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Abstract Background Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA. Methods Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children’s Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women’s cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders. Results We studied 4683 mother–child pairings from 103,060 pregnancies included in the Japan Environment and Children’s Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children. Conclusion Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children’s growth.

This study used the nationally representative prospective study of the Household, Income and Labour Dynamics in Australia (HILDA) survey cohort to examine the association of pet ownership (dog, cat, bird, fish, and others) with the risk of all-cause mortality using propensity score matching based on a wide range of factors. The study sample included 15,735 participants who completed the questionnaire on pet ownership in 2018. The HILDA survey sample was matched to the National Death Index through 2022 to assess death during the follow-up period. Statistical analysis was weighted by the inverse of the propensity score in the generalized estimating equation. During the 4-year follow-up period, 377 of 15,735 (2.4%) participants died. The odds ratios (ORs) for all-cause mortality were 0.77 (95%CI: 0.59-0.99) for dog owners compared to non-pet owners after controlling for related socio-demographic, physical, psychological, and social factors. The Sobel test showed a partial mediating effect of physical activity level on the relationship between dog ownership and all-cause mortality. Ownership of cats, birds, fish, and others showed no clear association with mortality, despite owners having similar socio-demographics characteristics to dog owners. Companionship and exercise of a pet dog may be recommended as a component of health promotion policy, and may have an important role to play in promoting health aging.

Background and purposeMean pulmonary artery pressure (mPAP) is a key index for chronic thromboembolic pulmonary hypertension (CTEPH). Using machine learning, we attempted to construct an accurate prediction model for mPAP in patients with CTEPH.MethodsA total of 136 patients diagnosed with CTEPH were included, for whom mPAP was measured. The following patient data were used as explanatory variables in the model: basic patient information (age and sex), blood tests (brain natriuretic peptide (BNP)), echocardiography (tricuspid valve pressure gradient (TRPG)), and chest radiography (cardiothoracic ratio (CTR), right second arc ratio, and presence of avascular area). Seven machine learning methods including linear regression were used for the multivariable prediction models. Additionally, prediction models were constructed using the AutoML software. Among the 136 patients, 2/3 and 1/3 were used as training and validation sets, respectively. The average of R squared was obtained from 10 different data splittings of the training and validation sets.ResultsThe optimal machine learning model was linear regression (averaged R squared, 0.360). The optimal combination of explanatory variables with linear regression was age, BNP level, TRPG level, and CTR (averaged R squared, 0.388). The R squared of the optimal multivariable linear regression model was higher than that of the univariable linear regression model with only TRPG.ConclusionWe constructed a more accurate prediction model for mPAP in patients with CTEPH than a model of TRPG only. The prediction performance of our model was improved by selecting the optimal machine learning method and combination of explanatory variables.

Abstract Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and critical malignancy‐related disease characterized by acute progressive pulmonary hypertension (PH). In most cases of PTTM, the cancer can be diagnosed in advance. Identification of the primary cancer is valuable for PTTM diagnosis. Here, we present the case of a patient with PTTM due to early gastric carcinoma in whom the diagnosis of malignant cancer was not revealed until macroscopic autopsy findings. This case highlights the importance of recognizing causative occult early gastric cancer leading to PTTM in cases of acute progressive PH.

This prospective study examined the associations of dog/cat ownership with incident disabling dementia using propensity score matching based on the physical, social, and psychological characteristics of dog and cat owners. We also examined associations of the interaction between dog/cat ownership and exercise habit and social isolation with dementia. Overall, 11,194 older adults selected using stratified and random sampling strategies in 2016 were analyzed. Dog/cat ownership was defined as “current” or “past and never”. Disabling dementia was defined according to physicians’ rating in the long-term care insurance system in Japan during the approximately 4-year follow-up period. Statistical analysis was weighted by the inverse of the propensity score in the generalized estimating equation after adjusting for follow-up period. Current dog owners (8.6 %) had an odds ratio (OR) of 0.60 (95 %CI: 0.37–0.977) of having disabling dementia compared to past and never owners. For cat ownership, the corresponding OR was 0.98 (95 %CI: 0.62–1.55). Current dog owners with a regular exercise habit had an OR of 0.37 (0.20–0.68) compared to past and never dog owners with no exercise habit. Further, current dog owners with no social isolation had an OR of 0.41 (0.23–0.73) compared to past and never dog owners with social isolation. Dog ownership had a suppressive effect on incident disabling dementia after adjusting for background factors over a 4-year follow-up period. Specifically, dog owners with an exercise habit and no social isolation had a significantly lower risk of disabling dementia.

Pulmonary arterial hypertension (PAH) remains a significant challenge in cardiology, necessitating advancements in treatment strategies. This study explores the safety and efficacy of transitioning patients from beraprost to selexipag, a novel selective prostacyclin receptor agonist, within a Japanese cohort. Employing a multicenter, open-label, prospective design, 25 PAH patients inadequately managed on beraprost were switched to selexipag. Key inclusion criteria included ongoing beraprost therapy for ≥3 months, a diagnosis of PAH confirmed by mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, and current treatment with endothelin receptor antagonists and/or phosphodiesterase type 5 inhibitors. Outcomes assessed were changes in hemodynamic parameters (mPAP, cardiac index, pulmonary vascular resistance) and the 6 min walk distance (6-MWD) over 3–6 months. The study found no statistically significant changes in these parameters post-switch. However, a subset of patients, defined as responders, demonstrated improvements in all measured hemodynamic parameters, suggesting a potential benefit in carefully selected patients. The transition was generally well-tolerated with no serious adverse events reported. This investigation underscores the importance of personalized treatment strategies in PAH, highlighting that certain patients may benefit from switching to selexipag, particularly those previously on higher doses of beraprost. Further research is needed to elucidate the predictors of positive response to selexipag and optimize treatment regimens for this complex condition.

Abstract Background Few studies have examined the state of oral function in older adults with sarcopenia. We assessed the oral functions of community‐dwelling older adults with sarcopenia from multiple perspectives to clarify their potentially low oral function. Methods A total of 1517 (86.2%; 990 women, 527 men; mean age 76.1 ± 7.6 years) participants were included in this study. Grip strength, gait speed and skeletal muscle mass index were assessed, and sarcopenia was evaluated according to the criteria of the Asian Working Group for Sarcopenia 2019. The degree of tongue coating, oral moisture, occlusal force, tongue–lip motor function, tongue pressure, masticatory function and swallowing function were assessed. The criteria for oral hypofunction (a disease that is a combination of multiple low oral functions) were used to assess oral function. Statistical analyses were performed using Kolmogorov–Smirnov test, unpaired t‐test, Mann–Whitney U test, χ2 test, and univariate and multivariable logistic regression analyses, with each oral function as the dependent variable and sarcopenia as one of the independent variables. The significance level was set at P

