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Abstract Background Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function. Methods This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models. Results The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p

Background: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants’ characteristics based on their participation type in the baseline survey. Methods: The second period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the second period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The second period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). Results: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the second period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the second period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. Conclusion: The second period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

Abstract Few population-based studies including younger adults have examined the potential of olfactory function tests to capture the degree of atrophy in memory-associated brain regions, which cannot be adequately explained by cognitive function tests screening for cognitive impairment. This population-based study investigated associations between high-resolution olfactory test data with few odours and grey matter volumes (GMVs) of the left and right hippocampi, amygdala, parahippocampi, and olfactory cortex, while accounting for differences in cognitive decline, in 1444 participants (aged 31–91 years). Regression analyses included intracranial volume (ICV)-normalised GMVs of eight memory-related regions as objective variables and age, sex, education duration, smoking history, olfaction test score, and the Montreal Cognitive Assessment-Japanese version (MoCA-J) score as explanatory variables. Significant relationships were found between olfactory test scores and ICV-normalised GMVs of the left and right hippocampi and left amygdala (p = 0.020, 0.024, and 0.028, respectively), adjusting for the MoCA-J score. The olfactory test score was significantly related to the right amygdalar GMV (p = 0.020) in older adults (age ≥ 65 years). These associations remained significant after applying Benjamini–Hochberg multiple testing correction (false discovery rate

Abstract Escherichia coli O157 can cause foodborne outbreaks, with infection leading to severe disease such as hemolytic-uremic syndrome. Although phage-based detection methods for E. coli O157 are being explored, research on their specificity with clinical isolates is lacking. Here, we describe an in vitro assembly-based synthesis of vB_Eco4M-7, an O157 antigen-specific phage with a 68-kb genome, and its use as a proof of concept for E. coli O157 detection. Linking the detection tag to the C-terminus of the tail fiber protein, gp27 produces the greatest detection sensitivity of the 20 insertions sites tested. The constructed phage detects all 53 diverse clinical isolates of E. coli O157, clearly distinguishing them from 35 clinical isolates of non-O157 Shiga toxin-producing E. coli. Our efficient phage synthesis methods can be applied to other pathogenic bacteria for a variety of applications, including phage-based detection and phage therapy.

Abstract Background Upper and lower extremity muscle strength can be used to predict health outcomes. However, the difference between the relation of upper extremity muscle and of lower extremity muscle with physiological factors is unclear. This study aimed to evaluate the association between physiological data and muscle strength, measured using grip and leg extension strength, among Japanese adults. Methods We conducted a cross-sectional study of 2,861 men and 6,717 women aged ≥ 20 years living in Miyagi Prefecture, Japan. Grip strength was measured using a dynamometer. Leg extension strength was measured using a hydraulic isokinetic leg press machine. Anthropometry and physiological data, including blood pressure, calcaneal ultrasound bone status, pulmonary function, carotid echography, and blood information, were assessed. We used a general linear model adjusted for age, body composition, and smoking status to evaluate the association between muscle strength and physiological factors. Results Grip and leg extension strength were positively associated with bone area ratio, vital capacity, forced vital capacity, forced expiratory volume in one second, and estimated glomerular filtration rate, and negatively associated with waist circumference and percentage body fat mass in both the sexes. Diastolic blood pressure was positively associated with grip strength in both the sexes and leg extension strength in men, but not women. High-density lipoprotein cholesterol and red blood cell counts were positively associated with grip and leg extension strength in women, but not men. In both the sexes, pulse rate, total cholesterol, and uric acid were consistently associated with only leg extension strength, but not grip strength. In women, glycated hemoglobin demonstrated negative and positive associations with grip and leg extension strength, respectively. Conclusions Grip and leg extension strength demonstrated similar associations with anthropometry, pulmonary function, and estimated glomerular filtration rate, but the associations with the other factors were not always consistent.

Background: Although fat mass index (FMI) and fat-free mass index (FFMI) affect lung function, FMI and FFMI are not independent of each other, since FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. We aimed to examine the association of combined FMI and FFMI with lung function. Methods: In this cross-sectional study, lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) measured using spirometry. Both FMI and FFMI were classified into sex-specific quartiles (16 groups). Analysis of covariance was used to assess the associations of combined FMI and FFMI with lung function. The trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1–4 (lowest–highest), and entering the number as a continuous term in the regression model. Results: This study included 3,736 men and 8,821 women aged ≥20 years living in Miyagi Prefecture, Japan. The mean FEV1 was 3.0 (standard deviation [SD], 0.7) L for men and 2.3 (SD, 0.5) L for women. The mean FVC was 3.8 (SD, 0.7) L for men and 2.8 (SD, 0.5) L for women. FMI was inversely associated with lung function among all FFMI subgroups in both sexes. Conversely, FFMI was positively associated with lung function in all FMI subgroups in both sexes. Conclusion: Higher FMI was associated with lower lung function independent of FFMI; higher FFMI was associated with higher lung function independent of FMI. Reducing FMI and maintaining FFMI might be important for respiratory health.

Background: Measurement of fractional exhaled nitric oxide (Feno) has been used in the diagnosis and management of asthma. Understanding the distribution of Feno in a larger resident population and its “healthy” subpopulation would contribute to the interpretation of Feno in clinical practice. Objective: This study aimed to investigate the distribution and its associated factors in the adult population and its healthy subpopulations. Methods: We conducted a cross-sectional study of 8,638 men and 17,288 women aged 20 years or older living in Miyagi prefecture, Japan. We investigated the distribution of Feno and its associated factors in all subjects, a subpopulation with no history of upper and lower airway diseases (healthy subpopulation 1), and a subpopulation with no history of upper and lower airway diseases, normal lung function, and no positivity for other biomarkers of type 2 inflammation (healthy subpopulation 2). Results: The distribution of Feno in healthy subpopulations, especially in healthy subpopulation 2 (median [interquartile range], 17 [12-23] with 95th percentile of 36 ppb) was lower than in all subjects (19 [13-26] ppb with 95th percentile of 47 ppb). In healthy subpopulation 1, 10.3% had elevated Feno (≥35 ppb), and elevated Feno was positively associated with factors including obstructive ventilatory defect, blood eosinophilia, house dust mite–specific IgE positivity, and history of hypertension. Male sex was associated with elevated Feno in all subjects and healthy subpopulations. Conclusion: The distribution of Feno in the healthy subpopulation supports the validity of the criteria (≥35 ppb) currently used in Japan for the diagnosis of asthma.

