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The mortality rate for acute kidney injury (AKI) due to sepsis remains high, and effective therapies based on its pathogenesis remain elusive. Macrophages are crucial for clearing bacteria from vital organs, including the kidney, under septic conditions. Excessive macrophage activation results in organ injury. C-reactive protein (CRP) peptide (174-185), a functional product of proteolyzed CRP in vivo, effectively activates macrophages. We investigated the therapeutic efficacy of synthetic CRP peptide on septic AKI, focusing on effects on kidney macrophages. Mice underwent cecal ligation and puncture (CLP) to induce septic AKI and were intraperitoneally administered 20 mg/kg of synthetic CRP peptide 1 h post-CLP. Early CRP peptide treatment improved AKI while still clearing infection. Ly6C-negative kidney tissue-resident macrophages did not significantly increase at 3 h after CLP, while Ly6C-positive monocyte-derived macrophages significantly accumulated in the kidney 3 h post-CLP. CRP peptide augmented the phagocytic ROS production in both subtypes of kidney macrophage at 3 h. Interestingly, both subtypes of macrophage increased ROS production 24 h post-CLP compared to the control group, while CRP peptide treatment maintained ROS production at the same level seen 3 h post-CLP. Although bacterium-phagocytic kidney macrophages produced TNF-α, CRP peptide reduced bacterial propagation and tissue TNF-α levels in the septic kidney at 24 h. Although both subsets of kidney macrophages showed populations of M1 at 24 h post-CLP, CRP peptide therapy skewed the macrophages population toward M2 at 24 h. CRP peptide alleviated murine septic AKI via the controlled activation of kidney macrophages and is an excellent candidate for future human therapeutic studies.

Recent studies have revealed that mammalian B cells ingest particulate Ags, such as bacteria, although little is known about the effect of this function on acquired immunity. We investigated the role of bacterium-phagocytosing B cells in acquired host immune responses. Cultured mouse liver B cells substantially phagocytosed serum-opsonized Streptococcus pneumoniae and produced IgM. On adoptive transfer of liver B cells that phagocytose S. pneumoniae labeled with pHrodo Red succinimidyl ester, recipient mice showed elevated plasma levels of IgG specific for bacterial Ags. In particular, the levels of IgG2a and IgG2b specific for pneumococcal surface protein A, as well as IgG3 for pneumococcal polysaccharide, were markedly increased compared with total IgG specific for each Ag. When phagocytic liver B cells were cultured with spleen CD4+ T cells obtained from mice primed with heat-killed S. pneumoniae 7 d before, they induced IL-2 production and proliferation of the CD4+ T cells, along with Th1 cytokine production. However, they induced neither the CD4+ T cell production of IL-21, a suggested marker promoting B cell proliferation and differentiation, nor the expression of genes important for somatic hypermutation or isotype switching; such responses were particularly evident when splenic B cells merely capturing S. pneumoniae without processing them were cultured with spleen CD4+ T cells. These findings suggest that phagocytic liver B cells may be involved in acquired immune responses by presenting derivative peptides to CD4+ T cells without their own somatic hypermutation or isotype switching.

Fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, is a validated surrogate marker of nonalcoholic fatty liver disease. We retrospectively investigated the relationship between FLI and the development of ischemic heart disease (IHD) during a 10-year period.Among subjects who received annual health checkups (n = 28 990), a total of 18 851 subjects (men/women: 11 659/7192) were enrolled after exclusion of subjects with missing data and those with IHD at baseline.FLI at baseline was significantly higher in men than in women. During the 10-year period, 450 men (3.9%) and 123 women (1.7%) had new onset of IHD determined by a self-reported questionnaire survey. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard risk (HR) for the development of IHD increased with a higher FLI at baseline after adjustment of age, sex, current smoking habit, family history of IHD and diagnosis of diabetes mellitus, hypertension, dyslipidemia and chronic kidney disease at baseline. There was no significant interaction between FLI and sex for the adjusted HR. When divided by tertiles of FLI at baseline (T1∼T3), the adjusted risk for development of IHD in the T3 group (HR [95% confidence interval]: 1.34 [1.05-1.71]) was significantly higher than that in the T1 group as the reference. The addition of FLI into traditional risk factors for IHD significantly improved the discriminatory capability.A high level of FLI is an independent predictor of new onset of IHD during a 10-year period.

