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Abstract The 1997/1998 El Niño event caused mass coral bleaching and mortality in many tropical and subtropical regions, including corals on Green Island, Taiwan, in the northwestern Pacific Ocean. This study analyzed coral carbon isotope ratios (δ13C), oxygen isotope ratios (δ18O), and Sr/Ca ratios for 29 years, including the 1997/1998 El Niño period, to examine how high water temperature events are recorded in coral geochemical indicators. Sr/Ca ratios in coral skeletons from Green Island show the lowest peak, means the highest temperature during the 1997/1998 El Niño period. However, we couldn’t observe high-temperature events on δ18O. Furthermore, a negative δ13C shift was observed after El Niño events. The regime shift of δ13C might have been caused by temporal bleaching and/or a decrease in symbiotic algae due to high water temperature stress under the continuous decrease in δ13C in DIC due to the Suess effect.

Abstract Background Lifestyle modifications by educational sessions are an important component of multidisciplinary treatment for chronic kidney disease (CKD). We attempted to identify the best method to teach these modifications in order to ensure their acceptance by patients and investigated its effectiveness in CKD practice. Methods This study is a post-hoc analysis of the FROM-J study. Subjects were 876 CKD patients in the advanced care group of the FROM-J study who had received lifestyle modification sessions every 3 months for 3.5 years. Two-hundred and ten males (32.6%) and 89 females (38.2%) showed success in sodium restriction. In this study, we examined factors affecting sodium restriction in these subjects. Results Subjects received three or more consecutive educational sessions about improvement of salt intake. The median salt-intake improvement maintenance period was 407 days. The number of dietary counseling sessions (OR 1.090, 95%CI: 1.012–1.174) in males and the number of dietary counseling sessions (OR 1.159, 95%CI: 1.019–1.318), CKD stage progression (OR 1.658, 95%CI: 1.177–2.335), and collaboration with a nephrologist (OR 2.060, 95%CI: 1.073–3.956) in females were identified as significant factors improving salt intake. The only factor contributing to the maintenance of improved salt intake was the continuation of dietary counseling (p = 0.013). Conclusion An increased number of educational sessions was the only successful approach for males to implement and maintain an improved salt intake. Providing the resources for continuous counseling is beneficial for lifestyle modifications and their maintenance in the long-term management of CKD. Continuous counseling for lifestyle modifications is highly cost-effective. Trial registration The FROM-J study was registered in UMIN000001159 on 16/05/2008.

Abstract Background Gait ability can be objectively assessed using gait analysis. Three-dimensional gait analysis, the most commonly used analytical method, has limitations, such as a prolonged examination, high system costs, and inconsistently reported gait symmetry in patients with knee osteoarthritis (OA). Therefore, we aimed to evaluate the gait symmetry and changes before and after unilateral total knee arthroplasty (TKA) using the Walkway analyzer, a sheet-type gait analyzer. Methods The healthy group included 38 participants from the Locomotor Frailty and Sarcopenia Registry study with lower limb pain or Kellgren–Lawrence classification grade 3 or 4 OA. The OA group included 34 participants from the registry study who underwent unilateral TKA. The walking speed, step length, step width, cadence, stride time, stance time, swing phase time, double-limb support phase time, stride, step length, and step width were analyzed per side using the Walkway gait analyzer. Results No significant differences between the right and left sides were observed in the healthy group. In the OA group, the time indices and stance phase (p = 0.011) and the double-limb support phase time (p = 0.039) were longer on the contralateral side and the swing phase was longer on the affected side (p = 0.004) pre-operatively. However, these differences disappeared post-operatively. There were no significant differences in the spatial indices. Thus, this study revealed that patients undergoing unilateral TKA had an asymmetric gait pre-operatively, with a time index compensating for the painful side, and an improved symmetric gait post-operatively. Conclusions The Walkway analyzer employs a simple test that requires only walking; hence, it is expected to be used for objective evaluation in actual clinical practice.

Abstract A higher heart rate is recognized as an independent risk factor for all-cause mortality and cardiovascular events in the general population. However, the association between elevated heart rate and clinical adverse outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD) has not been sufficiently investigated. A total of 1353 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between resting heart rate and clinical adverse outcomes using Cox proportional hazards analysis. The primary outcome of the present study was all-cause mortality, with cardiovascular events as the secondary outcome. Participants were stratified into four groups based on resting heart rate levels at baseline (heart rate

Abstract Background Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis. Methods MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen‐inducible MP‐specific VDR‐deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross‐sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3–4). In addition, a vitamin D‐deficient diet was provided to wild‐type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation. Results Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1‐mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR‐deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil‐Red O+ area). In consistency with in‐vitro findings, VdrMPcKO mice and mice fed a vitamin D‐deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively. Conclusions Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.

Abstract Predicting the transition of kidney function in chronic kidney disease is difficult as specific symptoms are lacking and often overlooked, and progress occurs due to complicating factors. In this study, we applied time-series cluster analysis and a light gradient boosting machine to predict the trajectories of kidney function in non-dialysis dependent chronic kidney disease patients with baseline estimated glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2. Based on 5-year changes in estimated GFR, participants were stratified into groups with similar trajectories by cluster analysis. Next, we applied the light gradient boosting machine algorithm and Shapley addictive explanation to develop a prediction model for clusters and identify important parameters for prediction. Data from 780 participants were available for analysis. Participants were classified into five classes (Class 1: n = 78, mean [± standard deviation] estimated GFR 100 ± 19.3 mL/min/1.73 m2; Class 2: n = 176, 76.0 ± 9.3 mL/min/1.73 m2; Class 3: n = 191, 59.8 ± 5.9 mL/min/1.73 m2; Class 4: n = 261, 52.7 ± 4.6 mL/min/1.73 m2; and Class 5: n = 74, 53.5 ± 12.0 mL/min/1.73 m2). Declines in estimated GFR were 8.9% in Class 1, 12.2% in Class 2, 4.9% in Class 3, 12.0% in Class 4, and 45.1% in Class 5 during the 5-year period. The accuracy of prediction was 0.675, and the top three most important Shapley addictive explanation values were 1.61 for baseline estimated GFR, 0.12 for hemoglobin, and 0.11 for body mass index. The estimated GFR transition of patients with preserved chronic kidney disease mostly depended on baseline estimated GFR, and the borderline for estimated GFR trajectory was nearly 50 mL/min/1.73 m2.