ABSTRACT Escherichia coli O157:H7 is a globally important foodborne pathogen with implications for food safety. Antibiotic treatment for O157 may potentially contribute to the exacerbation of hemolytic uremic syndrome, and the increasing prevalence of antibiotic-resistant strains necessitates the development of new treatment strategies. In this study, the bactericidal effects and resistance development of antibiotic and bacteriophage monotherapy were compared with those of combination therapy against O157. Experiments involving continuous exposure of O157 to phages and antibiotics, along with genetic deletion studies, revealed that the deletion of glpT and uhpT significantly increased resistance to fosfomycin. Furthermore, we found that OmpC functions as a receptor for the PP01 phage, which infects O157, and FhuA functions as a receptor for the newly isolated SP15 phage, targeting O157. In the glpT and uhpT deletion mutants, additional deletion in ompC, the receptor for the PP01 phage, increased resistance to fosfomycin. These findings suggest that specific phages may contribute to antibiotic resistance by selecting the emergence of gene mutations responsible for both phage and antibiotic resistance. While combination therapy with phages and antibiotics holds promise for the treatment of bacterial infections, careful consideration of phage selection is necessary.IMPORTANCEThe combination treatment of fosfomycin and bacteriophages against Escherichia coli O157 demonstrated superior bactericidal efficacy compared to monotherapy, effectively suppressing the emergence of resistance. However, mutations selected by phage PP01 led to enhanced resistance not only to the phage but also to fosfomycin. These findings underscore the importance of exercising caution in selecting phages for combination therapy, as resistance selected by specific phages may increase the risk of developing antibiotic resistance.

Abstract In Alzheimer's disease (AD), dysfunctional mitochondrial metabolism is associated with synaptic loss, the major pathological correlate of cognitive decline. Mechanistic insight for this relationship, however, is still lacking. Here, comparing isogenic wild‐type and AD mutant human induced pluripotent stem cell (hiPSC)‐derived cerebrocortical neurons (hiN), evidence is found for compromised mitochondrial energy in AD using the Seahorse platform to analyze glycolysis and oxidative phosphorylation (OXPHOS). Isotope‐labeled metabolic flux experiments revealed a major block in activity in the tricarboxylic acid (TCA) cycle at the α‐ketoglutarate dehydrogenase (αKGDH)/succinyl coenzyme‐A synthetase step, metabolizing α‐ketoglutarate to succinate. Associated with this block, aberrant protein S‐nitrosylation of αKGDH subunits inhibited their enzyme function. This aberrant S‐nitrosylation is documented not only in AD‐hiN but also in postmortem human AD brains versus controls, as assessed by two separate unbiased mass spectrometry platforms using both SNOTRAP identification of S‐nitrosothiols and chemoselective‐enrichment of S‐nitrosoproteins. Treatment with dimethyl succinate, a cell‐permeable derivative of a TCA substrate downstream to the block, resulted in partial rescue of mitochondrial bioenergetic function as well as reversal of synapse loss in AD‐hiN. These findings have therapeutic implications that rescue of mitochondrial energy metabolism can ameliorate synaptic loss in hiPSC‐based models of AD.

Background: Cavernous malformation (CM) is a well-known cause of epilepsy. Although the location of the CM is usually consistent with the side of seizure onset, some reports have described discrepancies between results from scalp electroencephalography (EEG) and CM location. This study investigated the prevalence and features of patients showing false lateralization (FL). Particularly, we tested the hypothesis that patients showing FL were more likely to have CM in medial and deep areas of the brain than in other areas. Methods: Patients diagnosed with CM-associated epilepsy in our institution between March 2009 and March 2023 were included in this retrospective analysis. We investigated the presence or absence of FL of interictal epileptiform discharges (IEDs) or ictal discharges against MRI findings or against the true focus as determined from surgical outcomes. We compared the FL group with the non-false-lateralization group (NFL group) to clarify features of CM-associated epilepsy patients showing FL. Results: Thirty-two epilepsy patients with CM were analyzed. The frequency of FL to MRI was 10.3% for IEDs and 7.7% for ictal discharges, while the frequency of FL to true focus after removal surgery was 10.5% for IEDs and 7.7% for ictal discharges. Regarding the FL of IEDs against MRI findings, the percentage of medial and deep lesions was significantly higher in the FL group (3/3, 100%) than in the NFL group (6/26, 23.1%; p = 0.023). No significant differences in age, sex, seizure type, or size of the CM were seen between groups. Conclusions: CM-associated epilepsy can also present with FL, particularly if the location of the CM is medial and deep. Caution may be needed in determining the area for resection based solely on scalp EEG findings.

Atrophy is characterized by muscle weakness and reduced mobility and results from inactivity, aging, cancer cachexia, and excessive glucocorticoid use. Skeletal muscle is essential for locomotion and energy production and accounts for a significant portion of body weight. Loss of muscle function adversely affects athletic performance and metabolism, affecting quality of life. Since there is no definitive cure, preventive measures such as diet and exercise are taken. The development of direct muscle atrophy therapeutics is urgently needed. Historically, animal studies have been used to predict pharmaceutical and food-derived functional ingredients efficacy in humans and to assess pharmacokinetics. However, in recent years there has been a global shift towards non-animal methods (alternatives to animal testing) due to animal welfare concerns. This study introduces a versatile assay for the development of Pharmaceutical and food-derived functional ingredients for the treatment of muscle atrophy using an artificial skeletal muscle contractility-based drug quantification platform. The effectiveness of this platform was demonstrated with quercetin, revealing its direct role in enhancing muscle contractility and promoting myotube formation via upregulation of Myh3 and cell migration by Cxcl5. This method provides a bridge between cellular assays and human studies and will advance research into the treatment of myopathies.

