.

Polyethylene microbeads are more critically toxic to the eyes and reproduction than the kidneys or growth in medaka, Oryzias latipes.

Many studies using experimental and wild animals have reported negative effects of microplastic beads (MPs) ingestion. However, data regarding the lowest observed adverse effect levels (LOAELs) of MPs remain limited. Our aim was to evaluate the adverse effect levels of polyethylene MPs (10-63 µm diameter) with respect to growth, reproduction, and the eyes and kidneys of medaka (Oryzias latipes) under breeding conditions to contribute to future research involving LOAEL determinations. Fish were exposed to 0.009 mg-MPs (approximately 1000 particles)/L to 0.32 mg-MPs (approximately 40,000 particles)/L for 12 weeks. The eyes and kidneys were evaluated by histopathologic analysis. Although histologic analyses indicated an absence of MPs in the tissues, the eyes and kidneys as well as reproduction were adversely affected by increasing MP concentrations. The number of spawned eggs decreased, and changes were noted in the eyes of fish exposed to ≥0.032 mg-MPs/L under breeding conditions. The eyes exhibited thinning of the optic nerve fiber layer and dilatation of retinal capillaries compared with medaka not treated with MPs. Changes in the kidneys were observed in fish exposed to ≥0.065 mg-MPs/L. The mesangial matrix in the glomerulus of the kidneys was expanded compared with non-treated medaka, suggesting a deterioration in renal function. Analyses of an oxidative stress marker in the tissues indicated that lesion progression was associated with increased oxidative stress. Furthermore, a comparison of adverse effect levels suggested that MPs were more toxic to the eyes and reproduction than the kidneys or growth. Our data should prove useful for determining the LOAELs of polyethylene beads on vertebrates and enhance understanding of the mechanism underlying the biological toxicity of polyethylene MPs.

Multicentre prospective observational study of sodium-glucose cotransporter-2 inhibitor-associated postoperative ketoacidosis: the SAPKA study protocol.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antihyperglycaemic agents that promote urinary glucose excretion in the renal proximal tubule and have cardio-protective and renal-protective properties. However, there are several safety concerns related to increased risks of hypoglycaemic, urinary tract infections and ketoacidosis. Ketoacidosis is a potentially fatal complication that often presents as euglycaemic ketoacidosis during SGLT2 inhibitor treatment. Furthermore, invasive treatment and related surgical stress may increase the risk of ketogenesis. Therefore, this study aims to clarify the incidence of SGLT2 inhibitor-associated postoperative ketoacidosis (SAPKA) among patients who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit 750 adult Japanese patients with diabetes who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. Urine samples will be collected on postoperative days 0, 1, 2 and 3. Blood gas analysis will be performed when urine ketone positivity is detected. The incidence of postoperative ketoacidosis will be identified based on urine ketone positivity and a blood pH of ≤7.3. The study will also collect data to identify risk factors for SAPKA. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committee of Kyorin University (approval number: 785, 26 October 2020) and local ethical approval will be required at each participating centre. Study findings will be submitted to peer-reviewed journals and abstracts will be submitted to relevant national and international meetings. TRIAL REGISTRATION NUMBER: UMIN000042795.

Combined effect of longevity-associated mitochondrial DNA 5178 C/A polymorphism and coffee consumption on the risk of hyper-LDL cholesterolemia in middle-aged Japanese men.

