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Background Stress coping strategies are related to health outcomes. However, there is no clear evidence for sex differences between stress-coping strategies and mortality. We investigated the relationship between all-cause mortality and stress-coping strategies, focusing on sex differences among Japanese adults. Methods A total of 79,580 individuals aged 35-69 years participated in the Japan Multi-Institutional Collaborative Cohort Study between 2004 and 2014 and were followed up for mortality. The frequency of use of the five coping strategies was assessed using a questionnaire. Sex-specific, multivariable-adjusted hazard ratios (HRs) for using each coping strategy "sometimes," and "often/very often" (versus "very few" use) were computed for all-cause mortality. Furthermore, relationships were analyzed in specific follow-up periods when the proportion assumption was violated. Results During the follow-up (median: 8.5 years), 1,861 mortalities were recorded. In women, three coping strategies were related to lower total mortality. The HRs (95% confidence intervals) for "sometimes" were 0.81 (0.67-0.97) for emotional expression, 0.79 (0.66-0.95) for emotional support-seeking, and 0.80 (0.66-0.98) for disengagement. Men who "sometimes" used emotional expression and sometimes or often used problem-solving and positive reappraisal had a 15-41% lower HRs for all-cause mortality. However, those relationships were dependent on the follow-up period. There was evidence that sex modified the relationships between emotional support-seeking and all-cause mortality (p for interaction = 0.03). Conclusions In a large Japanese population, selected coping strategies were associated with all-cause mortality. The relationship of emotional support-seeking was different between men and women.

BACKGROUND Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. METHODS Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). RESULTS We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. CONCLUSIONS The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

Background: Inflammation is thought to be a risk factor for kidney disease. However, whether inflammatory status is either a cause or an outcome of chronic kidney disease remains controversial. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using Mendelian randomization (MR) approaches. Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively. Results: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 0.000; 95% confidence interval [CI], −0.019 to 0.020 and −0.003; 95% CI, −0.019 to 0.014, respectively). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 0.005; 95% CI, −0.020 to 0.010 and −0.004; 95% CI, −0.020 to 0.012, respectively). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: −0.008; 95% CI, −0.058 to 0.042; IVAsian: 0.001; 95% CI, −0.036 to 0.036). Conclusion: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.

The glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) is an important molecule in neurotransmission. We have recently developed the first positron emission tomography (PET) tracer [11C]K-2 to visualize and quantify AMPARs in the living human brain. After injection, [11C]K-2 is hydrolyzed at the terminal amide (and is thus metabolized to a major metabolite, [11C]K-2OH) within 10 min, representing the PET image in rodents and humans. Here, we found that K-2OH did not penetrate the cell membrane but slowly passed through the blood brain barrier (BBB) with paracellular transport. Furthermore, major efflux transporters in the BBB did not carry K-2OH. Logan graphical analysis exhibited reversible binding kinetics of this radiotracer in healthy individuals; these results demonstrated that the PET image of this tracer represents cell surface AMPARs with passive penetration of [11C]K-2OH through the BBB, resulting in reversible binding kinetics. Thus, PET images with this tracer depict the physiologically crucial fraction of AMPARs.

