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In occupational therapy, crafts and groups are used as therapeutic tools, but their electrophysiological effects have not been well described. This study aimed to investigate the effects of group crafting on the physiological synchrony (PS) of dyadic heartbeats and on the autonomic activity and electroencephalogram (EEG) of individuals. In this cross-sectional study, individuals' EEG and dyadic electrocardiogram (ECG) were measured during the task in a variety of conditions. The three conditions were alone, parallel, nonparallel. Autonomic activity from the subjects' ECG, PS from the dyadic ECG, and current source density from exact Low Resolution Brain Electromagnetic Tomography (eLORETA) from subjects' EEG were analyzed. Measurements from 30 healthy young adults showed that the parallel condition significantly increased subjects' parasympathetic activity and dyadic PS. Parallel condition and frontal midline theta influenced parasympathetic activity, whereas parasympathetic activity was not associated with PS. Dyadic lag value were correlated with frontal delta, beta, and gamma activity. The results suggest that crafting in parallel groups increases parasympathetic activity and PS through different mechanisms, despite the absence of direct interaction. They also explain the electrophysiological evidence for the use of crafts and groups in psychiatric occupational therapy, such as increased relaxation and PS., (© 2024. The Author(s).)

Background: Affinity chrome-mediated immunoassays (ACMIA) do not require pretreatment and have a wide calibration range and good analytical performance. To date, no studies have compared ACMIA and latex agglutination turbidimetry immunoassays (LTIA). The objective of this study was to evaluate the interchangeability of ACMIA, LTIA, and the previously developed ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS)., Methods: A total of 111 whole blood samples were collected from 25 patients undergoing routine everolimus therapeutic drug monitoring. The interchangeability between the 3 methods was assessed using robust Passing-Bablok regression analysis and Bland-Altman plots., Results: All samples were quantifiable by UHPLC-MS/MS, whereas 56 and 1 samples were below the lower limits of quantification by LTIA and ACMIA, respectively. In the robust Passing-Bablok regression plots, the slopes of the regression equations between ACMIA and UHPLC-MS/MS, LTIA and UHPLC-MS/MS, and ACMIA and LTIA were 1.23 (95% [confidence interval] CI, 1.13-1.33), 0.67 (95% CI, 0.57-0.77), and 1.71 (95% CI, 1.43-2.33), respectively, with significant proportional biases indicating no interchangeability among all 3 methods. Bland-Altman plots also revealed statistically significant proportional biases between ACMIA and UHPLC-MS/MS (P = 0.012), LTIA and UHPLC-MS/MS (P < 0.001), and ACMIA and LTIA (P < 0.001)., Conclusions: Statistically significant proportional biases were observed among the 3 methods. Blood everolimus concentration measurements should be interpreted with caution when switching the quantification methods for therapeutic drug monitoring., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

At Oita University Hospital, we switched our usage of pemetrexed(PEM)from brand-name to generic drugs. We conducted a comparative study of the preparation efficiency and therapeutic safety with the brand-name product and examined the economic effect thereof. The incidence of adverse drug reactions was investigated retrospectively using electronic medical records for patients who received PEM brand-name and generic drugs at our hospital between April 2021 and December 2022. The preparation time per mg was significantly shorter in the generic group at 0.17(0.08-0.38)seconds compared to 0.34(0.15-0.94)seconds for the brand-name group(p<0.01). Regarding the safety comparison, none of the 13 eligible patients developed new hematologic or non-hematologic toxicities of Grade 2 or higher after switching to the generic product. The switch to generics had an economic impact of 7,369,278 yen during the study period. The results suggest that switching from brand-name to generic products is reasonable from the perspectives of therapeutic safety and economic benefits, as well as the expected improvement in preparation efficiency.

