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There have been no systematic epidemiological evaluations of the relationship between thyroid autoimmunity and the clinical background of young patients with thyroid nodules. We aimed to clarify the clinical features associated with thyroglobulin or thyroperoxidase antibodies (thyroid autoantibodies [Tabs]) in children and young adults with nodules. We performed a cross-sectional study using data from 3,018 participants of 3–29 years of age with nodules, including thyroid cancer, from the Fukushima Health Management Survey. After stratification of the data for body mass index (BMI) and the bilateral width and thickness of the area (BWTAR) as indicators of thyroid volume for age, sex, body surface area (BSA), and sex-adjusted standard deviation score (SDS), trend analyses were performed. A logistic regression analysis was performed using tab-positivity as an objective variable. The overall prevalence of tab-positivity is 13.9%. It was high in females (17%), participants with diffuse goiter (DG) (19.2%), and those with papillary thyroid carcinoma (PTC) (12.8%). The age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS, BWTAR-SDS, presence of DG, diagnosis of PTC, and TSH concentrations were 0.962 (0.863–1.073), 1.263 (1.171–1.361), 7.357 (4.816–11.239), 2.787 (1.965–4.014), and 1.403 (1.257–1.564), respectively. Tab positivity was independently associated with a large thyroid, the presence of DG, the presence of PTC, and a high TSH concentration in patients with nodules. Based on the systematic epidemiologic evidence shown in young patients, Tab positivity might complement ultrasonography for the assessment of the thyroid function and identification of malignancy in younger patients with asymptomatic thyroid nodules.

Previous atomic force microscopy studies have suggested that surface micro- and nanobubbles exhibit a flat shape. In this study, we directly observed surface microbubbles formed in an NH3BH3 solution using an optical microscope. No flat microbubbles were observed. Instead, on an SiO2/Si substrate, we discovered a relationship where the sum of the contact angle of a microbubble and the contact angle of a droplet equaled ∼180°. This relationship allowed us to control the shape of surface microbubbles by manipulating the wettability of the surface and the surface tension of the liquid, similar to droplet control. We were able to produce almost perfectly spherical microbubbles. Conversely, on a Cu foil, this relationship did not hold, although we still observed the formation of nearly spherical microbubbles. In this scenario, the shape of microbubbles appeared to be influenced by contact line pinning.

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto’s thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1–23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21–1.27), 3.21 (3.13–3.29), 0.53 (0.50–0.58), and 1.38 (1.17–1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08–16.08), 1.76 (1.01–3.07), 1.80 (1.32–2.45), and 1.34 (1.08–1.67) in the age groups 1–7, 8–11, 12–15, and 16–23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

Abstract The drug absorption profile is dependent on the luminal drug concentration, which in turn is influenced by the gastrointestinal (GI) fluid dynamics. In the present study, therefore, we aimed to examine the luminal fluid dynamics by kinetically analyzing fluid absorption and secretion along the GI tract in rats using the in situ closed-loop technique with non-absorbable fluorescein isothiocyanate-dextran 4000 (FD-4) and tritium water labeling ([3H]water) under different osmotic conditions. We found that the luminal fluid volume in the jejunum and ileum, but not the colon, gradually decreased and reached a steady state. In contrast, [3H]water almost completely disappeared in all intestinal regions. Kinetic analysis revealed the following rank order for the rate constant of fluid secretion: jejunum > ileum > colon, whereas a negligible regional difference was observed in the rate constant of fluid absorption. Fluid secretion under an isosmotic condition (300 mOsm/kg) was higher than that at 0 mOsm/kg in all intestinal regions, though no significant changes in fluid absorption were observed. Thus, the fluid secretion process appears to be the major determinant of the regional differences in GI fluid dynamics. Our findings indicate that the luminal fluid volume is altered as a result of water ingestion, absorption, and secretion, and finally reaches an apparent steady state, which is regulated mainly by the process of fluid secretion.

Prior research has identified a variety of task-dependent networks that form through inter-regional phase-locking of oscillatory activity that are neural correlates of specific behaviors. Despite ample knowledge of task-specific functional networks, general rules governing global phase relations have not been investigated. To discover such general rules, we focused on phase modularity, measured as the degree to which global phase relations in EEG comprised distinct synchronized clusters interacting with one another at large phase lags. Synchronized clusters were detected with a standard community-detection algorithm, and the degree of phase modularity was quantified by the index q. Notably, we found that the mechanism controlling phase modularity is remarkably simple. A network comprising anterior-posterior long-distance connectivity coherently shifted phase relations from low-angles (|Δθ| < π/4) in low-modularity states (bottom 5% in q) to high-angles (|Δθ| > 3π/4) in high-modularity states (top 5% in q), accounting for fluctuations in phase modularity. This anterior-posterior network may play a fundamental functional role as (1) it controls phase modularity across a broad range of frequencies (3-50 Hz examined) in different behavioral conditions (resting with the eyes closed or watching a silent nature video) and (2) neural interactions (measured as power correlations) in beta-to-gamma bands were consistently elevated in high-modularity states. These results may motivate future investigations into the functional roles of phase modularity as well as the anterior-posterior network that controls it.

