Search

Particle dark matter could belong to a multiplet that includes an electrically charged state. WIMP dark matter (χ0) accompanied by a negatively charged excited state (χ−) with a small mass difference (e.g. < 20 MeV) can form a bound-state with a nucleus such as xenon. This bound-state formation is rare and the released energy is O(1−10) MeV depending on the nucleus, making large liquid scintillator detectors suitable for detection. We searched for bound-state formation events with xenon in two experimental phases of the KamLAND-Zen experiment, a xenon-doped liquid scintillator detector. No statistically significant events were observed. For a benchmark parameter set of WIMP mass mχ0=1 TeV and mass difference Δm=17 MeV, we set the most stringent upper limits on the recombination cross section times velocity 〈σv〉 and the decay-width of χ− to 9.2×10−30 cm3/s and 8.7×10−14 GeV, respectively at 90% confidence level.

Cosmic-ray muons produce various radioisotopes when passing through material. These spallation products can be backgrounds for rare event searches such as in solar neutrino, double-β decay, and dark matter search experiments. The KamLAND-Zen experiment searches for neutrinoless double-β decay in 745 kg of xenon dissolved in liquid scintillator. The experiment includes dead-time-free electronics with a high efficiency for detecting muon-induced neutrons. The production yields of different radioisotopes are measured with a combination of delayed coincidence techniques, newly developed muon reconstruction, and xenon spallation identification methods. The observed xenon spallation products are consistent with results from the fluka and geant4 simulation codes.

We report a measurement of the strange axial coupling constant gAs using atmospheric neutrino data at KamLAND. This constant is a component of the axial form factor of the neutral-current quasielastic (NCQE) interaction. The value of gAs significantly changes the ratio of proton and neutron NCQE cross sections. KamLAND is suitable for measuring NCQE interactions as it can detect nucleon recoils with low-energy thresholds and measure neutron multiplicity with high efficiency. KamLAND data, including the information on neutron multiplicity associated with the NCQE interactions, makes it possible to measure gAs with a suppressed dependence on the axial mass MA, which has not yet been determined. For a comprehensive prediction of the neutron emission associated with neutrino interactions, we establish a simulation of particle emission via nuclear deexcitation of C12, a process not considered in existing neutrino Monte Carlo event generators. Energy spectrum fitting for each neutron multiplicity gives gAs=-0.14-0.26+0.25, which is the most stringent limit obtained using NCQE interactions without MA constraints. The two-body current contribution considered in this analysis relies on a theoretically effective model and electron scattering experiments and requires future verification by direct measurements and future model improvement.

The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νββ) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νββ decay half-life of T_{1/2}^{0ν}>2.3×10^{26}  yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.

We report the results of a search for MeV-scale astrophysical neutrinos in KamLAND presented as an excess in the number of coincident neutrino interactions associated with the publicly available high-energy neutrino datasets from the IceCube Neutrino Observatory. We find no statistically significant excess in the number of observed low-energy electron antineutrinos in KamLAND, given a coincidence time window of ±500 s, ±1,000 s, ±3,600 s, and ±10,000 s around each of the IceCube neutrinos. We use this observation to present limits from 1.8 MeV to 100 MeV on the electron antineutrino fluence, assuming a mono-energetic flux. We then compare the results to several astrophysical measurements performed by IceCube and place a limit at the 90% confidence level on the electron antineutrino isotropic thermal luminosity from the TXS 0506+056 blazar.

The decay of the primordial isotopes 238U, 235U, 232Th, and 40K has contributed to the terrestrial heat budget throughout the Earth's history. Hence, the individual abundance of those isotopes are key parameters in reconstructing contemporary Earth models. The geoneutrinos produced by the radioactive decays of uranium and thorium have been observed with the Kamioka Liquid-Scintillator Antineutrino Detector (KamLAND). Those measurements have been improved with more than 18-year observation time, and improvement in detector background levels mainly with an 8-year nearly reactor-free period, which now permit spectroscopy with geoneutrinos. Our results yield the first constraint on both uranium and thorium heat contributions. The KamLAND result is consistent with geochemical estimations based on elemental abundances of chondritic meteorites and mantle peridotites. The High-Q model is disfavored at 99.76% C.L. and a fully radiogenic model is excluded at 5.2σ assuming a homogeneous heat producing element distribution in the mantle.