This study investigated the relationship between subjective grip strength and physical function in community-dwelling older women. Subjective grip strength was assessed using a questionnaire, and physical function and body composition were compared between groups with strong and weak subjective grip strength. Additionally, the two groups were compared in those with mild cognitive impairment (MCI) and those with normal cognitive function, respectively. The results showed significant differences in grip strength ( p < 0.001), 30 s chair-stand (CS-30) test ( p = 0.039), timed up-and-go (TUG) test ( p = 0.027), maximal gait speed ( p = 0.029), and skeletal muscle mass ( p < 0.001). Older adults with normal cognitive function showed significant differences in grip strength ( p < 0.001), quadriceps muscle strength ( p < 0.009), one-leg standing time ( p = 0.041), CS-30 ( p = 0.002), TUG ( p = 0.014), gait speed ( p = 0.006), and skeletal muscle mass ( p = 0.003). Older adults with low subjective grip strength had lower physical function and skeletal muscle mass. However, no items showed significant differences between groups among older adults with MCI. Thus, subjective grip strength is an indicator of an overall decline in physical function and a reduction in skeletal muscle mass in older adults, and cognitive function should be considered when assessing subjective grip strength in older adults.

Neurotransmitter receptors are essential components of synapses for communication between neurons in the brain. Because the spatiotemporal expression profiles and dynamics of neurotransmitter receptors involved in many functions are delicately governed in the brain, in vivo research tools with high spatiotemporal resolution for receptors in intact brains are highly desirable. Covalent labeling by chemical reaction (chemical labeling) of proteins without genetic manipulation is now a powerful method for analyzing receptors in vitro. However, selective target receptor labeling in the brain has not yet been achieved. This study shows that ligand-directed alkoxyacylimidazole (LDAI) chemistry can be used to selectively tether synthetic probes to target endogenous receptors in living mouse brains. The reactive LDAI reagents with negative charges were found to diffuse well over the whole brain and could selectively label target endogenous receptors, including AMPAR, NMDAR, mGlu1, and GABA A R. This simple and robust labeling protocol was then used for various applications: three-dimensional spatial mapping of endogenous receptors in the brains of healthy and disease-model mice; multi-color receptor imaging; and pulse-chase analysis of the receptor dynamics in postnatal mouse brains. Here, results demonstrated that bioorthogonal receptor modification in living animal brains may provide innovative molecular tools that contribute to the in-depth understanding of complicated brain functions., Competing Interests: Competing interests statement:The authors declare no competing interest.

Mild cognitive impairment (MCI) is associated with a high risk of dementia. Reportedly, 54.6% of older adults with MCI fall into the pre-frailty category. However, it is unclear what differences exist in older adults with regard to their physical, psychological, and functional capacities, which depend on MCI, pre-frailty, or a combination of the two. This study aimed to examine the differences between the association between physical function, psychological function, and functional capacity by examining a combination of MCI and pre-frailty among community-dwelling older Japanese individuals. The participants in the analysis were 236 older people living in the community. They were classified into four groups, as follows: normal, MCI only, pre-frailty only, and pre-frailty/MCI; furthermore, their physical, psychological, and functional capacities were compared. In addition, a multinomial logistic regression analysis was performed using MCI and pre-frailty as dependent variables. No associated factors were identified for MCI only, and a depressive mood was only associated with pre-frailty. When pre-frailty and MCI were combined, knee extension muscle strength, fastest gait speed, the s30 s chair stand test, depressed moods, and the instrumental activities of daily living (IADL) were correlated. Our results suggest that when MCI and pre-frailty are combined, declines in both physical and psychological functions and IADL are likely to occur.

Introduction: The therapeutic structure of occupational therapy (OT) includes groups. Although the presence of others is expected to be relaxing due to the social buffering effect and the tend and befriend theory, it has not been sufficiently validated in accordance with the therapeutic structure of OT. The aim of this study was to investigate the electrophysiological evidence for the effectiveness of parallel groups and states of concentration on craft activities used in OT., Methods: Thirty healthy young adults were used as controls to measure EEG and autonomic activity during craft activities in three conditions: alone, parallel, and nonparallel. EEG was analyzed using exact low-resolution electromagnetic tomography, and autonomic activity was analyzed using Lorenz plot analysis., Results: Parasympathetic activity was significantly higher in the parallel condition than in the alone condition. A significant negative correlation was found between current source density and parasympathetic activity in the region centered on the right insular cortex in the α1 band, and functional connectivity in regions including the anterior cingulate cortex and insular cortex was associated with autonomic activity., Conclusion: Craft activities that occurred during frontal midline theta rhythm also increased parasympathetic activity. The results suggest that the parallel groups used in OT and the intensive state of craft activities induce a social buffering effect that increases parasympathetic activity despite the absence of physical contact or social support. This provides evidence for the effectiveness of the therapeutic structure of occupational activities and groups in OT., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