Abstract The red blood cell distribution width–albumin ratio (RAR) is a prognostic factor for adverse outcomes in various populations. However, whether RAR is associated with renal outcomes remains unclear. Therefore, we aimed to investigate the impact of RAR on the prognosis in patients with chronic kidney disease (CKD). We conducted a retrospective cohort study using 997 CKD patients who were enrolled in the Fukushima Cohort Study. Patients were categorized into tertiles (T1-3) according to the baseline RAR. The associations of RAR with end-stage kidney disease (ESKD) were assessed using Kaplan–Meier curves and multivariable cox regression analyses. Receiver operating characteristic (ROC) curves were performed to test whether significant differences were present between red cell distribution width (RDW) and RAR. The median age was 66, 57% were men, the median eGFR was 47.8 ml/min/1.73 m2, and the median value of RAR was 3.5. The higher RAR group showed an increased risk for ESKD in the Kaplan–Meier curve analysis. Compared to the lowest RAR group, higher RAR groups had a higher risk of ESKD (hazard ratio [HR] 1.37, 95% CI 0.68–2.78 and 2.92, 95% CI 1.44–5.94) for T2 and T3 groups, respectively. ROC curve analysis proved that the discriminating ability of RAR for ESKD was superior to RDW. A higher RAR value was associated with worse renal outcomes in patients with CKD. RAR could be a convenient and useful prognostic marker for renal prognosis.

IntroductionProprioceptive function declines with age, leading to falls, pain, and difficulties in performing activities of daily living among older adults. Although individuals with low back pain (LBP) exhibit decreased lumbosacral proprioception in various postures, the mechanism by which reduced proprioceptive function causes LBP remains uncertain. Vibratory stimulation may enhance proprioceptive function; however, its efficacy in treating LBP has not been investigated. Thus, we investigated the feasibility of improving proprioceptive function and its effect on alleviating chronic LBP in older patients through targeted vibratory therapy (TVT) administration.MethodsThis single arm designed trial included older patients aged >65 years with non-specific chronic LBP. TVT involved applying vibratory stimulation, matching the frequency of dysfunctional receptors, for 1 min daily over 14 days to activate proprioceptors; patients performed TVT three times daily at home. In cases of reduced proprioceptive function at multiple sites, TVT was aimed at the lowest frequency band value. LBP and proprioceptive function were evaluated at 2 weeks after TVT and at 2 weeks after the end of TVT in patients with declined proprioception in the trunk or lower extremities.ResultsOverall, 56 patients with chronic LBP were enrolled; 32 patients were recruited for treatment based on a proprioceptive dysfunction diagnosis and 24 patients were recruited with a normal diagnosis with no significant differences observed between the two sets of patients in sarcopenia-related factors and clinical proprioception-related characteristics. No patient had any adverse events. Two weeks after TVT, the numerical pain rating scale score improved to ConclusionsTVT demonstrated efficacy in improving proprioception and alleviating LBP in older patients with impaired proprioceptive function without affecting non-targeted proprioceptors.

Objective To compare the performance of the diagnostic model for fall risk based on the short physical performance battery (SPPB) developed using commercial machine learning software (MLS) and binomial logistic regression analysis (BLRA). Methods We enrolled 797 out of 850 outpatients who visited the clinic between March 2016 and November 2021. Patients were categorized into the development ( n = 642) and validation ( n = 155) datasets. Age, sex, number of comorbidities, number of medications, body mass index (BMI), calf circumference (left–right average), handgrip strength (left–right average), total SPPB score, and history of falls were determined. We defined fall risk by an SPPB score of ≤6 in men and ≤9 in women. The main metrics used for evaluating the machine learning model and BLRA were the area under the curve (AUC), accuracy, precision, recall (sensitivity), specificity, and F-measure. The commercial MLS automatically calculates the parameter range of the highest contribution. Results The participants included 797 outpatients (mean age, 76.3 years; interquartile range, 73.0–81.0; 288 men). The metrics of the current diagnostic model in the commercial MLS were as follows: AUC = 0.78, accuracy = 0.74, precision = 0.46, recall (sensitivity) = 0.81, specificity = 0.71, F-measure = 0.59. The metrics of the current diagnostic model in the BLRA were as follows: AUC = 0.77, accuracy = 0.75, precision = 0.47, recall (sensitivity) = 0.67, specificity = 0.77, F-measure = 0.55. The risk factors for falls in older adult outpatients were handgrip strength, female sex, experience of falls, BMI, and calf circumference in the commercial MLS. Conclusions The diagnostic model for fall risk based on SPPB scores constructed using commercial MLS is noninferior to BLRA.

Abstract Lifestyle factors, including smoking habit, diet, and physical activity, affect the prognosis of various diseases. We elucidated the effect of lifestyle factors and health status on deaths from respiratory diseases in the general Japanese population using data from a community health examination database. Data of the nationwide screening program of the Specific Health Check-up and Guidance System (Tokutei-Kenshin), targeting the general population in Japan, from 2008 to 2010 were analyzed. The underlying causes of death were coded according to the International Classification of Diseases (ICD)-10. The hazard ratios of the incidence of mortality associated with respiratory disease were estimated using the Cox regression model. This study included 664,926 participants aged 40–74 years, who were followed up for 7 years. There were 8051 deaths, including 1263 (15.69%) deaths from respiratory diseases. The independent risk factors of mortality associated with respiratory diseases were male sex, older age, low body mass index, no exercise habit, slow walking speed, no drinking habit, smoking history, history of cerebrovascular diseases, high hemoglobin A1c and uric acid levels, low low-density lipoprotein cholesterol level, and proteinuria. Aging and decline of physical activity are significant risk factors for mortality associated with respiratory diseases, regardless of the smoking status.

