Search for Periodic Time Variations of the Solar

We report a search for time variations of the solar ^{8}B neutrino flux using 5804 live days of Super-Kamiokande data collected between May 31, 1996, and May 30, 2018. Super-Kamiokande measured the precise time of each solar neutrino interaction over 22 calendar years to search for solar neutrino flux modulations with unprecedented precision. Periodic modulations are searched for in a dataset comprising five-day interval solar neutrino flux measurements with a maximum likelihood method. We also applied the Lomb-Scargle method to this dataset to compare it with previous reports. The only significant modulation found is due to the elliptic orbit of the Earth around the Sun. The observed modulation is consistent with astronomical data: we measured an eccentricity of (1.53±0.35)%, and a perihelion shift of (-1.5±13.5) days.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande.

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.

Erratum: Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande [Phys. Rev. Lett. 130, 031802 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.031802.

Concomitant assessment of DNA oxidation and bone resorption over a rapid body mass reduction period in female judokas.

The purpose of this study was to concomitantly determine oxidative DNAdamage and bone resorption following a rapid body mass reduction in association with energy restriction and exercise training, considering 17ß-estradiol level, in female collegiate judokas. Eighteen nationally ranked university female judokas were enrolled as participants in this study. All participants continuously managed to reduce their body mass 8 days just before a competition. To detect cumulative effects of oxidative DNA damage and bone resorption, urinary samples were collected in the morning on three different days (Day 1= the beginning of body mass reduction; Day 4=mid-term of body mass reduction; Day 7=the day before the competition) for the later analysis of 8-hydroxy-2’- deoxyguanosine (8-OHdG) as well as cross-linked N-terminal telopeptides of Type I collagen (NTx). Urinary 8-OHdG and NTx levels were determined with high performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. No significant alterations were observed in urinary 8-OHdG or NTx levels over a rapid body mass reduction period. The findings of the present study indicate that female judokas appear to have relatively less oxidative DNA damage determined by quantification of 8-OHdG and bone resorption over a rapid body mass reduction period, potentially due to the enhanced endogenous defense responses (training adaptation). These data can provide athletes and coaches with valuable information in considering an optimal body mass management program to avoid detrimental physiological and biological conditions.

Calcineurin inhibitors exacerbate coronary arteritis via the MyD88 signalling pathway in a murine model of Kawasaki disease.

Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)-/- and myeloid differentiation primary response gene 88 (MyD88)-/- mice. We also performed in-vitro studies with vascular and monocytic cells and vascular tissues. A histopathological analysis showed that both cyclosporin A and tacrolimus exacerbated the NOD1-mediated coronary arteritis in a dose-dependent manner. Cyclosporin A induced the exacerbation of coronary arteritis in mice only in high doses, while tacrolimus exacerbated it within the therapeutic range in humans. Similar effects were obtained in SCID and CARD9-/- mice but not in MyD88-/- mice. CNIs enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells in our KD model. These data indicated that both vascular and monocytic cells were involved in the exacerbation of coronary arteritis. Activation of MyD88-dependent inflammatory signals in both vascular cells and macrophages appears to contribute to their adverse effects. Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD.

Effect of sodium-glucose co-transporter-2 inhibitors on impaired ventricular repolarization in people with Type 2 diabetes.

AIMS: To test the hypothesis that treatment with a sodium-glucose co-transporter-2 inhibitor would reverse ventricular repolarization heterogeneity, a predictor of cardiovascular mortality, in people with Type 2 diabetes. METHODS: We retrospectively analysed changes in indices of ventricular repolarization before and after treatment with a sodium-glucose co-transporter-2 inhibitor in 46 people with Type 2 diabetes. RESULTS: Sodium-glucose co-transporter-2 inhibitor treatment reduced HbA1c concentration [62±13 mmol/mol (7.7±1.2%) vs 59±16 mmol/mol (7.5±1.4%)], body weight (77.8±13.9 vs 74.7±12.5 kg) and systolic blood pressure (133±18 vs 126±12 mmHg) in the study participants. Heart rate and QTc interval were not changed by sodium-glucose co-transporter-2 inhibitor treatment, but QTc dispersion was significantly reduced (median, 48.8 vs 44.2 ms). Sodium-glucose co-transporter-2 inhibitor treatment reversed QTc dispersion more in participants who had larger QTc dispersion before the treatment. Changes in systolic blood pressure (Spearman's ρ= 0.319; P=0.031), but not in HbA1c concentration, were correlated with changes in QTc dispersion after sodium-glucose co-transporter-2 inhibitor treatment. CONCLUSIONS: The findings suggest that sodium-glucose co-transporter-2 inhibitor treatment reverses ventricular repolarization heterogeneity in people with Type 2 diabetes, independently of its effect on glycaemic control. The favourable effect on ventricular repolarization heterogeneity could be the mechanism by which empaglifozin reduced cardiovascular events in a recent study.