Antibiotic resistance genes (ARGs) are widespread environmental pollutants of biological origin that pose a significant threat to human, animal, and plant health, as well as to ecosystems. ARGs are found in soil, water, air, and waste, and several pathways for global dissemination in the environment have been described. However, studies on airborne ARG transport through atmospheric particles are limited. The ARGs in microorganisms inhabiting an environment are referred to as the “resistome”. A global search was conducted of air-resistome studies by retrieving bioaerosol ARG-related papers published in the last 30 years from PubMed. We found that there is no dedicated methodology for isolating ARGs in bioaerosols; instead, conventional methods for microbial culture and metagenomic analysis are used in combination with standard aerosol sampling techniques. There is a dearth of information on the bioaerosol resistomes of freshwater environments and their impact on freshwater sources used for drinking and recreational activities. More studies of aerobiome freshwater environments are needed to ensure the safe use of water and sanitation. In this review we outline and synthesize the few studies that address the freshwater air microbiome (from tap water, bathroom showers, rivers, lakes, and swimming pools) and their resistomes, as well as the likely impacts on drinking and recreational waters. We also discuss current knowledge gaps for the freshwater airborne resistome. This review will stimulate new investigations of the atmospheric microbiome, particularly in areas where both air and water quality are of public health concern.

There is much evidence that the environment is a reservoir of antibiotic resistance genes (ARGs). For ARG latency and stability, environmental factors should play a role since ARGs are transferred among bacterial species, which results in their evolution and dissemination. Recent findings have expanded the novel mechanisms of horizontal gene transfer (HGT) beyond classically accepted HGT mechanisms such as conjugation, transformation, and transduction. In these HGT processes, environmental factors directly or indirectly affect the transfer rate and mechanism. Here, we focus on the effect of protists that affect HGT, because HGT is regulated among the microbial community, in which protist grazing is one factor that enhances HGT. Protist grazing eliminates planktonic bacteria. However, it is reported that environmental DNA release and HGT in protist vacuoles are increased by the grazing, although the effect is not uniform and depends on the environmental conditions. Biofilms protect bacteria and accelerate HGT. In these processes, quorum sensing and organic matter contribute to HGT. Although HGT occurs between bacterial cells, other microorganisms such as protists should be recognized as factors relating to HGT. We should pay attention to microbial ecosystem when consider ARG risk from water environment in terms of “one health” aspect.

Marine bacteria are possible reservoirs of antibiotic-resistance genes (ARGs) originating not only from clinical and terrestrial hot spots but also from the marine environment. We report here for the first time a higher rate of the sulfonamide-resistance gene sul4 in marine bacterial isolates compared with other sul genes. Among four sulfonamide-resistance genes (sul1, sul2, sul3, and sul4), sul4 was most abundant (45%) in 74 sulfonamide-resistant marine isolates by PCR screening. The order of abundance was sul4 (33 isolates) >sul2 (6 isolates) >sul3 (5 isolates) >sul1 (1 isolate). Whole-genome sequencing of 23 isolates of sul4-expressing α- and γ-proteobacteria and bacilli revealed that sul4 was not accompanied by known mobile genetic elements. This suggests that sul4 in these marine isolates is clonally transferred and not horizontally transferable. Folate metabolism genes formed a cluster with sul4, suggesting that the cluster area plays a role in folate metabolism, at which sul4 functions as a dihydropteroate synthase. Thus, sul4 might be expressed in marine species and function in folate synthesis, but it is not a transferable ARG.

We investigated the mechanism of polytetrafluoroethylene (PTFE) chain scission through in situ hard X-ray photoelectron spectroscopy at room temperature, 200 °C, and 230 °C. The C–C bonds in the main chain and C–F bonds in the side chains were broken, and F desorption from the PTFE surface was observed at room temperature. The formation of CF3 was also observed from the recombination of broken C–C bonds in the main chain and detached F, which were not induced by soft X-rays. In contrast, when the PTFE substrate was irradiated with hard X-rays at 200 °C, the CF3 intensity initially produced by recombination reactions decreased with irradiation time, and the photoelectron spectrum retained the original PTFE spectrum. Under these conditions, the F1s/C1s intensity ratio did not change with the irradiation time; hence, the fragment containing only CF2, the chemical composition of the original PTFE, was desorbed. When the substrate temperature was 230 °C, the CF3 intensity increased in relation to that at 200 °C. This result indicated that the formation of CF3 via recombination reactions of broken molecular chains is enhanced by thermal assistance. These phenomena were considered to be based on the balance between recombination and desorption by photochemical and pyrochemical reactions. These results will lead to a better understanding of the use of X-ray-irradiated fluorine resins and PTFE in potential space-based environments. This study will also promote the improvement of PTFE microfabrication methods and thin-film formation using synchrotron radiation.

ABSTRACT: Objectives: Macrolides have a long history of use in animals and humans. Dynamics of macrolide-antibiotic resistance genes (ARGs) in waterways from the origin to the sea has not been reported. Methods: Resistant bacterial rate was measured by culture method, and copy numbers of macrolide-ARGs, mef(A), erm(B), mph(B), mef(C)-mph(G), and mobile genetic elements (MGEs) traI and IntI1 were quantitated in environmental DNA. Community composition in each site was investigated by 16S rRNA gene metagenomic sequencing. In Yilan area, antibiotics were quantitated. Results: Surface water samples from pig farms to the sea in southern and northern areas in Taiwan were monitored. Macrolide-resistant bacteria accounted for 3%–28% of total colony-forming bacteria in aquaculture ponds and rivers, whereas in pig farm wastewater it was 26%–100%. Three common macrolide-ARGs mef(A), erm(B), and mph(B) and the relatively new mef(C)-mph(G) were frequently detected in pig farms, but not in aquaculture ponds and the sea. Rivers receiving pig wastewater showed ARG contamination similar to the pig farms. Among the MGEs, IntI1 was frequently distributed in all sites and was positively related to mef(A), erm(B), and mph(B) but not to mef(C)-mph(G). Conclusion: Pig farms are the origin of macrolide-ARGs, although macrolide contamination is low. Since lincomycin was detected in pig farms in the northern area, the increase of macrolide-ARGs is a future concern due to cross-resistance to lincomycin. ARGs abundance in aquaculture ponds was low, though MGEs were detected. Relation of IntI1 to ARG suggests convergence of ARGs to specific MGEs might be time/history dependent.