Objective: To assess the utility of examining the nigrostriatal system with MRI and dopamine transporter (DAT) imaging for evaluating the preclinical phase of Parkinson’s disease (PD). Methods: The subjects were 32 patients with early PD and a history of probable rapid eye movement sleep behavior disorder (RBD; PD group), 15 patients with idiopathic RBD (RBD group), and 24 age-matched healthy controls (HC group) who underwent neuromelanin and diffusion tensor MRI for analysis of the substantia nigra pars compacta (SNpc). The RBD and PD groups underwent DAT imaging. In the RBD group, totals of 39 MRI and 27 DAT imaging examinations were obtained longitudinally. For each value, intergroup differences and receiver operating characteristic analysis for diagnostic performance were examined statistically. Results: The neuromelanin value was significantly lower and the diffusion tensor values except fractional anisotropy were significantly higher in the RBD and PD groups than in the HC group. The DAT specific binding ratio (SBR) was significantly lower in the PD group than in the RBD group. The areas under the receiver operating characteristic curves (AUCs) for neuromelanin/mean diffusivity value in the SNpc were 0.76/0.82 for diagnosing RBD and 0.83/0.80 for diagnosing PD. The area under the receiver operating characteristic curves for the SBR for discriminating PD from RBD was 0.87. Conclusion: MRI and DAT imaging may be useful for evaluating sequential nigrostriatal changes during the preclinical phase of PD. Advances in knowledge: MRI detects nigrostriatal changes in both RBD and early PD, and DAT imaging detects nigrostriatal changes during the transition to PD in RBD.

BACKGROUND: Low-level laser therapy (LLLT) and human amniotic membrane (HAM) application have been shown to be viable options for use in wound healing. PURPOSE: This study sought to compare LLLT and HAM to a control treatment (hydrogel, saline, and gauze) in persons with diabetes mellitus (DM) and foot ulcers. METHODS: Using a prospective pilot clinical study design, patients receiving care at a health center that specializes in the treatment of diabetic foot wounds between November 2016 and August 2017 were recruited. Eligible patients had to be 30 to 59 years of age; diagnosed with type 2 DM (postprandial capillary glucose levels between 140 and 350 mg/dL); and have uninfected, granulating stage 2 or 3 foot ulcers measuring less than 7 cm by 3 cm. Immunosuppressed and malnourished patients or those with neoplasms or in critical condition were not eligible to participate. Patients received the control treatment (2 mg hydrogel, saline, and gauze), HAM (patches of thawed HAM, applied with overlapping edges), or LLLT (phototherapy session, 2 mg hydrogel, saline, and gauze) for 28 days. Variables, wound area measurements, Pressure Ulcer Scale for Healing (PUSH) scores, and Visual Analog Scale (VAS) scores were used to assess wound improvement progress and pain on days 7, 14, 21, and 28. Descriptive statistics were used to analyze the participant anthropometric and clinical profiles. The Kolmogorov-Smirnov test was used to analyze the sample distribution. The Kruskal-Wallis test with Dunn’s post-test was used to evaluate differences in PUSH and VAS scores and wound size for intergroup analysis, and the Mann-Whitney U test was used for the same outcomes in intragroup analysis. The level of significance was 5% (P < .05). RESULTS: Twenty-seven (27) patients participated (mean age, 51.4 years; mean body mass index, 26.5 kg/m2), with 9 patients in each treatment group. No statistically significant differences were noted in clinical or anthropometric variables among the groups, but mean baseline wound areas were different (2.6 cm² for the control, 1.9 cm² for the LLLT, and 5.5 cm² for the HAM groups). Intragroup comparisons showed a significant reduction in PUSH score in the LLT group between days 0 and 21 (8.2 vs 4.9; P < .01) and days 21 to 28 (4.9 vs 3.2; P < .001). In all treatment groups the percent reduction was significantly different between days 7 and 28. No outcomes were significantly different between groups. CONCLUSION: Diabetic foot ulcer wound area as well as PUSH and VAS scores showed more improvement for patients with DM receiving LLLT or HAM than for the control group, but the differences were not significant. Larger studies are needed to compare these treatment modalities.

Ethambutol-induced optic neuropathy (EON) is a well-known complication, although low-dose ethambutol seldom causes EON. An 85-year-old man with non-tuberculous mycobacterial lung disease was taking antibiotics, including low-dose ethambutol. On day 85 of treatment, the diagnosis of EON was made. Despite prior discontinuation, his best corrected visual acuity drastically deteriorated from 20/17 (right eye) and 20/20 (left eye) to 20/330 (right eye) and 20/1,000 (left eye) within 3 weeks, and this symptom did not resolve. To our knowledge, there have been no reported cases with drastically progressing and irreversible EON even after the withdrawal of low-dose and short-term ethambutol.