Background: Ramp lesions (RLs), associated with anterior cruciate ligament (ACL) injuries, should be repaired to ensure postoperative knee stability. However, it is difficult to identify all RLs before surgery using conventional sagittal magnetic resonance (MR) images and arthroscopy from the anterior, medial, and lateral portals that are usually used during ACL reconstruction. We report the effectiveness of axial images for detecting RL. Methods: From January 2018, a total of 316 knees underwent primary ACL reconstruction with preoperative magnetic resonance imaging (MRI) examination at our hospital. Among these, 149 knees, which required meniscal suturing at the same time, were retrospectively investigated. This study evaluated 22 knees with confirmed RLs around the posterior horn of the medial meniscus. The effectiveness of the preoperative sagittal and axial MR images for detecting RL was assessed. With the MR image, a three-dimensional double-echo steady-state image with a flip angle of 25° was reconstructed into the sagittal and axial planes, respectively. Reconstructed images with 3-mm slices for sagittal slices and 1-mm slices for axial sections were used. The diagnosis was made based on the presence of RL (RL was present, RL may be present, and RL was not present) by four knee surgeons with more than 10 years of experience. Results: Approximately 53% of knee cases were diagnosed with RLs using sagittal images. Meanwhile, a diagnosis was achieved using axial images in 89% of cases. Conclusion: Axial MRI may be superior in detecting RLs.

Abstract Compared with the relatively well-investigated effects of childhood exposure to lead on neurocognitive deficits, those of prenatal exposure remain relatively inconclusive. We aimed to investigate the association between prenatal blood lead levels and neurodevelopmental delay during the first three years of life. From a prospective cohort of the Japan Environment and Children’s Study, we analyzed a total of 80,759 children. The exposure factors were prenatal lead concentrations measured from maternal whole blood in the second/third trimesters and umbilical cord blood at birth. Neurodevelopment was assessed at 6, 12, 18, 24, 30, and 36 months old using a screening tool, the Ages and Stages Questionnaires, third edition (ASQ). The outcome measures were any suspected neurodevelopmental delay (sNDD) identified via the ASQ during the first (sNDD-1Y), second (sNDD-2Y), and third (sNDD-3Y) years of life. sNDD-1Y, 2Y, and 3Y were identified in 18.0%, 16.2%, and 17.2% of children, respectively. The geometric means of blood lead concentration in this study were much lower (0.62 μg/dL in maternal blood and 0.50 μg/dL in cord blood) than previously investigated levels. Multivariable regression models revealed that there were no associations between maternal blood lead and sNDD-1Y and 2Y and between cord blood lead and sNDD-1Y, 2Y, and 3Y. Although a higher maternal blood lead was associated with a reduced risk of sNDD-3Y (adjusted relative risk: 0.84, 95% confidence interval 0.75–0.94, per 1 increase in common logarithm of lead concentration), there were no dose–response relationships in the analysis using quintiles of lead concentrations. Using a large-scale data set, the present study demonstrated no convincing evidence for an inverse association between levels of prenatal blood lead and neurodevelopment in early childhood. Longitudinal measurements of prenatal and postnatal lead levels are needed to understand the relationship between lead exposure and neurocognitive development.

Objectives Balloon pulmonary angioplasty (BPA) and medical therapy, such as soluble guanylate cyclase stimulators, are recommended treatments for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA). However, monotherapy with BPA or medical therapy cannot always eliminate symptoms such as exertional dyspnoea. Thus, this study aims to clarify the efficacy of continuous treatment with riociguat in inoperable CTEPH patients with normalised haemodynamics after BPA.Methods and analysis This is a double-blind, multicentre, randomised, placebo-controlled trial. Participants with CTEPH who are ineligible for PEA will receive riociguat followed by BPA. Subsequently, participants will be randomised (1:1) into either riociguat continuing or discontinuing groups and will be observed for 16 weeks after randomisation. The primary endpoint will be the change in peak cardiac index (CI) during the cardiopulmonary exercise test. In the primary analysis, the least square mean differences and 95% CIs for the change in peak CI at 16 weeks between the groups will be estimated by a linear mixed-effects model with baseline value as a covariate, treatment group as a fixed effect and study institution as a random effect.Ethics and dissemination National Hospital Organisation Review Board for Clinical Trials (Nagoya) and each participating institution approved this study and its protocols. Written informed consent will be obtained from all participants. The results will be disseminated at medical conferences and in journal publications.Registration details Japan Registry of Clinical Trials: jRCT no. 041200052. ClinicalTrials.gov by National Library of Medicine Registry ID: NCT04600492.Trial registration number NCT04600492.

Abstract Background The prognostic value of mixed venous oxygen tension (PvO2) at pulmonary hypertension diagnosis treated with selective pulmonary vasodilators remains unclear. This study sought to investigate the association of PvO2 with long-term prognosis in pulmonary arterial hypertension (PAH) and medically treated chronic thromboembolic pulmonary hypertension (CTEPH) and to identify the distinct mechanisms influencing tissue hypoxia in patients with CTEPH or PAH. Methods We retrospectively analyzed data from 138 (age: 50.2 ± 16.6 years, 81.9% women) and 268 (age: 57.4 ± 13.1 years, 72.8% women) patients with PAH and CTEPH, respectively, diagnosed at our institution from 1983 to 2018. We analyzed the survival rates of patients with/without tissue hypoxia (PvO2

Abstract Pulmonary arterial hypertension (PAH), an intractable disease with a poor prognosis, is commonly treated using pulmonary vasodilators modulating the endothelin, cGMP, and prostacyclin pathway. Since the 2010s, drugs for treating pulmonary hypertension based on mechanisms other than pulmonary vasodilation have been actively developed. However, precision medicine is based on tailoring disease treatment to particular phenotypes by molecular‐targeted drugs. Since interleukin‐6 (IL‐6) is involved in the development of PAH in animal models, and some patients with PAH have elevated IL‐6 levels, the cytokine is expected to obtain potentials for therapeutic targeting. Accordingly, we identified a phenotype with elevated cytokine activity of the IL‐6 family in the PAH population by combining case data extracted from the Japan Pulmonary Hypertension Registry with a comprehensive analysis of 48 cytokines using artificial intelligence clustering techniques. Including an IL‐6 threshold ≥2.73 pg/mL as inclusion criteria for reducing the risk of insufficient efficacy, an investigator‐initiated clinical study using satralizumab, a recycling anti‐IL6 receptor monoclonal antibody, for patients with an immune‐responsive phenotype is underway. This study is intended to test whether use of patient biomarker profile can identify a phenotype responsive to anti‐IL6 therapy.