Abstract White blood cell (WBC) count profiles in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are still unknown. This study evaluated the total WBC count, differential WBC counts, monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with these diseases within three months from an attack before acute treatment or relapse prevention and compared the profiles with those in matched volunteers or in multiple sclerosis (MS) patients. AQP4-NMOSD patients (n = 13) had a higher neutrophil count (p = 0.0247), monocyte count (p = 0.0359), MLR (p = 0.0004), and NLR (p = 0.0037) and lower eosinophil (p = 0.0111) and basophil (p = 0.0283) counts than those of AQP4-NMOSD-matched volunteers (n = 65). Moreover, patients with MOGAD (n = 26) had a higher overall WBC count (p = 0.0001), neutrophil count (p

Here the authors demonstrate that de novo DNA methylation mediated by DNMT3B is regulated by nitric oxide (NO). They also isolate a unique modulator (DBIC) that inhibits S-nitrosylation of DNMT3B, which mitigates cell proliferation and tumorigenic conversion in vivo.

Abstract Staphylococcus virus ΦSA012 has a wide host range and efficient lytic activity. Here, we assessed the biological stability of ΦSA012 against temperature, freeze-thawing, and pH to clinically apply the phage. In addition, inoculation of ΦSA012 through i.p. and i.v. injections into mice revealed that phages were reached the limit of detection in serum and accumulated notably spleens without inflammation at 48 h post-inoculation. Furthermore, inoculation of ΦSA012 through s.c. injections in mice significantly induced IgG, which possesses neutralizing activity against ΦSA012 and other Staphylococcus viruses, ΦSA039 and ΦMR003, but not Pseudomonas viruses ΦS12-3 and ΦR18 or Escherichia viruses T1, T4, and T7 in vitro. Immunoelectron microscopic analysis showed that purified anti-phage IgG recognizes the long-tail fiber of staphylococcus viruses. Although S. aureus inoculation resulted in a 25% survival rate in a mouse i.p. model, ΦSA012 inoculation (i.p.) improved the survival rate to 75%; however, the survival rate of ΦSA012-immunized mice decreased to less than non-immunized mice with phage i.v. injection at a MOI of 100. These results indicated that ΦSA012 possesses promise for use against staphylococcal infections but we should carefully address the appropriate dose and periods of phage administration. Our findings facilitate understandings of staphylococcus viruses for phage therapy.

Abstract Development of methods for population screening is necessary to improve the efficiency of secondary prevention of diseases. Until now, a common cutoff has been used for all people in the data set. However, if big data for health information can be used to modify individual cutoffs according to background factors, it may avoid wasting medical resources. Here we show that the estimated prevalence of the Center for Epidemiologic Studies Depression Scale positivity can be visualized by a heatmap using background factors from epidemiological big data and scores from the Athens Insomnia Scale. We also show that cutoffs based on the estimated prevalence can be used to decrease the number of people screened without decreasing the number of prevalent cases detected. Since this method can be applied to the screening of different outcomes, we believe our work can contribute to the development of efficient screening methods for various diseases.

Background: Several cases of temporal lobe epilepsy (TLE) showing false lateralization of ictal scalp electroencephalography (EEG) have been reported. However, TLE with cavernous malformation indicating false lateralization of both ictal scalp EEG and semiology as in the present case is rare. The aim of this report is to call attention to avoiding overestimation of ictal scalp EEG findings in epilepsy patients with cavernous malformation. Case report: A 25-year-old man without any medical history suffered from seizures for a year despite appropriate anti-epileptic medication. Magnetic resonance imaging (MRI) revealed cavernous malformation in the left amygdala. The seizure type was brief impaired consciousness with left dystonic posturing, preceded by a sensation of blood rushing to the head. Long-term video EEG with scalp electrodes showed periodic sharp waves beginning from the right temporal area during seizures. Although both semiology and ictal scalp EEG indicated right TLE, intracranial EEG revealed the onset of low-voltage fast activity from the left hippocampus near the cavernous malformation. This patient therefore underwent removal of cavernous malformation and left amygdala, and achieved freedom from seizures postoperatively. Conclusion: We reinforce the importance of performing intracranial EEG for cavernous malformation-associated epilepsy when discrepancies between scalp EEG and MRI are evident.

Purpose: Acute (immediate) or regular (mid- or long-term) stretching increases arterial compliance and reduces arterial stiffness. Stretching is widely known to induce arterial functional factor changes, but it is unclear whether stretching alters arterial structural factors. Ultrasound shear wave elastography can quantify the distribution of tissue elastic properties as an index of arterial structural factors. This study thus aimed to examine the effects of acute cervical stretching on arterial wall tissue elastic properties.Methods: Seventeen healthy young adults participated in two different trials for 15 min in random order on separate days: a resting and sitting trial (CON) and a supervised cervical stretching trial (CS). In CS, subjects performed 10 different stretches. At each site, the stretch was held for 30 s followed by a 10-s relaxation period. In CON, subjects rested on a chair for 15 min.Results: After the experiment, carotid arterial compliance, assessed by combined ultrasound imaging and applanation tonometry, was significantly increased in CS, but not in CON. However, there was no significant change in tissue elasticity properties of the arterial wall in either trial, as assessed by ultrasound shear wave elastography.Conclusion: Acute cervical stretching significantly increased carotid artery compliance in young participants, but did not reduce elastic tissue properties (i.e., arterial structural factors) of the carotid artery wall. These results strongly suggest that changes in structural factors have little relation to stretching-induced acute increases in arterial compliance.