Background/aim Indoleamine 2,3-dioxygenase (IDO) is regarded as an important molecular target for cancer immune therapy. This study aimed to examine the IDO1 inhibitory activity of newly synthesized indomethacin derivatives to develop an IDO1 inhibitor. Materials and methods The inhibitory effects of indole-containing compounds against recombinant human IDO1 (rhIDO1) were evaluated. Results While some drugs including those with an indole scaffold could inhibit rhIDO1, simple indole compounds were inactive. A total of 27 indomethacin derivatives, including 18 newly synthesized derivatives, were evaluated. Numerous derivatives showed enhanced IDO1 inhibitory activity. The functional group at the 3-position had a strong effect on IDO1 inhibitory activity. The IDO1 inhibitory activity was not directly correlated with tumor cell cytotoxicity. Conclusion We report the finding of novel IDO1 inhibitors and the structure-activity relationship based on indomethacin derivatives. Our findings will be beneficial for the development of IDO1 inhibitors for cancer immune therapy.

Objective: This study was designed to clarify the association of the MAFK polymorphisms (rs4268033, rs3735656, and rs10226620) with the degree of gastric mucosal atrophy and CDKN2A CpG methylation ...

BackgroundIn preoperative embolization for intracranial meningioma, endovascular intratumoral embolization is considered to be more effective for the reduction of tumorous vascularity than proximal feeder occlusion. In this study, we aimed to reveal different efficacies for reducing tumor blood flow in meningiomas by comparing endovascular intratumoral embolization and proximal feeder occlusion using dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI).Methods28 consecutive patients were included. DSC-PWI was performed before and after embolization for intracranial meningiomas. Normalized tumor blood volume (nTBV) of voxels of interest of whole tumors were measured from the DSC-PWI data before and after embolization. ΔnTBV% was compared between the cases that received intratumoral embolization and proximal feeder occlusion.ResultsΔnTBV% in the intratumoral embolization group (42.4±29.8%) was higher than that of the proximal feeder occlusion group (15.3±14.3%, p=0.0039). We used three types of embolic materials and ΔnTBV% did not differ between treatments with or without the use of each material: 42.8±42.4% vs 28.7±20.1% for microspheres (p=0.12), 36.1±20.6% vs 28.1±41.1% for n-butyl cyanoacrylate (p=0.33), and 32.3±37.3% vs 34.1±19.0% for bare platinum coils (p=0.77).ConclusionsThe flow reduction effect of intratumoral embolization was superior to that of proximal feeder occlusion in preoperative embolization for intracranial meningioma in an assessment using DSC-PWI.

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two‐sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome‐wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP‐BMI associations, we undertook a meta‐analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J‐CGE), comprising normal populations. For the analysis of SNP‐CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta‐analysis. Mendelian randomization analysis of inverse‐variance weighted method indicated that a one‐unit (kg/m2) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06‐1.20; P value, Traditional observational studies reported a positive association between higher body mass index (BMI) and colorectal cancer (CRC) risk. However, these studies suffer from biases such as reverse causality and confounding. This Mendelian randomization study consistently showed that the genetically predicted higher BMI was associated with an increased risk of CRC in Japanese populations.