Music can evoke pleasurable and rewarding experiences. Past studies that examined task-related brain activity revealed individual differences in musical reward sensitivity traits, and linked them to interactions between the auditory and reward systems. However, state-dependent fluctuations in spontaneous neural activity in relation to music-driven rewarding experiences have not been studied. Here, we used functional MRI (N=49) to examine whether the coupling of auditory-reward networks during a silent period immediately before music listening can predict the degree of musical rewarding experience. We used machine learning models and showed that the functional connectivity between auditory and reward networks, but not others, could robustly predict subjective, physiological, and neurobiological aspects of the strong musical reward of chills. Specifically, the right auditory cortex-striatum/orbitofrontal connections were related to neural positive arousal responses, whereas the auditory-amygdala connection was associated with physiological arousal. Moreover, the predictive model of auditory-reward network derived from one sample of individuals replicated in an independent dataset using different music samples. The current study reveals the role of pre-task brain state in efficiently connecting sensory and reward systems leading to an intensely rewarding experience.

In molluscs, migration of hemocytes and epithelial cells is believed to play central roles in wound healing. Here, we assessed cellular and molecular mechanisms of wound healing in Pacific abalone, a marine gastropod. Light and electron microscopy in the wounds showed early accumulation of putative hemocytes, collagen deposition by fibroblasts, and further coverage of this tissue by migration of adjacent epithelial cells. Cell labelling technique allowed us to track hemocytes, which migrated to wound surface within 24 h. The migrated cells first expressed PCNA and SoxF weakly, and then the epithelial cells expressed abundant PCNA and SoxB1, SoxB2, and SoxC. These findings imply that abalone SoxF is involved in hemocyte migration or their differentiation into fibroblasts, and suggest that the migrated epithelia acquire stem cell-like property and undergo active proliferation. This study is the first to show direct evidence of hemocyte migration to wounds and expression of Sox genes in molluscan wound healing.

Supplemental Digital Content is available in the text., Severe acute respiratory syndrome coronavirus 2 in coronavirus disease 2019 invades the host through ACE (angiotensin-converting enzyme) 2 as the host cellular receptor for a viral spike protein. ACE2 converts angiotensin II to angiotensin-(1–7) and cleaved ACE2 is detectable in urine and plasma. However, regulation of U-ACE2 (urinary ACE2) and P-ACE2 (plasma ACE2) and their alterations by renin-angiotensin-aldosterone system inhibitors remain unclear. We simultaneously investigated U-ACE2 and P-ACE2 in 605 Japanese participants (male/female: 280/325, mean age: 65±15 years) in the Tanno-Sobetsu cohort study in 2017. Males had significantly lower U-ACE2 and higher P-ACE2 than did females. There was no significant correlation between U-ACE2 and P-ACE2. P-ACE2 was significantly lower in subjects treated with renin-angiotensin-aldosterone system inhibitors than in those not treated with renin-angiotensin-aldosterone system inhibitors, but there was no significant difference in U-ACE2 between the groups. Multivariable regression analyses showed that female sex, high levels of systolic blood pressure, hemoglobin A1c, and urinary albumin-to-creatinine ratio, and low uric acid level were independent predictors of high U-ACE2 level and that high levels of γ-glutamyl transpeptidase, estimated glomerular filtration rate, and uric acid were independent predictors of high P-ACE2 level. In conclusion, U-ACE2 and P-ACE2 are distinctly regulated and the use of renin-angiotensin-aldosterone system inhibitors is not an independent predictor of their levels in a Japanese general population. U-ACE2 is associated with high blood pressure, high glucose level, and microalbuminuria, and low urate level, whereas P-ACE2 is associated with liver dysfunction, high glomerular filtration rate, and high urate level.