IntroductionPerinatal women tend to have difficulties with sleep along with autonomic characteristics. This study aimed to identify a machine learning algorithm capable of achieving high accuracy in predicting sleep–wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability (HRV).MethodsNine HRV indicators (features) and sleep–wake conditions of 154 pregnant women were measured for 1 week, from the 23rd to the 32nd weeks of pregnancy. Ten machine learning and three deep learning methods were applied to predict three types of sleep–wake conditions (wake, shallow sleep, and deep sleep). In addition, the prediction of four conditions, in which the wake conditions before and after sleep were differentiated—shallow sleep, deep sleep, and the two types of wake conditions—was also tested.Results and DiscussionIn the test for predicting three types of sleep–wake conditions, most of the algorithms, except for Naïve Bayes, showed higher areas under the curve (AUCs; 0.82–0.88) and accuracy (0.78–0.81). The test using four types of sleep–wake conditions with differentiation between the wake conditions before and after sleep also resulted in successful prediction by the gated recurrent unit with the highest AUC (0.86) and accuracy (0.79). Among the nine features, seven made major contributions to predicting sleep–wake conditions. Among the seven features, “the number of interval differences of successive RR intervals greater than 50 ms (NN50)” and “the proportion dividing NN50 by the total number of RR intervals (pNN50)” were useful to predict sleep–wake conditions unique to pregnancy. These findings suggest alterations in the vagal tone system specific to pregnancy.

Autophagy (in the form of macroautophagy) is the major intracellular protein quality control system for removal of damaged organelles and abnormally aggregated proteins. We and others have shown that dysregulated autophagic pathways contribute to accumulation and spread of misfolded proteins in many neurodegenerative disorders, including Parkinson disease (PD) and Lewy body dementia (LBD). Additionally, generation of excessive reactive oxygen and nitrogen species, such as nitric oxide (NO), accelerates neuronal and synaptic damage mediated, at least in part, via aberrant protein S-nitrosylation. Using cell-based models, including human induced pluripotent stem cell (hiPSC)-derived neurons, CRISPR-Cas9 technology, and transgenic PD/LBD mice, plus vetting in human postmortem brains, we found that S-nitrosylation of the autophagic receptor protein SQSTM1/p62 (forming SNO-SQSTM1/p62) inhibits autophagic flux, thus contributing to accumulation of misfolded SNCA/α-synuclein. Consequently, this impairment in autophagy increases extracellular vesicle-dependent secretion and spread of aggregated SNCA. Taken together, our evidence suggests that aberrant formation of SNO-SQSTM1/p62 represents a pathogenic event contributing not only to inhibition of autophagic flux and potentiation of neuronal damage, but also to propagation of α-synucleinopathy between cells in the diseased brain.

Background: Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) are enzymes associated with diabetes mellitus (DM) prevalence. However, limited information is available regarding the association of liver enzymes and DM consistently present in obese and non-obese individuals. We examined whether the combination of ALT and GGT enzymes is associated with the prevalence of DM, regardless of obesity, in a general Japanese population. Methods: We conducted a cross-sectional study of 62,786 participants aged ≥20 years who lived in Miyagi and Iwate, Japan. We divided all the participants into eight groups according to the ALT level (low:

Abstract Aims/Introduction Fat mass and fat‐free mass affect glycated hemoglobin A1c (HbA1c) levels and blood glucose levels, respectively. The aim of the present study was to examine the association between the fat mass index and fat‐free mass index with HbA1c. Materials and Methods We carried out a cross‐sectional study that included 3,731 men and 9,191 women aged ≥20 years, living in Miyagi Prefecture, Japan, who were not treated for diabetes. The fat mass index and fat‐free mass index were calculated as fat mass and fat‐free mass divided by the height squared, respectively. The indices were classified into sex‐specific quartiles and combined into 16 groups. An analysis of covariance was used to assess associations between the combined fat mass index and fat‐free mass index with HbA1c adjusted for potential confounders. The linear trend test was carried out by stratifying the fat mass index and fat‐free mass index, entering the number as a continuous term in the regression model. Results In multivariable models, a higher fat mass index was related to higher HbA1c levels in men and women in all fat‐free mass index subgroups (P

In recent decades, phage therapy has been overshadowed by the widespread use of antibiotics in Western countries. However, it has been revitalized as a powerful approach due to the increasing prevalence of antimicrobial-resistant bacteria. Although bacterial resistance to phages has been reported in clinical cases, recent studies on the fitness trade-offs between phage and antibiotic resistance have revealed new avenues in the field of phage therapy. This strategy aims to restore the antibiotic susceptibility of antimicrobial-resistant bacteria, even if phage-resistant variants develop. Here, we summarize the basic virological properties of phages and their applications within the context of antimicrobial resistance. In addition, we review the occurrence of phage resistance in clinical cases, and examine fitness trade-offs between phage and antibiotic sensitivity, exploring the potential of an evolutionary fitness cost as a countermeasure against phage resistance in therapy. Finally, we discuss future strategies and directions for phage-based therapy from the aspect of fitness trade-offs. This approach is expected to provide robust options when combined with antibiotics in this era of phage ‘re’-discovery.

Since 3D-EM closely resembles in vivo muscles, the aim of this study was to investigate the effects of exercise (electrical pulse stimulation (EPS)) and nutrition (maca), which contains triterpenes, on muscle hypertrophy by using 3D-EM for the first time. The 3D-EM was composed of C2C12 cells and type 1 collagen gel, was differentiated for 14 days, and was divided into four groups: control, maca, EPS, and maca + EPS. The medium was replaced every two days before each EPS intervention, and the concentration of maca in the culture solution was 1 mg/mL. The intervention conditions of the EPS were 30 V, 1 Hz, and 2 ms (24 h on, 24 h off, for one week). The expression levels of proteins were examined by Western blotting. The intervention of maca and EPS upregulated the expression of MHC-fast/slow (both p < 0.05) compared with the control group, and the addition of maca had no effect on the phosphorylation of mTOR (p = 0.287) but increased the AMPK phosphorylation (p = 0.001). These findings suggest that intervention with maca and EPS has a positive effect on muscle hypertrophy, which has a positive impact on sarcopenia. However, the underlying mechanisms remain to be further explored.