We present the results of a search for core-collapse supernova neutrinos, using long-term KamLAND data from 2002 March 9 to 2020 April 25. We focus on the electron antineutrinos emitted from supernovae in the energy range of 1.8-111 MeV. Supernovae will make a neutrino event cluster with the duration of ∼10 s in the KamLAND data. We find no neutrino clusters and give the upper limit on the supernova rate to be 0.15 yr−1 with a 90% confidence level. The detectable range, which corresponds to a >95% detection probability, is 40-59 kpc and 65-81 kpc for core-collapse supernovae and failed core-collapse supernovae, respectively. This paper proposes to convert the supernova rate obtained by the neutrino observation to the Galactic star formation rate. Assuming a modified Salpeter-type initial mass function, the upper limit on the Galactic star formation rate is

We present two results of a search for MeV-scale neutrino and anti-neutrino events correlated with gravitational wave events/candidates and large solar flares with KamLAND. The KamLAND detector is a large-volume neutrino detector using liquid scintillator, which is located at 1 km underground under the top of Mt. Ikenoyama in Kamioka, Japan. KamLAND has multiple reaction channels to detect neutrinos. Electron antineutrino can be detected via inverse-beta decay with 1.8 MeV neutrino energy threshold. All flavors of neutrinos can be detected via neutrino-electron scattering without neutrino energy threshold. KamLAND has continued the neutrino observation since 2002 March. We use the data set of 60 gravitational waves provided by the LIGO/Virgo collaboration during their second and third observing runs and search for coincident electron antineutrino events in KamLAND. We find no significant coincident signals within a ±500 s timing window from each gravitational wave and present 90% C.L. upper limits on the electron antineutrino fluence between 108–1013 cm−2 for neutrino energies of 1.8–111 MeV. For a solar-flare neutrino search at KamLAND, we determine the timing window using the solar X-ray data set provided by the GOES satellite series from 2002 to 2019 and search for the excess of coincident event rate on the all-flavor neutrinos. We find no significant event rate excess in the flare time windows and get 90% C.L. upper limits on the fluence of neutrinos of all flavors (electron anti-neutrinos) between 1010–1013 cm−2 (108–1013 cm−2) for neutrino energies in the energy range of 0.4–35 MeV.

We present the results of a time-coincident event search for low-energy electron antineutrinos in the KamLAND detector with gamma-ray bursts (GRBs) from the Gamma-ray Coordinates Network and Fermi Gamma-ray Burst Monitor. Using a variable coincidence time window of ±500 s plus the duration of each GRB, no statistically significant excess above the background is observed. We place the world's most stringent 90% confidence level upper limit on the electron antineutrino fluence below 17.5 MeV. Assuming a Fermi-Dirac neutrino energy spectrum from the GRB source, we use the available redshift data to constrain the electron antineutrino luminosity and effective temperature.

We report on a search for electron antineutrinos ( ) from astrophysical sources in the neutrino energy range 8.3-30.8 MeV with the KamLAND detector. In an exposure of 6.72 kton-year of the liquid scintillator, we observe 18 candidate events via the inverse beta decay reaction. Although there is a large background uncertainty from neutral current atmospheric neutrino interactions, we find no significant excess over background model predictions. Assuming several supernova relic neutrino spectra, we give upper flux limits of 60-110 cm-2 s-1 (90% confidence level, CL) in the analysis range and present a model-independent flux. We also set limits on the annihilation rates for light dark matter pairs to neutrino pairs. These data improve on the upper probability limit of 8B solar neutrinos converting into , (90% CL) assuming an undistorted shape. This corresponds to a solar flux of 60 cm-2 s-1 (90% CL) in the analysis energy range.