Abstract Background Heart failure (HF)‐related congestive hepatopathy is a well‐recognized problem in management of HF. The fibrosis‐4 (FIB4) index calculated by [age × aspartate aminotransferase (IU/L)/platelet count (109/L) × square root of alanine aminotransferase (IU/L)] is useful for evaluating liver stiffness. We aimed to investigate the impact of the FIB4 index on prognosis in patients with HF. Methods and results Consecutive HF patients referred for hospitalization at Kumamoto University Hospital, Japan, were registered between 2006 and 2015. We observed cardiovascular outcomes in each type of HF [HF with reduced left ventricular ejection fraction (LVEF) (HFrEF), HF with mid‐range LVEF (HFmrEF) and with preserved LVEF (HFpEF)] according to their FIB4 index; Group 1 (FIB4 index 2.67). This study enrolled 83 HFrEF patients, 117 HFmrEF patients, and 504 HFpEF patients. In HFpEF patients, the Kaplan–Meier curve revealed that Group 3 had a significantly higher rate of total cardiovascular events compared with the other two groups. By contrast, the occurrences of total cardiovascular events were not different among three groups in HFrEF and HFmrEF patients. Multivariate Cox proportional hazard analysis with significant factors in univariate analysis identified that the FIB4 index as an independent and significant predictor for future total cardiovascular events in HFpEF patients (hazard ratio: 1.09, 95% confidence interval: 1.03–1.15, P = 0.001). Conclusions The FIB4 index was a significant predictor for total cardiovascular events in HFpEF.

The Great East Japan Earthquake on March 11, 2011, and the subsequent tsunami caused an accident at the Fukushima Daiichi Nuclear Power Plant, in which extensive damage to the nuclear power reactors resulted in massive radioactive contamination. Fukushima Prefecture implemented the Thyroid Ultrasound Examination (TUE) program as part of the Fukushima Health Management Survey project in response to residents’ anxieties about health risks due to radiation exposure for residents aged 0–18 years at the time of the nuclear accident. This program consisted of the primary examination and the confirmatory examination. In the primary examination, thyroid nodules and cysts were examined using portable ultrasound apparatuses. The confirmatory examination was performed to have clinical or cytological diagnosis. As of June 30, 2021, 116, 71, 31, 36, and 9 examinees in the first, second, third, and fourth round of surveys, and the survey at age 25 years, respectively, were determined to have nodules cytologically diagnosed as malignant or suspicious for malignancy. The confirmatory examination of the fourth-round survey and the primary and confirmatory examination of fifth-round survey are currently in progress. Together with the low thyroid absorbed radiation dose estimated in the United Nations Scientific Committee on the Effects of Atomic Radiation 2020 report, our results suggested that the increased incidence of childhood thyroid cancer in Fukushima Prefecture was not caused by radiation exposure, but rather by the highly sensitive detection method. As detailed in this review, there were ongoing challenges in our program, such as actions against the risk of overdiagnosis and psychological support for participants and their families.

Background: After the first-round (Preliminary Baseline Survey) ultrasound-based examination for thyroid cancer in response to the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, two rounds of surveys (Full-scale Survey) have been carried out in Fukushima Prefecture. Using the data from these surveys, the geographical distribution of thyroid cancer incidence over 6 or 7 years after the disaster was examined. Methods: Children and adolescents who underwent the ultrasound-based examinations in the second- and/or third-round (Full-scale) survey in addition to the first-round survey were included. With a discrete survival model, we computed age, sex, and body mass index standardized incidence ratios (SIRs) for municipalities. Then, we employed spatial statistics to assess geographic clustering tendency in SIRs and Poisson regression to assess the association of SIRs with the municipal average absorbed dose to the thyroid gland at the 59-municipality level. Results: Throughout the second- and third-round surveys, 99 thyroid cancer cases were diagnosed in the study population of 252,502 individuals. Both flexibly shaped spatial scan statistics and maximized excess events test did not detect statistically significant spatial clustering (P = 0.17 and 0.54, respectively). Poisson regression showed no significant dose-response relationship: the estimated relative risks of lowest, middle-low, middle-high, and highest areas were 1.16 (95% confidence interval [CI], 0.52–2.59), 0.55 (95% CI, 0.31–0.97), 1.05 (95% CI, 0.79–1.40), and 1.24 (95% CI, 0.89–1.74). Conclusion: There was no statistical support for geographic clustering or regional association with radiation dose measures of the thyroid cancer incidence in the cohort followed up to the third-round survey (fiscal years 2016–2017) in Fukushima Prefecture.

