Quantification of thermodynamic effects of carbohydrate multivalency on avidity using synthetic discrete glycooligomers.

A quantitative understanding of thermodynamic effects of avidity in biomolecular interactions is important. Herein, we synthesized discrete glycooligomers and evaluated their interactions with a model protein using isothermal titration calorimetry. The dimeric glycooligomer exhibited higher binding constants compared to the glycomonomer, attributed to the reduced conformational entropy loss through local presentation of multiple carbohydrate units. Conversely, divalent glycoligands with polyethylene glycol linkers, aiming for multivalent binding, showed enhanced interactions through increased enthalpy. These findings emphasize the importance of distinguishing between the "local avidity" and the "multipoint avidity".

Bayesian optimization of glycopolymer structures for the interaction with cholera toxin B subunit.

The optimal structure of synthetic glycopolymers for GM1 mimetics was determined through Bayesian optimization. The interactions of glycopolymers carrying galactose and neuraminic acid units in different compositions with cholera toxin B subunit (CTB) were assessed by an enzyme-linked immunosorbent assay (ELISA). Gaussian process regression, using the ELISA results, predicted the composition of glycopolymers that would exhibit stronger interactions with CTB. Following five cycles of optimization, the glycopolymers carrying 60 mol% galactose and 25 mol% neuraminic acid demonstrated an IC50 value of 75 µM for CTB, representing the lowest value among the synthesized glycopolymers.

Effects of Cyclic Glycopolymers Molecular Mobility on their Interactions with Lectins.

Cyclic polymers, which are found in the field of biopolymers, exhibit unique physical properties such as suppressed molecular mobility. Considering thermodynamics, the suppressed molecular mobility of cyclic polymers is expected to prevent unfavorable entropy loss in molecular interactions. In this study, we synthesized cyclic glycopolymers carrying galactose units and investigated the effects of their molecular mobility on the interactions with a lectin (peanut agglutinin). The synthesized cyclic glycopolymers exhibited delayed elution time on size exclusion chromatography and a short spin-spin relaxation time, indicating typical characteristics of cyclic polymers, including smaller hydrodynamic size and suppressed molecular mobility. The hemagglutination inhibition assay revealed that the cyclic glycopolymers exhibited weakened interactions with PNA compared to the linear counterparts, attributable to the suppressed molecular mobility. Although the results are contrary to our expectations, the impact of polymer topology on molecular recognition remains intriguing, particularly in the context of protein repellent activity in the biomedical field.

Effects of Overweight on Risk of Thyroid Nodules in Children and Adolescents: The Fukushima Health Management Survey.

CONTEXT: Examining how overweight/obesity impacts thyroid nodule development in children and adolescents by sex and age can speculate on the mechanism. OBJECTIVE: We examined whether overweight in children and adolescents are associated with thyroid nodule development by sex and age. DESIGN: Approximately 300,000 participants who underwent thyroid ultrasonography in the Fukushima Health Management Survey after a nuclear accident were enrolled. Those without nodules in the initial two examinations (1-3 and 4-5 years postaccident) were prospectively assessed for nodule development in the third examination (6-7 years postaccident) relative to baseline overweight status, with an average follow-up of 4.2 years. SETTING: A population-based prospective cohort study. PARTICIPANTS: The first and second thyroid examinations involved 299,939 and 237,691 participants, respectively, excluding those with thyroid nodules. After the third examination, 184,519 participants were finalized for analysis. MAIN OUTCOME MEASURES: Multivariable-adjusted odds ratios of new detected thyroid nodules for overweight participants compared with normal-weight participants. RESULTS: New thyroid nodules were detected in 660 participants. Being overweight was positively associated with thyroid nodules. The adjusted odds ratio (95% confidence interval) of thyroid nodules for overweight participants compared with other participants was 1.27 (1.04-1.57). Additionally, the multivariable-adjusted odds ratios for males and females with overweight were 1.21 and 1.32, respectively, and those for different age groups (0-9, 10-14, and 15-19 years) ranged from 1.17 to 1.75. CONCLUSIONS: Being overweight was associated with thyroid nodules in children and adolescents, mostly adolescent females, regardless of their proximity to the nuclear power plant.