Xanthine oxidoreductase (XOR), a rate-limiting and catalyzing enzyme of uric acid formation in purine metabolism, is involved in reactive oxygen species generation. Plasma XOR activity has been shown to be a novel metabolic biomarker related to obesity, liver dysfunction, hyperuricemia, dyslipidemia, and insulin resistance. However, the association between plasma XOR activity and hypertension has not been fully elucidated. We investigated the association of hypertension with plasma XOR activity in 271 nondiabetic subjects (male/female: 119/152) who had not taken any medications in the Tanno-Sobetsu Study, a population-based cohort. Males had higher plasma XOR activity than females. Plasma XOR activity was positively correlated with mean arterial pressure (r = 0.128, P = 0.036). When the subjects were divided by the presence and absence of hypertension into an HT group (male/female: 34/40) and a non-HT group (male/female: 85/112), plasma XOR activity in the HT group was significantly higher than that in the non-HT group (median: 39 vs. 28 pmol/h/mL, P = 0.028). There was no significant difference in uric acid levels between the two groups. Multivariable logistic regression analysis showed that plasma XOR activity (odds ratio: 1.091 [95% confidence interval: 1.023-1.177] per 10 pmol/h/mL, P = 0.007) was an independent determinant of the risk for hypertension after adjustment for age, sex, current smoking and alcohol consumption, estimated glomerular filtration rate, brain natriuretic peptide, and insulin resistance index. The interaction of sex with plasma XOR activity was not significant for the risk of hypertension. In conclusion, plasma XOR activity is independently associated with hypertension in nondiabetic individuals who are not taking any medications.

People require multimodal emotional interactions to live in a social environment. Several studies using dynamic facial expressions and emotional voices have reported that multimodal emotional incongruency evokes an early sensory component of event-related potentials (ERPs), while others have found a late cognitive component. The integration mechanism of two different results remains unclear. We speculate that it is semantic analysis in a multimodal integration framework that evokes the late ERP component. An electrophysiological experiment was conducted using emotionally congruent or incongruent dynamic faces and natural voices to promote semantic analysis. To investigate the top-down modulation of the ERP component, attention was manipulated via two tasks that directed participants to attend to facial versus vocal expressions. Our results revealed interactions between facial and vocal emotional expressions, manifested as modulations of the auditory N400 ERP amplitudes but not N1 and P2 amplitudes, for incongruent emotional face-voice combinations only in the face-attentive task. A late occipital positive potential amplitude emerged only during the voice-attentive task. Overall, these findings support the idea that semantic analysis is a key factor in evoking the late cognitive component. The task effect for these ERPs suggests that top-down attention alters not only the amplitude of ERP but also the ERP component per se. Our results implicate a principle of emotional face-voice processing in the brain that may underlie complex audiovisual interactions in everyday communication.

While hyperuricemia is recognized as a risk factor for chronic kidney disease (CKD), the risk of CKD in subjects with a low level of serum uric acid (UA) remains controversial. Here, we examined whether the association of CKD risk with serum UA level differs depending on the sex and age of subjects in a general population. Of subjects who received annual health checkups, we enrolled 6,779 subjects (male/female: 4,454/2,325; age: 45 ± 9 years) with data from a 10-year follow-up after excluding subjects taking anti-hyperuricemic drugs and those with CKD at baseline. During the follow-up period, 11.4% of the males and 11.7% of the females developed CKD. A significant interaction of sex, but not age, with the effect of baseline UA level on CKD risk was found. A restricted cubic spline analysis showed a U-shaped association of the baseline UA level with the risk of CKD in females. Multivariable Cox proportional hazard analyses for females showed that baseline UA levels in the 5th quintile (Q5, ≥5 mg/dL; HR: 1.68) and the 1st quintile (Q1, ≤3.5 mg/dL; HR: 1.73) were independent risk factors for CKD when compared with UA levels in the 4th quintile (Q4, 4.5-4.9 mg/dL). In males, restricted cubic spline analysis indicated increased CKD risk in subjects with a higher baseline UA level but not in those with a low UA level. In conclusion, a low UA level is a significant risk factor for CKD in females, while an elevated UA level increases the risk of CKD in both sexes.