Abstract Selecting diverse molecules from unexplored areas of chemical space is one of the most important tasks for discovering novel molecules and reactions. This paper proposes a new approach for selecting a subset of diverse molecules from a given molecular list by using two existing techniques studied in machine learning and mathematical optimization: graph neural networks (GNNs) for learning vector representation of molecules and a diverse-selection framework called submodular function maximization. Our method, called SubMo-GNN, first trains a GNN with property prediction tasks, and then the trained GNN transforms molecular graphs into molecular vectors, which capture both properties and structures of molecules. Finally, to obtain a subset of diverse molecules, we define a submodular function, which quantifies the diversity of molecular vectors, and find a subset of molecular vectors with a large submodular function value. This can be done efficiently by using the greedy algorithm, and the diversity of selected molecules measured by the submodular function value is mathematically guaranteed to be at least 63% of that of an optimal selection. We also introduce a new evaluation criterion to measure the diversity of selected molecules based on molecular properties. Computational experiments confirm that our SubMo-GNN successfully selects diverse molecules from the QM9 dataset regarding the property-based criterion, while performing comparably to existing methods regarding standard structure-based criteria. We also demonstrate that SubMo-GNN with a GNN trained on the QM9 dataset can select diverse molecules even from other MoleculeNet datasets whose domains are different from the QM9 dataset. The proposed method enables researchers to obtain diverse sets of molecules for discovering new molecules and novel chemical reactions, and the proposed diversity criterion is useful for discussing the diversity of molecular libraries from a new property-based perspective.

Alzheimer’s disease (AD) is arguably the most common cause of dementia in the elderly and is marked by progressive synaptic degeneration, which in turn leads to cognitive decline. Studies in patients and in various AD models have shown that one of the early signatures of AD is neuronal hyperactivity. This excessive electrical activity contributes to dysregulated neural network function and synaptic damage. Mechanistically, evidence suggests that hyperexcitability accelerates production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute to neural network impairment and synapse loss. This review focuses on the pathways and molecular changes that cause hyperexcitability and how RNS-dependent posttranslational modifications, represented predominantly by protein S-nitrosylation, mediate, at least in part, the deleterious effects of hyperexcitability on single neurons and the neural network, resulting in synaptic loss in AD.

Akira Uruno et al. report the volume of epidydimal white adipose tissue and plasma glycerophospholipid and sphingolipid levels in mice increase during spaceflight. These metabolic and physiological changes were largely driven by Nrf2 (NF-E2-related factor-2), ultimately providing a mechanistic target for altering lipid metabolism on Earth and the Great Beyond.

Databases: Integrating megadata for disease research A database integrating 1.3 trillion genome cohort data entries from 157,191 individuals in Japan will facilitate research into the gene-environment interactions underlying common diseases. The Tohoku Medical Megabank integrated database called dbTMM was developed by Soichi Ogishima, Masayuki Yamamoto and colleagues at Tohoku University in Japan. It incorporates the genome, metabolome, proteome, clinical, sociodemographic, lifestyle and environmental data from 84,073 adults, and 73,529 pregnant women and their families, including children. Blood and urine samples were collected from participants and analysed, then obtained genome/multiomics data were stored in dbTMM. Users can stratify the entire population into smaller populations based on multiple data variables, including whole genome variants, to search for statistically significant differences that might warrant further research. The dbTMM is expected to help clarify the genes and gene-environment interactions underlying common diseases and improve disease risk prediction.

Abstract Background We determined the prevalence of current cigarette smokers and alcohol drinkers among cancer survivors and subjects with no history of cancer in Japan and compared the findings with nationally representative studies in other countries. Methods We conducted a cross‐sectional study of baseline data from a prospective cohort study. A self‐administered questionnaire was surveyed during 2013–2015 with residents aged ≥20 years attending a community‐based cardiometabolic screening program in Miyagi prefecture in north‐eastern Japan. Subjects with past cancer histories were classified as cancer survivors. Sex‐specific, age‐standardized prevalence of current smokers, and drinkers were calculated. Age‐adjusted prevalence ratios (PRs: the cancer survivors’ rate divided by the rate of subjects with no history of cancer) and 95% confidence intervals (CIs) were estimated with log‐binomial regressions. Results 36,786 subjects, including 2760 cancer survivors, responded and provided usable information (58.9% of recruited subjects). For men, the age‐standardized prevalence of current smokers and drinkers among survivors was 18.8% and 74.4%, respectively, with an age‐adjusted PR (95%CI) of 0.76 (0.66–0.86, p

Abstract After disasters, people are often forced to reconstruct or move to new residences. This study aimed to reveal the association between the types of reconstructed residences and psychosocial or psychiatric conditions among the population. A total of 1071 adult residents in a coastal town, whose houses were destroyed by the tsunami caused by the Great East Japan Earthquake, enrolled in the study five years after the disaster. The type of reconstructed post-disaster residences (reconstructed on the same site/disaster-recovery public condominium/mass-translocation to higher ground/privately moving to remote areas) and the current psychosocial indicators were investigated. The results revealed that individuals living in public condominiums showed significantly worse scores on the Lubben Social Network Scale-6 (p

Yamada, Motoike, Kojima et al. undertake a GWAS study on 19,722 participants from two Japanese populations for lung function with adjustment for fractional exhaled nitric oxide levels to account for airway inflammation. The authors identify variants of the RNF5/AGER locus and explore their three-dimensional protein interactions to better investigate the association between these variants and lung function.

Abstract Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system; however, its exact mechanism is unknown. This study aimed to elucidate the profile of white blood cells (WBCs) in the acute phase of an MS attack. Sixty-four patients with MS at the time of diagnosis and 2492 age- and sex-adjusted healthy controls (HCs) were enrolled. Data regarding the blood cell counts were compared between the groups. The total WBC (p

Background A higher body fat percentage is associated with hypertension, even in non-obese individuals. The difference in body composition may be related to hypertension. The fat mass index (FMI) and fat-free mass index (FFMI) are proposed indicators of body composition. This study aimed to examine the relationship of a combination of FMI and FFMI with hypertension. Methods We conducted a cross-sectional study of 5,058 men and 11,842 women aged ≥ 20 years in the Miyagi Prefecture, northeastern Japan. The FMI and FFMI were calculated as the fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into quartiles and combined into 16 groups. Hypertension was defined as casual blood pressure ≥ 140/90 mmHg and/or self-reported treatment for hypertension. Multivariable logistic regression models, adjusted for potential confounders, were used to assess the relationship of a combination of FMI and FFMI with hypertension. Results Higher FMI was associated with hypertension in most of the FFMI subgroups. Similarly, a higher FFMI was associated with hypertension in most of FMI subgroups. For men, the association between FFMI and hypertension in the lowest FMI group was not significant. Conclusions Reducing the FMI and FFMI may be important in preventing hypertension. For men, the relationship between the FFMI and hypertension in the lowest FMI group might be weak.