Nitrogen-Rich Molybdenum Nitride Synthesized in a Crucible under Air.

The triple bond in N2 is significantly stronger than the double bond in O2, meaning that synthesizing nitrogen-rich nitrides typically requires activated nitrogen precursors, such as ammonia, plasma-cracked atomic nitrogen, or high-pressure N2. Here, we report a synthesis of nitrogen-rich nitrides under ambient pressure and atmosphere. Using Na2MoO4 and dicyandiamide precursors, we synthesized nitrogen-rich γ-Mo2N3 in an alumina crucible under an ambient atmosphere, heated in a box furnace between 500 and 600 °C. Byproducts of this metathesis reaction include volatile gases and solid Na(OCN), which can be washed away with water. X-ray diffraction and neutron diffraction showed Mo2N3 with a rock salt structure having cation vacancies, with no oxygen incorporation, in contrast to the more common nitrogen-poor rock salt Mo2N with anion vacancies. Moreover, an increase in temperature to 700 °C resulted in molybdenum oxynitride, Mo0.84N0.72O0.27. This work illustrates the potential for dicyandiamide as an ambient-temperature metathesis precursor for an increased effective nitrogen chemical potential under ambient conditions. The classical experimental setting often used for solid-state oxide synthesis, therefore, has the potential to expand the nitride chemistry.

Preparation of cellular membrane-mimicking glycopolymer interfaces by a solvent-assisted method on QCM-D sensor chips and their molecular recognition.

Carbohydrate-based membranes that show molecular recognition ability are interesting mimics of biointerfaces. Herein, we prepared glycopolymer membranes on QCM-D sensor chips using a solvent-assisted method and investigated their interactions with a target lectin. The membrane containing the glycopolymer with a random arrangement of the carbohydrate units adsorbed more lectin than that containing the glycopolymer with an organized block of carbohydrate units.

Mushroom intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study (CIRCS).

It is uncertain whether dietary intake of mushrooms rich in dietary fibre and several antioxidants is associated with a lower risk of dementia. We sought to examine prospectively the association between mushroom intake and the risk of disabling dementia. We performed a prospective study involving 3750 people aged 40 to 64 years residing in three communities who participated in an annual cardiovascular risk survey from 1985 to 1999. Cases of incident disabling dementia were surveyed from 1999 to 2020. We calculated the hazard ratios (HR) and 95 % CI for incident total dementia according to mushroom intake among participants with or without a history of stroke. During a mean 16·0 years' follow-up in 3739 eligible participants, 670 people developed disabling dementia. For women, mushroom intake was inversely associated with the risk of total dementia and the association was confined to dementia without a history of stroke. The multivariable HR (95 % CI) for total dementia in women were 0·81 (0·62, 1·06) for mushroom intake of 0·1-14·9 g/d and 0·56 (0·42, 0·75) for mushroom intake above 15·0 g/d (Pfor trend = 0·003) compared with no intake. The corresponding HR (95 % CI) for dementia without a history of stroke were 0·66 (0·47, 0·93) and 0·55 (0·38, 0·79) (Pfor trend = 0·01). In men, no associations were observed between mushroom intake and the risk of disabling dementia. Among Japanese women, dietary mushroom intake was associated with a lower risk of disabling dementia.

Relationship between evacuation after the Great East Japan Earthquake and new-onset hyperuricemia: A 7-year prospective longitudinal study of the Fukushima Health Management Survey.

INTRODUCTION: On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. However, the effect of evacuation on the new-onset of hyperuricemia have not been sufficiently elucidated. This study assessed the association between evacuation and new-onset hyperuricemia after the earthquake based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective. MATERIALS AND METHODS: This is a 7-year prospective longitudinal study included 18,140 residents (6,961 men and 11,179 women) with non-hyperuricemia who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between new-onset hyperuricemia and lifestyle- and disaster-related factors, including evacuation, were estimated using a Cox proportional hazards regression model analysis. Hyperuricemia was defined as uric acid levels > 7.0 mg/dL for men and > 6.0 mg/dL for women. RESULTS: During a median follow-up of 4.3 years, 2,996 participants (1,608 men, 23.1%, 1,388 women, 12.4%) newly developed hyperuricemia. Significant associations were observed between evacuation and onset of hyperuricemia in women (adjusted hazard ratio 1.18, 95% confidence interval, 1.05-1.32, p = 0.007), but not in men (adjusted hazard ratio 1.11, 95% confidence interval, 0.99-1.24, p = 0.067). DISCUSSION: Evacuation after a natural disaster is an independent risk factor for the new-onset of hyperuricemia in women. The possibility of hyperuricemia developing in response to natural disasters should be considered.