Objective Previous studies have shown that digital footprints (mainly Social Networking Services, or SNS) can predict personality traits centered on the Big Five. The present study investigates to what extent different types of SNS information predicts wider traits and attributes. Method We collected an intensive set of 24 (52 subscales) personality traits and attributes (N = 239) and examined whether machine learning models trained on four different types of SNS (i.e., Twitter) information (network, time, word statistics, and bag of words) predict the traits and attributes. Results We found that four types of SNS information can predict 23 subscales collectively. Furthermore, we validated our hypothesis that the network and word statistics information, respectively, exhibit unique strengths for the prediction of inter‐personal traits such as autism and mental health traits such as schizophrenia and anxiety. We also found that intelligence is predicted by all four types of SNS information. Conclusions These results reveal that the different types of SNS information can collectivity predict wider human traits and attributes than previously recognized, and also that each information type has unique predictive strengths for specific traits and attributes, suggesting that personality prediction from SNS is a powerful tool for both personality psychology and information technology.

Facial expressions are produced by specific muscle movements. Although past studies have investigated the association between the facial action unit (AU) and emotion, how the intensity and speed of movement contribute to each emotion is unknown. Here, to reveal the role of intensity and speed cues for facial emotion recognition, we examined the machine learning model with AUs extracted using the computer vision method. Participants (n = 39) classified the stimuli of dynamic facial expressions into six emotions. Using the two-dimensional AU features of the stimuli, the machine learning models classified emotion with high accuracy. From the classification model’s contribution weighting, we found the emotion-related specificity of the intensity and speed cues. The strong contribution of intensity was for happiness, whereas speed was for anger and surprise. Sadness, fear, and disgust were not clearly differentiated by intensity and speed. Our findings suggest that people judge facial emotions by balancing appropriate intensity and speed cues.

Background Possible associations of chronic kidney disease (CKD) with fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) have recently been focused on. Metabolic dysfunction–associated fatty liver disease (MAFLD), defined as FL with overweight/obesity, type 2 diabetes mellitus or metabolic abnormalities, has been proposed as a new feature of chronic liver disease. However, the relationship between MAFLD and new onset of CKD has not been fully addressed. Methods We investigated the associations of FL, NAFLD and MAFLD with the development of CKD, defined as an estimated glomerular filtration rate (eGFR) Results The prevalence of FL, NAFLD and MAFLD was 34.6% (men 45.1%, women 15.1%), 32.8% (men 42.7%, women 14.5%) and 32.3% (men 42.4%, women 13.4%), respectively. During the 10-year follow-up period, 2163 subjects (men 1475, women 688) had new onset of CKD. Multivariable Cox proportional hazards model analyses showed that MAFLD [hazard ratio 1.12 (95% confidence interval 1.02–1.26); P = .027] but not FL or NAFLD was an independent risk factor for new onset of CKD after adjustment of age, sex, eGFR, current smoking habit, ischemic heart disease, diabetes mellitus, overweight/obesity, hypertension and dyslipidemia. The addition of MAFLD [continuous net reclassification improvement (NRI) 0.154, integrated discrimination improvement (IDI) 0.0024] to traditional risk factors without metabolic abnormalities significantly improved the discriminatory capacity better than did the addition of FL (NRI 0.138, IDI 0.0018) or NAFLD (NRI 0.132, IDI 0.0017). Conclusions MAFLD is modestly and independently associated with new onset of CKD and predicts the risk for development of CKD better than FL or NAFLD.