We report the result of a search for neutrinos in coincidence with solar flares from the GOES flare database. The search was performed on a 10.8 kton-year exposure of KamLAND collected from 2002 to 2019. This large exposure allows us to explore previously unconstrained parameter space for solar flare neutrinos. We found no statistical excess of neutrinos and established 90% confidence level upper limits of 8.4 × 107 cm-2 (3.0 × 109 cm-2) on the electron antineutrino (electron neutrino) fluence at 20 MeV normalized to the X12 flare, assuming that the neutrino fluence is proportional to the X-ray intensity.

Anamorelin, a non-peptide ghrelin analog and growth hormone secretagogue, is a novel oral drug used to treat cancer cachexia. Patients with cancer cachexia frequently use several drugs and anamorelin is a substrate of cytochrome P450 (CYP) 3A4; therefore, drug-drug interactions with CYP3A4 inhibitors and inducers pose a clinical problem. In this study, we aimed to determine the concentration of anamorelin in human plasma using a simple high-performance liquid chromatography-ultraviolet (HPLC-UV)-based method. The analysis involved extracting a 200-μL plasma sample and protein precipitation using solid-phase extraction. Anamorelin was isocratically separated using a mobile phase consisting of 0.5% potassium dihydrogen phosphate (pH 4.5) and acetonitrile (61:39, v/v) on a Capcell Pack C18 MG II column (250 mm × 4.6 mm) at a flow rate of 1.0 mL/min and monitored at a detection wavelength of 220 nm. The calibration curve was linear within a plasma concentration range of 12.5-1,500 ng/mL, with a coefficient of determination of 0.9999. The intra- and inter-day coefficients of variation were 0.37-6.71% and 2.05-4.77%, respectively. The accuracy of the assay and recovery were 85.25-112.94% and > 86.58%, respectively. This proposed HPLC-UV method is simple and can be applied in clinical settings.

Objectives: Poor cardiorespiratory fitness (CRF) and high body mass index (BMI) increased the risk of developing metabolic Syndrome (MetS) mostly in Caucasians. However, the sex-specific combined association of CRF and BMI on MetS considering health-related behaviors has yet to be thoroughly examined in Japanese. This study aims to investigate the sex-specific independent and combined associations of CRF and BMI with MetS in middle-aged Japanese adults., Methods: 421 participants were included in this cross-sectional study. CRF was estimated using a submaximal cycle ergometer. CRF and BMI were respectively divided into three categories according to tertile distribution. MetS was diagnosed based on five risk factors: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were used to estimate independent and combined association of CRF and BMI with MetS., Results: Results showed that 154 (57.5%) and 70 (45.8%) of men and women had MetS, respectively. Compared to men with lower CRF or higher BMI, men with middle and higher CRF or middle and lower BMI were less likely to have MetS. Compared with 'unfit and higher BMI' group, 'unfit and lower BMI', 'fit and higher BMI', and 'fit and lower BMI' groups in men showed statistically significant decreased prevalences of MetS. However, no significant associations were found in women., Conclusions: This study found significant independent and combined associations of CRF and BMI with MetS only in men, but not in women. However, prospective studies are warranted to confirm sex-specific associations of CRF and BMI with MetS., (© 2024. The Author(s).)