Novel double step approach for optical sensing via microsphere WGM resonance.

The use of resonant whispering gallery modes (WGMs) for sensing exhibits various drawbacks and critical points related to the microsphere and tapered optical fiber fabrication tolerance. The uncertainty on the fiber taper and microsphere geometry or the gap between the microsphere and the fiber taper can complicate or limit the actual use of these devices for sensing, requiring peculiar calibration of the WGM based sensing set-up. An alternative double-step approach is proposed in this paper. In particular, the geometrical parameters of the set-up are recovered preliminarily and then the rare earth parameters are recovered via simple transmittance/gain measurements. The method is based on a refined electromagnetic model of the device suitably integrated with a particle swarm optimization (PSO) approach. The percent errors made on the up-conversion coefficients Cup and C3 are extremely low, being 0.75%, 0.05%, respectively. The procedure is very robust. It can be applied more in general, allowing the sensing of other physical parameters via simple transmittance measurements instead of wavelength shift ones, in both microsphere and microbubble based set-up.

Postcomparison of [(18) F]-fluorodeoxyglucose uptake in the brain after short-term bright light exposure and no intervention.

OBJECTIVE: Bright light therapy is widely used as the treatment of choice for seasonal affective disorder. Nonetheless, our understanding of the mechanisms of bright light is limited and it is important to investigate the mechanisms. The purpose of this study is to examine the hypothesis that bright light exposure may increase [(18) F]-fluorodeoxyglucose (FDG) uptake in olfactory bulb and/or hippocampus which may be associated neurogenesis in the human brain. METHOD: A randomized controlled trial comparing 5-day bright light exposure + environmental light (bright light exposure group) with environmental light alone (no intervention group) was performed for 55 participants in a university hospital. The uptake of [(18) F]FDG in olfactory bulb and hippocampus using FDG positron emission tomography was compared between two groups. RESULTS: There was a significant increase of uptake in both right and left olfactory bulb for bright light exposure group vs. no intervention group. After adjustment of log-transformed illuminance, there remained a significant increase of uptake in the right olfactory bulb. CONCLUSION: The present findings suggest a possibility that 5-day bright light exposure may increase [(18) F]FDG in the right olfactory bulb of the human brain, suggesting a possibility of neurogenesis. Further studies are warranted to directly confirm this possibility.

IQ is an independent predictor of glycated haemoglobin level in young and middle-aged adults with intellectual disability.

AIMS: Here we examined whether intellectual disability is independently associated with hyperglycaemia. METHODS: We recruited 233 consecutive young and middle-aged adults with intellectual disability. After exclusion of subjects on medication for metabolic diseases or with severe intellectual disability (IQ < 35), 121 subjects were divided by IQ into a group with moderate intellectual disability (35 ≤ IQ ≤ 50), a mild intellectual disability group (51 ≤ IQ ≤ 70) and a borderline group (IQ > 70). RESULTS: HbA1c level was higher in subjects with moderate intellectual disability (42 ± 9 mmol/mol; 6.0 ± 0.8%) than those in the borderline group (36 ± 4 mmol/mol; 5.5 ± 0.3%) and mild intellectual disability group (37 ± 5 mmol/mol; 5.5 ± 0.5%) groups. HbA1c level was correlated with age, BMI, blood pressure, serum triglycerides and IQ in simple linear regression analysis. Multiple regression analysis indicated that IQ, age, BMI and diastolic blood pressure were independent explanatory factors of HbA1c level. CONCLUSIONS: An unfavourable effect of intellectual disability on lifestyle and untoward effect of hyperglycaemia on cognitive function may underlie the association of low IQ with hyperglycaemia.

Muscle pump in the vastus lateralis in the supine position in light prolonged exercise.

AIM: The purpose of this study was to examine whether the muscle pump in the supine position is attenuated during light prolonged exercise. METHODS: After rest for 5 min, constant-load exercise with 50% of peak oxygen uptake (VO2) determined by incremental exercises in the supine position was performed for 60 min with a pedaling rate of 60 rpm. Total hemoglobin and myoglobin (total Hb) in the vastus lateralis was determined by using a near-infrared spectroscopy (NIRS) system. The instrument was operating at 2 Hz. VO2, heart rate (HR), mean blood pressure (MBP) and muscle deep temperature (Tm) were measured in the constant-load exercise. RESULTS: After an increase at the onset of exercise, VO2 showed a steady state, HR showed a significant gradual increase and MBP significantly decreased. After an increase until 20 min of exercise, Tm showed a steady state. Level of total Hb increased until 20 min and showed a steady state in all subjects. Average Tm was significantly related to average total Hb (r=0.978). Total Hb oscillated, but its oscillation occasionally disappeared. Peak amplitude of oscillation in total Hb for 30 s after the start of exercise was significantly higher than that for 1 min before the end of exercise. CONCLUSION: The results suggest that the muscle pump operates in light exercise but is attenuated in the vastus lateralis in the supine position at the late phase of prolonged exercise.