Background: Although the Khorana venous thromboembolism (VTE) risk score (KRS) is well recognized as a simple VTE risk assessment method in patients with cancer, whether it is suitable for Asian populations is unclear. Objectives: This study validated KRS for the prediction of VTE and investigated the value of the KRS in predicting mortality in Japanese patients with cancer. Methods: A body mass index value of 25 kg/m2 or more was defined as obesity according to World Health Organization consensus. A total of 27,687 patients with cancer were subdivided into low- (0), intermediate- (1-2), and high-score (3) groups by the KRS. The primary and secondary endpoints were VTE and all-cause mortality, respectively. Results: The prevalence of VTE was 1.7%, 7.3%, and 11.0% for low-, intermediate-, and high-score patients, respectively. Receiver operating characteristic (ROC) analysis showed that the KRS significantly predicted VTE (area under the curve, 0.679; 95% confidence interval [CI] 0.666-0.692; P < 0.001). The cutoff value for the KRS was 1.0. Logistic regression analysis demonstrated that the KRS was an independent predictor of VTE (odds ratio 1.766; 95% CI 1.673-1.865; P < 0.01). The cutoff value of the KRS for all-cause mortality determined by ROC analysis was 2.0. Kaplan–Meier analysis demonstrated a significantly higher incidence of mortality in the KRS ≥2 group than in the KRS 0-1 group (log-rank: P < 0.01). Conclusions: The KRS was useful in Japanese patients with cancer and might be a potentially useful marker for the prediction of mortality. Establishing optimal scores for Japanese subjects is mandatory because of its low diagnostic ability. (KUMAMON Cancer registry; UMIN000047554)

Abstract Aims The focus on wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM) is increasing because of novel treatment options. There is currently no report on a large number of Japanese patients with ATTRwt‐CM. The study aimed to examine the characteristics and prognosis of ATTRwt‐CM in Japan. Methods and results Consecutive patients (78.5 ± 6.4 years old at diagnosis) with ATTRwt‐CM diagnosed at Kumamoto University Hospital between December 2002 and December 2019 were retrospectively reviewed. Data, including demographic characteristics, co‐morbidities, clinical manifestations at diagnosis, laboratory results, electrocardiographic and echocardiographic data, imaging and pathological findings, and treatment were obtained. Of 129 patients included in this study, 110 patients (85%) were male. The median period from initial symptom onset to diagnosis was 15.5 (2–75) months. Heart failure was the most common clinical manifestation leading to diagnosis (61%) and initial manifestations (49%). Of 106 patients, carpal tunnel syndrome was observed in 57 patients (54%), and the median period from initial symptom onset to diagnosis was 96 (48–120) months. Histopathological confirmation of transthyretin amyloid was achieved in 94 patients (73%), including 66 (51%) and 28 cases (22%) with endomyocardial and extracardiac biopsies. During the observation period (median 15.0 [inter‐quartile range, 5.4–33.2] months after diagnosis), 34 patients (26%) died. Of these, 27 patients (79%) had cardiovascular deaths (heart failure, 25; sudden death, two). The median survival duration was 58.9 months and the 5 years' survival rate was 48%. According to a multivariate Cox hazard analysis, age [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05–1.23, P = 0.002] and low serum sodium levels (HR, 0.89; 95% CI, 0.79–0.996; P = 0.04) contributed to all‐cause mortality, and low serum sodium levels contributed to hospitalization for heart failure (HR, 0.86; 95% CI, 0.77–0.96; P = 0.005). Conclusions Clinical characteristics and prognosis of ATTRwt‐CM patients in Japan were examined. Carpal tunnel syndrome can be considered an indication for diagnosis of ATTRwt‐CM. Age and low serum sodium level were significant predictive factors of all survival outcomes. The clinical features of ATTRwt‐CM should be recognized to provide appropriate treatment.

Abstract Background Thyrotoxicosis is common disorder among endocrine dysfunctions. It is not rare that the free thyroid hormone level exceeds the measurement range of immunoassay. Such extreme high concentration of free thyroid hormone is generally considered to be impossible to measure correctly because of changes in the balance between free hormones and binding proteins by dilution of serum. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), however, higher concentrations are able to be determined. Case presentation We present a case of a 21-year-old female with congenital hypothyroidism who had taken a total of 5 mg levothyroxine over three consecutive days following discontinuance of the medication for a month. Immunoassay performed 3 hours after the last ingestion showed that the patient’s free thyroxine (FT4) was over 100 pmol/L and her free triiodothyronine (FT3) was 24.5 pmol/L. With a temporary cessation of levothyroxine, the patient was kept for observation without any other medication. Two days after the last ingestion, FT4 was still over 100 pmol/L and FT3 was increased to 28.8 pmol/L. After an additional 4 days, both FT4 and FT3 levels decreased. Through this period, no thyrotoxic symptom or physical sign had appeared. We also measured FT4 and FT3 levels in her cryopreserved serum by ultrafiltration LC-MS/MS. Her FT4 level measured by ultrafiltration LC-MS/MS on the visiting day and 2 days later were 160.0 and 135.5 pmol/L, respectively, indicating that the toxic dose of levothyroxine was partly changed to T3 during the 2 days. The FT3/FT4 ratios were revealed to be low, accounting for the patient’s benign clinical course despite temporal toxic exposure to levothyroxine. It is implied that prior discontinuation of supplementary levothyroxine increases potential vacant binding sites for thyroid hormone as a buffer to prevent toxic T3 effect. Conclusion It was helpful to clarify the time dependent changes in free thyroid hormone levels by ultrafiltration LC-MS/MS in discussing the clinical course in this case. Though mass spectrometry has a disadvantage in speed for routine laboratory use, its accurate measurement, particularly of levels exceeding the measurable range of the immunoassay, provides valuable information for more appropriate management of extreme thyrotoxicosis.