Ivosidenib is used for the treatment of acute myeloid leukemia (AML) with isocitrate dehydrogenase 1 (IDH1) mutations. However, increased blood concentrations of ivosidenib are associated with a risk of a prolonged QT interval in patients with AML. Therapeutic drug monitoring in patients with AML with IDH1 mutation offers the potential to improve treatment efficacy while minimizing toxicity. In this study, we developed an efficient high-performance liquid chromatography-ultraviolet (HPLC-UV) method for the quantification of ivosidenib in plasma. Human plasma samples (50 μL) were processed by protein precipitation using acetonitrile, followed by chromatographic separation on a reversed-phase column with an isocratic mobile phase of 0.5% KH₂PO₄ (pH 4.5) and acetonitrile (45:55, v/v) at a flow rate of 1.0 mL/min, with ultraviolet detection at 245 nm. Calibration curves were linear over the range of 0.25-20 μg/mL with a coefficient of determination (r2) of 0.99999. Intra-day and inter-day precision were 1.20-8.04% and 0.69-4.20%, respectively. The assay accuracy was -2.00% to 1.93% and recovery was >91.2%. These findings support the effectiveness of the newly developed HPLC-UV method for the quantification of ivosidenib in human plasma. This simple and cost-effective method is expected to expand ivosidenib monitoring in laboratories lacking LC-MS/MS instruments., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Fat-free mass (FFM) is a heterogeneous compartment comprising body cell mass (BCM), intracellular water (ICW), extracellular solids, and extracellular water (ECW). The BCM/FFM and ECW/ICW ratios vary among individuals and decrease with age. This study aimed to determine whether BCM/FFM and ECW/ICW ratios are predictors of maximal oxygen uptake (V̇̇O2peak) independently of age, sex, and objectively measured physical activity (PA). A total of 115 Japanese males and females, aged 55.3 ± 8.0 years (mean ± standard deviation), were included in the study. Anthropometry, explosive leg muscle power, and V̇̇O2peak were measured, and BCM, FFM, ICW, and ECW were estimated. Step count and PA were objectively measured using a triaxial accelerometer. Blood flow volume was assessed using ultrasonography. BCM and ICW were negatively correlated with age, whereas FFM and ECW were not significantly correlated with age. FFM, ICW/ECW, BCM/FFM, step counts, moderate and vigorous PA, and leg muscle power were positively correlated with V̇̇O2peak, even after adjusting for age and sex (p < .05). Multiple regression analysis indicated that either BCM/FFM or ECW/ICW, leg power, and objectively measured PA were associated with V̇̇O2peak independent of age, sex, and FFM. Blood flow volume was significantly correlated with ECW (p < .05), but not with BCM. The BCM/FFM and ECW/ICW ratios were significant predictors of V̇̇O2peak, independent of age, sex, FFM, leg power, and objectively measured PA., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sotorasib, an oral small-molecule inhibitor, reportedly exerts promising activity against Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors. However, the currently administered dose may fail to represent the optimal dose based on the therapeutic efficacy. Herein, we developed a simple and sensitive method using high-performance liquid chromatography with ultraviolet (HPLC-UV) to measure the sotorasib concentration in human plasma. The sotorasib calibration curve exhibited linearity across the concentration range of 0.10-20.0 μg/mL (r 2 = 0.9999). The coefficients of intra- and inter-day validation ranged between 0.79-9.75% and 3.01-6.13%, respectively. The assay accuracy ranged between -3.14 and 5.18%, with > 98.5% recovery. Subsequently, we applied the developed method to estimate sotorasib concentrations in a patient with KRAS G12C-mutated non-small cell lung cancer. We anticipate that our HPLC-UV method will be valuable for assessing the safety and efficacy of sotorasib in larger patient cohorts.