Effects of heat exposure in the absence of hyperthermia on power output during repeated cycling sprints.

The aim of this study was to investigate the effects of heat exposure in the absence of hyperthermia on power output during repeated cycling sprints. Seven males performed four 10-s cycling sprints interspersed by 30 s of active recovery on a cycle ergometer in hot-dry and thermoneutral environments. Changes in rectal temperature were similar under the two ambient conditions. The mean 2-s power output over the 1st-4th sprints was significantly lower under the hot-dry condition than under the thermoneutral condition. The amplitude of the electromyogram was lower under the hot-dry condition than under the thermoneutral condition during the early phase (0-3 s) of each cycling sprint. No significant difference was observed for blood lactate concentration between the two ambient conditions. Power output at the onset of a cycling sprint during repeated cycling sprints is decreased due to heat exposure in the absence of hyperthermia.

Estimation of kidney injury molecule-1 (Kim-1) in patients with lupus nephritis.

OBJECTIVE: Biomarkers of disease activity in lupus nephritis (LN) are needed. Ideally, such biomarkers would be capable of detecting early sub-clinical disease and could be used to gauge response to therapy, thus obviating the need for serial renal biopsies. Much of the focus in the search for LN biomarkers has been on the measurement of urinary chemokines and cytokines in LN patients. However, these have yet to be widely implemented in clinical practice. Kidney injury molecule-1 (Kim-1) is expressed in damaged tubules, but whether urinary (u) and tubular (t)-Kim-1 could serve as a biomarker of active LN is unknown. To investigate the disease activity and histological findings in LN, we evaluated u-Kim-1 levels and t-Kim-1 cells in patients with systemic lupus erythematosus (SLE). METHOD: We measured u-Kim-1 levels and stained t-Kim-1 expression in 57 patients with LN using an ELISA and immunohistochemistry staining. Patients were classified into two groups (active LN, n = 37; inactive LN, n = 20) based on the presence of active renal disease according to the renal SLE disease activity index. correlations of clinical, laboratory data, and histological findings with urinary and t-Kim-1 expression were assessed. RESULT: The u-Kim-1 levels were significantly correlated with the expression of t-Kim-1 (R = 0.64; P = 0.004) in the SLE patients. The active LN patients exhibited elevated u-Kim-1 levels compared to the inactive LN patients. The number of t-Kim-1 cells was also correlated with histological findings (both glomerular and interstitial inflammation). The u-Kim-1 levels were also correlated with proteinuria and tubular damage in the active LN group. The number of t-Kim-1 cells at baseline was significantly correlated with the estimated glomerular filtration rate (R = 0.72; P = 0.005) and serum creatinine (R = 0.53; P = 0.005) after 6-8 months of treatment. CONCLUSION: These data suggest the potential use of the u-Kim-1 levels to screen for active LN and for the estimation of t-Kim-1 expression in renal biopsies to predict renal damage, ongoing glomerular nephritis and tubulointerstitial inflammation, and tubular atrophy.

Peptides derived from phage display libraries as potential neutralizers of Shiga toxin-induced cytotoxicity in vitro and in vivo.

AIMS: To use the phage display technique to develop peptides with the capability to neutralize the cytotoxicity induced by Stx1 and Stx2 toxins produced by Shiga toxin-producing Escherichia coli (STEC). METHODS AND RESULTS: The phage display technique permitted the development of three peptides, named PC7-12, P12-26 and PC7-30, which bind to the globotriaosylceramide (Gb3) receptor for Shiga toxins produced by STEC. Moreover, these peptides were capable of competing efficiently with the Shiga toxins for binding to Gb3. The peptides described herein partially inhibited the Stx-induced cytotoxicity of cell-free filtrates of STEC O157 : H7 and purified Stx toxins in Vero cells. The inhibition of lethality induced by Stx toxins in mice indicated that peptide PC7-30 inhibited the lethality caused by Stx1 (2LD50) in mice. CONCLUSIONS: The phage display technique permitted the development of peptides that inhibited the cytotoxicity induced by Stx toxins in vitro. Peptide PC7-30 inhibited the lethality of Stx1 in vivo; this molecule would be a promising candidate for the development of therapeutic agents for STEC-related diseases in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: The selection of Gb3, the common receptor for Stx1 and Stx2, may contribute to the development of efficient neutralizers for both toxins, and our approach would be an interesting alternative for the development of therapeutic molecules for the treatment of diseases caused by STEC strains.