Portopulmonary hypertension (PoPH) is a rare subtype of Group 1 pulmonary arterial hypertension (PAH) with a poor prognosis. According to the most up-to-date definition, PoPH is characterized by a mean pulmonary arterial pressure (PAP) of >20 mmHg at rest, a pulmonary artery wedge pressure of ≤15 mmHg, and a pulmonary vascular resistance (PVR) of >2 Wood units with portal hypertension. Like PAH, PoPH is underpinned by an imbalance in vasoactive substances. Therefore, current guidelines recommend PAH-specific therapies for PoPH treatment; however, descriptions of the actual treatment approaches are inconsistent. Given the small patient population, PoPH is often studied in combination with idiopathic PAH; however, recent evidence suggests important differences between PoPH and idiopathic PAH in terms of hemodynamic parameters, treatment approaches, survival, socioeconomic status, and healthcare utilization. Therefore, large, multi-center registry studies are needed to examine PoPH in isolation while obtaining statistically meaningful results. PoPH has conventionally been excluded from clinical drug trials because of concerns over hepatotoxicity. Nevertheless, newer-generation endothelin receptor antagonists have shown great promise in the treatment of PoPH, reducing PVR, PAP, and World Health Organization functional class without causing hepatotoxicity. The role of liver transplantation as a treatment option for PoPH has also been controversial; however, recent evidence shows that this procedure may be beneficial in this patient population. In the future, given the shortage of liver donors, predictors of a favorable response to liver transplantation should be determined to select the most eligible patients. Collectively, advances in these three areas could help to standardize PoPH treatment in the clinic.

Background: The Japan Environment and Children’s Study (JECS) is a nationwide birth cohort study investigating environmental effects on children’s health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants’ baseline profiles. Methods: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician’s examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion. Results: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study. Conclusion: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

Abstract Background Sarcopenia‐related parameters may have differential impacts on health‐related outcomes in older adults. We examined dose–response relationships of body composition, muscle strength, and physical performance with incident disability and mortality. Methods This prospective study included 1765 Japanese residents (862 men; 903 women) aged ≥65 years who participated in health check‐ups. Outcomes were incident disability and all‐cause mortality. Fat mass index (FMI) and skeletal muscle mass index (SMI), determined using segmental multi‐frequency bioelectrical impedance analysis, handgrip strength (HGS), and usual gait speed (UGS) were measured. We determined multivariate‐adjusted hazard ratios (HRs) for disability and mortality relative to sex‐specific reference values (FMI: medians; SMI: 7.0 kg/m2 for men and 5.7 kg/m2 for women; HGS: 28 kg for men and 18 kg for women; or UGS: 1.0 m/s for both sexes). Association shapes were examined using restricted cubic splines or fractional polynomial functions. Results The median follow‐up was 5.3 years; 107 (12.7%) men and 123 (14.2%) women developed disability, and 101 (11.7%) men and 56 (6.2%) women died. FMI did not impact any outcome in men and disability in women, while an FMI ≤ 7.3 kg/m2 (median) was significantly associated with higher mortality risk in women, compared with median FMI. SMI did not impact disability in either sex and mortality in women, but showed a significant inverse dose–response relationship with mortality risk in men [HRs (95% confidence intervals) of minimum and maximum values compared with the reference value: 2.18 (1.07–4.46) and 0.43 (0.20–0.93), respectively], independent of HGS and UGS. HGS and UGS showed a significant inverse dose–response relationship with disability in both sexes [HGS: 1.71 (1.00–2.91) and 0.31 (0.09–0.99), respectively, in men, 2.42 (1.18–4.96) and 0.41 (0.20–0.85), respectively, in women; UGS: 2.14 (1.23–3.74) and 0.23 (0.08–0.67), respectively, in men, 3.26 (2.07–5.14) and 0.11 (0.05–0.26), respectively, in women] and mortality in women [HGS: 6.84 (2.84–16.47) and 0.06 (0.02–0.21), respectively; UGS: 2.67 (1.14–6.27) and 0.30 (0.11–0.85), respectively], independent of body composition, but did not impact mortality in men. Conclusions Disability risk was more dependent on muscle strength and physical performance in both sexes. Mortality risk in men was more dependent on muscle mass, and mortality risk in women was influenced by lower fat mass along with muscle strength and physical performance. Although improving muscle strength and physical performance should be the first target for health promotion, it is also necessary to pay attention to body composition to extend life expectancy in older adults.

Antibiotic-loaded acrylic cement beads have a large surface area and excellent sustained-release properties. However, there are some difficulty manufacturing reasonably sized beads and their careful handling. We developed a self-made cement bead maker using a mold of a sphere with a diameter of 8 and 10 mm with a 2-mm-diameter connecting hole. With this instrument, approximately 32 beads can be made from 40 g of bone cement. We clinically applied this technique to 11 cases of periprosthetic joint infection. There was no recurrence of infection noted. The advantages of this device were that it was possible to adjust the combination of antimicrobial agents and that the shape was uniform and easy to handle during surgery.

Background Balloon pulmonary angioplasty (BPA) is a promising treatment modality for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for atypical CTEPH with concurrent chronic obstructive pulmonary disease (COPD) remains controversial owing to the risk of exacerbation of ventilation‐perfusion mismatch. We aimed to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Methods and Results Data from 149 patients with CTEPH, who underwent BPA from March 2011 to June 2021, were retrospectively analyzed. Patients were divided based on COPD comorbidity: the COPD group (n=32, defined as forced expiratory volume in 1 second/forced vital capacity

The sex of the conceived child is a significant concern for parents. To verify whether there women have pregnancy bias toward boys or girls, we investigated whether the history of continuous same-sex pregnancy was associated with the subsequent child's sex. We prospectively analyzed data from the Japan Environment and Children's Study, a birth cohort study. We included all cases of singleton live births (n = 98 412). Women with pregnancy due to infertility treatment were excluded (n = 6255); Similarly, women with a history of miscarriage, artificial abortion, stillbirth, and multiple pregnancies, and those with missing data on the sex of the previous child were excluded. Altogether, 62 718 women were included. For the first live birth, a male-biased sex ratio of 1.055 was observed. Further, no significant difference was found in the sex ratio of the conceived child between women with one boy and those with one girl previously. However, when there were more than two children previously, the subsequently conceived child's male/female sex ratio was significantly higher among boy-only mothers than among girl-only mothers. The results indicated that several pregnant women are biased toward conceiving either boys or girls.

Findings on the relationship between pet exposure and asthma in western countries are inconsistent. This retrospective study examined the association of owning a dog or cat with the onset of asthma in Japanese people. We also investigated whether there is a critical window during which exposure to dogs and cats can reduce the risk of asthma by stratifying the analysis by the age at which pet ownership began. We analyzed data collected in an internet survey conducted by the Japan Pet Food Association in 2021. Valid data were obtained from 4290 participants for analysis of dog ownership and 4308 participants for analysis of cat ownership. In these respective groups, 41.2% had owned a dog and 26.5% had owned a cat. During the follow-up period, 5.7% of dog owners and 14.8% of non-dog owners developed asthma, as did 5.6% of cat owners and 13.5% of non-cat owners. On binomial logistic regression analysis, participants who had not owned a dog had an odds ratio (OR) of 2.01 (95% confidence interval (CI): 1.45-2.78) of developing asthma compared to those who had owned a dog after adjustment for sociodemographic characteristics. The corresponding OR of asthma onset among participants who had not owned a cat was 2.24 (95%CI: 1.56-3.23). Stratified analysis showed that while younger participants who had not owned a dog had higher ORs of developing asthma, those who had not owned a cat had similar ORs of asthma onset across all age categories. These results suggest that while there may be a critical window in early life during which exposure to dogs can prevent asthma onset, the protective effect of cat exposure is constant across all ages in Japan.