Abstract The interbasin exchange between the Sea of Okhotsk and the North Pacific governs the intermediate water ventilation and fertilization of the nutrient-rich subpolar Pacific, and thus has an enormous influence on the North Pacific. However, the mechanism of this exchange is puzzling; current studies have not explained how the western boundary current (WBC) of the subarctic North Pacific intrudes only partially into the Sea of Okhotsk. High-resolution models often exhibit unrealistically small exchanges, as the WBC overshoots passing by deep straits and does not induce exchange flows. Therefore, partial intrusion cannot be solely explained by large-scale, wind-driven circulation. Here, we demonstrate that tidal forcing is the missing mechanism that drives the exchange by steering the WBC pathway. Upstream of the deep straits, tidally-generated topographically trapped waves over a bank lead to cross-slope upwelling. This upwelling enhances bottom pressure, thereby steering the WBC pathway toward the deep straits. The upwelling is identified as the source of joint-effect-of-baroclinicity-and-relief (JEBAR) in the potential vorticity equation, which is caused by tidal oscillation instead of tidally-enhanced vertical mixing. The WBC then hits the island chain and induces exchange flows. This tidal control of WBC pathways is applicable on subpolar and polar regions globally.

Objectives: The aim of this study was to search for routine blood test biomarkers in patients with physical symptoms but without a diagnosis after comprehensive routine screening diagnostic examinations. Methods: A total of 228 adults aged 0.25 were likely to have unexplained nonfocal physical symptoms ( p 0.25.

Abstract Background Social isolation and mental health issues have become a severe problem in disaster areas in the Great East Japan Earthquake. This study examined whether the combination of the house damage and social isolation or the combination of the death of family members and social isolation is associated with depressive symptoms among survivors using the baseline study data of the Tohoku Medical Megabank Project Community-Based Cohort Study (TMM CommCohort Study). Methods We used cross-sectional data from a baseline survey of 48,958 participants (18,423 males, 30,535 females; aged 60.1 ± 11.2 years) to examine the association between social isolation measured by the Lubben social network scale 6 (LSNS-6) and depressive symptoms measured by the Center for Epidemiological Studies-Depressive Scale (CES-D). The presence of social isolation and depressive symptoms was defined by an LSNS-6 score of

Background: Major reasons for long-term care insurance certification in Japan are stroke, dementia, and fracture. These diseases are reported to be associated with calcium intake. This study examined the association between calcium intake and impaired activities of daily living (ADL) using the data from NIPPON DATA90, consisting of representative sample of the Japanese population. Methods: A population-based nested case-control study was performed. A baseline survey was conducted in 1990, followed by ADL surveys of individuals ≥65 years old in 2000. Individuals with impaired ADL and selected age- and sex-matched controls were then identified. We obtained 132 pairs. Calcium intake was energy-adjusted using the residual method. The association between calcium intake and impaired ADL was examined using conditional logistic regression models. To assess the accuracy of the estimates, we conducted bootstrap analyses. Results: The adjusted odds ratios (ORs) for impaired ADL compared with the group with a calcium intake of

Background: We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major diseases, such as cancer and cardiovascular diseases. Methods: We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely. Results: As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex. Conclusion: This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.

Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged > 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL.

Abstract Background Lymph node metastasis is one of the pivotal factors of the clinical outcomes of patients with esophageal cancer receiving neoadjuvant chemoradiation therapy (NACRT). Both the nuclear factor‐erythroid 2‐related factor 2 (Nrf2) signaling pathway and heme oxygenase‐1 (HO‐1) are frequently upregulated in various human malignancies and associated with resistance to chemoradiation therapy, subsequently resulting in adverse clinical outcomes. However, the Nrf2 and HO‐1 status in lymph node metastasis and their differences between primary and metastatic lesions are unknown. Aims To examine the levels of Nrf2 signaling proteins and HO‐1 in primary and metastatic lesions of patients with esophageal squamous cell carcinoma using immunohistochemistry. Methods and Results We immunolocalized Nrf2 signaling proteins in 69 patients with lymph node metastases, who received NACRT with 5‐fluorouracil and cisplatin before esophagectomy. We also compared the findings between primary and metastatic lesions. Residual lymph node metastases were detected in 30 patients and among them, both primary and metastatic lesions were available for evaluation in 25 patients. Subsequently, we correlated the results with patients' survival. Nrf2, HO‐1, and the Ki‐67 labeling index were all significantly lower in the patients with lymph node metastases than in those with primary tumors. Carcinoma cells with high HO‐1 levels were significantly associated with pathological resistance to NACRT. These results suggested that overall and disease‐free survival of esophageal squamous cell carcinoma were significantly associated with both pN2 and high HO‐1 levels, respectively. Conclusions Protein expression in the Nrf2 pathway was significantly lower in patients with lymph node metastases than in those with primary lesions. HO‐1 levels in lymph node metastases could be used to predict the eventual clinical outcome of patients with esophageal cancer receiving NACRT.

Background: It has been reported that chronic inflammation may play an important role in the pathogenesis of several serious diseases and could be modulated by diet. Recently, the Dietary Inflammatory Index (DII®) was developed to assess the inflammatory potential of the overall diet. The DII has been reported as relevant to various diseases but has not been validated in Japanese. Thus, in the present study, we analyzed the relationship between DII scores and high-sensitivity C-reactive protein (hs-CRP) levels in a Japanese population. Methods: Data of the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 2010 (NIPPON DATA2010), which contained 2,898 participants aged 20 years or older from the National Health and Nutrition Survey of Japan (NHNS2010), were analyzed. Nutrient intakes derived from 1-day semi-weighing dietary records were used to calculate DII scores. Energy was adjusted using the residual method. Levels of hs-CRP were evaluated using nephelometric immunoassay. Multiple linear regression analyses were performed. Results: After adjusting for age, sex, smoking status, BMI, and physical activity, a significant association was observed between DII scores and log(CRP+1) (standard regression coefficient = 0.05, P < 0.01). Although it was not statistically significant, the positive association was consistently observed in almost all age-sex subgroups and the non-smoker subgroup. Conclusions: The current study confirmed that DII score was positively associated with hs-CRP in Japanese.