Background: While duodenal ulcer (DU) and gastric cancer (GC) are both H. pylori infection-related diseases, individuals with DU are known to have lower risk for GC. Many epidemiological studies have identified the PSCA rs2294008 T-allele as a risk factor of GC, while others have found an association between the rs2294008 C-allele and risk of DU and gastric ulcer (GU). Following these initial reports, however, few studies have since validated these associations. Here, we aimed to validate the association between variations in PSCA and the risk of DU/GU and evaluate its interaction with environmental factors in a Japanese population. Methods: Six PSCA SNPs were genotyped in 584 DU cases, 925 GU cases, and 8,105 controls from the Japan Multi-Institutional Collaborative Cohort (J-MICC). Unconditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the SNPs and risk of DU/GU. Results: PSCA rs2294008 C-allele was associated with per allele OR of 1.34 (95% CI, 1.18–1.51; P = 2.28 × 10−6) for the risk of DU. This association was independent of age, sex, study site, smoking habit, drinking habit, and H. pylori status. On the other hand, we did not observe an association between the risk of GU and PSCA SNPs. Conclusions: Our study confirms an association between the PSCA rs2294008 C-allele and the risk of DU in a Japanese population.

[11C]K-2, a radiotracer exhibiting high affinity and selectivity for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), is suitable for the quantification of AMPARs in living human brains and potentially useful in the identification of epileptogenic foci in patients. This study aimed to estimate the radiation doses of [11C]K-2 in various organs and calculate the effective dose after injection of [11C]K-2 in healthy human subjects. Twelve healthy male subjects were registered and divided into two groups (370 or 555 MBq of [11C]K-2), followed by 2 h whole-body scans. We estimated the radiation dose of each organ and then calculated the effective dose for each subject. The highest uptake of [11C]K-2 was observed in the liver, while the brain also showed relatively high uptake. The urinary bladder exhibited the highest radiation dose. The kidneys and liver also showed high radiation doses after [11C]K-2 injections. The effective dose of [11C]K-2 ranged from 5.0 to 5.2 μSv/MBq. Our findings suggest that [11C]K-2 is safe in terms of the radiation dose and adverse effects. The injection of 370–555 MBq (10 to 15 mCi) for PET studies using this radiotracer is applicable in healthy human subjects and enables serial PET scans in a single subject.

Individual eating habits may be influenced by genetic factors, in addition to environmental factors. Previous studies suggested that adherence to Japanese food patterns was associated with a decreased risk of all-cause and cardiovascular disease mortality. We conducted a genome-wide association study (GWAS) in a Japanese population to find genetic variations that affect adherence to a Japanese food pattern. We analyzed GWAS data using 14,079 participants from the Japan Multi-Institutional Collaborative Cohort study. We made a Japanese food score based on six food groups. Association of the imputed variants with the Japanese food score was performed by linear regression analysis with adjustments for age, sex, total energy intake, alcohol intake (g/day), and principal components 1–10 omitting variants in the major histocompatibility region. We found one SNP in the 14q11.2 locus that was significantly associated with the Japanese food score with P values

To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. We detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improve the clinical characterization of CAD genetics and suggest the utility of trans-ancestry meta-analysis for PRS derivation in non-European populations.

Background CpG methylation of tumor suppressor genes occurs in the early stage of carcinogenesis. Detecting risk factors for aberrant CpG methylation is clinically important for predicting cancer development. DNA methyltransferase (DNMT) 3a is considered to play critical roles in the DNA methylation process during pathogenesis. In this study, we evaluated the association between DNMT3A polymorphisms (rs6733868 and rs13428812) and CpG methylation status in non-cancerous gastric mucosa. Methods We determined the DNMT3A genotype and CpG methylation status of 4 genes (p14ARF, p16INK4a, DAPK, and CDH1) in 510 subjects without gastric cancer. Helicobacter pylori (HP) infection status was determined by the rapid urease test, urea breath test, speculum examination, or serum antibody test. We determined the DNMT3A genotype using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). CpG methylation status was determined by methylation-specific polymerase chain reaction (MSP). When the methylated band was stronger than 10 ng/μL according to the DNA marker, we judged CpG island hypermethylation (CIHM) to be present. Associations between genotypes and susceptibilities were assessed by logistic regression analysis. Results The minor allele frequencies of both polymorphisms (rs6733868 and rs13428812) were lower in the CpG methylated groups of each of the 4 genes (p14ARF, p16INK4a, DAPK, and CDH1). Using a dominant genetic model, rs6733868 was significantly associated with the hypermethylation of each gene, whereas rs13428812 was associated with the methylation of 3 genes (all except p14ARF). When low-CIHM was defined as 1 or 2 CpG islands methylated and high-CIHM was defined as 3 or more CpG islands methylated, carrying the minor allele of rs6733868 was associated with both decreased low- and high-CIHM, and that of rs13428812 also was associated with a decrease. Comparing low-CIHM with high-CIHM, carrying the minor alleles of rs6733868 or rs13428812 was related to decreased susceptibility to high-CIHM. In HP-infected subjects, carrying the minor alleles of rs6733868 or rs13428812 had a significantly greater association with decreased susceptibility to high-CIHM. Conclusions Our study indicates that polymorphisms of DNMT3A are associated with the accumulation of gene methylation in gastric mucosa. Carrying the minor alleles of rs6733868 or rs13428812 inhibits aberrant gene methylations, which are typically enhanced by HP infection.