This study examined the differences in medical and long-term care costs over 18 months between pet owners and non-owners among community-dwelling older Japanese. Pet ownership data were collected from 460 community-dwelling adults age 65 years and older. These data were matched with data from the National Health Insurance, health insurance for older people, and Long-Term Care Insurance beneficiaries for 17 months back from the survey on pet ownership. Pet-ownership group-specific trajectories in monthly medical and long-term care costs were modeled by a generalized estimating equation. Among pet owners (n = 96, 20.9%) and non-pet owners (n = 364, 79.1%) there were no significant differences in baseline demographic or health characteristics including chronic disease and self-reported long-term care level. At baseline, pet owners had estimated monthly medical costs of ¥48,054 (SE = 0.11; $418), compared to ¥42,260 (SE = 0.06; $367) for non-pet owners. The monthly medical costs did not differ significantly between the two groups during the 18-month follow-up period. At baseline, estimated monthly long-term care costs of pet owners and non-pet owners were ¥676 (SE = 0.75; $6) and ¥1,420 (SE = 0.52; $12), respectively. During the follow-up period, the non-pet owner to owner ratio of monthly long-term care costs was 1.2 at minimum and 2.3 at maximum. This study showed that monthly long-term care costs for pet owners were approximately half those of non-pet owners. Pet owners might use long-term care services less frequently, or use lighter care services.

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus formation. Warfarin, a vitamin K antagonist, is commonly used for anticoagulation in CTEPH based on historical experience and evidence. The anticoagulant activity of warfarin is affected by food and drug interactions, requiring regular monitoring of prothrombin time. The lability of anticoagulant effect often results in haemorrhagic and thromboembolic complications. Thus, lifelong warfarin is a handicap in terms of safety and convenience. Currently, the use of direct oral anticoagulants (DOACs) in CTEPH has increased with the advent of four DOACs. The safety of DOACs is superior to warfarin, with less intracranial bleeding in patients with non-valvular atrial fibrillation and venous thromboembolism. Edoxaban, the latest DOAC, also has proven efficacy and safety for those diseases in two large clinical trials; the ENGAGE-AF trial and HOKUSAI-VTE trial. The present trial seeks to evaluate whether edoxaban is non-inferior to warfarin in preventing worsening of CTEPH.Methods and analysis The KABUKI trial (is an investigator-initiated, multicentre, phase 3, randomised, single-blind, parallel-group, warfarin-controlled, non-inferiority trial to evaluate the efficacy and safety of edoxaban versus warfarin (vitamin K Antagonist) in subjects with chronic thromBoembolic pUlmonary hypertension taking warfarin (vitamin K antagonIst) at baseline) is designed to prove the non-inferiority of edoxaban to warfarin in terms of efficacy and safety in patients with CTEPH.Ethics and dissemination This study is approved by the Institutional Review Board of each participating institution. The findings will be published in a peer-reviewed journal, including positive, negative and inconclusive results.Trial registration number NCT04730037.Protocol version This paper was written per the study protocol V.4.0, dated 29 January 2021.

Background: Growth restriction in the prenatal period is a significant public health concern. Metals can negatively affect birth size, and pregnant women may be exposed to metal mixtures. Comprehensive studies analyzing the effects of combined metal exposure with accurate individual blood metal concentrations are limited. The current study investigated the associations between maternal metal exposure and birth size in a large, nationwide Japanese cohort using individual and mixed model approaches. Methods: Lead, cadmium, mercury, selenium, and manganese blood concentrations were measured in pregnant women in the Japan Environment and Children’s Study (JECS). Measurements of infant birth size—including body weight, body length, and head and chest circumference—were collected. Linear and logistic regressions were used for birth size measurements and the odds of an infant being small in size for gestational age, respectively. Associations between combined metal mixtures and measurements at birth were evaluated using quantile g-computation and Bayesian kernel machine regression (BKMR). Results: Of the 103,060 JECS pregnancies, 93,739 mother–infant pairs were analyzed. The linear regression models showed that lead, selenium, cadmium, and manganese—but not mercury—were associated with body weight. Cadmium was associated with length and chest circumference and mercury was associated with head circumference. Quantile g-computation revealed that manganese increased infant birth weight, length, head circumference, and chest circumference. Lead was the strongest negative factor for infant birth weight, length, head circumference, and chest circumference. The BKMR analysis revealed that the metals had an additive, rather than a synergistic effect. Conclusion: Metal exposure is associated with infant birth size, with lead and manganese playing a more significant role in Japan. The effects of prenatal combined metal exposure at low levels warrant public health attention.

Background: Right ventricular (RV) afterload is widely assessed by pulmonary vascular resistance (PVR). However, RV afterload is underestimated because PVR does not account for the pulsatile load. The pulsatile load is often evaluated by pulmonary arterial compliance (PAC). The RC (resistance-compliance) time, which is calculated from the product of PVR and PAC, is considered to remain constant under medical therapy. However, little is known on how RC time is affected by invasive therapy in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to evaluate change of RC time in patients underwent pulmonary endarterectomy (PEA). Furthermore, we investigated the clinical relevance of RC time. Methods: We reviewed consecutive 50 patients except for death case underwent PEA. Baseline clinical parameters including RC time before performing PEA and follow-up were evaluated. Patients was classified as decrease or non-decrease according to change of RC time. Furthermore, we classified patients into a NYHA I group who had no symptom after treatment and a residual symptom group in order to investigate the relationship of RC time to residual symptoms. Results: RC time was significantly decreased after PEA (0.54 ± 0.16 to 0.45 ± 0.12 sec, p

Abstract Background There is limited evidence on sarcopenia in Asian populations. This study aimed to clarify the prevalence, associated factors, and the magnitude of association with mortality and incident disability for sarcopenia and combinations of its components among Japanese community‐dwelling older adults. Methods We conducted a 5.8 year prospective study of 1851 Japanese residents aged 65 years or older (50.5% women; mean age 72.0 ± 5.9) who participated in health check‐ups. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Appendicular lean mass index (ALMI) was measured using direct segmental multi‐frequency bioelectrical impedance analysis. A Cox proportional hazards regression model was used to identify associations of sarcopenia and the combinations of its components with all‐cause mortality and incident disability. Results The prevalence of sarcopenia was 11.5% (105/917) in men and 16.7% (156/934) in women. Significant sarcopenia‐related factors other than ageing were hypoalbuminaemia, cognitive impairment, low activity, and recent hospitalization (all P‐values

Background/purpose: Color-changeable chewing gum is used for the evaluation of masticatory performance. However, it is currently unclear whether colorimetric and visual assessment methods yield consistent results. This study aimed to clarify the consistency between colorimetric and visual methods used for the evaluation of color changes in color-changeable chewing gum. Materials and methods: The sample comprised 644 older persons (mean age, 75.4 ± 6.4 years). The chewing gum was masticated 60 times at the participant's own chewing rate and then expectorated. The color of the chewing gum was evaluated with the ΔE values and a∗ values, measured using a colorimeter, and the 10 Color Shades (10CSh) and 5 Color Scales (5CSc), using visual evaluation. Spearman's correlation analysis was performed to examine the correlation between the results obtained by the four methods. The significance level was set at α = 0.05. Results: The ΔE values, a∗ values, 10CSh scores, and 5CSc scores were all significantly correlated. The highest correlation coefficient (0.979) was between the ΔE values and a∗ values. The lowest correlation coefficient (0.847) was between the a∗ values and 5CSc scores. Decreased masticatory performance was observed with increased age. Conclusion: Significant correlations were found for all four methods used in the assessment of masticatory performance with color-changeable chewing gum. While visually based assessments are valid, colorimetric methods are more sensitive to smaller changes in masticatory performance.