Abstract Height loss is caused by osteoporosis, vertebral fractures, disc reduction, postural changes, and kyphosis. Marked long-term height loss is reportedly associated with cardiovascular disease and mortality in the elderly. The present study investigated the relationship between short-term height loss and the risk of mortality using the longitudinal cohort data of the Japan Specific Health Checkup Study (J-SHC). Included individuals were aged 40 years or older and received periodic health checkups in 2008 and 2010. The exposure of interest was height loss over the 2 years, and the outcome was all-cause mortality over subsequent follow up. Cox proportional hazard models were used to examine the association between height loss and all-cause mortality. Of the 222,392 individuals (88,285 men, 134,107 women) included in this study, 1436 died during the observation period (mean 4.8 ± 1.1 years). The subjects were divided into two groups based on a cut-off value of height loss of 0.5 cm over 2 years. The adjusted hazard ratio (95% confidence interval) was 1.26 (1.13–1.41) for exposure to height loss ≥ 0.5 cm compared to height loss

BackgroundThe quadriceps muscle is one of the human body’s largest and most clinically important muscles and is evaluated using mid-thigh computed tomography (CT); however, its relationship with motor function and sarcopenia remains unclear. Herein, we investigated the relationship between the cross-sectional area (CSA) of the quadriceps muscle, CT attenuation value (CTV), dual-energy X-ray absorptiometry muscle mass measurements, and muscle strength and motor function to evaluate the relationship between muscle mass loss and motor function decline, determine the diagnostic ability for sarcopenia, and confirm the usefulness of quadriceps muscle CT evaluation.MethodsA total of 472 middle-aged and older community dwellers (254 men and 218 women) aged ≥40 years (mean age: 62.3 years) were included in this study. The quantity and quality of the quadriceps muscle were assessed using CSA and CTV (CSA×CTV) as a composite index multiplied by quality and quantity. Age-adjusted partial correlations by sex with eight motor functions (knee extension muscle strength, power, normal walking speed, fast walking speed, grip strength, sit-up ability, balance ability, and reaction time) were evaluated, including correction methods for height, weight, and body mass index (BMI). Further, the accuracy of sarcopenia diagnosis was evaluated using appendicular muscle mass with dual-energy X-ray absorptiometry measurements, grip strength, and walking speed as the gold standard, and receiver operating characteristic curves were plotted to evaluate diagnostic performance.ResultsIn men, CSA and CSA×CTV were significantly associated with seven of the eight motor functions (p

Abstract The Sr/Ca ratio of modern coral skeletons can record local seawater temperature (T) and is an important tool for reconstructing past environments. However, site‐specific calibrations are required to ensure accurate temperature reconstructions. Here, we examine three modern coral skeletons collected at contrasting sites on the island of Oahu, Hawaii to establish the first accurate calibrations for this region and investigate site specific influences on the calibration process. Satellite T data, which is used for many calibrations, may not be able to derive an accurate thermometer. For our shallow lagoonal sites, satellite T had smaller seasonal T ranges, which resulted in significantly higher slopes of Sr/Ca‐T compared to using in situ T. The traditional age model based on aligning only min/max values can lead to errors in the Sr/Ca‐T calibration due to variable growth rates. An enhanced age model which adds midpoint alignments between the min/max peak values can account for seasonal changes in growth rate and reduce the error. On the same island, site‐ and time period specific conditions can cause notable differences in the Sr/Ca‐T calibrations. The coral from an estuarine embayment showed a high Sr/Ca offset, likely due to high Sr/Ca in ambient seawater. For corals which experienced thermal stress, lower slopes were observed probably due to elevated Sr/Ca values during the period of thermal stress.

Abstract Severe hyponatremia can cause life-threatening cerebral edema. Treatment comprises rapid elevation of serum sodium concentration; however, overcorrection can result in osmotic demyelination. This study investigated potential factors, including predictive correction based on the Edelman equation, associated with appropriate correction in 221 patients with a serum sodium concentration ≤ 120 mEq/L who were admitted to a hospital in Nagoya, Japan. Appropriate correction was defined as an elevation in serum sodium concentration in the range of 4–10 mEq/L in the first 24 h and within 18 mEq/L in the first 48 h after the start of the correction. Appropriate corrections were made in 132 (59.7%) of the 221 patients. Multivariate analysis revealed that predictive correction with an infusate and fluid loss formula derived from the Edelman equation was associated with appropriate correction of serum sodium concentration (adjusted odds ratio, 7.84; 95% confidence interval, 2.97–20.64). Relative without its use, the predictive equation results in a lower proportion of undercorrection (14.3% vs. 48.0%, respectively) and overcorrection (1.0% vs. 12.2%, respectively). These results suggest that predictive correction of serum sodium concentrations using the formula derived from the Edelman equation can play an essential role in the appropriate management of patients with severe hyponatremia.

Combined with other westerly-sensitive records, a new stalagmite hydroclimate record from northern Italy reveals changing westerly wind directions over the past 6500 years that correspond to a migration of the North Atlantic centres of action.

Abstract The Mekong River Delta (MRD) is an essential agricultural area for the worldwide rice supply. Floods and droughts triggered by El Niño southern oscillation (ENSO) have been threatening sustenance in the MRD. Sustainable food supplies require understanding the response of the MRD hydrology to the changing ENSO behaviour in recent decades. Here, we reconstructed the annual rainfall maxima in the MRD using the oceanic paleoclimate proxy from coral skeletons and compared them with ENSO indexes. Annual minima of coral-based seawater oxygen isotope (δ18Osw) correlated with annual rainfall maxima, which allowed to extend rainfall data from 1924 to the recent. The annual rainfall maxima based on δ18Osw negatively correlated with the central Pacific El Niño index. This suggested that La Niña and central Pacific El Niño events lead to heavy and light rainy seasons. The heavy rainy season had more serious impacts in recent decades, which likely increases the flood risk. In contrast, the frequency and rainfall amount of the light rainy season has not changed significantly, although a catastrophic drought has hit the MRD. Our finding concludes that the impact of the ENSO event on MRD hydrology is inconsistent in the past century.

Proprioception is a deep sensation that perceives the position of each part of the body, state of movement and muscle contraction, and resistance and mass applied to the body. Proprioceptive feedback influences movement and positional accuracy, resulting in key somatosensory functions for human postural control. Proprioception encompasses signals received from proprioceptors located in the skin, subcutaneous tissue, muscles, tendons, and joint capsules, commonly known as mechanoreceptors. The muscle spindle, a crucial proprioceptor, is stretched during eccentric contraction of muscle, thus generating an action potential on afferent fibers to convey a proprioceptive information to the sensorimotor cortex in the brain. For exercise therapy in patients with locomotor disease, proprioception serves an essential function for motor control; thus, this should be considered to obtain effective muscle output. As postural control is achieved by proprioceptive function according to the balance between the lower limb and trunk, relative proprioceptive weighting ratio can help clarify proprioceptive control using muscle response to mechanical vibration. The absence of proprioceptive information congruent with motor intention activates cortical center monitoring incongruence of sensation, leading to pathological pain. Therapeutic procedures may aim to restore the integrity of cortical information processing in musculoskeletal chronic pain. Poor proprioception is one of the main causes of decreased postural balance control in elderly patients with low back pain (LBP). It has been hypothesized that proprioception of the lower limbs deteriorates with age-related muscle mass loss (sarcopenia), which increases the proprioceptive burden on the lumbar spine. Accurate diagnosis of the proprioceptive function is important for establishing a treatment procedure for proprioceptive recovery, and further prospective research is required to clarify the relationship between proprioception and LBP improvement.