Venetoclax is an oral B-cell lymphoma-2 protein inhibitor. It is a key drug for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia. However, venetoclax is administered at a fixed dose, irrespective of body surface area or weight. Furthermore, the plasma concentration of venetoclax varies widely between individuals and is influenced by diet. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help to optimize treatment in clinical practice. In this study, we aimed to develop a simple method to determine venetoclax concentrations in plasma. The analysis required the extraction of a 50-μL plasma sample and precipitation of proteins using acetonitrile extraction. Venetoclax and the internal standard (12.5-μg/mL ibrutinib) were separated by high-performance liquid chromatography (HPLC). The calibration curve was linear over the plasma venetoclax concentration range 0.25-10 μg/mL with a coefficient of determination (r2) of 0.9999. The coefficients of intra-day and inter-day validation were 0.8-4.1% and 1.3-3.3%, respectively. The assay accuracy was -2.8 to 1.6%, and the recovery was >97.2%. These results demonstrate a very simple, novel and sensitive HPLC-UV-based method for determining the concentration of plasma venetoclax, and confirm its applicability to the TDM of venetoclax in a clinical setting., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cabozantinib, which is used to treat renal cell and hepatocellular carcinomas, is often associated with dose-dependent adverse events. Monitoring the levels of cabozantinib in the blood may maximize the therapeutic effect and prevent serious adverse events. In this study, we developed a high-performance liquid chromatography-ultraviolet (HPLC-UV) method of measuring plasma cabozantinib concentration. Human plasma samples (50 µL) were processed by simple deproteinization with acetonitrile, followed by chromatographic separation on a reversed-phase column with an isocratic mobile phase of 0.5% KH₂PO 4 (pH 4.5) and acetonitrile (43:57, v / v ) at a flow rate of 1.0 mL/min, with a 250 nm ultraviolet detector. The calibration curve was linear over the concentration range (0.05-5 µg/mL) with a coefficient of determination of 0.99999. The accuracy of the assay ranged from -4.35% to 0.98%, and recovery was >96.04%. The measurement time was 9 min. These findings confirm the effectiveness of this HPLC-UV method for cabozantinib quantification in human plasma, which is sufficiently simple for use for monitoring patients in clinical settings.

This study aimed to identify the modifiable cardiovascular risk factors associated with longitudinal changes, which are nine functional and structural biological vascular aging indicators (BVAIs), to propose an effective method to prevent biological vascular aging. We conducted a longitudinal study of 697 adults (a maximum of 3636 BVAI measurements) who were, at baseline, aged between 26 and 85 years and whose BVAIs were measured at least twice between 2007 and 2018. The nine BVAIs were measured using vascular testing and an ultrasound device. Covariates were assessed using validated questionnaires and devices. During the mean follow-up period of 6.7 years, the average number of BVAI measurements ranged from 4.3 to 5.3. The longitudinal analysis showed a moderate positive correlation between the common carotid intima-media thickness (IMT) and chronological age in both men (r = 0.53) and women (r = 0.54). In the multivariate analysis, BVAIs were associated with factors such as age, sex, residential area, smoking status, blood clinical chemistry test levels, number of comorbidities, physical fitness, body mass, physical activity, and dietary intake. The IMT is the most useful BVAI. Our findings suggest that modifiable cardiovascular risk factors are associated with longitudinal changes in BVAI as represented by IMT., (© 2023. The Author(s).)