Blood data trends of children in Fukushima after the Great East Japan Earthquake: Fukushima health management survey.

BACKGROUND: After the Great East Japan Earthquake on March 11, 2011 and the subsequent accident at the Tokyo Electric Power Company-operated Daiichi Nuclear Power Plant, the Fukushima Prefecture government initiated the Fukushima Health Management Survey (FHMS) to assess the long-term health effects of the disaster on Fukushima residents. The blood tests of children aged ≤15 years between 2011 and 2012 did not reveal any changes regarding peripheral blood data; however, long-term monitoring is still necessary. Therefore, this study aimed to investigate the long-term health status of children aged ≤15 years who had evacuated the Fukushima Prefecture. METHODS: From 2011 to 2018, 71,250 evacuees aged 15 years or younger participated in the FMHS and were subjected to blood tests. By analyzing the data of the comprehensive health check survey managed by the FHMS, we examined the changes in hemoglobin (Hb) levels, white blood cell (WBC) counts, including fractions, and platelet (PLT) counts among children from 2011 to 2018. RESULTS: Minor fluctuations in Hb levels, PLT counts, and WBC counts were observed during the study period, but the central 95% intervals of distribution of the laboratory values were generally within previously reported reference intervals. In particular, there was no increase in the proportions of patients with anemia, polycythemia, or deviating WBC counts. CONCLUSION: From 2011 to 2018, there was no increase in the percentages of children with anemia, polycythemia, or deviating WBC counts among the Fukushima Prefecture evacuees.

Design of Glycopolymers for Controlling the Interactions with Lectins.

Carbohydrates are involved in life activities through the interactions with their corresponding proteins (lectins). Pathogen infection and the regulation of cell activity are controlled by the binding between lectins and glycoconjugates on cell surfaces. A deeper understanding of the interactions of glycoconjugates has led to the development of therapeutic and preventive methods for infectious diseases. Glycopolymer is one of the classes of the materials present multiple carbohydrates. The properties of glycopolymers can be tuned through the molecular design of the polymer structures. This review focuses on research over the past decade on the design of glycopolymers with the aim of developing inhibitors against pathogens and manipulator of cellular functions.

Confounding factors and biases involved in regional differences in the detection rate of thyroid cancer in the second-round Thyroid Ultrasound Examination: the Fukushima Health Management Survey.

In response to concerns about health due to radiation exposure, the Fukushima Prefecture launched the Thyroid Ultrasound Examination program for residents aged 0-18 years at the time of the earthquake. Herein, we considered the confounding factors involved in the regional differences in the development of thyroid cancer. In this study, the 242 065 individuals who participated in both first- and second-round surveys were classified into four groups by address according to their air radiation dose. The number of participants diagnosed as malignant or suspicious for malignancy by cytological examination were 17, 38, 10 and 4 with detection rates of 53.8, 27.8, 21.7 and 14.5 per 100 000 participants in Regions 1, 2, 3 and 4, respectively. Sex (P = 0.0400), age at the time of the primary examination (P < 0.0001) and interval between the first- and second-round surveys (P < 0.0001) were significantly different among the four regions, and these were suspected to be confounding factors affecting regional differences in malignant nodule detection rates. In addition, significant regional differences were observed in the participation rate in the confirmatory examination (P = 0.0037) and the fine needle aspiration cytology implementation rate (P = 0.0037), which could be potential biases. No significant regional differences in the detection of malignant nodules were found in the multivariate logistic regression analysis after adjusting for the survey interval alone or for sex, age and survey interval. The confounding factors and biases identified in this study that may have important impacts on thyroid cancer detection rate should be fully considered in future studies.