There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B12 as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B12, and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41–3.96) in men and 1.86 (95% CI 1.11–3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B12 was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B12.

Summary Introduction Bone defect reconstruction in orbital wall fractures with absorbable alloplastic such as the unsintered hydroxyapatite and poly L-lactide composite (u-HA/PLLA) system is gaining popularity. The u-HA/PLLA material has osteoconductive and osteosynthetic properties. However, quantitative, long-term outcome data after the use of u-HA/PLLA for orbital wall fractures are lacking. Patients and Methods We retrospectively analyzed 115 patients who underwent surgical repair of orbital wall fractures with a u-HA/PLLA sheet from 2011 to 2016. A chart review was performed, and the time-dependent changes at fracture sites were assessed by imaging. The immediate postoperative and the latest follow-up bony orbital volumes of the affected side were compared. Results Seventy patients were eligible for this study (mean age, 44.6 ± 22.1 years; 48 men and 22 women; mean follow-up period, 29.7 ± 12.8 months). Except for one case of hematoma, there were no postoperative wound complications. Of the 70 patients, 10 had postoperative diplopia and 2 had enophthalmos; these conditions were presumably caused by the extension and severity of the fracture. Satisfactory reduction in the entire orbital wall, without pathological changes, was demonstrated. There were no significant differences in the mean bony orbital volumes of the affected side immediately after surgery (24.774 ± 3.092 cm3) and at the latest follow-up (24.749 ± 3.205 cm3) (p = 0.756). Conclusion The u-HA/PLLA sheet is useful for orbital wall fracture reconstruction because of its desirable handling characteristics, initial mechanical strength, long-term maintenance of structural stability, radiopacity, and few associated complications. Future randomized controlled trials need to be performed to compare u-HA/PLLA with other conventional materials.

Background Little is known about whether insufficient moderate-to-vigorous physical activity (MVPA) and longer sedentary behavior (SB) are independently associated with estimated glomerular filtration rate (eGFR) and CKD, whether they interact with known risk factors for CKD, and the effect of replacing sedentary time with an equivalent duration of physical activity on kidney function. Methods We examined the cross-sectional association of MVPA and SB with eGFR and CKD in 66,603 Japanese cohort study in 14 areas from 2004 to 2013. MVPA and SB were estimated using a self-reported questionnaire, and CKD was defined as eGFR Results After adjusting for potential confounders, higher MVPA and longer SB were independently associated with higher eGFR (Pfor trend MVPA Conclusions These findings indicate that replacing SB with physical activity may benefit kidney function, especially in men, adding to the possible evidence on CKD prevention.