Factors associated with dynamic changes in the objectively measured physical activity have not been well understood. We aimed to 1) evaluate the longitudinal change in the physical activity trajectory according to sex which is associated with age and to 2) determine the factors associated with the dynamic change in physical activity-related variables across a wide age range among Japanese adults. This longitudinal prospective study included 689 Japanese adults (3914 measurements) aged 26-85 years, whose physical activity data in at least two surveys were available. Physical activity-related variables, such as intensity (inactive, light [LPA; 1.5 to 2.9 metabolic equivalents (METs)], moderate-to-vigorous [MVPA; ≥3.0 METs]), total energy expenditure (TEE), physical activity level (PAL), and step count, were evaluated using a validated triaxial accelerometer. Statistical analysis involved the latent growth curve models and random-effect panel data multivariate regression analysis. During a mean follow-up period of 6.8 years, physical activity was assessed an average of 5.1 times in men and 5.9 times in women. The profiles for the inactive time, LPA (only men), MVPA, step count, PAL, and TEE showed clear curvature, indicating an accelerated rate of change around the age of 70. In contrast, other variables exhibited minimal or no curvature over the age span. The MVPA trajectory was positively associated with alcohol consumption, hand grips, leg power, and trunk flexibility and negatively associated with age, local area, body mass index (BMI), comorbidity score, and heart rate over time. Our results indicated that the physical activity trajectory revealed clear curvature, accelerated rate of change around the age of 70, and determined physical health and fitness and BMI as dynamic factors associated with physical activity changes. These findings may be useful to help support populations to achieve and maintain the recommended level of physical activity., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Watanabe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The phase angle (PhA), measured via bioelectrical impedance analysis, is considered an indicator of cellular health, where higher values reflect higher cellularity, cell membrane integrity, and better cell function. This study aimed to examine the relationship between PhA and exercise habits or objectively measured physical activity. We included 115 people aged 32-69 years. The body composition and PhA were measured using a bioelectrical impedance device. Physical activity and sedentary behavior (SB) were assessed using a triaxial accelerometer. Exercise habits were also obtained through structured interviews, and participants were categorized into the no exercise habit (No-Ex), resistance training exercise habit (RT), or aerobic training exercise habit (AT) groups. Objectively measured moderate-to-vigorous physical activity or step count significantly correlated with PhA, independent of age, sex, height, percent body fat, body cell mass, and leg muscle power. In contrast, SB was not significant determinants of PhA. People who exercised regularly (RT or AT) had significantly higher PhA values than did those in the No-Ex group. Furthermore, the PhA was not significantly different between the RT and AT groups. Regularly engaging in exercise with moderate-to-vigorous intensity may improve or maintain muscle cellular health and muscle quality., (© 2022. The Author(s).)

Previous cross-sectional studies have indicated that low relative appendicular lean mass (ALM) against body weight (divided by body weight, ALM/Wt, or divided by body mass index, ALM/BMI) was negatively associated with metabolic syndrome (MetS). Conversely, previous cross-sectional studies have indicated that the absolute ALM or ALM divided by squared height (ALM/Ht2) were positively associated with MetS. The aim of this longitudinal study was to investigate the association between low absolute or relative skeletal muscle mass, leg muscle power, or percent body fat and the development of MetS in Japanese women in a 7-y prospective study. The study participants included 346 Japanese women aged 26 to 85 years. The participants were divided into low and high groups based on the median values of ALM/Wt, ALM/BMI, ALM/Ht2, absolute ALM, or leg power. The longitudinal relationship between ALM indices or leg power and MetS development was examined using Kaplan-Meier curves and Cox regression models (average follow-up duration 7 years, range 1 to 10 years). During follow-up, 24 participants developed MetS. MetS incidence was higher in the low ALM/Wt group than the high ALM/Wt group even after controlling for age, obesity, waist circumference, family history of diabetes, smoking, and physical activity [adjusted hazard ratio = 5.60 (95% CI; 1.04-30.0)]. In contrast, MetS incidence was lower in the low ALM/Ht2 group than the high ALM/Ht2 group [adjusted hazard ratio = 10.6 (95%CI; 1.27-89.1)]. MetS incidence was not significantly different between the low and high ALM/BMI, absolute ALM, and leg power groups. Both ALM/Ht2 and ALM/Wt were not significant predictive variables for MetS development when fat mass or percent body fat was taken into account in the Cox model. At the very least, the results of this study underscore the importance of body composition measurements in that percent body fat, but not ALM, is associated with MetS development., Competing Interests: The authors have declared that no competing interests exist.