Aims The fibrosis-4 (FIB-4) index, calculated using age, platelet count, and levels of aspartate aminotransferase and alanine aminotransferase, is a non-invasive indicator for the detection of liver fibrosis. Advanced hepatic fibrosis is associated with morbidity and mortality in patients with non-alcoholic fatty liver disease. However, the relationship between liver fibrosis and the development of ischaemic heart disease (IHD) has not fully been addressed. Methods and results We investigated the association between the FIB-4 index and the new onset of IHD during a 10-year period in a general population of subjects who received annual health examinations (n = 28 990). After exclusion of subjects with missing data and those with a history of IHD at baseline, a total of 13 448 subjects (men/women: 8774/4674, mean age: 48 years) were included. During the 10-year period, 378 men (4.3%) and 77 women (1.6%) had a new onset of IHD. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard risk for the development of IHD increased with a higher FIB-4 index at baseline after adjustment of age, sex, fatty liver (FL) determined by ultrasonography, estimated glomerular filtration rate, habits of current smoking and alcohol drinking, family history of IHD, and diagnosis of hypertension, diabetes mellitus and dyslipidaemia. When divided by FL, the FIB-4 index becomes an independent predictor for the development of IHD in subjects with FL but not in those without FL. The addition of the FIB-4 index to traditional risk factors for IHD significantly improved the discriminatory capability. Conclusion A high level of the FIB-4 index predicts the new onset of IHD during a 10-year period.

The size of an individual active social network is a key parameter of human social behavior and is correlated with subjective well-being. However, it remains unknown how the social network size of active interactions is represented in the brain. Here, we examined whether resting-state functional magnetic resonance imaging (fMRI) connectivity is associated with the social network size of active interactions using behavioral data of a large sample (N = 222) on Twitter. Region of interest (ROI)-to-ROI analysis, graph theory analysis, seed-based analysis, and decoding analysis together provided compelling evidence that people who have a large social network size of active interactions, as measured by "reply," show higher fMRI connectivity of the left inferior frontal gyrus with the dorsomedial prefrontal cortex and temporoparietal junction, which represents the core of the theory of mind network. These results demonstrated that people who have a large social network size of active interactions maintain activity of the identified functional connectivity in daily life, possibly providing a mechanism for efficient information transmission between the brain networks related to language and theory-of-mind.

Current in vivo developmental neurotoxicity (DNT) tests are not performed routinely for chemical risk assessment because they are time and resource intensive and require many animals. Therefore, new methodologies are required that can detect and evaluate the DNT potential of chemicals in a more simple, quantitative, and objective manner. Toward this end, we generated transgenic mice expressing reporter genes (luciferase and lacZ) under the control of the rat synapsin 1 promoter (Syn-Rep mice) and evaluated their usefulness as a DNT detection tool. Brain luciferase expression levels in Syn-Rep mice increased dramatically from just before to after birth, peaked early in the postnatal period, subsequently decreased sharply, and then remained low after weaning. This pattern is analogous to the generally recognized temporal changes in synapse numbers in the developing mammal brain. To evaluate further the responsiveness of Syn-Rep mice during DNT induction, we administered valproic acid (VPA), a reference DNT-inducing chemical, to pregnant mice and evaluated its effect on reporter gene expression in the developing brains of Syn-Rep pups. In vivo luminescence in the brains of VPA-exposed pups was significantly lower than in controls from postnatal days 4 to 13. Moreover, luciferase activity in the prefrontal cortexes of 8-week-old VPA-exposed offspring was significantly lower than in controls, reflecting the reduced number of neurons in the prefrontal cortex. These results suggest that the Syn-Rep mice are potentially useful tools for streamlined detection of chemical-induced DNT in the developing mammalian brain.