BackgroundOral health is a key factor of overall health and closely associated with well-being and quality of life. Mastication is one the most important oral functions and may deteriorate with aging. Evidence on association between masticatory dysfunction and frailty in the literature is scarce and not coherent.MethodsA search strategy was developed to conduct a systematic review of the literature in PubMed, CINAHL, and AMED in accordance with the PRISMA 2020 guidelines. We searched for studies published in 2000 or later that examined associations between self-reported masticatory dysfunction and frailty risk. The reference lists of the relevant articles were reviewed for additional studies. We calculated pooled odds ratios (OR) of association between self-reported masticatory dysfunction and the risk of frailty by fixed-effects meta-analysis. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess risk of bias. Publication bias was assessed by visually inspecting a funnel plot.ResultsA total of 285 studies were identified by the literature search. Among 5 studies selected for this review, 4 cross-sectional studies including a total of 7425 individuals were used for meta-analysis. The pooled results by a fixed-effects model showed that there was a significant association between self-reported masticatory dysfunction and frailty risk (pooled OR = 1.83, 95%CI = 1.55-2.18, pConclusionsThis systematic review and meta-analysis highlighted pooled cross-sectional evidence that community-dwelling older people who report masticatory dysfunction are significantly more likely to be frail than those who do not. The limitations of this study are: inclusion of only cross-sectional studies, no gold standard to measure masticatory functions, self-reported information on masticatory function, and the limited number of included studies. More longitudinal studies are warranted for further understanding of the causal pathways and elucidate underlying mechanisms. Registration: PROSPERO CRD42021277173.

Objectives This study examined the association between dog and cat ownership, the onset of disability and all-cause mortality in an older population. Dog and cat owners take more regular exercise and have closer social relationships than non-owners. We further assess the beneficial effects of these moderating variables on the onset of disability and mortality. Methods Dog and cat ownership data were collected from 11233 community-dwelling adults age 65 years and older. These data were matched with data about the onset of disability held by the Japanese long-term care insurance system. Local registry data were used to ascertain all-cause mortality. Results During the approximately 3.5 year follow-up period, 17.1% of the sample suffered onset of disability, and 5.2% died. Logistic regression analysis indicated that, compared with a reference group of those who had never owned a dog (odds ratio fixed at 1.0), older adults who were currently dog owners had a significantly lower odds ratio of onset of disability (OR = 0.54 95% CI: 0.37–0.79). Our results further show that regular exercise interacts with dog ownership to reduce the risk of disability. The association of dog and/or cat ownership with all-cause mortality was not statistically significant. Conclusions Dog ownership appears to protect against incident disability among older Japanese adults. Additional benefits are gained from ownership combined with regular exercise. Daily dog care may have an important role to play in health promotion and successful aging.

Background: Prenatal cadmium exposure has been associated with adverse neurodevelopmental outcomes. However, previous findings are contradictory, and little is known about the potential modifiers of the cadmium-related neurodevelopmental risk. We investigated the associations between prenatal cadmium exposure and neurodevelopment in 2-year-old children and examined the influence of mother/child characteristics. Methods: We recruited 3545 mother–child pairs from the Japan Environment and Children’s Study. We collected maternal blood during mid/late pregnancy and cord blood at delivery, and measured cadmium concentrations using inductively coupled plasma mass spectrometry. Neurodevelopment was assessed using the Kyoto Scale of Psychological Development (KSPD), which includes cognitive-adaptive (C-A), language-social (L-S), postural-motor (P-M) and developmental quotient (DQ) domains. Associations between cadmium and KSPD scores were tested using multivariable models after controlling for confounders. Results: Median levels (interquartile ranges) of cadmium in maternal and cord blood were 0.70 (0.52–0.95) and 0.04 (0.03–0.06) μg/L, respectively. Maternal blood cadmium concentrations were inversely associated with P-M scores in boys (β = −1.4, 95% confidence interval (CI): −2.7, −0.038), DQ in children of mothers who smoked during pregnancy (β = −2.9, 95% CI: −5.7, −0.12), P-M (β = −5.4, 95% CI: −10, −0.67), C-A (β = −6.1, 95% CI: −11, −1.8), L-S (β = −9.0, 95% CI: −13, −4.8) and DQ scores (β = −6.4, 95% CI: −9.6, −3.1) in children born to mothers with gestational diabetes. Cord blood cadmium concentrations were negatively associated with L-S scores (β = −6.0., 95% CI: −11, −0.91) in children born to mothers with gestational diabetes. Conclusions: Prenatal cadmium exposure was negatively associated with neurodevelopment in boys, in children whose mothers smoked, and in children born to mothers with gestational diabetes. Further studies in other populations are needed to confirm our findings.

Summary: Evidence linking the gut-brain axis to Alzheimer’s disease (AD) is accumulating, but the characteristics of causally important microbes are poorly understood. We perform a fecal microbiome analysis in healthy subjects and those with mild cognitive impairment (MCI) and AD. We find that Faecalibacterium prausnitzii (F. prausnitzii) correlates with cognitive scores and decreases in the MCI group compared with the healthy group. Two isolated strains from the healthy group, live Fp360 and pasteurized Fp14, improve cognitive impairment in an AD mouse model. Whole-genome comparison of isolated strains reveals specific orthologs that are found only in the effective strains and are more abundant in the healthy group compared with the MCI group. Metabolome and RNA sequencing analyses of mouse brains provides mechanistic insights into the relationship between the efficacy of pasteurized Fp14, oxidative stress, and mitochondrial function. We conclude that F. prausnitzii strains with these specific orthologs are candidates for gut microbiome-based intervention in Alzheimer's-type dementia.