Voriconazole is an antifungal drug used to treat invasive aspergillosis. Voriconazole exhibits nonlinear behavior and considerable individual variability in its pharmacokinetic profile. Invasive aspergillosis has a poor prognosis, and failure of treatment owing to low voriconazole blood levels is undesirable. Thus, therapeutic drug monitoring (TDM) of voriconazole is recommended. However, plasma voriconazole concentration is rarely measured in hospitals, and the TDM of voriconazole is not widely practiced in Japan. We aimed to develop an ultra-simple method to measure plasma voriconazole concentration. Ten microliters of plasma sample was extracted, and proteins were precipitated using methanol extraction. Voriconazole and ketoconazole (internal standard) were separated using high-performance liquid chromatography. A calibration curve was prepared, which was linear over plasma voriconazole concentrations of 0.125−12.5 µg/mL, with a coefficient of determination of 0.9999. The intra-day and inter-day validation coefficients were 0.9−2.2% and 1.3−6.1%, respectively. The assay accuracy was −4.2% to 1.6%, and recovery was >97.8%. Our ultra-simple, sensitive, and inexpensive high-performance liquid chromatography ultraviolet method to determine plasma voriconazole concentration will help improve the voriconazole TDM implementation rate and contribute to effective and safe voriconazole use.

Background: Many cross-sectional studies have identified modifiable factors such as dietary intake, physique, and physical activity associated with diet quality but were unable to determine how a specific individual's diet quality changes with these factors. These relationships may vary depending on an individual's dietary intake. We aimed to determine the association between temporal changes in diet quality and concurrent changes in dietary intake, body mass index (BMI), and physical activity according to the diet quality trajectory pattern., Methods: This longitudinal prospective study included 697 Japanese adults aged 26-85 years, at baseline, with available data from at least two dietary intake surveys (4,118 measurements). Dietary intake and physical activity were evaluated using validated dietary questionnaires and a triaxial accelerometer. Diet quality was calculated using the Nutrient-Rich Food Index 9.3 (NRF9.3), while physical activity was calculated based on the duration of activity performed at each level of intensity (sedentary, light, moderate, and vigorous). Body mass index was calculated from the measured height and weight. Statistical analyses involved latent class growth models (LCGM) and random-effect panel data analysis., Results: During a mean follow-up period of 6.8 years, NRF9.3 scores were assessed, on average, 5.4 times in men and 6.1 times in women. Based on the NRF9.3 score, three separate trajectory groups-"low-increasing," "medium-increasing," and "high-stable"-among individuals aged 26-90 years were identified using LCGM. In the multivariate analysis, the NRF9.3 score trajectory was positively associated with intake of energy, protein, dietary fiber, vitamins A and C, magnesium, and food items, such as fruits and vegetables, and was negatively associated with BMI and the intake of added sugar, saturated fats, sodium, and food items, such as meat and sugar and confectioneries, even after adjusting for covariates. These relationships displayed heterogeneity across the identified NRF9.3 score trajectory groups. In the low-increasing group, an inverse relationship was observed between sedentary behavior and NRF9.3 score trajectory., Conclusions: We identified modifiable factors associated with temporal changes in diet quality across a wide age range; however, these factors may vary according to the diet quality trajectories. Our findings may help develop effective strategies for improving diet quality, according to the trajectory of diet quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MY declared a shared affiliation with one of the authors KK at the time of the review., (Copyright © 2022 Watanabe, Murakami, Gando, Kawakami, Tanisawa, Ohno, Konishi, Sasaki, Morishita, Miyatake and Miyachi.)