Fatty liver index (FLI) calculated by using body mass index (BMI), waist circumference and levels of γ-glutamyl transferase and triglycerides is a non-invasive predictor of nonalcoholic fatty liver disease (NAFLD). The original study in Italy showed that the cutoff level for prediction of NAFLD was FLI ≥60. However, the sex difference in FLI was not taken into consideration, and it is unclear whether the cutoff value can be applied to other races. We investigated the cutoff value of FLI for prediction of NAFLD determined by abdominal ultrasonography using receiver operating characteristic curve analyses in 14,471 Japanese subjects (men/women: 9,240/5,231; mean age: 48 ± 9 years). There was a significant interaction between sex and FLI for detection of NAFLD (p < 0.001). The cutoff values of FLI in men and women were 35.1 (area under the curve [AUC]: 0.82) and 15.6 (AUC: 0.91), respectively. When the subjects were divided by the absence and presence of obesity (BMI ≥25), there was a significant interaction between FLI and obesity for detection of NAFLD in women (p < 0.001) but not in men (p = 0.679). The cutoff values of FLI in non-obese/obese men and women were 22.6/52.6 and 11.2/33.2, respectively. In conclusion, the cutoff value of FLI for prediction of NAFLD in Japanese individuals was lower than that in the original study, and there is a significant sex difference. The simple and useful cutoff values in Japanese men and women are FLI ≥35 (non-obese/obese: 23/53) and FLI ≥16 (non-obese/obese: 11/33), respectively.

Background Fatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. Because of a sex difference in FLI level, we hypothesized that FLI is associated with development of hypertension to a greater extent in men or women. Methods and Results We investigated the relationship between FLI and development of hypertension during a 10‐year period in a general population of subjects who received annual health examinations (n=28 990). After exclusion (44.9%) of subjects with missing data and those with hypertension at baseline, a total of 15 965 subjects (men/women: 9466/6499) were included. FLI level was significantly higher in men than in women. During the 10‐year period, 2304 men (24.3%) and 745 women (11.5%) had new onset of hypertension. Multivariable Cox proportional hazard models with a restricted cubic spline showed that the hazard ratios (HRs) for development of hypertension after adjustment of age, systolic blood pressure, estimated glomerular filtration rate, habits of smoking and alcohol drinking, family history of hypertension, and diagnosis of diabetes mellitus and dyslipidemia increased gradually with increase in FLI in men and increased rapidly and then slowly with increase in FLI in women. There was a significant interaction between FLI and sex for the risk of hypertension in all of the subjects ( P =0.049). The addition of FLI to traditional risk factors significantly improved the discriminatory capability. Conclusions A high level of FLI predicts the development of hypertension in both men and women, although distribution patterns of HRs were different between sexes.

Whether hyperuricemia is a true risk factor for elevated blood pressure (BP) is controversial, and the sex-specific effects of serum uric acid (SUA) on BP during a follow-up period remain unclear. We investigated whether the association of SUA level with systolic or diastolic BP during a 10-year period differs by sex in a Japanese general population of individuals who received annual health examinations (n = 28,990). After exclusion of subjects who had no BP or SUA data at baseline, a total of 22,994 subjects (male/female: 14,603/8391, age: 47 ± 11 years) were recruited. After adjustment for age; body mass index; BP; SUA level; use of drugs for hyperuricemia and hypertension; diagnosis of diabetes mellitus, dyslipidemia, and chronic kidney disease; family history of hypertension; habits of current smoking and alcohol consumption at baseline; the duration of the observation period; and the interaction between each covariate and the duration of the observation period indicated a significant association of SUA level with change in systolic or diastolic BP over time. There was a significant interaction between sex and SUA level for the change in systolic BP (P = 0.003) but not the change in diastolic BP (P = 0.081). The SUA level at baseline (per 1 mg/dL) was significantly associated with a change in systolic BP over time in females (estimate: 0.073 mmHg/year, P = 0.003) but not in males (estimate: 0.020 mmHg/year, P = 0.160). In conclusion, a high SUA level at baseline is significantly associated with an increase in systolic BP over time in female individuals but not in male individuals. A high uric acid level at baseline is significantly associated with an increase in systolic blood pressure over time in female individuals but not in male individuals.