Abstract Aims The prediction of future heart failure (HF) in stable outpatients is often difficult for general practitioners and cardiologists. Recently, the H2FPEF score (0–9 points) has been proposed for the discrimination of HF with preserved ejection fraction from non‐cardiac causes of dyspnoea. The six clinical and echocardiographic variables that constitute the H2FPEF score include the following: (i) obesity (H); (ii) the use of ≥2 antihypertensive drugs (H); (iii) atrial fibrillation (F); (iv) pulmonary hypertension (P); (v) an age > 60 years (E); and (vi) E/e' > 9 (F). We performed an external validation study that investigated whether the H2FPEF score could predict future HF‐related events in stable outpatients with cardiovascular risk factor(s) in Japan. Methods and results In this prospective cohort study, after exclusion of 195 from 551 consecutive, stable Japanese outpatients with at least one cardiovascular risk factor who were enrolled between September 2010 and July 2013, the remaining 356 outpatients (171 men, 185 women, mean age 73.2 years) were eligible for the analysis. We calculated the H2FPEF score (0–9 points), and followed up the patients for an average of 517 days. In all of the 356 patients, the mean H2FPEF score was 3.1 ± 1.8, and 15 developed HF‐related events during the follow‐up period, including cardiovascular death (n = 2) and hospitalization for HF decompensation (n = 13). Multivariate Cox proportional hazards analysis showed that the H2FPEF score was an independent predictor of future HF‐related events (P < 0.001 for all three models). Kaplan–Meier survival curves showed a significantly higher probability of HF‐related events in the outpatients with a high H2FPEF score (P < 0.001). In receiver operating characteristic (ROC) curve analysis, the H2FPEF score was significantly associated with the occurrence of future HF‐related events (P < 0.001). In ROC curve analysis, the sensitivity, specificity, and positive likelihood ratio of a H2FPEF score of 7 points to predict HF‐related events were 47%, 96%, and 11.4%, respectively. Conclusions The H2FPEF score could provide useful information for future HF‐related events in stable outpatients with cardiovascular risk factor(s) in Japan.

Background The clinical implication of vascular endothelial dysfunction in patients with atrial fibrillation (AF) remains unclear. This study aimed to elucidate the correlation between changes in vascular endothelial function assessed by reactive hyperemia‐peripheral arterial tonometry and the effect of sinus rhythm restoration after catheter ablation (CA) for AF. Methods and Results Consecutive 214 patients who underwent CA for AF were included in this single center, retrospective study. The natural logarithmic transformed reactive hyperemia‐peripheral arterial tonometry index (LnRHI) of all patients was measured before CA as well as 3 and 6 months after CA. LnRHI in sinus rhythm was significantly higher than that in AF before CA. Multivariate logistic regression analysis revealed that the presence of AF was an independent risk factor for lowering of LnRHI (odds ratio, 4.092; P=0.002) before CA. The LnRHI was significantly improved 3 and 6 months after CA in patients without AF recurrence. Multivariate Cox hazard analysis revealed that changes in LnRHI from before to 3 months after CA independently correlated with recurrence of AF (hazard ratio, 0.106; P=0.001). Receiver operating characteristic analysis showed the decrease in LnRHI levels from before to 3 months after CA as a significant marker that suspects AF recurrence (area under the curve, 0.792; log‐rank test, P

Background We investigated the clinical significance of derivatives of reactive oxygen metabolites (DROMs), a new marker of reactive oxygen species, in patients with nonischemic heart failure (HF) and compared them among new categories of HF. Methods and Results We recruited 201 consecutively hospitalized patients with HF and measured DROM under stable conditions. Then, we divided them according to new categories of HF (HF with reduced ejection fraction [EF], HF with midrangeEF, and HF with preserved EF) without coronary artery disease. In subgroup analysis, we followed EF changes in patients with HF with reduced EF and classified them into HF with recovered EF or nonrecovered EF according to whether EF had improved to >40%. DROMs are significantly and independently associated with HF‐related events in patients with NIHF. There were no significant differences in DROM and the probability of HF‐related events among HF categories in Kaplan–Meier analysis. However, patients with HF with reduced EF and HF with preserved EF but not HF with midrange EF with HF‐related events had higher DROM than those without HF‐related events. In subgroup analysis, Kaplan–Meier analysis demonstrated that the probabilities of HF‐related events in HF with recovered EF were dramatically decreased. DROM were significantly higher in patients with HF with nonrecovered EF than in HF with recovered EF. In receiver operating characteristic analysis, the cutoff level of DROM for predicting improvements in HF with recovered EF was 347 Carratelli units. Furthermore, the C‐statistic value for predicting EF improvement for the DROM levels was 0.703. In multivariable logistic regression analysis, DROM was independently and significantly associated with the prediction of HF with recovered EF. Conclusions DROM measurements can provide important prognostic information for risk stratification in any category of NIHF. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000035827.