Background: Although meals that combine a staple food, main dish, and side dish (balanced meals) are recommended in Japan, the health effects of such meals are unclear. We investigated the association of frequency of eating balanced meals with frailty among community-dwelling older Japanese. Methods: We analyzed data from 912 persons aged 65 years or older who participated in the Hatoyama Cohort Study or Kusatsu Longitudinal Study. The frequency of eating two or more balanced meals daily was self-reported as ≤1 day/week, 2 or 3 days/week, 4 or 5 days/week, and daily. Frailty was defined as the presence of at least three, and pre-frailty as the presence of one or two, of the following criteria: weight loss, muscle weakness, exhaustion, slowness, and low physical activity. Adjusted logistic regression was used to study associations of frequency of balanced-meal consumption with frailty (prefrailty and frailty combined) and frailty criteria. Results: Participants reporting a frequency of balanced-meal consumption of ≤2 or 3 days/week had a higher prevalence of frailty (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.21–2.64) than did those reporting a frequency of daily. Lower frequency of balanced-meal consumption was also associated with higher prevalences of weight loss (OR, 4.10; 95% CI, 1.90–8.85), exhaustion (OR, 6.35; 95% CI, 2.49–16.17), and low physical activity (OR, 1.92; 95% CI, 1.22–3.01). Conclusions: Our findings suggest that more frequent twice daily consumption of meals with a staple food, main dish, and side dish decreases the risks of prefrailty and frailty.

Abstract Background Alternative methods of platelet-rich plasma (PRP) preparation, storage, and activation that can be stably reproduced are needed to improve PRP production. The purpose of this study was to investigate the effect of the preparer’s experience on the quality of prepared PRP, chronological changes occurring in PRP, and the effect of the activation procedures on the release of several growth factors from PRP, using PRP prepared with the PRGF-Endoret Kit. Methods Leukocyte-poor PRP samples from seventeen healthy volunteers were prepared using the PRGF-Endoret Kit and the PRGF IV System Centrifuge. The platelet and leukocyte concentrations were compared based on the preparer’s experience. The concentrations of platelets, hepatocyte growth factor (HGF), platelet-derived growth factor-BB (PDGF-BB), and insulin-like growth factor-1 (IGF-1) were determined at 0 and 60 min after PRP preparation, and compared. Concentrations of the above growth factors from PRP activated by freeze–thaw cycling and by calcium chloride (CaCl2) were also compared. Results No significant difference was observed in the platelet concentrations and leukocyte contamination rates, based on the preparer’s experience. At 60 min after PRP preparation, the platelet concentration decreased significantly, while the HGF, PDGF-BB, and IGF-1 concentrations remained unchanged. Activation with CaCl2 resulted in a significant increase in the PDGF-BB levels, although the HGF and IGF-1 concentrations remained unchanged. Conclusions The results of this study show that leukocyte-poor PRP prepared using the PRGF-Endoret Kit did not result in any qualitative difference that depended on the experience of the preparer. However, PRP preparation required standardization in terms of the time of blood count measurement. Growth factor concentrations in PRP differed according to the platelet-activation method used.

Abstract Introduction Xanthoma disseminatum is a very rare disease classified as a benign non-Langerhans cell histiocytosis, which is rarely associated with osteoarticular lesions. There is only a report of tumor abrasion during treatment of osteoarticular lesions of this disease, artificial joint replacement has not been reported. We describe a patient in whom bilateral total joint replacement was performed for disseminated xanthoma lesions of the hip joints. Case presentation A 34-year-old Japanese woman had a chief complaint of bilateral coxalgia. She had been diagnosed as having disseminated xanthoma. Radiographs showed numerous 5-mm radiolucent bands that resembled worm-eaten tracks in the lower part of the femoral heads adjacent to the joint surface. In addition, short tau inversion recovery imaging scans showed high-intensity areas from the femoral head to the neck in both femurs, suggesting bone marrow edema. Total hip arthroplasty was performed for hip arthrosis on both hip joints caused by disseminated xanthoma. Deflection of the implants was a concern from the early stages postoperatively, but both the imaging and clinical findings have been satisfactory for 4 years of follow-up. Conclusions A very unusual hip joint lesion of xanthoma disseminatum was replaced with a total artificial joint replacement, and the course over 4 years was good. Our patient’s course will continue to be followed carefully.

Abstract Background Clinical application of platelet-rich-plasma (PRP) has been accelerated to investigate early recovery from various musculoskeletal conditions. It involves the promotion of tissue damage repair through the action of multiple growth factors at physiological concentrations. The composition of PRP differs based on many factors, which may include age and gender. Therefore, we analyzed correlations between age, gender, and platelet counts in PRP with growth factors in Japanese subjects. Method Peripheral blood was drawn from 39 healthy volunteers between 20 and 49 years of age (age, mean ± standard deviation = 33 ± 8.7 years; gender ratio, male:female = 19:20; BMI, mean ± standard deviation = 22 ± 4.0) and prepared through centrifugation (volume, 6 mL per sample). After being activated with CaCl2, the supernatant was stored. The mean platelet count in PRP was 41.4 ± 12.2 × 104/μL. PRP concentration rate (i.e., PRP/peripheral platelet counts) was 1.8 ± 0.4 times. Growth factor levels (platelet-derived growth factor-BB, transforming growth factor-β1, vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor, insulin-like growth factor-1, and hepatocyte growth factor) were measured using enzyme-linked immunosorbent assay (ELISA), and correlations with age, gender, and PRP platelet counts were statistically analyzed by calculating Spearman’s rank correlation coefficients (r). Results Age was negatively correlated with platelet-derived growth factor-BB and insulin-like growth factor-1 (r = − 0.32, − 0.39), and gender had no influence on growth factors. Platelet counts in PRP positively correlated with platelet-derived growth factor-BB, transforming growth factor-β1, epidermal growth factor, and hepatocyte growth factor (r = 0.39, 0.75, 0.71, and 0.48, respectively). Conclusions This clinical study shows a significant variation of PRP among individual patients and that this variation is influenced by the age and the platelet counts of the subjects. Our data demonstrate that patient characteristics account for the differences in PRP physiological activity.

Background: Preventing and reducing frailty is an important challenge for Japan in the next decade, especially in metropolitan areas. We launched a community-wide intervention trial (the Ota Genki Senior Project) in 2016 to develop effective community-based strategies for frailty prevention in metropolitan areas. This report describes the study design and baseline survey. Methods: This study is a community-wide intervention trial that integrates participatory action research into a cluster non-randomized controlled trial for adults aged 65 years or older living in Ota City, Tokyo. We allocated 3 of 18 districts to an intervention group and the other 15 to a control group. Using a mailed self-administered questionnaire, we conducted a baseline survey of 15,500 residents (8,000 and 7,500 in the intervention and control groups, respectively) from July through August 2016. In addition to socioeconomic status and lifestyle variables, we assessed frailty status (primary outcome) and physical, nutritional, and psychosocial variables (secondary outcomes). Based on the baseline findings, an intervention to improve outcomes will be implemented as participatory action research. Follow-up surveys will be conducted in the same manner as the baseline survey. Results: A total of 11,925 questionnaires were returned (76.9% response rate; 6,105 [76.3%] and 5,820 [77.6%] in the intervention and control groups, respectively), and 11,701 were included in the analysis (mean age, 74.3 [standard deviation, 5.5] years; 48.5% were men). Conclusions: This study is expected to contribute to development of a prototype of a community-wide frailty prevention strategy, especially in metropolitan areas in Japan. Trial registration: UMIN Clinical Trials Registry (UMIN000026515).