In this study, the extent to which different emotions of pregnant women can be predicted based on heart rate-relevant information as indicators of autonomic nervous system functioning was explored using various machine learning algorithms. Nine heart rate-relevant autonomic system indicators, including the coefficient of variation R-R interval (CVRR), standard deviation of all NN intervals (SDNN), and square root of the mean squared differences of successive NN intervals (RMSSD), were measured using a heart rate monitor (MyBeat) and four different emotions including “happy,” as a positive emotion and “anxiety,” “sad,” “frustrated,” as negative emotions were self-recorded on a smartphone application, during 1 week starting from 23rd to 32nd weeks of pregnancy from 85 pregnant women. The k-nearest neighbor (k-NN), support vector machine (SVM), logistic regression (LR), random forest (RF), naïve bayes (NB), decision tree (DT), gradient boosting trees (GBT), stochastic gradient descent (SGD), extreme gradient boosting (XGBoost), and artificial neural network (ANN) machine learning methods were applied to predict the four different emotions based on the heart rate-relevant information. To predict four different emotions, RF also showed a modest area under the receiver operating characteristic curve (AUC-ROC) of 0.70. CVRR, RMSSD, SDNN, high frequency (HF), and low frequency (LF) mostly contributed to the predictions. GBT displayed the second highest AUC (0.69). Comprehensive analyses revealed the benefits of the prediction accuracy of the RF and GBT methods and were beneficial to establish models to predict emotions based on autonomic nervous system indicators. The results implicated SDNN, RMSSD, CVRR, LF, and HF as important parameters for the predictions.

Dandy-Walker malformation (DWM) is a common prenatally diagnosed cerebellar malformation, characterized by cystic dilatation of the fourth ventricle, upward rotation of the hypoplastic vermis, and posterior fossa enlargement with torcular elevation. DWM is associated with a broad spectrum of neurodevelopmental abnormalities such as cognitive, motor, and behavioral impairments, which cannot be explained solely by cerebellar malformations. Notably, the pathogenesis of these symptoms remains poorly understood. This study investigated whether fetal structural developmental abnormalities in DWM extended beyond the posterior fossa to the cerebrum even in fetuses without apparent cerebral anomalies. Post-acquisition volumetric fetal magnetic resonance imaging (MRI) analysis was performed in 12 fetuses with DWM and 14 control fetuses. Growth trajectories of the volumes of the cortical plate, subcortical parenchyma, cerebellar hemispheres, and vermis between 18 and 33 weeks of gestation were compared. The median (interquartile range) gestational ages at the time of MRI were 22.4 (19.4–24.0) and 23.9 (20.6–29.2) weeks in the DWM and control groups, respectively (p = 0.269). Eight of the 12 fetuses with DWM presented with associated cerebral anomalies, including hydrocephalus (n = 3), cerebral ventriculomegaly (n = 3), and complete (n = 2) and partial (n = 2) agenesis of the corpus callosum (ACC); 7 presented with extracerebral abnormalities. Chromosomal abnormalities were detected by microarray analysis in 4 of 11 fetuses with DWM, using amniocentesis. Volumetric analysis revealed that the cortical plate was significantly larger in fetuses with DWM than in controls (p = 0.040). Even without ACC, the subcortical parenchyma, whole cerebrum, cerebellar hemispheres, and whole brain were significantly larger in fetuses with DWM (n = 8) than in controls (p = 0.004, 0.025, 0.033, and 0.026, respectively). In conclusion, volumetric fetal MRI analysis demonstrated that the development of DWM extends throughout the brain during the fetal period, even without apparent cerebral anomalies.

Abstract Diabetic skeletal muscles show reduced contractile force and increased fatigability. Hands are a target for several diabetes‐induced complications. Therefore, reduced handgrip strength often occurs as a consequence of diabetes. The aim of this study was to examine whether long‐term exercise can prevent reduction of grip strength in type 2 diabetes mellitus (T2DM) model OLETF rats, and to explore the mechanisms underlying diabetes‐induced grip strength reduction. Ten 5‐week‐old OLETF rats were used as experimental animals, and five non‐diabetic LETO rats as controls of OLETF rats. Half OLETF rats performed daily voluntary wheel‐running for 17 months (OLETF + EXE), and the rest of OLETF and LETO rats were sedentary. Grip strength was higher in OLETF + EXE and LETO groups than in OLETF group. OLETF group with hyperglycemia showed an increase in HbA1c, serum TNF‐α, and muscle SERCA activity, but a decrease in circulating insulin. Each fiber area, total fiber area, and % total fiber area in type IIb fibers of extensor digitorum longus muscles were larger in OLETF + EXE and LETO groups than in OLETF group. There was a positive correlation between grip strength and the above three parameters concerning type IIb fiber area. Therefore, type IIb fiber atrophy may be the major direct cause of grip strength reduction in OLETF group, although there seems multiple etiological mechanisms. Long‐term wheel‐running may have blocked the diabetes‐induced reduction of grip strength by preventing type IIb fiber atrophy. Regular exercise may be a potent modality for preventing not only the progression of diabetes but muscle dysfunction in T2DM patients.

Patients with advanced heart failure often experience dyspnea, fatigue, edema, and appetite loss. If these symptoms are refractory to treatment, palliative care via a team approach is necessary. We describe a patient with stage D heart failure whose dyspnea and overall condition improved with comprehensive medical treatments including conventional medications for heart failure, continuous infusions of catecholamine and diuretic, and oral hydromorphone. A 67-year-old man with a 12-year history of dilated cardiomyopathy was admitted to our hospital due to exacerbation of heart failure. Despite continuous infusion of catecholamine and diuretic, his dyspnea and liver and renal function continued to worsen. Oral hydromorphone was administered to relieve his refractory dyspnea, which also improved his conditions, continuous infusion of the catecholamine and diuretic could withdraw. Oral low-dose hydromorphone used in the present case might be a helpful agent for treating dyspnea in stage D heart failure patients with renal dysfunction.