Impact of Lifestyle and Psychosocial Factors on the Incidence of Hepatobiliary Enzyme Abnormalities After the Great East Japan Earthquake: Seven-Year Follow-up of the Fukushima Health Management Survey.

OBJECTIVE: Residents who lived near the Fukushima Power Plant accident were forced to change their lifestyle after the 2011 accident. This study aimed to elucidate the association of resident lifestyle and psychological factors with onset of hepatobiliary enzyme abnormalities (HEA) after the accident. METHODS: This longitudinal study included 15705 residents who underwent a comprehensive health check, as well as a mental health and lifestyle survey between June 2011 and March 2012. Follow-up surveys were conducted between June, 2012 and March 2018. Risk factors for new HEA onset were evaluated using the Cox proportional hazards model, moreover, population attributable risks for new HEA onset were calculated. RESULTS: HEA developed in 29.7% of subjects. In addition to metabolic factors such as overweight, hyperglycemia, and hyperlipidemia; there were differences in alcohol intake, evacuation, unemployment, educational background, and psychological distress between subjects with and without HEA onset. After we adjusted for potential confounding factors, an association of being overweight, hypertension, and dyslipidemia, as well as alcohol consumption, evacuation, and psychological distress with increased risk of HEA onset was realized. Among these identified risk factors, evacuation accounted for the greatest share. CONCLUSIONS: Metabolic characteristics and disaster-related lifestyle aspects, including mental status, were risk factors for HAE onset after the Fukushima Power Plant accident.

Correlation between Self-Folding Behavior of Amphiphilic Polymers and Their Molecular Flexibility.

Self-folding behavior of amphiphilic polymers in aqueous environments mimics the structures of biomacromolecules (e.g., proteins). Since both the three-dimensional structure (static) and the molecular flexibility (dynamic) of a protein are essential for its biological functions, the latter should be considered when designing synthetic polymers that are intended to mimic proteins. Herein, we investigated the correlation between the self-folding behavior of amphiphilic polymers and their molecular flexibility. We synthesized amphiphilic polymers by subjecting N,N-dimethylacrylamide (hydrophilic) and N-benzylacrylamide (hydrophobic) to living radical polymerization. Polymers containing 10, 15, and 20 mol % of N-benzylacrylamide demonstrated self-folding behavior in an aqueous phase. The spin-spin relaxation time (T2) of the hydrophobic segments decreased with the percent collapse of the polymer molecules, indicating that mobility was restricted by the self-folding behavior. Furthermore, comparison of the polymers with random and block sequences revealed that the mobility of hydrophobic segments was not affected by the component of the local segments.

Longitudinal Trends in Blood Pressure Associated with The Changes in Living Environment Caused by the Great East Japan Earthquake: The Fukushima Health Management Survey.

The Great East Japan Earthquake occurred on 11 March 2011, forcing Fukushima Prefecture residents to change their living environment. Such sudden changes possibly have long-term effects on cardiovascular-related diseases. We therefore sought to identify temporal relationships between living environment changes and blood pressure levels over three years following the earthquake. Participants included 14,941 men and 21,533 women aged 16 years or older who answered self-administered questionnaires, including questions on living environment changes at baseline (2012). Blood pressure levels were measured each year from 2012 to 2015. Linear mixed-effects models were used to analyze associations between living environment changes and blood pressure levels. Men with changes in living environment (i.e., those living in shelters or in temporary housing, rental apartments, relatives' houses, or others) showed significantly higher diastolic blood pressure levels than those who lived in their home at baseline (77.3 mmHg vs. 77.8 mmHg; p < 0.001). The time-dependent effect of diastolic blood pressure levels associated with living environment was not statistically significant, indicating a sustained difference in diastolic blood pressure associated with living environment changes at baseline after three years. The effect of living environment changes on diastolic blood pressure increment was also evident in men without antihypertensive medication use during the study period and in men who were current drinkers at baseline. There were no associations between living environment changes and diastolic blood pressure levels among women. Sudden changes in living environment due to the disaster had an impact on the long-term effects of higher diastolic blood pressure among middle-aged men.