Abstract The transtheoretical model (TTM) is a commonly used model of health-related behavioral change. However, the practical effect of using this model for chronic kidney disease (CKD) self-management remains unclear. This study aimed to investigate the association between stages of change for lifestyle behavior and the incidence of CKD in the general Japanese population. A retrospective cohort study was conducted among 178,780 non-CKD participants aged 40–74 years who underwent annual health check-ups for two consecutive years between 2008 and 2009. Health behavior change was determined using questionnaires based on the TTM, which consists of five stages of change (precontemplation, contemplation, preparation, action, and maintenance). The exposure of interest was the change in stages between two years. Participants were categorized into 3 groups ‘improved’, ‘unchanged’, or ‘deteriorated’. The association between the change in stages and the incidence of CKD was examined using logistic regression analysis. After one year of follow-up, 20.0% of participants developed CKD. Participants in the deteriorated group showed a significantly higher risk of CKD incidence than in the improved group. Promoting the stage of change for healthy lifestyle behaviors evaluated by the TTM was associated with a risk reduction for the incidence of CKD.

Objectives: The prevalence of chronic pain increases with age. It has been reported that chronic pain is associated with sarcopenia and obesity. Age-related skeletal muscle loss and fat gain are known to occur due to chronic inflammation. The aim of this study was to analyze how skeletal muscle and fat, caused by chronic inflammation due to aging, regulate the development of geriatric chronic pain. Methods: The results of skeletal muscle and fat mass, 412 participants aged ≥65 years with non-specific chronic pain lasting ≥6 months, including low back, neck, and knee pain, was compared with the control without chronic pain. Body composition threshold regulating chronic pain was calculated. Results: A significantly lower skeletal muscle mass index and higher body fat percentage were observed in patients with chronic pain than that in the control. The muscle fat ratio (MFR) was significantly lower in the chronic pain group than in the control group. When the MFR threshold related to chronic pain was calculated by sex, it was 2.984 for men and 1.867 for women. Conclusions: Evaluation of the body composition of elderly patients with non-specific chronic pain revealed that the MFR was useful as an index related to chronic pain.

Background Zooplankton plays an important role in the marine ecosystem. A high level of taxonomic expertise is necessary for accurate species identification based on morphological characteristics. As an alternative method to morphological classification, we focused on a molecular approach using 18S and 28S ribosomal RNA (rRNA) gene sequences. This study investigates how the accuracy of species identification by metabarcoding improves when taxonomically verified sequences of dominant zooplankton species are added to the public database. The improvement was tested by using natural zooplankton samples. Methods rRNA gene sequences were obtained from dominant zooplankton species from six sea areas around Japan and registered in the public database for improving the accuracy of taxonomic classifications. Two reference databases with and without newly registered sequences were created. Comparison of detected OTUs associated with single species between the two references was done using field-collected zooplankton samples from the Sea of Okhotsk for metabarcoding analysis to verify whether or not the newly registered sequences improved the accuracy of taxonomic classifications. Results A total of 166 sequences in 96 species based on the 18S marker and 165 sequences in 95 species based on the 28S marker belonging to Arthropoda (mostly Copepoda) and Chaetognatha were registered in the public database. The newly registered sequences were mainly composed of small non-calanoid copepods, such as species belonging to Oithona and Oncaea. Based on the metabarcoding analysis of field samples, a total of 18 out of 92 OTUs were identified at the species level based on newly registered sequences in the data obtained by the 18S marker. Based on the 28S marker, 42 out of 89 OTUs were classified at the species level based on taxonomically verified sequences. Thanks to the newly registered sequences, the number of OTUs associated with a single species based on the 18S marker increased by 16% in total and by 10% per sample. Based on the 28S marker, the number of OTUs associated with a single species increased by 39% in total and by 15% per sample. The improved accuracy of species identification was confirmed by comparing different sequences obtained from the same species. The newly registered sequences had higher similarity values (mean >0.003) than the pre-existing sequences based on both rRNA genes. These OTUs were identified at the species level based on sequences not only present in the Sea of Okhotsk but also in other areas. Discussion The results of the registration of new taxonomically verified sequences and the subsequent comparison of databases based on metabarcoding data of natural zooplankton samples clearly showed an increase in accuracy in species identification. Continuous registration of sequence data covering various environmental conditions is necessary for further improvement of metabarcoding analysis of zooplankton for monitoring marine ecosystems.

Abstract Early detection and treatment of diseases through health checkups are effective in improving life expectancy. In this study, we compared the predictive ability for 5-year mortality between two machine learning-based models (gradient boosting decision tree [XGBoost] and neural network) and a conventional logistic regression model in 116,749 health checkup participants. We built prediction models using a training dataset consisting of 85,361 participants in 2008 and evaluated the models using a test dataset consisting of 31,388 participants from 2009 to 2014. The predictive ability was evaluated by the values of the area under the receiver operating characteristic curve (AUC) in the test dataset. The AUC values were 0.811 for XGBoost, 0.774 for neural network, and 0.772 for logistic regression models, indicating that the predictive ability of XGBoost was the highest. The importance rating of each explanatory variable was evaluated using the SHapley Additive exPlanations (SHAP) values, which were similar among these models. This study showed that the machine learning-based model has a higher predictive ability than the conventional logistic regression model and may be useful for risk assessment and health guidance for health checkup participants.