The wind force acted on a tree constantly changes in magnitude, direction, and distribution. We developed a method to measure simultaneously the amount of force (F), centroid of the distributed force (C), and direction of force (D) on a tree trunk using four strain gauges. F and C were estimated from the difference in the bending moments at two different positions along the long axis of the stem. D was estimated using the difference in the sensor outputs at two different radial positions at the same height. In principle, the two strain gauges should be oriented precisely 90° apart; however, this is unrealistic on an actual tree trunk. To calculate D, we developed a new method to detect the radial position and modulus of elasticity of each strain gauge after attaching it. We conducted three types of experiment. First, we loaded a wood pole with weights arranged in 11 patterns to test the accuracies of F and C for a distributed load. Next, we applied tensile forces to the wood pole and an evergreen conifer sapling from eight directions to test the accuracy of D, F, and C. On average, estimation errors were < 2% for both the distributed load and circumferential tensile load. Our method can estimate F, C, and D precisely, even if the wood is uneven and the strain gauges are not aligned. This is a great advantage for field wind force measurements.

Oscillatory neural activity is dynamically controlled to coordinate perceptual, attentional and cognitive processes. On the macroscopic scale, this control is reflected in the U-shaped deviations of EEG spectral-power dynamics from stochastic dynamics, characterized by disproportionately elevated occurrences of the lowest and highest ranges of power. To understand the mechanisms that generate these low- and high-power states, we fit a simple mathematical model of synchronization of oscillatory activity to human EEG data. The results consistently indicated that the majority (~95%) of synchronization dynamics is controlled by slowly adjusting the probability of synchronization while maintaining maximum entropy within the timescale of a few seconds. This strategy appears to be universal as the results generalized across oscillation frequencies, EEG current sources, and participants (N = 52) whether they rested with their eyes closed, rested with their eyes open in a darkened room, or viewed a silent nature video. Given that precisely coordinated behavior requires tightly controlled oscillatory dynamics, the current results suggest that the large-scale spatial synchronization of oscillatory activity is controlled by the relatively slow, entropy-maximizing adjustments of synchronization probability (demonstrated here) in combination with temporally precise phase adjustments (e.g., phase resetting generated by sensorimotor interactions). Interestingly, we observed a modest but consistent spatial pattern of deviations from the maximum-entropy rule, potentially suggesting that the mid-central-posterior region serves as an "entropy dump" to facilitate the temporally precise control of spectral-power dynamics in the surrounding regions.

Background and Objectives: One major source of antibiotic contamination in the sea is from aquaculture. We monitored the concentration of commonly used antibiotic classes and antibiotic resistance genes (tet(M), sul1, sul2 and sul3) in aquaculture farms in Peninsular Malaysia. Methods: Antibiotic residues and resistance genes were quantified using high-performance liquid chromatography and real-time PCR respectively. Risk quotients in European technical guidance document on risk assessment was used to assess the potential environmental risk. Results: We detected 23 antibiotics with tetracyclines, sulfonamides and quinolones were the most frequently detected classes, indicating a wide distribution of antibiotics in Malaysian aquaculture farms. The dendrogram and heatmap revealed three groups of antibiotic concentration patterns but with no differences in the types of antibiotics usage among aquaculture farms. The ARGs (10−3 copies/16S) were detected in >90% of the sites except for sul3. Ciprofloxacin, enrofloxacin, norfloxacin and lincomycin posed risks to cyanobacteria and algae in Kelantan, Perak and Pahang. Conclusion: Relative to Asian aquaculture farms, the residues detected here were at low or moderate levels except for quinolones. This study will be useful to develop effective management of aquaculture wastewater in order to mitigate antibiotic pollution and transmission of ARGs to humans through the food chain.

Oscillatory neural activities are prevalent in the brain with their phase realignment contributing to the coordination of neural communication. Phase realignments may have especially strong (or weak) impact when neural activities are strongly synchronized (or desynchronized) within the interacting populations. We report that the spatiotemporal dynamics of strong regional synchronization measured as maximal EEG spectral power-referred to as activation-and strong regional desynchronization measured as minimal EEG spectral power-referred to as suppression-are characterized by the spatial segregation of small-scale and large-scale networks. Specifically, small-scale spectral-power activations and suppressions involving only 2-7% (1-4 of 60) of EEG scalp sites were prolonged (relative to stochastic dynamics) and consistently co-localized in a frequency specific manner. For example, the small-scale networks for θ, α, β1, and β2 bands (4-30 Hz) consistently included frontal sites when the eyes were closed, whereas the small-scale network for γ band (31-55 Hz) consistently clustered in medial-central-posterior sites whether the eyes were open or closed. Large-scale activations and suppressions involving over 17-30% (10-18 of 60) of EEG sites were also prolonged and generally clustered in regions complementary to where small-scale activations and suppressions clustered. In contrast, intermediate-scale activations and suppressions (involving 7-17% of EEG sites) tended to follow stochastic dynamics and were less consistently localized. These results suggest that strong synchronizations and desynchronizations tend to occur in small-scale and large-scale networks that are spatially segregated and frequency specific. These synchronization networks may broadly segregate the relatively independent and highly cooperative oscillatory processes while phase realignments fine-tune the network configurations based on behavioral demands.