Although bone is the second-most frequent site of distant metastases of head and neck squamous cell carcinoma (HNSCC), variable prognostic factors in patients with bone metastases from HNSCC have not been fully investigated. The aim of the present study was to assess the prognostic factors affecting overall survival (OS) in these patients. The medical records of 97 patients at two institutions who developed bone metastases from HNSCC between January 2010 and December 2020 were retrospectively reviewed. A multivariate analysis using a Cox proportional hazards model was performed to identify potential clinical predictive factors for longer OS. The median OS was 7 months, and the 1- and 2-year OS rates for all patients were 35.4 and 19.2%, respectively. The independent predictive factors for longer OS were single bone metastasis, good performance status and administration of systemic chemotherapy. The median OS with each predictor was 10, 10 and 10.5 months, respectively. In a selected group of patients with these three factors, the OS was 14.5 months. In conclusion, single bone metastasis, a good performance status and systemic chemotherapy were independent predictors of longer OS in patients with HNSCC, but their contributions were limited.

Context: Nowadays, people with paraplegia and quadriplegia have greater opportunities to venture into the general public. However, there is also an increased risk of associated hazards. Findings: This report describes a 42-year-old man with paraplegia, who was insensate below the T7 level and sustained burns from sitting on a gel wheelchair cushion that had been left on the driver-side seat of a hand control car on a sunny day. Physical examination revealed deep partial-thickness burns on both his buttocks. He underwent surgical debridement and received an autologous split-thickness skin graft, and healed well. Conclusion In modern times, the lives of people with paralysis are no longer restricted to the bed and wheelchair. Active people with spinal cord injuries inevitably diversify the use of wheelchair cushions in many ways; therefore, there is a greater possibility for the occurrence of associated hazards. This is a preventable issue, so both the user and manufacturers should recognize this potential hazard of gel wheelchair cushions.

Background Elbow injuries are common in young baseball players and evaluating the characteristics of young baseball players in a large-scale population is necessary. However, few studies have compared playing position, length of baseball experience, physical findings, and elbow pain in young baseball players. This retrospective multi-regional cohort study sought to document the physical findings at the elbow in Japanese elementary school baseball players and to examine the relationship between playing position, length of baseball experience, physical findings at the elbow, and elbow pain. Methods In 2014, 720 fifth-grade baseball players from four regions in Japan were invited to participate in a questionnaire survey and undergo physical examination to obtain data on position played, length of baseball experience, presence of elbow pain, and physical findings at the elbow, including range of motion, tenderness, and valgus stress test results. Potential risk factors associated with elbow pain and correlations between physical findings and playing position, length of baseball experience, and elbow pain were investigated. Results The 720 subjects had a mean age of 10.4 years and 29.4% reported having experienced elbow pain for ≥1 week. Risk factors for elbow pain included playing pitcher and catcher, playing pitcher and fielder, and length of baseball experience. The most frequent finding was limitation of flexion (21.1%) followed by tenderness of the medial epicondyle (18.3%) and a positive valgus stress test (14.3%). These three findings were also significantly associated with elbow pain. Elbow extension was limited in 14.9% of subjects but there was no correlation with length of baseball experience or elbow pain. Conclusions Our data show that elementary school baseball players who experienced elbow pain are likely to have valgus stress overload. Elbow pain might be prevented by not playing pitcher and catcher.

Development of extracranial carotid artery aneurysm (ECCA) after carotid endarterectomy (CEA) is a rare complication, occurring in connection with

Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P = 6.12 × 10−25 with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma.