Previous cohort study reported that high physical activity was associated with a low risk of self-reported hearing loss in women. However, no studies have examined the association between physical activity and the development of hearing loss as measured using an objective assessment of hearing loss in men and women. Here, we used cohort data to examine the association between leisure-time physical activity and incidence of objectively assessed hearing loss in men and women. Participants included 27 537 Japanese adults aged 20-80 years without hearing loss, who completed a self-administered physical activity questionnaire between April 2001 and March 2002. The participants were followed up for the development of hearing loss as measured by audiometry between April 2002 and March 2008. During follow-up, 3691 participants developed hearing loss. Compared with the none physical activity group, multivariable adjusted hazard ratios (HRs) for developing hearing loss were 0.93 (95% confidence interval (CI), 0.86-1.01) and 0.87 (0.81-0.95) for the medium (<525 MET-min/week) and high (≥525 MET-min/week) physical activity groups, respectively (p for trend = 0.001). The magnitude of risk reduction was slightly greater in vigorous-intensity activity than in moderate-intensity activity (p for interaction = 0.01). Analysis by sound frequency showed that the amount of physical activity was inversely associated with high frequency hearing loss development (p for trend <0.001), but not with low frequency hearing loss development (p for trend = 0.19). Higher level of leisure-time physical activity was associated with lower incidence of hearing loss, particularly for vigorous-intensity activities and high sound frequencies., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cardiorespiratory fitness (CRF) is an independent predictor of morbidity and mortality. In Japan, annual physical exams are mandatory in workplace settings, and most healthcare settings have electronic medical records (EMRs). However, in both settings, CRF is not usually determined, thereby limiting the potential for epidemiological investigations using EMR data., Purpose: To estimate CRF (mL/kg/min) using variables commonly recorded in EMRs., Methods: Participants were 5293 Japanese adults (11.7% women) who completed an annual physical exam at a large gas company in Tokyo, Japan, in 2004. The mean age was 48.3 ± 8.0 years. Estimated CRF (eCRF) was based on age, measured body mass index, resting heart rate, systolic and diastolic blood pressure, and smoking. Measured CRF was determined by a submaximal cycle ergometer graded exercise test., Results: Regression models were used for males and females to calculate Pearson's correlation and regression coefficients. Cross-classification of measured CRF and eCRF was conducted using the lowest quintile, quartile, and tertile as the unfit categories. R's for eCRF were 0.61 (MD 4.41) for men and 0.64 (MD 4.22) for women. The overall accuracy level was reasonable and consistent across models, yet the unfit lower tertile model provided the best overall model when considering the positive predictive value and sensitivity., Conclusion: eCRF may provide a useful method for conducting investigations using data derived from EMRs or datasets devoid of CRF or physical activity measures.

Background: In an effort to increase people's adherence to active lifestyles, contemporary physical activity (PA) guidelines now include low-dose PA., Methods: PA was evaluated in 583 participants of the Nutritional and Physical Activity Intervention Study (NEXIS) cohort (30-65 years old); 349 inactive participants (MVPA, 2.7 ± 1.0 MET-h/day) were randomly assigned to the intervention or control groups, and 235 active participants participated in follow-up visits. The intervention aimed to increase MVPA and comprised five brief counseling sessions over 1 year. The 1-year target for the participant was increasing their step-count to 10,000 steps/d or +3000 steps/d, relative to the baseline score. The counseling sessions were designed to stimulate progressive changes in physical behaviors by recommendations promoting small and/or light-intensity bouts of PA. PA was measured at baseline, the end of the intervention, and 1 year after the intervention ended. Additionally, several nutrition, health, and fitness parameters were measured., Results: Participants in the intervention group significantly increased their step-count from 8415 ± 1924 at baseline to 9493 ± 2575 at the end of the 1-year period. During the same period, MVPA significantly increased by 0.9 MET-h. The daily time spent in ≥ 3, ≥ 4 and ≥ 5 MET activities increased by 11, 6, and 3 min, respectively. This increase in PA remained observable 1 year after intervention concluded. The active group maintained higher physical activity levels throughout the two years. The intervention group showed smaller energy intakes at the end of the 2-year period. Significant correlations were noted between the 1-year change in MVPA and the change in resting heart rate (r =  - 0.22), and between the 2-year change in MVPA and the change in waist circumference (r =  - 0.08) and peak oxygen consumption capacity (r = 0.23) in the intervention group only., Conclusions: A prolonged and progressive PA intervention promoting small bouts of light-to-moderate PA may be used in healthy, not-optimally-active people to increase PA beyond the strict period of the intervention. Further studies are necessary to understand whether low-dose PA messages can be effective in initiating a progressive increase toward larger amounts of PA., Trial Registration: Clinical Trials.gov, NCT00926744, retrospectively registered., (© 2021. The Author(s).)