Backgrounds: The relationship between cardiovascular outcomes and the Controlling Nutritional Status (CONUT) score in heart failure (HF) with preserved ejection fraction (HFpEF) patients is unknown. This study aimed to evaluate the relationship between the score and cardiovascular outcomes in HFpEF patients. Methods and results: A total of 506 consecutive HFpEF patients were prospectively observed for up to 1500 days or until the occurrence of cardiovascular events. The mean age was 71.6 ± 9.4 years. Cardiovascular outcomes were compared between the CONUT score 0–1 group with a normal nutritional state (normal group), the CONUT score 2–4 group with a light degree of undernutrition (light group), and the CONUT score 5–8 group with a moderate degree of undernutrition (moderate group). In this study, there were no patients who scored 9–12, which was defined as a severe state of undernutrition. Overall, 238 cardiovascular events were observed during the follow-up period (median: 1159 days). Kaplan–Meier analysis showed that the moderate group was at higher risk of composite cardiovascular events than the normal group (P

Marine aquaculture fish and the environment are possible hot spots for the maintenance and spread of antibiotic resistance genes (ARGs). We here show the time courses of changes of six tetracycline resistance genes (tet) in fish rearing seawater and fish intestine in tank experiments. Experimental tanks were prepared as oxytetracycline (OTC) administration tanks and those without OTC. It was found that tet(B), tet(M), and tet(W) were dominant in seawater among the six tet genes. tet(B) and tet(M) abundances increased immediately after OTC administration, indicating that OTC served as a selective pressure to increase the proportion of tet-possessing bacteria. In contrast, the abundance of tet genes in the fish intestine did not differ between the with- and without-OTC administration groups, and clearly was not altered by OTC administration. Profile changing of tet in seawater and fish intestine did not synchronize. These observations suggested that the dynamics of intestinal tet-possessing bacteria do not directly reflect the environment, but reflect selection within the intestine.

Quantifying wind risk in planted forests is critical to ensure the provision of wood-based biomaterials and forest ecosystem services in the future. Tree sway dynamics play a major role in determining their vulnerability to wind storms. While structural engineering theory can greatly assist in predicting tree and branch motion accurately, the effects of forest aging and silvicultural treatments on motion and the likelihood of mechanical failure are still poorly understood. In this study, we simulate the growth of an individual model tree and its architecture for a managed, even-aged pure Cryptomeria japonica D. Don. stand. The dynamic behavior of the tree is predicted for a rotation period at a 5-year interval using finite element analysis. Results show that tree natural sway frequency is subject to a 5-fold decrease over the tree's lifetime. The tree is thus more susceptible to absorb turbulent kinetic energy from the wind as it grows older. The damping ratio, which measures how rapidly the tree can return to its rest position after being deflected, is predicted to increase by a factor of four. By simulating the mechanical response to a wind gust, the model predicts a quick transition from a low risk of failure in the juvenile phase to a high-risk situation in the mature phase. The transition occurs between ages 15 and 30 when canopy closure takes place, when juvenile wood formation stops in the lower stem region and when the first thinning is carried out. Wind risk plateaus after the transition period. The age-risk relationship shown by the model is consistent with post-typhoon damage patterns documented by inventories in Japanese planted forests, albeit with a sharper transition.

[This corrects the article DOI: 10.1371/journal.pone.0219107.].

Spatiotemporal dynamics of EEG/MEG (electro-/magneto-encephalogram) have typically been investigated by applying time-frequency decomposition and examining amplitude-amplitude, phase-phase, or phase-amplitude associations between combinations of frequency bands and scalp sites, primarily to identify neural correlates of behaviors and traits. Instead, we directly extracted global EEG spatiotemporal dynamics as trajectories of k-dimensional state vectors (k = the number of estimated current sources) to investigate potential global rules governing neural dynamics. We chose timescale-dependent measures of trajectory instability (approximately the 2nd temporal derivative) and speed (approximately the 1st temporal derivative) as state variables, that succinctly characterized trajectory forms. We compared trajectories across posterior, central, anterior, and lateral scalp regions as the current sources under those regions may serve distinct functions. We recorded EEG while participants rested with their eyes closed (likely engaged in spontaneous thoughts) to investigate intrinsic neural dynamics. Some potential global rules emerged. Time-averaged trajectory instability from all five regions tightly converged (with their variability minimized) at the level of generating nearly unconstrained but slightly conservative turns (~100° on average) on the timescale of ~25 ms, suggesting that spectral-amplitude profiles are globally adjusted to maintain this convergence. Further, within-frequency and cross-frequency phase relations appear to be independently coordinated to reduce average trajectory speed and increase the variability in trajectory speed and instability in a relatively timescale-invariant manner, and to make trajectories less oscillatory. Future research may investigate the functional relevance of these intrinsic global-dynamics rules by examining how they adjust to various sensory environments and task demands or remain invariant. The current results also provide macroscopic constraints for quantitative modeling of neural dynamics as the timescale dependencies of trajectory instability and speed are relatable to oscillatory dynamics.