Stroke results in impairment of basic motor functions, such as muscle weakness in limbs affected by spasticity, leading to peripheral fatigue and impaired functionality. The clinical use of photobiomodulation therapy (PBMT) has provided major advances in the treatment of muscular disorders and prevention of muscle fatigue. The aim of this study was to analyze the effects of two distinct therapies in biceps spasticity of chronic hemiparetic patients. We analyzed range of elbow motion, torque, electromyography, and mean spectral frequency after 10 sessions of PBMT (Laser 100 mW, 808 nm, 159.24 J/cm2/point, 5 J/point); PBMT active or placebo was associated with exoskeleton-assisted functional treatment. A double-blind placebo-controlled sequential clinical trial was conducted with 12 healthy volunteers and 15 poststroke patients who presented upper-limb spasticity. The healthy volunteers performed only the evaluation protocol, and the poststroke volunteers participated in three consecutive phases (PBMT, PBMT + exoskeleton, placebo + PBMT) with a washout period of 4 weeks between each phase. We could observe significant increases in range of elbow motion after PBMT from 57.7 ± 14 to 84.3 ± 27.6 degrees (p < 0.001). The root mean square (RMS) values also increased after PBMT + exoskeleton from 23.2 ± 15 to 34.9 ± 21 μV (p = 0.0178). Our results suggest that the application of PBMT may contribute to an increased range of elbow motion and muscle fiber recruitment, increases in muscle strength, and, hence, to increase signal conduction on spastic muscle fibers in spastic patients.

Androgen receptor splice variant-7 (AR-V7) is a constitutively active AR variant implicated in castration-resistant prostate cancers. Here, we show that the RNA splicing factor SF3B2, identified by in silico and CRISPR/Cas9 analyses, is a critical determinant of AR-V7 expression and is correlated with aggressive cancer phenotypes. Transcriptome and PAR-CLIP analyses revealed that SF3B2 controls the splicing of target genes, including AR, to drive aggressive phenotypes. SF3B2-mediated aggressive phenotypes in vivo were reversed by AR-V7 knockout. Pladienolide B, an inhibitor of a splicing modulator of the SF3b complex, suppressed the growth of tumors addicted to high SF3B2 expression. These findings support the idea that alteration of the splicing pattern by high SF3B2 expression is one mechanism underlying prostate cancer progression and therapeutic resistance. This study also provides evidence supporting SF3B2 as a candidate therapeutic target for treating patients with cancer. Significance: RNA splicing factor SF3B2 is essential for the generation of an androgen receptor (AR) variant that renders prostate cancer cells resistant to AR-targeting therapy.

The aim of this study is to show the combined effect of weight gain within normal weight range in adulthood and parental HT on the prevalence of HT. The study subjects were 44,998 individuals (19,039 men and 25,959 women) with normal weight (body mass index [BMI] 18.5–24.9) aged 35–69 years who participated in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. They were categorized into six groups by weight gain from age 20 years (

ObjectiveThe first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout.MethodsWe carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia).ResultsThis new approach enabled us to identify two novel gout loci (rs7927466 of CNTN5 and rs9952962 of MIR302F) and one suggestive locus (rs12980365 of ZNF724) at the genome-wide significance level (p–8). The present study also identified the loci of ABCG2, ALDH2 and SLC2A9. One of them, rs671 of ALDH2, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three ‘gout vs AHUA GWAS’-specific loci (CNTN5, MIR302F and ZNF724) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level.ConclusionsThis meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals.

Introduction Allergen‐specific immunoglobulin isotype formation associated with immunoglobulin class‐switching during the lactation period is the immunological background for food allergy in infants. We analyzed the serial changes in the production of feeding type‐related egg‐ and milk‐specific immunoglobulin isotypes from birth to 6 months of age with or without eczema in 84 infants. Methods Allergen‐specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA, and IgE levels of hen's egg and bovine milk were measured in cord blood and blood samples from infants at 2, 4, and 6 months of age by the densely carboxylated protein microarray. Results Formula and mixed feeding were associated with a rapid increase in cow's milk allergen‐specific immunoglobulins and feeding type‐related significant differences in casein‐specific immunoglobulin levels were detected. Breast and mixed feeding were associated with slow but significant increase in ovalbumin‐specific IgG1 and IgE levels, but not other immunoglobulins. We found two different immunoglobulin isotype formation at 6 months of age with low‐ or high‐affinity IgE against ovalbumin. One isotype formation pattern had relatively high ovalbumin‐specific IgG1 levels, detectable IgG2, and low‐affinity IgE, while the other had low ovalbumin‐specific IgG1 levels, undetectable IgG2, and high levels of high‐affinity IgE. The incidence of eczema was significantly higher in the latter pattern (84.6%), compared with the remaining infants (42.2%). Conclusions Feeding practice‐related allergen sensitization and immunoglobulin isotype formation were identified during the lactation period. The development of eczema during the lactation period could potentially modify the immunoglobulin isotype formation with high levels of high‐affinity IgE.