Background: Poor subpleural perfusion (PSP) on dual-energy computed tomography (DE-CT) suggests microvasculopathy in chronic thromboembolic pulmonary hypertension (CTEPH). However, whether the microvasculopathy findings are equivalent to those in pulmonary arterial hypertension (PAH) remains unclear. The aim of this study was to elucidate the characteristics of microvasculopathy in CTEPH compared to those of that in PAH. Methods: We retrospectively reviewed subpleural perfusion on DE-CT and the hemodynamics of 23 patients with PAH and 113 with inoperable CTEPH. Subpleural perfusion on DE-CT was classified as poor (subpleural spaces in all segments with little or no perfusion) or normal. Results: PSP was observed in 51% of patients with CTEPH and in 4% of those with PAH (p < 0.01). CTEPH patients with PSP had poorer baseline hemodynamics and lower diffusing capacity for carbon monoxide divided by the alveolar volume (DLCO/VA) than those with CTEPH with normal perfusion (pulmonary vascular resistance [PVR]: 768 ± 445 dynes-sec/cm5 vs. 463 ± 284 dynes-sec/cm5, p < 0.01; DLCO/VA, 60.4 ± 16.8% vs. 75.9 ± 15.7%, p < 0.001). Despite the existence of PSP, hemodynamics improved to nearly normal in both groups after balloon pulmonary angioplasty. Conclusions: PSP on DE-CT, which is one of the specific imaging findings in CTEPH, might suggest a different mechanism of microvasculopathy from that in PAH.

Clinical guidelines including those set by the US Institute of Medicine, have based optimal gestational weight gain (GWG) on maternal pre-pregnancy body mass index (BMI), but have not considered the role of environmental toxicants such as heavy metals that can disrupt these processes. This study designed to determine optimal GWG ranges in women grouped according to BMI, and to assess whether blood concentrations of heavy metals alter the relationships between GWG and outcomes. A total of 103,060 participants in the Japan Environment and Children’s Study recruited between 2011 and 2014 were followed until their children reached 3 years of age. Outcomes included 1 min Apgar score 5.21 ng/g and overweight women with Hg 3.67–5.21 ng/g, Pb > 7.31 ng/g and Cd > 0.66 ng/g had null effects. Heavy metals can modify the associations between GWG and outcomes, particularly for underweight and overweight women. Because of the complex interactions of environmental toxicants with pre-pregnancy BMI, GWG and adverse outcomes, GWG guidelines should be interpreted cautiously. Environmental toxicants may influence the determination of a clinical guideline.

The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension has been suggested. Recently, dual-energy computed tomography has been used to produce a sensitive iodine distribution map in lung fields to indicate microvasculopathy according to poor subpleural perfusion. Our aim was to evaluate the impact of microvasculopathy on pathophysiology in chronic thromboembolic pulmonary hypertension. According to the extent of poor subpleural perfusion, ninety-three interventional treatment-naïve patients were divided into poorly perfused ( n = 49) or normally perfused group ( n = 44). We assessed cardiopulmonary exercise test, right heart catheterization, and dual-energy computed tomography parameters for quantitative evaluation of lung perfusion of blood volume score. Lung perfusion of blood volume score in normally perfused group was significantly inversely correlated with pulmonary vascular resistance (pulmonary vascular resistance = 6816.1 × lung perfusion of blood volume score −0.793 , R 2 = 0.225, p

We report the cases of two patients with life-threatening acute pulmonary embolism (PE) on chronic thromboembolic pulmonary hypertension (CTEPH) who were treated with rescue balloon pulmonary angioplasty (BPA). These cases highlight the effect of rescue BPA on acute PE on CTEPH, which requires veno-arterial extracorporeal membrane oxygenation.

BackgroundThe relationship between allergic individuals and their responsiveness to routine vaccines has rarely been investigated. This study examined whether the seroprevalence of measles antibody differed between children with and without allergic diseases in the general pediatric population.MethodsThe cross-sectional study was performed within a prospective general birth cohort (a pilot study of the Japan Environment & Children's Pilot Study [JECS]) of children aged 8 years. The clinical history of allergic diseases, measles, and the concentration of measles immunoglobulin G titers in serum enzyme immunoassay were examined. Fisher's exact tests were used to assess the relationships between the allergic characteristics of the children and their measles antibody positivity rates.ResultsThis study included 162 children. Any allergic disease was reported in 75 (46.3%). The measles antibody positivity rate was 94.7% among children with any allergic diseases and 92.0% among children without allergic diseases. Our results revealed no differences in measles antibody seropositivity between children with allergies and controls.ConclusionsChildren with allergies mount and maintain a comparable immune response to the measles vaccine.

OBJECTIVES:No previous study has used repeated measures data to examine the associations of dog/cat ownership with wheezing and asthma prevalence among children. This prospective study used repeated measurers analysis to determine whether dog/cat ownership in childhood is an independent risk factor for wheezing and asthma, after adjustment for gestational, socio-economical, and demographical confounders confounders, in Japan. METHODS:We conducted a multicenter pilot study of the Japan Environment and Children's Study (JECS) during 2009-2010. Among 440 newborn infants enrolled, 410 (52.8% males) were evaluated for dog/cat ownership in the home and history of wheezing and asthma in five follow-up questionnaire surveys (until age 6 years). Dog/cat ownership during follow-up period was categorized into four groups: 7.6% were long-term dog/cat owners, 5.9% were toddler-age owners, 5.9% were preschool-age owners, and 80.7% were never owners. RESULTS:The prevalence of wheezing during follow-up period increased from 20.8% to 35.4% and the prevalence of asthma increased from 1.3% to 16.3%. A fitted logistic generalized estimating equation models including important confounders showed no significant associations of the interaction between dog and/or cat ownership and follow-up time with the risks of wheezing and asthma. However, the risks of wheezing and asthma were slightly lower for long-term and toddler-age dog/cat owners than for preschool-age and never owners. CONCLUSIONS:The present findings suggest that dog and cat ownership from toddler-age does not increase the risks of wheezing and asthma compared with never owners among Japanese children.

Pulmonary arterial hypertension can be associated with exposure to certain drugs or toxins. However, only a few cases of drug-induced pulmonary arterial hypertension have been previously reported. Anagrelide is an oral imidazoquinazoline agent that is prescribed for reducing elevated platelet counts in patients with myeloproliferative disorders. We report the case of a 70-year-old female patient who developed pulmonary arterial hypertension after taking anagrelide for the treatment of polycythemia vera. Pulmonary arterial hypertension promptly improved after the discontinuation of anagrelide. Anagrelide-induced pulmonary arterial hypertension is a very rare disease, and our case shows that it might be reversible.