Prospective study comparing the new sclerotherapy and hemorrhoidectomy in terms of therapeutic outcomes at 4 years after the treatment.

PURPOSE: Recently, sclerotherapy using a new sclerosing agent (aluminum potassium sulfate and tannic acid) has become widespread in Japan as a treatment for hemorrhoids. In the present study, we investigated whether sclerotherapy or surgical therapy (hemorrhoidectomy) is superior in terms of the therapeutic outcomes at 4 years. METHODS: We sent a questionnaire on symptoms and the degree of satisfaction to patients who underwent sclerotherapy or hemorrhoidectomy for grade 3 or 4 hemorrhoids in 2007, and compared the two therapies based on the responses, with respect to superiority of the therapeutic outcomes at 4 years. To identify the factors affecting the symptom-free and satisfaction rates, the univariate and multivariate analyses were performed for the following seven parameters: age, sex, degree of hemorrhoids, presence of external hemorrhoids, past history of treatment for hemorrhoids, number of hemorrhoids treated and the type of treatment. RESULTS: Overall, 75 % of the patients (195/260) responded to the questionnaire. In this study, the symptom-free rates were 53 % (30/57 patients) in the sclerotherapy group and 80 % (111/138 patients) in the hemorrhoidectomy group, and the satisfaction rates were 70 % (40/57 patients) in the sclerotherapy group and 88 % (121/138 patients) in the hemorrhoidectomy group. The results revealed that the type of treatment was the only factor affecting these two outcomes. CONCLUSIONS: Our results indicate that hemorrhoidectomy is superior to sclerotherapy. These findings may be useful in the treatment of hemorrhoid patients.

Comparison of oscillations of skin blood flow and deoxygenation in vastus lateralis in light exercise.

The purpose of the present study was to compare oscillation of skin blood flow with that of deoxygenation in muscle during light exercise in order to determine the physiological significance of oscillations in deoxygenation. Prolonged exercise with 50% of peak oxygen uptake was performed for 60 min. Skin blood flow (SBF) was measured using a laser blood flow meter on the right vastus lateralis muscle. Deoxygenated haemoglobin/myoglobin (DHb/Mb) concentration in the left vastus lateralis were measured using a near-infrared spectroscopy system. SBF and DHb/Mb during exercise were analysed by fast Fourier transform. We classified frequency bands according to previous studies (Kvernmo et al. 1999, Kvandal et al. 2006) into phase I (0.005-0.0095 and 0.0095-0.02 Hz), phase II (0.02-0.06 Hz: phase II) and phase III (0.06-0.16 Hz). The first peak of power spectra density (PSD) in SBF appeared at 0.0078 Hz in phase I. The second peak of PSD in SBF appeared at 0.035 Hz. The third peak of PSD in SBF appeared at 0.078 Hz. The first peak of PSD in DHb/Mb appeared at 0.0039 Hz, which was out of phase I. The second peak of PSD in DHb/Mb appeared at 0.016 Hz. The third peak of PSD in DHb/Mb appeared at 0.035 Hz. The coefficient of cross correlation was very low. Cross power spectra density showed peaks of 0.0039, 0.016 and 0.035 Hz. It is concluded that a peak of 0.016 Hz in oscillations of DHb/Mb observed in muscle during exercise is associated with endothelium-dependent vasodilation (phase I) and that a peak of 0.035 Hz in DHb/Mb is associated with sympathetic nerve activity (phase II). It is also confirmed that each peak of SBF oscillations is observed in each phase.

Listening evaluation of cochlear implant users: comparison of subjective and objective evaluation by visual analogue scale.

OBJECTIVE: This study aimed to use short-form visual analogue scale cochlear implantation questionnaires to evaluate subjective aspects at each out-patient visit. The correlation between subjective hearing tests using the short-form visual analogue scale and objective hearing outcomes was evaluated. METHOD: This study was conducted in a single centre. Cochlear implant users (n = 199) evaluated their hearing on a scale of 0 to 100 for the right, left and both ears. The Japanese speech perception test (CI-2004) Japanese monosyllable speech perception test (67-S) and cochlear implantation threshold were used for the objective cochlear implantation evaluation. RESULTS: A significant correlation was found between the short-form visual analogue scale questionnaire and objective hearing outcome, for words (r = 0.64) and sentences (r = 0.62) in CI-2004 and 67-S (r = 0.56) tests. No significant correlation was found between the short-form visual analogue scale score and cochlear implantation threshold (r = -0.18). CONCLUSION: Short-form visual analogue scale cochlear implantation questionnaires mean cochlear implant users spend less time answering subjective visual analogue scale questionnaires, and clinicians estimate a patient's cochlear implantation hearing and abnormality by chronological evaluation.