Abstract Extreme positive Indian Ocean Dipole (pIOD) events are amplified by non-linear ocean–atmosphere interactions and are characterized by pronounced cooling in the eastern equatorial Indian Ocean. These non-linear feedbacks are not adequately represented in historical products of sea surface temperatures that underestimate the magnitude of extreme pIOD events. Here, we present a sea surface temperature (SST) reconstruction based on monthly coral Sr/Ca ratios measured in two coral cores from Enggano Island (Indonesia), that lies in the eastern pole of the IOD. The coral SST reconstruction extends from 1930 to 2008 and captures the magnitude of cooling during extreme pIOD events as shown in recent satellite and reanalysis data of SST that include ocean dynamics. The corals indicate that the 1961 pIOD event was at least as severe as the 1997 event, while the 1963 pIOD was more comparable to the 2006 event. The magnitude 1967 pIOD is difficult to assess at present due to poor replication between coral cores, and may be comparable to either 1997 or 2006. Cooling during the 1972 pIOD was short-lived and followed by pronounced warming, as seen in the moderate pIOD event of 1982. A combination of coral SST reconstructions and an extension of new reanalysis products of SST to historical time scales could help to better assess the severity and impact of past pIOD events such as the ones seen in the 1960s.

Abstract A comprehensive analysis of clinical information in patients with chronic low back pain (CLBP) was performed to clarify the clinical characteristics of geriatric LBP from the perspective of body composition, spinal alignment, and blood findings related to senescence. We enrolled 203 patients with an average age of 79.0 years (77 men and 126 women), with non-specific CLBP as a single-center prospective cohort study, the patients were compared with age- and sex-matched controls without CLBP using a propensity score-matching. We performed laboratory analysis, radiographic evaluations for global spinal parameter and lumbar degeneration, and body composition analysis using whole-body dual-energy X-ray absorptiometry. We observed a higher red blood cell distribution width (RDW) (p

Abstract Growing evidence has demonstrated an association between nondialysis chronic kidney disease and cancer incidence, although the association between trace proteinuria and cancer death remains unclear. The aim of this study was to investigate the association between trace proteinuria and cancer death in a community-based population in Japan. This was a prospective cohort study of 377,202 adults who participated in the Japanese Specific Health Check and Guidance System from 2008 to 2011. Exposure was dipstick proteinuria categorized as − (negative), ± (trace), 1 + (mild), or ≥ 2 + (moderate to heavy). Outcome was cancer death based on information from the national database of death certificates. Adjusted Cox hazard regression model was used to evaluate the associations between trace proteinuria and cancer death. During median follow-up of 3.7 years, 3056 cancer deaths occurred, corresponding to overall cancer death rate of 21.7/10,000 person-years. In the fully adjusted model, risk of cancer death increased significantly in each successive category of proteinuria: hazard ratio (HR) (95% confidence interval [95% CI]) for risk of cancer death was 1.16 (1.03–1.31), 1.47 (1.27–1.70), and 1.61 (1.33–1.96) for trace, mild, and moderate to heavy proteinuria, respectively. Sensitivity analyses revealed a similar association between trace proteinuria and cancer death, and participants with trace proteinuria had greater risk of mortality from hematological cancers (HR: 1.59 [95% CI: 1.09–2.31]). Both mild to heavy and trace proteinuria were significantly associated with risk of mortality from cancer in a general population.

Abstract It is well-known that hypertension exacerbates chronic kidney disease (CKD) progression, however, the optimal target blood pressure (BP) level in patients with CKD remains unclear. This study aimed to assess the optimal BP level for preventing CKD progression. The risk of renal outcome among different BP categories at baseline as well as 1 year after, were evaluated using individual CKD patient data aged between 40 and 74 years from FROM-J [Frontier of Renal Outcome Modifications in Japan] study. The renal outcome was defined as ≥ 40% reduction in estimated glomerular filtration rate to

Abstract Background Correctly identifying anaerobic bloodstream infections (BSIs) is difficult. However, a new technique, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), enables more accurate identification and appropriate treatment. Anaerobic BSIs identified by MALDI-TOF MS were retrospectively analyzed to determine the clinical and microbiological features and patient outcomes based on the anaerobic genera or group. Methods Medical records of patients with anaerobic BSIs were used to conduct a single-center retrospective cohort study from January 2016 to December 2020 in Nagoya, Japan. Multivariate logistic regression analysis was performed to determine the independent risk factors for in-hospital mortality. Results Of the 215 patients with anaerobic BSIs, 31 had multiple anaerobic organisms in the blood culture, including 264 total episodes of anaerobic BSIs. Bacteroides spp. were isolated the most (n = 74), followed by gram-positive non-spore-forming bacilli (n = 57), Clostridium spp. (n = 52), gram-positive anaerobic cocci (GPAC) (n = 27), and gram-negative cocci (n = 7). The median patient age was 76 years; 56.7% were male. The most common focal infection site was intra-abdominal (36.7%). The in-hospital mortality caused by anaerobic BSIs was 21.3%, and was highest with Clostridium spp. (36.5%) and lowest with GPAC (3.7%). Age, solid tumors, and Clostridium spp. were independent risk factors for in-hospital mortality. Conclusions We identified current anaerobic BSI trends using MALDI-TOF MS and reported that mortality in patients with anaerobic BSIs patients was highest with Clostridium spp. infections.

Abstract Although numerous metagenome, amplicon sequencing-based studies have been conducted to date to characterize marine microbial communities, relatively few have employed full metagenome shotgun sequencing to obtain a broader picture of the functional features of these marine microbial communities. Moreover, most of these studies only performed sporadic sampling, which is insufficient to understand an ecosystem comprehensively. In this study, we regularly conducted seawater sampling along the northeastern Pacific coast of Japan between March 2012 and May 2016. We collected 213 seawater samples and prepared size-based fractions to generate 454 subsets of samples for shotgun metagenome sequencing and analysis. We also determined the sequences of 16S rRNA (n = 111) and 18S rRNA (n = 47) gene amplicons from smaller sample subsets. We thereafter developed the Ocean Monitoring Database for time-series metagenomic data ( http://marine-meta.healthscience.sci.waseda.ac.jp/omd/ ), which provides a three-dimensional bird’s-eye view of the data. This database includes results of digital DNA chip analysis, a novel method for estimating ocean characteristics such as water temperature from metagenomic data. Furthermore, we developed a novel classification method that includes more information about viruses than that acquired using BLAST. We further report the discovery of a large number of previously overlooked (TAG)n repeat sequences in the genomes of marine microbes. We predict that the availability of this time-series database will lead to major discoveries in marine microbiome research.

Blue light penetrates deeper than red light in ocean, thus blue light sensing is critical for adaptation to marine environments. Here, the authors report the genome of Pyconococcus provasolii and identify a chimeric dual orange/far-red and blue light receptor composed of a phytochrome and a cryptochrome by analyzing the marine metagenomes.