Abstract Background Informal neighbor relationships (NRs) are considered a structural aspect of social relationships. Although NRs might affect physical activity (PA), no previous study has simultaneously examined compositional and contextual associations of NRs with PA. In this study, we examined whether individual- and community-level NRs were independently associated with PA. Methods We analyzed cross-sectional data from 8592 (4340 men and 4252 women) non-disabled residents aged 65–84 years from all 18 districts of Ota City, Tokyo. PA was assessed by using the International Physical Activity Questionnaire-Short Form. In addition, we calculated moderate-to-vigorous PA (MVPA), its components (vigorous PA [VPA], moderate PA [MPA], and walking time [WT]), and sitting time (ST). Individual-level NRs were categorized as “visiting each other,” “standing and chatting,” “exchange of greetings,” or “none.” Community-level NRs were defined as the proportions of residents with active NRs (i.e., those in the categories visiting each other and standing and chatting) in the 18 districts. Using multilevel regression analyses, we examined independent associations of individual- and community-level NRs with PA variables and adjusted for important confounders. Results Individual-level NRs were consistently positively associated with MVPA and its components (VPA, MPA [in men], and WT) in both sexes, and the dose–response relationships were significant (all P < 0.041 for trend). In men, community-level NRs (by 1% estimation) were positively associated with individual MVPA (2.1 metabolic equivalent-hours/week, 95% confidence interval: 0.7–3.4), VPA (8.6 min/week, 2.7–14.4), and WT (11.6 min/week, 2.2–20.9), regardless of the degree of individual-level NRs. Significant cross-level interactions of NRs with MVPA and VPA were observed among men, and the dose–response relationships were significant (both P

Abstract Background Maintenance or restoration of a good range of motion of the knee is one of the most important outcomes following knee surgery. According to previous studies, opening wedge high tibial osteotomy enables better recovery of range of motion in knee flexion than that achievable after total knee arthroplasty or unicompartmental knee arthroplasty. However, few reports provide a detailed description of the postoperative recovery of knee extension range of motion after opening wedge high tibial osteotomy. We describe our experience with a knee extension training program using a single-joint hybrid assistive limb device (HAL-SJ; Cyberdyne Inc., Tsukuba, Japan) during the acute recovery phase after opening wedge high tibial osteotomy. The HAL-SJ is a wearable robotic device that facilitates voluntary control of knee joint motion. Case presentation A 67-year-old Japanese woman who underwent opening wedge high tibial osteotomy for spontaneous osteonecrosis of the left medial femoral condyle received HAL-SJ-based knee extension training postoperatively. Our experience with this patient revealed that knee extension training with the HAL-SJ during the acute phase following opening wedge high tibial osteotomy is feasible. Furthermore, the patient’s knee extension range of motion improved to values similar to those seen during the preoperative stage, and her flexion range of motion was improved at 3 months after the surgery. Conclusions HAL-SJ-based knee extension training could be used as a novel post-opening wedge high tibial osteotomy rehabilitation modality. Further exploration of individualized optimal settings of the HAL-SJ is required to improve its safety and efficacy.

Background: Although apolipoprotein E polymorphism ε4 allele (ApoE4) and slow gait are well-known risk factors for cognitive impairment, examination of their combined effect on cognitive function is lacking. Our objective was to elucidate whether a combination of ApoE4 phenotyping and slow gait resulted in greater cognitive impairment.Methods: Overall, 1,085 community-dwelling older adults, either ApoE4 carriers (n = 167, 15.4%) or non-ApoE4 carriers, were included from the “Takashimadaira study.” Gait speed was assessed with an electronic walkway and slow gait was defined as

Reperfusion pulmonary edema (RPE) is a common complication after pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, the precise mechanisms underlying the development of RPE remain unclear. To evaluate the effects of pulmonary vasculopathy on RPE, the severity of the pulmonary arteriopathies and venopathies of lung tissues biopsied during PEA were pathologically quantified in 33 CTEPH patients. The severity of RPE was classified from grade 0 (no RPE) to 4 (death due to RPE) based on the arterial oxygen tension/inspiratory oxygen fraction (P/F ratio) and necessity of respiratory management. Among the 33 patients (27 women; mean age = 63.3 years), 17 (51.5%) patients developed RPE. The severity of pulmonary arteriopathy (obstruction ratio) correlated with the grade of RPE (r = 0.576, P = 0.0005). The obstruction ratio also correlated with the P/F ratio (r = −0.543, P = 0.001) and the perioperative mean pulmonary arterial pressure (r = 0.445, P = 0.009). Multivariate logistic regression analysis revealed that the obstruction ratio was a significant independent determinant for the development of RPE (odds ratio = 15.7; 95% confidence interval = 2.29–108.00, P = 0.005). In conclusion, pulmonary arteriopathy could be a determinant of the development and severity of RPE after PEA.

OBJECTIVES:Recent studies reported that several gait parameters were associated with lower cognitive function or cognitive decline, however, known gait parameters were limited and no study has used large-scale data. We identified the characteristics for gait parameters of community-dwelling elderly Japanese with lower cognitive function. METHODS:1,240 community-dwelling adults (mean [SD] age, 77.2 [4.8] years; women, 59.4%) aged 70 or older participated in geriatric health assessments in 2016. We measured comprehensive gait parameters using resistive pressure platform. Cognition was assessed by Mini-Mental State Examination (MMSE). RESULTS:There are possible correlations between gait measures (gait speed, stride length, step length, step width, average foot pressure, double support duration, and single support duration) and CVs (CV of stride length, step length, average foot pressure, and single support duration) with MMSE score, respectively. After adjustment for important confounders, multiple regression models showed that gait speed (β = .080, p = 0.006), stride length (β = .123, p

[This corrects the article DOI: 10.1371/journal.pone.0206399.].

Prenatal exposure to methylmercury (MeHg) affects child development after birth. However, many epidemiological studies have evaluated total mercury levels without analyzing speciation. Biomonitoring of MeHg and inorganic mercury (IHg) is essential to reveal each exposure level. In this study, we compared a high-throughput analysis for mercury speciation in blood using liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS) and liquid chromatography-cold vapor atomic fluorescence spectrometry (LC-CVAFS). The validated LC-ICP-MS method was applied to 101 maternal blood and 366 cord blood samples in the pilot study of the Japan Environment and Children’s Study (JECS). The accuracy of the LC-CVAFS method ranged 90–115% determined by reference material analysis. To evaluate the reliability of 366 cord blood samples, fifty cord blood samples were randomly selected and analyzed using LC-CVAFS. The median (5th–95th percentile) concentrations of MeHg and IHg were 5.4 (1.9–15) and 0.33 (0.12–0.86) ng/mL, respectively, in maternal blood, and 6.3 (2.5–15) and 0.21 (0.08–0.49) ng/mL, respectively, in cord blood. Inter-laboratory comparison showed a relatively good agreement between LC-ICP-MS and LC-CVAFS. The median cord blood:maternal blood ratios of MeHg and IHg were 1.3 and 0.5, respectively. By analyzing speciation, we could focus on the health effects of each chemical form.