Recent studies have revealed that mammalian B cells ingest particulate Ags, such as bacteria, although little is known about the effect of this function on acquired immunity. We investigated the role of bacterium-phagocytosing B cells in acquired host immune responses. Cultured mouse liver B cells substantially phagocytosed serum-opsonized

Music can evoke strong emotions. Research has suggested that pleasurable chills (shivering) and tears (weeping) are peak emotional responses to music. The present study examines whether computational acoustic and lyrical features can decode chills and tears. The experiment comprises 186 pieces of self-selected music to evoke emotional responses from 54 Japanese participants. Machine learning analysis with L2-norm-regularization regression revealed the decoding accuracy and specified well-defined features. In Study 1, time-series acoustic features significantly decoded emotional chills, tears, and the absence of chills or tears by using information within a few seconds before and after the onset of the three responses. The classification results showed three significant periods, indicating that complex anticipation-resolution mechanisms lead to chills and tears. Evoking chills was particularly associated with rhythm uncertainty, while evoking tears was related to harmony. Violating rhythm expectancy may have been a trigger for chills, while the harmonious overlapping of acoustic spectra may have played a role in evoking tears. In Study 2, acoustic and lyrical features from the entire piece decoded tears but not chill frequency. Mixed emotions stemming from happiness were associated with major chords, while lyric content related to sad farewells can contribute to the prediction of emotional tears, indicating that distinctive emotions in music may evoke a tear response. When considered in tandem with theoretical studies, the violation of rhythm may biologically boost both the pleasure- and fight-related physiological response of chills, whereas tears may be evolutionarily embedded in the social bonding effect of musical harmony and play a unique role in emotional regulation.

Serum vitamin D level shows a seasonal variation, being lower in winter than in summer in healthy subjects. The aim of this study was to determine whether there is presence of such a seasonal variation in hemodialysis patients. A total of 102 patients on hemodialysis were enrolled in February 2017 (winter) for analyses of serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and treatments for chronic kidney disease-mineral and bone disorder (CKD-MBD). The examinations were repeated in August 2017 (summer). After exclusion of patients with malignancy, loss of follow-up and missing data, 78 patients contributed to the analyses. Serum level of 25(OH)D, but not that of 1,25(OH)2D, was significantly lower in winter (14.0 ng/mL) than in summer (15.5 ng/mL), though there was no significant difference in regimen for CKD-MBD treatment including vitamin D receptor activators (VDRAs) between the two seasons. Serum intact parathyroid hormone level tended to be higher and alkaline phosphatase was significantly higher in winter than in summer. Linear mixed-effects model analysis showed that level of 25(OH)D, but not that of 1,25(OH)2D, was significantly associated with season (winter and summer) after adjustment of age, sex, dialysis vintage, albumin level and use of drugs for CKD-MBD. Serum 25(OH)D has a seasonal variation, being lower in winter than in summer, independent of CKD-MBD treatment including treatment with VDRAs in Japanese hemodialysis patients. The impact of the seasonal variation on risk of vitamin D deficiency and its effect on prognosis remain to be investigated.

A 40-year-old man was admitted to our hospital for COVID-19. He had been treated for essential thrombocythemia (ET). He was diagnosed severe illness of COVID-19, oxygen therapy and dexamethasone were administered. There was a possibility of thromboembolic events in this case, apixaban for prophylaxis was added. With these treatments, the patient has made a good recovery, and he was discharged on hospital day 11. There is no standard strategy for prophylaxis of thrombosis in patients with ET, and apixaban could be a clinical benefit for these patients.