Unprecedented, large-scale harmful algal blooms (HABs) dominated by Karenia selliformis occurred off the southeastern coast of Hokkaido, Japan, from late September to early November 2021, about a month after intense and extensive marine heatwaves (MHWs) had subsided. The aims of the present study were to understand the mechanism of development, maintenance, and decay of the HABs as well as to investigate the effect of the MHWs on the HABs. We developed a one-dimensional, lower trophic-level ecosystem model (NEMURO+) to simulate the HABs. The model successfully simulated the 2021 HABs and indicated that their development, maintenance, and decay were controlled primarily by changes of water temperature. Nitrate supply from subsurface layers by seasonal vertical diffusion in autumn also helped to maintain the HABs. Vertical diffusion following MHWs in 2021 contributed to the long duration of the preferred temperature for K. selliformis and the occurrence of pre-bloom of K. selliformis, resulting in preconditioning and accelerating the HABs. However, simulations for normal years (i.e., the climatological mean during 2003–2018) showed that HABs could have occurred, even in the absence of MHWs. The simulations indicated that massive blooms of other phytoplankton species (e.g., diatoms) would not have occurred in 2021, even in the absence of a K. selliformis bloom. The implication was that the HABs in 2021 were the species-specific responses of K. selliformis. The proposed mechanism of the HABs was peculiar to our study area and differed from that previously reported for other K. selliformis blooms. Specifically, the preferred temperature for the HABs of K. selliformis was clearly lower than the previously reported preferred temperature of K. selliformis; thus, the physiological characteristics of the K. selliformis that bloomed in our study area differed from those of other K. selliformis strains. These discoveries provide the first evidence to explain how MHWs affect HABs, and to understand how inter-regional dissimilarities of K. selliformis can lead to large-scale, devastating outbreaks under different oceanographic conditions.

Abstract Background For the diagnosis of Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP) revised the algorisms in 2019, where they added computed tomography (CT) as an assessment tool not only for quantity but also for quality in research purpose. However, the evidence for clinical appreciation of CT has been lacking. Therefore, we investigated the correlation between CT and various motor function tests to assess the utility of CT as a potential diagnostic tool for sarcopenia. Methods In total, 214 patients who were examined at our center during the study period (2016–2017) were included in the study. Single-slice CT scan of the mid-thigh region was performed, from which cross-sectional area (CSA) and CT attenuation value (CTV) of quadriceps femoris were evaluated for each subject. Other assessments included skeletal muscle mass index by DXA and BIA, muscle strength and physical performance. Furthermore, subjects were classified into four groups as per the Asia Working Group of Sarcopenia (AWGS) 2019 criteria as those with: normal, poor muscle function/strength (poor function), sarcopenia and severe sarcopenia. Results Knee muscle strength correlated with CSA (r = 0.60) and the correlation was significantly greater than that with DXA and BIA. For physical performance, standing-up test correlated with CSA (r = − 0.20) and CTV (r = − 0.40) and walking speed with CTV (r = 0.43), which was significantly greater than that with DXA and BIA. The CSA was significantly lower in women with sarcopenia group and in both men and women with severe sarcopenia (all p

Abstract Hyperuricaemia is a risk for premature death. This study evaluated the burden of hyperuricaemia (serum urate > 7 mg/dL) for all-cause and cardiovascular mortality in 515,979 health checkup participants using an index of population attributable fraction (PAF). Prevalence of hyperuricaemia at baseline was 10.8% in total subjects (21.8% for men and 2.5% for women). During 9-year follow-up, 5952 deaths were noted, including 1164 cardiovascular deaths. In the Cox proportional hazard analysis adjusted for confounding factors, hyperuricaemia was independently associated with all-cause and cardiovascular mortality (adjusted hazard ratios [95% confidence interval]; 1.36 [1.25–1.49] and 1.69 [1.41–2.01], respectively). Adjusted PAFs of hyperuricaemia for all-cause and cardiovascular deaths were 2.9% and 4.4% (approximately 1 in 34 all-cause deaths and 1 in 23 cardiovascular deaths), respectively. In the subgroup analysis, the association between hyperuricaemia and death was stronger in men, smokers, and subjects with renal insufficiency. Adjusted PAFs for all-cause and cardiovascular deaths were 5.3% and 8.1% in men; 5.8% and 7.5% in smokers; and 5.5% and 7.3% in subjects with renal insufficiency. These results disclosed that a substantial number of all-cause and cardiovascular deaths were statistically relevant to hyperuricaemia in the community-based population, especially men, smokers, and subjects with renal insufficiency.

Abstract Background Although sarcopenia has been known as a risk factor for hip fracture, only a few reports have described the impact of muscle mass on hip fracture treatment outcomes. The current study aimed to investigate the impact of muscle mass on hip fracture treatment outcomes. Methods This case–control study involved 337 patients (67 males and 270 females) with hip fracture aged ≥65 years (mean age: 84.1 ± 7.1 years) who underwent orthopedic surgery from January 2013 to June 2019. The mean follow-up period was 17.1 (1–60) months. Upon admission, all patients were assessed for low muscle mass according to the Asian Working Group for Sarcopenia criteria (male, SMI

Abstract Eel larvae apparently feed on marine snow, but many aspects of their feeding ecology remain unknown. The eukaryotic 18S rRNA gene sequence compositions in the gut contents of four taxa of anguilliform eel larvae were compared with the sequence compositions of vertically sampled seawater particulate organic matter (POM) in the oligotrophic western North Pacific Ocean. Both gut contents and POM were mainly composed of dinoflagellates as well as other phytoplankton (cryptophytes and diatoms) and zooplankton (ciliophoran and copepod) sequences. Gut contents also contained cryptophyte and ciliophoran genera and a few other taxa. Dinoflagellates (family Gymnodiniaceae) may be an important food source and these phytoplankton were predominant in gut contents and POM as evidenced by DNA analysis and phytoplankton cell counting. The compositions of the gut contents were not specific to the species of eel larvae or the different sampling areas, and they were most similar to POM at the chlorophyll maximum in the upper part of the thermocline (mean depth: 112 m). Our results are consistent with eel larvae feeding on marine snow at a low trophic level, and feeding may frequently occur in the chlorophyll maximum in the western North Pacific.

Abstract As previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19–2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26–0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.