Dietary fiber intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study.

OBJECTIVES: It has been hypothesized that dietary fiber intake has a beneficial impact on prevention of dementia, but the epidemiological evidence is scant. We sought to examine whether dietary fiber intake is inversely associated with risk of dementia requiring care under the national insurance (disabling dementia). METHODS: The study setting was the Circulatory Risk in Communities Study, involving 3739 Japanese individuals aged 40-64 years at the dietary surveys (1985-99). Dietary fiber intake was estimated using the 24-hour dietary recall method. Incident disabling dementia was followed up from 1999 through 2020. Disabling dementia was further classified into that with or without a history of stroke. Hazard ratios of disabling dementia according to quartiles of total, soluble, and insoluble fiber intake were calculated using the Cox proportional hazards model. RESULTS: During a median 19.7-year follow-up, a total of 670 cases of disabling dementia developed. Dietary fiber intake was inversely associated with risk of dementia: the multivariate hazards ratios (95% confidence intervals) were 0.83 (0.67-1.04), 0.81 (0.65-1.02), and 0.74 (0.57-0.96) for individuals with the second, third, and highest quartiles of dietary fiber intake, respectively, as compared with the lowest quartile (P for trend = 0.03). The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke. As for fiber-containing foods, potatoes, but not vegetables or fruits, showed a similar association. CONCLUSIONS: Dietary fiber intake, especially soluble fiber, was inversely associated with risk of disabling dementia in a general Japanese population.

Trends in Lifestyle-related Diseases and Their Risk Factors After the Fukushima Daiichi Nuclear Power Plant Accident: Results of the Comprehensive Health Check in the Fukushima Health Management Survey.

Residents were forced to evacuate owing to the radiation released after the Fukushima Nuclear Power Plant (NPP) accident following the Great East Japan Earthquake on 11/03/2021; thus, their lifestyles drastically changed. The Comprehensive Health Check (CHC) of the Fukushima Health Management Survey (FHMS) was performed to evaluate health statuses and prevent lifestyle-related diseases in evacuation area residents. The first part of the CHC survey is a retrospective analysis of pre- and post-disaster data on health check-ups of evacuation area residents. The second part is a cross-sectional, prospective analysis of post-disaster (fiscal year (FY) 2011-2017) data on health check-ups. Subjects were men and women living in 13 municipalities in areas surrounding the NPP in Fukushima Prefecture. Post-disaster (FY 2011-2012) overweight, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, liver dysfunction, hyperuricemia, polycythemia and atrial fibrillation cases increased from the pre-disaster (FY 2008-2010) levels. This tendency was strongest among residents who were forced to evacuate. Proportion of overweight people remained unchanged, the prevalence of liver dysfunction decreased and the proportion of people with treated hypertension and dyslipidemia increased during FY 2011-2017. Meanwhile, the prevalence of diabetes mellitus and mean levels of HbA1c increased. Furthermore, Evacuees showed higher risks of diabetes mellitus, dyslipidemia, chronic kidney diseases and liver dysfunction than non-evacuees. Therefore, residents in the evacuation area, especially evacuees, are at high risk of developing lifestyle-related diseases, especially cardiovascular diseases; therefore, it is necessary to observe health statuses and implement measures to prevent lifestyle-related diseases.

Effects of External Radiation Exposure Resulting From the Fukushima Daiichi Nuclear Power Plant Accident on the Health of Residents in the Evacuation Zones: the Fukushima Health Management Survey.