Tools to control protein-protein interactions by external stimuli have been extensively developed. For this purpose, thermal stimulation can be utilized in addition to light. In this study, we identify a monoclonal antibody termed C13 mAb, which shows an approximately 480-fold decrease in the affinity constant at 37 °C compared to that at 4 °C. Next, we apply this temperature-dependent protein-peptide interaction for one-step protein purifications. We term this THermal-Elution-based TAg system as the THETA system, in which gel-immobilized C13 mAb-derived single-chain variable fragment (scFv) (termed THETAL) is able to bind with proteins tagged by C13 mAb-epitope(s) (THETAS) at 4 °C and thermally release at 37–42 °C. Moreover, to reveal the temperature-dependent interaction mechanism, molecular dynamics simulations are performed along with epitope mapping experiments. Overall, the high specificity and reversibility of the temperature-dependent features of the THETA system will support a wide variety of future applications such as thermogenetics., Kota Miura et al. develop the THermal-Elution-based TAg (THETA) system that allows one-step isolation of tagged proteins. The temperature-dependent protein-peptide interaction used in the THETA system ensures high specificity for protein purification.

Lymphoid papillary hyperplasia of the tonsils is a rare, benign lesion and is characterized by a papillomatous appearance with reactive follicular hyperplasia. Our case was unique because the lesion involved the unilateral and focal palatine tonsil, as the lesion usually involves the bilateral and entire palatine tonsils.

Chronic kidney disease (CKD) is a public health problem worldwide including Japan. Recent genome-wide association studies have discovered CKD susceptibility variants. We developed a genetic risk score (GRS) based on CKD-associated variants and assessed a possibility that the GRS can improve the discrimination capability for the prevalence of CKD in a Japanese population. The present study consists of 11 283 participants randomly selected from 12 Japan Multi-Institutional Collaborative Cohort Study sites. Individual GRS was constructed combining 18 single-nucleotide polymorphisms identified in a Japanese population. Participants with eGFR

This study aimed to investigate independent relationships of daily non-exercise life activity and leisure-time exercise volume and intensity with the prevalence of metabolic syndrome and its traits in Japanese adults. Data of 24,625 eligible subjects (12,709 men, 11,916 women) who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study were analyzed. Information about lifestyle characteristics was obtained from a questionnaire. Logistic regression analyses were performed to evaluate the independent associations of daily life activity as well as leisure-time exercise volume and intensity with the prevalence of metabolic syndrome and its traits by sex. Male subjects with higher daily life activity as well as with higher leisure-time exercise volume had a lower prevalence of metabolic syndrome, independently with each other. Female subjects with higher daily life activity also had a lower prevalence of metabolic syndrome. Particularly, male and female subjects with the highest daily life activity quartile showed considerably low odds ratios of 0.66 (95% CI, 0.53–0.81) and 0.64 (0.52–0.79), respectively, for low HDL-cholesterol even after the adjustment for BMI compared with the first quartile. Meanwhile, male subjects with the higher leisure-time exercise showed a quite lower prevalence of elevated triglycerides. Higher moderate-intensity exercise was more intensely associated with a lower prevalence of metabolic syndrome and some of its traits in both sexes. Our results suggest that higher daily life activity and higher moderate-intensity exercise may be independently associated with a lower risk of metabolic syndrome in Japanese adults.