Sinus arrest caused by sinus node (SN) artery occlusion during coronary intervention can take place, but it is usually transient and seldom influences hemodynamic instability. We encounter cases requiring revascularization of the SN artery because of cardiogenic shock, although it is very rare. Acute occlusion of SN artery during PCI should be noted, especially if hemodynamics is unstable.

Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by heterozygous mutations in the TSC1 or TSC2 gene. TSC is often associated with neurological, cognitive, and behavioral deficits. TSC patients also express co-morbidity with anxiety and mood disorders. The mechanism of pathogenesis in TSC is not entirely clear, but TSC-related neurological symptoms are accompanied by excessive glutamatergic activity and altered synaptic spine structures. To address whether extrasynaptic (e)NMDA-type glutamate receptor (NMDAR) antagonists, as opposed to antagonists that block physiological phasic synaptic activity, can ameliorate the synaptic and behavioral features of this disease, we utilized the Tsc2+/− mouse model of TSC to measure biochemical, electrophysiological, histological, and behavioral parameters in the mice. We found that antagonists that preferentially block tonic activity as found at eNMDARs, particularly the newer drug NitroSynapsin, provide biological and statistically significant improvement in Tsc2+/− phenotypes. Accompanying this improvement was correction of activity in the p38 MAPK-TSC-Rheb-mTORC1-S6K1 pathway. Deficits in hippocampal long-term potentiation (LTP), histological loss of synapses, and behavioral fear conditioning in Tsc2+/− mice were all improved after treatment with NitroSynapsin. Taken together, these results suggest that amelioration of excessive excitation, by limiting aberrant eNMDAR activity, may represent a novel treatment approach for TSC.

Diabetes is a major cause of kidney disease. Here Kikuchi et al. show that phenol sulfate, a gut microbiota-derived metabolite, is increased in diabetic kidney disease and contributes to the pathology by promoting kidney injury, suggesting phenyl sulfate could be used a marker and therapeutic target for the treatment of diabetic kidney disease.

An assessment of mood or emotion is important in developing mental health measures, and facial expressions are strongly related to mood or emotion. This study thus aimed to examine the relationship between levels of negative mood and characteristics of mouth parts when moods are drawn as facial expressions on a common platform. A cross-sectional study of Japanese college freshmen was conducted, and 1,068 valid responses were analyzed. The questionnaire survey consisted of participants’ characteristics, the Profile of Mood States (POMS), and a sheet of facial expression drawing (FACED), and the sheet was digitized and analyzed using an image-analysis software. Based on the total POMS score as an index of negative mood, the participants were divided into four groups: low (L), normal (N), high (H), and very high (VH). Lengths of drawn lines and between both mouth corners were significantly longer, and circularity and roundness were significantly higher in the L group. With increasing levels of negative mood, significant decreasing trends were observed in these lengths. Convex downward and enclosed figures were significantly predominant in the L group, while convex upward figures were significantly predominant and a tendency toward predominance of no drawn mouths or line figures was found in the H and VH groups. Our results suggest that mood states can be significantly related to the size and figure characteristics of drawn mouths of FACED on a non-verbal common platform. That is, these findings mean that subjects with low negative mood may draw a greater and rounder mouth and figures that may be enclosed and downward convex, while subjects with a high negative mood may not draw the line, or if any, may draw the line shorter and upward convex.

Brain function-related myokines, such as lactate, irisin, and cathepsin B (CTSB), are upstream factors that control brain-derived neurotrophic factor (BDNF) expression and are secreted from skeletal muscle by exercise. However, whether irisin and CTSB are secreted by muscle contraction remains controversial. Three-dimensional (3D)-engineered muscle (3D-EM) may help determine whether skeletal muscle contraction leads to the secretion of irisin and CTSB, which has never been identified with the addition of drugs in conventional 2D muscle cell cultures. We aimed to investigate the effects of electrical pulse stimulation (EPS)-evoked muscle contraction on irisin and CTSB secretion in 3D-EM. The 3D-EM, which consisted of C2C12 myoblasts and type-1 collagen gel, was allowed to differentiate for 2 weeks and divided into the control and EPS groups. EPS was applied at 13 V, 66 Hz, and 2 msec for 3 h (on: 5 s/off: 5 s). Irisin and CTSB secretion into the culture medium was measured by Western blotting. Irisin secretion was significantly increased following EPS (p < 0.05). However, there was no significant difference in CTSB secretion between the two groups. The present study suggests that irisin may be a contractile muscle-derived myokine, but CTSB is not secreted by EPS-evoked muscle contractile stimulation in 3D-EM.

Walking speed as one index of gait ability is an important component of physical fitness among older adults. Walking speed-arterial stiffness relationships have been studied, but whether poor walking speed is associated with higher segment-specific arterial stiffness in older adults is unclear. We thus aimed to examine the relationship between walking speed and segmental arterial stiffness among older community dwellers. This study was a cross-sectional study of 492 older Japanese community dwellers (age range, 65 to 96 years). Heart-brachial PWV (hbPWV), brachial-ankle PWV (baPWV), heart-ankle PWV (haPWV), and cardio-ankle vascular index (CAVI) were used as arterial stiffness indices. Walking speed, strength, flexibility, and cognitive function were also assessed. The participants were categorized into low (Slow), middle (Middle), and high (Fast) tertiles according to walking speed. The CAVI and baPWV were significantly lower in Fast than in Slow. Significant decreasing trends in CAVI and baPWV and a tendency toward decreasing trend in haPWV were observed from Slow to Fast, whereas hbPWV did not significantly differ among tertiles and no trend was evident. The results remained significant after normalizing CAVI and PWVs for multicollinearity of arterial stiffness indices and major confounding factors, such as age, gender, body mass index, blood pressure, cognitive function, and each physical fitness. Therefore, these findings suggest that poor walking speed is associated with higher segment-specific arterial stiffness of the central and lower limbs, but not of upper, in older adult community dwellers.