Role of multifunctional transcription factor TFII-I and putative tumour suppressor DBC1 in cell cycle and DNA double strand damage repair.

BACKGROUND: In multicellular organisms, precise control of cell cycle and the maintenance of genomic stability are crucial to prevent chromosomal alterations. The accurate function of the DNA damage pathway is maintained by DNA repair mechanisms including homologous recombination (HR). Herein, we show that both TFII-I and DBC1 mediate cellular mechanisms of cell-cycle regulation and DNA double strand damage repair. METHODS: Regulation of cell cycle by TFII-I and DBC1 was investigated using Trypan blue dye exclusion test, luciferase assay, and flow cytometry analysis. We also analysed the role of TFII-I and DBC1 in DNA double strand damage repair after irradiation by immunofluorescence study, clonogenicity assay, and HR assay. RESULTS: Flow cytometry analysis revealed a novel function that siRNA-mediated knockdown of endogenous DBC1 resulted in G2/M phase arrest. We also have shown that both endogenous TFII-I and DBC1 activate DNA repair mechanisms after irradiation because irradiation-induced foci formation of TFII-I-γH2AX was observed, and the depletion of endogenous TFII-I or DBC1 resulted in the inhibition of normal HR efficiency. CONCLUSION: These results reveal novel mechanisms by which TFII-I and DBC1 can modulate cellular fate by affecting cell-cycle control as well as HR pathway.

Radial incision and cutting method for refractory stricture after nonsurgical treatment of esophageal cancer.

Strictures remaining after nonsurgical treatment for esophageal cancer are generally more refractory to endoscopic balloon dilation (EBD) when compared with anastomotic strictures. The aim of the present study was to evaluate the efficacy and safety of a radial incision and cutting (RIC) method for the treatment of refractory strictures after nonsurgical treatment of esophageal cancer. All subjects complained of grade 2 or worse dysphagia, even after at least 10 sessions of EBD. Between August 2009 and May 2012, eight consecutive patients with refractory esophageal stricture after nonsurgical treatments, including chemoradiotherapy (CRT) alone (n = 3), CRT followed by salvage endoscopic treatment (n = 3), or endoscopic submucosal dissection (ESD; n = 2), underwent the RIC procedure. After the RIC procedure, dysphagia in all the patients dramatically improved to grade 1 or 0 without any major complications; however, the long-term efficacy was unfavorable as only 37.5 % (3 /8) demonstrated adequate lumen patency at 3 months, and re-intervention was necessary in six patients (75 %).

Lack of GPR40/FFAR1 does not induce diabetes even under insulin resistance condition.

AIMS: G protein-coupled receptor/free fatty acid receptor 1 (GPR40/FFAR1 ) regulates free fatty acid-induced insulin secretion. This study has been performed to clarify whether or not loss of GPR40/FFAR1 function exacerbates diabetes, that is, whether GPR40 has an essential physiological role in the development of diabetes or not. METHODS: We generated GPR40/FFAR1 knockout (KO) mice and analysed their phenotypes in vitro and in vivo under the condition of dietary or genetically induced insulin resistance. RESULTS: GPR40/FFAR1 KO mice kept on a high-fat diet became obese, developed glucose intolerance to a similar degree as GPR40/FFAR1 wild-type (WT) mice. In addition, the phenotype of KO mice harbouring diabetogenic KK background genes showed glucose intolerance at a level similar to level for control KK mice. In both mouse models with insulin resistance, insulin secretion after oral glucose load and homeostasis model assessment-insulin resistance (HOMA-IR) did not change between GPR40/FFAR1 KO and WT mice. Although glucose-induced insulin secretion under high palmitate concentration was significantly lower in KO than in WT islets, pancreatic insulin content and insulin secretion stimulated with glucose alone were not different between KO and WT mice. CONCLUSIONS: GPR40/FFAR1 has a major role in regulating fatty-acid-mediated insulin secretion, but the lack of GPR40/FFAR1 does not exacerbate glucose intolerance and insulin resistance induced by high-fat diet or diabetogenic KK gene. Our findings indicate that loss of GPR40/FFAR1 function does not play an important role in inducing or exacerbating diabetes.