The objective of this study was to investigate whether the mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modifies the effects of coffee consumption on serum lipid levels and the risk of dyslipidemia in middle-aged Japanese men. A total of 397 male subjects (age, 53.9±7.8 years; mean±s.d.) were selected from among individuals visiting the hospital for regular medical check-ups. After adjustment for age, body mass index, habitual alcohol consumption, habitual smoking and use of antihypertensive medication, among subjects who consumed <1 cup of coffee per day, the odds ratio (OR) for hyper-low-density lipoprotein (LDL) cholesterolemia (serum LDL cholesterol > or =140 mg per 100 ml) was significantly lower in those with Mt5178A than in those with Mt5178C (OR=0.378, 95% confidence interval: 0.153-0.919). After adjustment, the association between the Mt5178A genotype and hyper-LDL cholesterolemia depended on coffee consumption (P for trend=0.018). Coffee consumption was positively associated with serum LDL cholesterol levels only in subjects with Mt5178A. However, in subjects with Mt5178C, serum LDL cholesterol level or risk of hyper-LDL cholesterolemia did not seem to depend on coffee consumption. These results suggest that for men with Mt5178A, coffee consumption negates the genetic benefit of lower risk for hyper-LDL cholesterolemia.

Association between PM10 and O3 levels and hospital visits for cardiovascular diseases in Bangkok, Thailand.

BACKGROUND: The association between air pollution and cardiovascular diseases is well known, but previous studies only assessed mortality and hospital admissions in North America, Europe, and Northeast Asia. Few studies have been conducted in less-developed countries in regions with a tropical climate. This study evaluated whether short-term exposures to fine particulate matter (PM(10)) and ozone (O(3)) were associated with hospital visits for cardiovascular diseases (CVD; ICD-10th, I00-I99) in central Bangkok, Thailand. METHODS: Data from hospital records were obtained from 3 major government hospitals. All hospital visits were stratified by age group and category of CVD. Daily PM(10) and O(3) levels reported by the Pollution Control Department from April 2002 to December 2006 (1736 days) were used in a time-series analysis with a generalized additive model procedure. RESULTS: Exposure on the previous day to PM(10) and O(3) had a positive association with hospital visits for CVD among elderly (>or=65 years) individuals. The increase in CVD hospital visits in this age group was 0.10% (95% CI, 0.03-0.19) with a 10 microg/m(3) increase in PM(10), and 0.50% (95% CI, 0.19-0.81) with an increase in O(3). CONCLUSIONS: In central Bangkok, a short-term association was observed between increases in daily levels of PM(10) and O(3) and the number of daily emergency hospital visits for CVD, particularly among individuals aged >or=65 years.

NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modulates the effects of coffee consumption on the risk of hypertension in middle-aged Japanese men.

BACKGROUND: Habitual coffee consumption has been reported to lower blood pressure in the Japanese population. The NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity and modifies the effects of alcohol consumption on blood pressure in the Japanese population. The objective of this study was to determine whether this polymorphism also modifies the effects of coffee consumption on blood pressure or the risk of hypertension in middle-aged Japanese men. METHODS: A total of 398 men (mean age +/- standard deviation, 53.8 +/- 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. Hypertension was defined as a systolic blood pressure > or =140 mm Hg, diastolic blood pressure > or =90 mm Hg, or antihypertensive drug treatment. Polymerase chain reaction-restriction fragment length polymorphism using the restriction enzyme AluI was performed to determine ND2-237 Leu/Met genotype. RESULTS: In subjects with ND2-237Leu, coffee consumption was significantly and negatively associated with diastolic blood pressure (P = 0.007). The odds ratio (OR) for hypertension was significantly lower in subjects with ND2-237Leu who consumed 2 or 3 cups of coffee per day than in those who consumed less than 1 cup of coffee per day (OR, 0.517; 95% confidence interval [CI], 0.276 to 0.968; P = 0.039). After adjustment, the OR remained significant (OR = 0.399; 95% CI, 0.184 to 0.869; P = 0.020). Moreover, after adjustment, the OR was significantly lower in subjects with ND2-237Leu who consumed more than 4 cups of coffee per day than in those who consumed less than 1 cup of coffee per day (OR, 0.246; 95% CI, 0.062 to 0.975; P = 0.046). However, the association between ND2-237Met genotype and hypertension did not depend on coffee consumption. CONCLUSIONS: The present results suggest that the ND2-237 Leu/Met polymorphism modulates the effects of coffee consumption on hypertension risk in middle-aged Japanese men.