BACKGROUND: Associations have been reported between lifestyle-related diseases and evacuation after the Great East Japan Earthquake (GEJE). However, the relationship between lifestyle-related diseases and the effective radiation dose due to external exposure (EDEE) after the GEJE remains unclear. METHODS: From among 72,869 residents of Fukushima Prefecture (31,982 men; 40,887 women) who underwent a comprehensive health check in fiscal year (FY) 2011, the data of 54,087 residents (22,599 men; 31,488 women) aged 16 to 84 years were analyzed. The EDEE data of 25,685 residents with incomplete results from the basic survey, performed to estimate the external radiation exposure dose, were supplemented using multiple imputation. The data were classified into three groups based on EDEE (0 to <1, 1 to <2, and ≥2 mSv groups and associations between the incidence of diseases and EDEE from FY2011 to FY2017 were examined using a Cox proportional hazards model, with FY2011 as the baseline. RESULTS: A higher EDEE was associated with a greater incidence of hypertension, diabetes mellitus, dyslipidemia, hyperuricemia, liver dysfunction, and polycythemia from FY2011 to FY2017 in the age- and sex-adjusted model. However, after further adjustment for evacuation status and lifestyle-related factors, the significant associations disappeared. No association was found between EDEE and other lifestyle-related diseases. CONCLUSION: EDEE was not directly associated with the incidence of lifestyle-related diseases after the GEJE. However, residents with higher external radiation doses in Fukushima Prefecture might suffer from lifestyle-related diseases related to evacuation and the resultant lifestyle changes.

Associations Between External Radiation Doses and the Risk of Psychological Distress or Post-traumatic Stress After the Fukushima Daiichi Nuclear Power Plant Accident: the Fukushima Health Management Survey.

BACKGROUND: The relationship between radiation levels and mental health status after a nuclear disaster is unknown. We examined the association between individual external radiation doses and psychological distress or post-traumatic stress after the Fukushima Daiichi nuclear power plant accident in March 2011 in Japan. METHODS: The Mental Health and Lifestyle Survey was conducted from January 2012. Based on the estimated external radiation doses for the first 4 months, a total of 64,184 subjects were classified into <1 mSv, 1 to <2 mSv, and ≥2 mSv groups. Odds ratios (ORs) and 95% confidence intervals (CIs) of psychological distress and post-traumatic stress, with the <1 mSv group as the reference, were calculated using logistic regression analysis adjusted for age, sex, evacuation, perception of radiation risk, and subjective health status. RESULTS: The prevalence of psychological distress/post-traumatic stress in the <1 mSv, 1 to <2 mSv, and ≥2 mSv groups was 15.1%/22.1%, 14.0%/20.1%, and 15.0%/21.7%, respectively. In women, although the ≥2 mSv group tended to have a higher risk of psychological distress with the age-adjusted OR of 1.13 (95% CI, 0.99-1.30), the adjusted OR decreased to 1.00 (95% CI, 0.86-1.16) after controlling for all variables. On the other hand, there were no dose-dependent associations between radiation dose and post-traumatic stress. CONCLUSION: Although external radiation doses were not associated with psychological distress, evacuation and perception of radiation risk may increase the risk of psychological distress in women in the higher dose group.

Psychological burden predicts new-onset diabetes in men: A longitudinal observational study in the Fukushima Health Management Survey after the Great East Japan earthquake.

Background: The burden of psychological distress and post-traumatic stress disorder (PTSD) has been suggested as a factor in developing type 2 diabetes mellitus. However, longitudinal features in psychological distress- and PTSD-related new-onset diabetes mellitus have not been thoroughly evaluated. Methods: The association between probable depression and probable PTSD and the risk of developing new-onset diabetes mellitus was evaluated in a 7-year prospective cohort of evacuees of the Great East Japan Earthquake in 2011. Probable depression was defined as a Kessler 6 scale (K6) ≥ 13 and probable PTSD as a PTSD Checklist-Stressor-Specific Version (PCL-S) ≥ 44. Results: The log-rank test for the Kaplan-Meier curve for new-onset diabetes mellitus was significant between K6 ≥ 13 vs. < 13 and PCL-S ≥ 44 vs. < 44 in men but not in women. In men, both K6 ≥ 13 and PCL-S ≥ 44 remained significant in the Cox proportional hazards model after multivariate adjustment for established risk factors and disaster-related factors, including evacuation, change in work situation, sleep dissatisfaction, and education. Conclusion: The post-disaster psychological burden of probable depression and probable PTSD was related to new-onset diabetes in men but not in women. In post-disaster circumstances, prevention strategies for new-onset diabetes might consider sex differences in terms of psychological burden.