Abstract Based on questionnaires from 197,825 non-diabetic participants in a large Japanese cohort, we determined impact of (1) habit of exercise, (2) habit of active physical activity (PA) and (3) walking pace on new-onset of type 2 diabetes mellitus. Unadjusted and multivariable-adjusted logistic regression models were used to determine the odds ratio of new-onset diabetes mellitus incidence in a 3-year follow-up. There were two major findings. First, habits of exercise and active PA were positively associated with incidence of diabetes mellitus. Second, fast walking, even after adjusting for multiple covariates, was associated with low incidence of diabetes mellitus. In the subgroup analysis, the association was also observed in participants aged ≥ 65 years, in men, and in those with a body mass index ≥ 25. Results suggest that fast walking is a simple and independent preventive factor for new-onset of diabetes mellitus in the health check-up and guidance system in Japan. Future studies may be warranted to verify whether interventions involving walking pace can reduce the onset of diabetes in a nation-wide scale.

Abstract This study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan–Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.

An unprecedented large-scale outbreak of harmful algae, including Karenia selliformis and Karenia mikimotoi, was reported in mid-September 2021 in the northwest Pacific Ocean off southeastern Hokkaido, Japan. It inflicted catastrophic damage on coastal fisheries in the ensuing months. To understand the spatiotemporal distribution of Karenia spp. abundance, we conducted extensive ship-based surveys across several water masses during 4–14 October, 2021 and analyzed in-situ data in combination with Sentinel-3-derived ocean color imagery with a horizontal resolution of 300 m. High chlorophyll-a concentrations (exceeding 10 mg m–3) were identified mainly in coastal shelf–slope waters of 103 cells mL–1) of Karenia spp. on the shelf were characterized by submesoscale (i.e., 1–10 km) patch- or streak-like distributions, or both. Within a roughly 24-h period from 12 to 13 October, Karenia-spp. abundances averaged over the shelf abruptly increased more than doubled; these abundance spikes were associated with the combined effects of physical advection and algal growth. The obtained maps and features of Karenia spp. abundance will provide basic estimates needed to understand the processes and mechanisms by which algal blooms can inflict damage on regional fisheries.

Abstract Background Gram-positive anaerobic (GPA) bacteria inhabit different parts of the human body as commensals but can also cause bacteremia. In this retrospective observational study, we analyzed GPA bacteremia pathogens before (2013–2015) and after (2016–2018) the introduction of the matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). Method We conducted a retrospective observational study by searching the microbiology database to identify all positive GPA blood cultures of patients with GPA bacteremia diagnosed using the new technique, MALDI-TOF MS, between January 1, 2016 and December 31, 2018; and using a conventional phenotypic method between January 1, 2013 and December 31, 2015 at a single tertiary center in Japan. Parvimonas micra (P. micra) (17.5%) was the second most frequently identified GPA (MALDI-TOF MS); we then retrospectively reviewed electronic medical records for 25 P. micra bacteremia cases at our hospital. We also conducted a literature review of published cases in PubMed from January 1, 1980, until December 31, 2019; 27 cases were retrieved. Results Most cases of P. micra bacteremia were identified after 2015, both, at our institute and from the literature review. They were of mostly elderly patients and had comorbid conditions (malignancies and diabetes). In our cases, laryngeal pharynx (7/25, 28%) and gastrointestinal tract (GIT; 6/25, 24%) were identified as the most likely sources of bacteremia; however, the infection source was not identified in 9 cases (36%). P. micra bacteremia were frequently associated with spondylodiscitis (29.6%), oropharyngeal infection (25.9%), intra-abdominal abscess (14.8%), infective endocarditis (11.1%), septic pulmonary emboli (11.1%), and GIT infection (11.1%) in the literature review. Almost all cases were treated successfully with antibiotics and by abscess drainage. The 30-day mortalities were 4 and 3.7% for our cases and the literature cases, respectively. Conclusions Infection sites of P. micra are predominantly associated with GIT, oropharyngeal, vertebral spine, intra-abdominal region, pulmonary, and heart valves. Patients with P. micra bacteremia could have good prognosis following appropriate treatment.

Scanning electron microscopy (SEM) has contributed to elucidating the ultrastructure of bio-specimens in three dimensions. SEM imagery detects several kinds of signals, of which secondary electrons (SEs) and backscattered electrons (BSEs) are the main electrons used in biological and biomedical research. SE and BSE signals provide a three-dimensional (3D) surface topography and information on the composition of specimens, respectively. Among the various sample preparation techniques for SE-mode SEM, the osmium maceration method is the only approach for examining the subcellular structure that does not require any reconstruction processes. The 3D ultrastructure of organelles, such as the Golgi apparatus, mitochondria, and endoplasmic reticulum has been uncovered using high-resolution SEM of osmium-macerated tissues. Recent instrumental advances in scanning electron microscopes have broadened the applications of SEM for examining bio-specimens and enabled imaging of resin-embedded tissue blocks and sections using BSE-mode SEM under low-accelerating voltages; such techniques are fundamental to the 3D-SEM methods that are now known as focused ion-beam SEM, serial block-face SEM, and array tomography (i.e., serial section SEM). This technical breakthrough has allowed us to establish an innovative BSE imaging technique called section-face imaging to acquire ultrathin information from resin-embedded tissue sections. In contrast, serial section SEM is a modern 3D imaging technique for creating 3D surface rendering models of cells and organelles from tomographic BSE images of consecutive ultrathin sections embedded in resin. In this article, we introduce our related SEM techniques that use SE and BSE signals, such as the osmium maceration method, semithin section SEM (section-face imaging of resin-embedded semithin sections), section-face imaging for correlative light and SEM, and serial section SEM, to summarize their applications to neural structure and discuss the future possibilities and directions for these methods.

Abstract Some peritoneal dialysis catheter infections cannot be detected via a physical examination. Ultrasound of the PD catheter tunnel should be performed in cases of suspected infection or clinical abnormality at the catheter tunnel site.