We investigated the global structure of intrinsic cross-frequency dynamics by systematically examining power-based temporal associations among a broad range of oscillation frequencies both within and across EEG-based current sources (sites). We focused on power-based associations that could reveal unique timescale dependence independently of interacting frequencies. Large spectral-power fluctuations across all sites occurred at two characteristic timescales, sub-second and seconds, yielding distinct patterns of cross-frequency associations. On the fast sub-second timescale, within-site (local) associations were consistently between pairs of β-γ frequencies differing by a constant Δf (particularly Δf ~ 10 Hz at posterior sites and Δf ~ 16 Hz at lateral sites) suggesting that higher-frequency oscillations are organized into Δf amplitude-modulated packets, whereas cross-site (long-distance) associations were all within-frequency (particularly in the >30 Hz and 6-12 Hz ranges, suggestive of feedforward and feedback interactions). On the slower seconds timescale, within-site (local) associations were characterized by a broad range of frequencies selectively associated with ~10 Hz at posterior sites and associations among higher (>20 Hz) frequencies at lateral sites, whereas cross-site (long-distance) associations were characterized by a broad range of frequencies at posterior sites selectively associated with ~10 Hz at other sites, associations among higher (>20 Hz) frequencies among lateral and anterior sites, and prevalent associations at ~10 Hz. Regardless of timescale, within-site (local) cross-frequency associations were weak at anterior sites indicative of frequency-specific operations. Overall, these results suggest that the fast sub-second-timescale coordination of spectral power is limited to local amplitude modulation and insulated within-frequency long-distance interactions (likely feedforward and feedback interactions), while characteristic patterns of cross-frequency interactions emerge on the slower seconds timescale. The results also suggest that the occipital α oscillations play a role in organizing higher-frequency oscillations into ~10 Hz amplitude-modulated packets to communicate with other regions. Functional implications of these timescale-dependent cross-frequency associations await future investigations.

Abstract Background The original ‘candy-plug’ technique has been reported to be beneficial for the treatment of residual perfused false lumen in patients with aortic dissection. However, this technique is also associated with several problems, such as narrowing of the true lumen and damage to the flap or vessel wall. Therefore, we modified the procedure to overcome these problems. Here we report a case in which the patient was successfully treated using the modified procedure. Case presentation A 59-year-old man presented with chronic type B aortic dissection with aneurysmal dilatation. The patient had undergone prosthetic graft replacement of the ascending aorta for acute type A aortic dissection 3 years previously and replacement of the descending aorta for residual type B aortic dissection with aneurysmal dilatation 1 year previously. After these procedures, the residual false lumen aneurysm of the distal descending aorta expanded to 57-mm in diameter. Endovascular stent grafting was successfully performed using the modified ‘candy-plug’ technique with relining of the true lumen and occlusion of the false lumen. The patient was discharged 10 days after the procedure. Follow-up imaging at 1 year showed a completely thrombosed false lumen aneurysm. Conclusion The modified ‘candy-plug’ technique is useful for treatment of residual type B aortic dissection with aneurysmal dilatation.

Abstract Temperature is an important controlling factor in the growth activity of all microorganisms. Aerobic anoxygenic phototrophic (AAP) bacteria actively grow in the ocean and are known as one of the main driving forces in organic matter cycling in surface seawater environments. Whether temperature change affects AAP bacteria activity from an ecological viewpoint remains an open question. To date, no known studies have reported the effect of temperature change on AAP bacteria growth in the ocean. We here show that the growth rate of AAP bacteria exceeded that of other bacterial types at high water temperatures in the absence of grazers. The slope of the regression line of the net growth rate of AAP bacteria as a function of water temperature was the same as that for non‐AAP bacteria at all temperatures (10, 20, and 30°C); however, when grazers were eliminated, it was 4.7 times higher than that of non‐AAP bacteria. This result suggests that AAP bacteria are more responsive to water temperature increases than other bacteria and that AAP bacteria might become more dominant than other bacteria under elevated water temperatures.

Spatially heterogeneous flicker, characterized by probabilistic and locally independent luminance modulations, abounds in nature. It is generated by flames, water surfaces, rustling leaves, and so on, and it is pleasant to the senses. It affords spatiotemporal multistability that allows sensory activation conforming to the biases of the visual system, thereby generating the perception of spontaneous motion and likely facilitating the calibration of motion detectors. One may thus hypothesize that spatially heterogeneous flicker might potentially provide restoring stimuli to the visual system that engage fluent (requiring minimal top-down control) and self-calibrating processes. Here, we present some converging behavioral and electrophysiological evidence consistent with this idea. Spatially heterogeneous (multistable) flicker (relative to controls matched in temporal statistics) reduced posterior EEG (electroencephalography) beta power implicated in long-range neural interactions that impose top-down influences on sensory processing. Further, the degree of spatiotemporal multistability, the amount of posterior beta-power reduction, and the aesthetic responses to flicker were closely associated. These results are consistent with the idea that the pleasantness of natural flicker may derive from its spatiotemporal multistability that affords fluent and self-calibrating visual processing.

The competition between magnetic shape anisotropy and the induced uniaxial magnetic anisotropy in the heterojunction between a ferromagnetic layer and a ferroelectric substrate serves to control magnetic domain structures as well as magnetization reversal characteristics. The uniaxial magnetic anisotropy, originating from the symmetry breaking effect in the heterojunction, plays a significant role in modifying the characteristics of magnetization dynamics. Magnetoelastic phenomena are known to generate uniaxial magnetic anisotropy; however, the interfacial electronic states that may contribute to the uniaxial magnetic anisotropy have not yet been adequately investigated. Here, we report experimental evidence concerning the binding energy change in the ferromagnetic layer/ferroelectric substrate heterojunction using X-ray photoemission spectroscopy. The binding energy shifts, corresponding to the chemical shifts, reveal the binding states near the interface. Our results shed light on the origin of the uniaxial magnetic anisotropy induced from the heterojunction. This knowledge can provide a means for the simultaneous control of magnetism, mechanics, and electronics in a nano/microsystem consisting of ferromagnetic/ferroelectric materials.