The experience of being emotionally “moved” is considered a valuable emotional experience. Although pleasant chills (goosebumps and shivers) and tears (weeping and a lump in the throat) are commonly associated with the experience of being emotionally moved, no previous studies have examined which of these psychophysiological responses is the most intrinsic to the phenomenon of being moved. We conducted two music listening experiments to examine this question. Both experiments revealed that, when chills and tears were reliably separated, chills evoked phasic increases in electrodermal activity, whereas tears induced phasic decreases in heart and respiration rate during tonic physiological arousal. Importantly, whereas tears predicted the experience of being moved, experiencing chills did not. Furthermore, psychoacoustic features of music did not explain the physiological response of chills and tears. The results demonstrated that the experience of being moved involved a sense of pleasure coupled with psychophysiological relief from tension. Based on extended attachment theory, the sequential process of physiological arousal to physiological calming, which is derived from abstract life-guiding ideas via the combination of sound and lyrics, may be important for evoking the experience of being emotionally moved. These psychophysiological characteristics could explain why people seek to be moved.

Hypouricemia is a high-risk factor of exercise-induced acute kidney injury (EIAKI) probably through a lack of an antioxidant effect of uric acid. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR has been proposed to promote oxidative stress-related tissue injury. We measured plasma XOR activity by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry in subjects with relatively low levels of uric acid (≤4.0 mg/dL) who were recruited from 627 subjects (male/female: 292/335) in the Tanno-Sobetsu Study, a population-based cohort. The numbers of subjects with uric acid ≤4.0 mg/dL, ≤3.0 mg/dL and ≤2.0 mg/dL were 72 (11.5%, male/female: 5/67), 13 (2.1%, all females) and 2 (0.3%, both females), respectively. Plasma XOR activities in 5 male subjects were below the median value of the 292 male subjects. In 12 (17.9%) of the 67 female subjects with uric acid ≤4.0 mg/dL, plasma XOR activities were above the upper quartile value of the 335 female subjects. Eleven of the 12 female subjects with high plasma XOR activity and a low uric acid level had liver dysfunction and/or insulin resistance. In conclusion, unexpected high plasma XOR activities were found in some female subjects with relatively low levels of uric acid. Measurement of plasma XOR activity may help to identify hypouricemic patients with a high risk for EIAKI.

Photoinduced electron transfer (PET) reactions promoted by 2-aryl substituted 1,3-dimethylbenzimidazolines (Ar-DMBIH) were investigated. Excited states of Ar-DMBIH, formed by irradiation using light above 360 nm, initiate PET reductions of various organic substrates, including transformations of epoxy ketones to aldols, free radical rearrangements such as the Dowd-Beckwith ring-expansion and 5- exo hexenyl cyclization, deprotection of N -sulfonyl-indols, and allylation of acyl formates. In these processes, Ar-DMBIH possessing 1-naphthyl, 2-naphthyl, 1-pyrenyl and 9-anthryl substituents formally act as two electron and one proton donors while the hydroxynaphthyl substituted derivative serves as a two electron and two proton donor. On the basis of the results of absorption spectroscopy studies, cyclic voltammetry and DFT calculation, a mechanistic sequence for these reduction reactions is proposed that involves initial photoexcitation of the aryl chromophore of the Ar-DMBIH followed by single electron transfer (SET) to the organic substrate to generate the radical cation of benzimidazoline and the radical anion of the substrate.

Chills (goose bumps or shivers) evoked by listening to one’s favorite music are an indicator of a rewarding experience. The current study examined the relationship between individual differences in general reward sensitivity and music-evoked chills. To assess this relationship, we measured the three subscales of the behavioral activation system (BAS) and the frequency and intensity of music-evoked chills in a large-sample survey (Study 1) and a psychophysiological experiment (Study 2). One result observed in both studies was that people with high BAS reward responsiveness experienced more intense chills from music. Moreover, the results showed that the experience of chills induced highly pleasurable emotions and psychophysiological arousal. The present study suggests that general reward sensitivity is a predictor of music-evoked chills. Although music is just a sequence of tones and not clearly related to survival value, music could create a rewarding experience partially similar to other rewarding actions or events.