Abstract The barium/calcium ratio (Ba/Ca) in coral skeletons has been used as a proxy to understand river floods and oceanic upwelling in the tropics and subtropics for the past centuries. Here, we establish a new method for Ba/Ca analysis using inductively coupled plasma optical emission spectrometry (ICP‐OES), which has been widely used for coral proxy analyses and can save analysis time compared to other methods. We analyze Ba/Ca by combining an ultrasonic nebulizer with the intensity ratio calibration method to improve the signal intensity of Ba. Our method can determine Ba/Ca in samples with a Ca concentration of 9 mg/L with excellent analytical precision (

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Background/Aims: The association of diastolic blood pressure (DBP) with incidence of chronic kidney disease (CKD) in the general population is not well examined. Methods: Using national health check-up database from 2008 to 2011 in the general Japanese population aged 39–74 years, we evaluated the association between DBP and incidence of CKD 2 years later in 127,954 participants without CKD. DBP was categorized by every 5 mm Hg from the lowest (100 mm Hg) and was further stratified into those with and without antihypertensive medications (BP meds). We calculated the OR for estimating adjusted risk of incident CKD using logistic regression model. Results: Participants were 62% female and 25.9% with BP meds, mean age of 76 years with estimated glomerular filtration rate of 78.2 ± 13.4 and DBP of 76 ± 11 mm Hg. Two years later, 12,379 (9.7%) developed CKD. Compared to DBP 60–64 mm Hg without BP meds as reference, multivariate analysis showed no difference in CKD risk at any DBP category among those without BP meds. However, in those with BP meds, risk increased according to lower DBP from 95 to 60 mm Hg (p for trend 0.05) with OR 1.51 (95% CI 1.14–1.99) in DBP

Abstract To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the “Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake” under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata‐Chuetsu Earthquakes, the current “Manual for Disaster Diabetes Care” has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

Abstract Background Periodontal disease, including periodontitis, has been reported to be a rare cause of septic pulmonary embolism (SPE). It is however extremely difficult to isolate the causative pathogen of periodontal disease-associated SPE from blood cultures of these patients. Case presentation In this study, an 85-year-old Japanese man was admitted with fever and worsening malaise. He was later noted to have multiple bilateral subpleural pulmonary nodules on chest computed tomography scan. After admission, Parvimonas micra (P. micra) was isolated from his blood culture. This was followed by a meticulous search for the primary source of SPE, focusing on the head and neck areas. Consequently, apical periodontitis and infratemporal fossa abscess were identified as the primary sources of SPE. Although P. micra is one of the most frequently detected bacteria in the infected root canals of teeth with chronic apical periodontitis, it has rarely been proven as a causative pathogen of periodontal disease-associated SPE. Conclusions This case study demonstrated that periodontal disease is an important primary source of SPE and P. micra could be a causative pathogen of SPE.

While primary productivity in the oligotrophic North Pacific Subtropical Gyre (NPSG) is changing, the micro-size plankton community has not been evaluated in the last 4 decades, prompting a re-evaluation. We collected samples over three years (2016-2018) from depths of 10 to 200 m (n = 127), and the micro-size plankton were identified and counted to understand the heterogeneity of micro-size plankton community structure. The assemblages were consistent to the those of 4 decades ago. Dinophyceae (dinoflagellates) were the most numerically abundant, followed by Cryptophyceae and Bacillariophyceae (diatoms). The other micro-size plankton classes (Cyanophyceae, Haptophyceae, Dictyochophyceae, Euglenophyceae, and Prasinophyceae) were not always detected, whereas only Trichodesmium spp. was counted in the Cyanophyceae. Other unidentified autotrophic and heterotrophic flagellates were also significantly present, and their numeric abundance was higher than or at the same level as was that of the Dinophyceae. In the Dinophyceae, Gymnodiniaceae and Peridiniales were abundant. The chlorophyll a concentration and these class-level assemblages suggested micro-size plankton is not a major primary producer in this area. We applied generalized additive models (GAMs) and principal coordination analyses (PCoAs) to evaluate the habitats of every plankton group and the heterogeneity of the assemblages. The GAMs suggested that every classified plankton abundance showed a similar response to salinity, and we observed differences in habitats in terms of temperature and nitrate concentrations. Based on the PCoAs, we observed unique communities at the 200 m depth layer compared with those at the other sampling layers. The site scores of PCoAs indicated that the micro-size plankton assemblages are most heterogeneous at the 10 m depth layer. At such depth, diazotrophic Cyanophyceae (Trichodesmium spp.) are abundant, particularly in less-saline water. Therefore, nitrogen fixation may contribute to the heterogeneity in the abundance and assemblages in the western NPSG.

BackgroundChanges in plasma volume, a marker of plasma volume expansion and contraction, are gaining attention in the field of cardiovascular disease because of its role in the prevention and management of heart failure. However, it remains unknown whether a 1-year change in plasma volume is a risk factor for all-cause, cardiovascular, and non-cardiovascular mortality in the general population.Methods and resultsWe used a nationwide database of 134,291 subjects (age 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" check-up for 2 consecutive years between 2008 and 2011. A 1-year change in plasm volume was calculated using the Strauss-Davis-Rosenbaum formula. There were 220 cardiovascular deaths, 1,001 non-cardiovascular deaths including 718 cancer deaths, and 1,221 all-cause deaths during the follow-up period of 3.9 years. All subjects were divided into quintiles based on the 1-year change in plasma volume. Kaplan-Meier analysis demonstrated that the highest 5th quintile had the greatest risk among the five groups. Multivariate Cox proportional hazard regression analysis demonstrated that a 1-year change in plasma volume was an independent risk factor for all-cause, cardiovascular, non-cardiovascular, and cancer deaths. The addition of a 1-year change in plasma volume to cardiovascular risk factors significantly improved the C-statistic, net reclassification, and integrated discrimination indexes.ConclusionsHere, we have demonstrated for the first time that a 1-year change in plasma volume could be an additional risk factor for all-cause, cardiovascular, and non-cardiovascular (mainly cancer) mortality in the general population.

The taxonomic compositions of marine prokaryotic communities are known to follow seasonal cycles, but functional metagenomic insights into this seasonality is still limited. We analyzed a total of 22 metagenomes collected at 11 time points over a 14-month period from two sites in Sendai Bay, Japan to obtain seasonal snapshots of predicted functional profiles of the non-cyanobacterial prokaryotic community. Along with taxonomic composition, functional gene composition varied seasonally and was related to chlorophyll a concentration, water temperature, and salinity. Spring phytoplankton bloom stimulated increased abundances of putative genes that encode enzymes in amino acid metabolism pathways. Several groups of functional genes, including those related to signal transduction and cellular communication, increased in abundance during the mid- to post-bloom period, which seemed to be associated with a particle-attached lifestyle. Alternatively, genes in carbon metabolism pathways were generally more abundant in the low chlorophyll a period than the bloom period. These results indicate that changes in trophic condition associated with seasonal phytoplankton succession altered the community function of prokaryotes. Our findings on seasonal changes of predicted function provide fundamental information for future research on the mechanisms that shape marine microbial communities.