To develop safe and highly effective live vaccines, rational vaccine design is necessary. Here, we sought a simple approach to rationally develop a safe attenuated vaccine against the genome-reduced pathogen Erysipelothrix rhusiopathiae. We examined the mRNA expression of all conserved amino acid biosynthetic genes remaining in the genome after the reductive evolution of E. rhusiopathiae . Reverse transcription-quantitative PCR (qRT-PCR) analysis revealed that half of the 14 genes examined were upregulated during the infection of murine J774A.1 macrophages. Gene deletion was possible only for three proline biosynthesis genes, proB , proA , and proC , the last of which was upregulated 29-fold during infection. Five mutants bearing an in-frame deletion of one (Δ proB , Δ proA , or Δ proC mutant), two (Δ proBA mutant), or three (Δ proBAC mutant) genes exhibited attenuated growth during J774A.1 infection, and the attenuation and vaccine efficacy of these mutants were confirmed in mice and pigs. Thus, for the rational design of live vaccines against genome-reduced bacteria, the selective targeting of genes that escaped chromosomal deletions during evolution may be a simple approach for identifying genes which are specifically upregulated during infection. IMPORTANCE Identification of bacterial genes that are specifically upregulated during infection can lead to the rational construction of live vaccines. For this purpose, genome-based approaches, including DNA microarray analysis and IVET ( in vivo expression technology), have been used so far; however, these methods can become laborious and time-consuming. In this study, we used a simple in silico approach and showed that in genome-reduced bacteria, the genes which evolutionarily remained conserved for metabolic adaptations during infection may be the best targets for the deletion and construction of live vaccines.

Age-related decline in skeletal muscle mass and function are risk factors for reduced walking ability. This study aimed to understand the characteristic gait parameters of presarcopenia (low muscle mass only), dynapenia (low muscle function only), and sarcopenia (low muscle mass and function), which have differing skeletal muscle characteristics. Skeletal muscle mass, grip strength, and gait parameters (walking speed, cadence, step length, step width, gait angle, foot angle, stance time, swing time, and double stance time) were evaluated in 307 older Japanese women. Low muscle function was determined by grip strength and normal walking speed. Participants were assessed and divided into the normal (60.9%, n = 187), presarcopenia (25.7%, n = 79), dynapenia (5.2%, n = 16), and sarcopenia (8.1%, n = 25) groups. When compared to the normal group, the sarcopenia group had significantly slower walking speed and shorter step length (p < 0.05); the dynapenia group had significantly slower walking speed, smaller cadence, shorter step length, wider step width, and longer stance time (p < 0.05); and the presarcopenia group showed no differences. Skeletal muscle function may therefore be more strongly related to reduced walking function in older adults than body composition factors. The decrease in walking function was most pronounced in older women with dynapenia., Competing Interests: The authors declare no conflicts of interest.

A decline in physical function is common among elderly people who have lost both bone and muscle mass. The aim of this study was to investigate the relationship between low bone and muscle mass and physical function in elderly women of different age groups who exercise regularly. The analysis included 299 elderly women. Low bone mass was determined by a T-score of −2.5 or less, and low muscle mass was determined by a skeletal muscle mass index of <5.7 kg/m2. Physical function was measured by grip strength, knee extension strength, standing ability, gait function, and balance function. The participants were divided into four groups based on bone and muscle mass (healthy, low bone mass, low muscle mass, and low bone and muscle mass groups), and their physical functions were compared. There were no statistically significant differences in physical function between the low bone and muscle mass and the healthy groups. There were also no statistically significant differences in physical function among the four groups in the late elderly stage (75 and older). Elderly women who exercise regularly are less likely to experience a decline in physical function, even if they have reduced bone and muscle mass.

Introduction: This study aimed to investigate the reliability of muscle thickness (MT) and echo intensity (EI) of the quadriceps muscles using ultrasound imaging for a novice examiner., Methods: Sixteen healthy adult women were included in the study, and images of the rectus femoris, vastus intermedius, vastus lateralis, and vastus medialis were obtained on the same day and after one week by an examiner who had not performed an experiment on the measurement of ultrasound imaging. The measurers who analyzed all images were completely blind to the subject's name and date and order of measurements. Intraclass correlation coefficients (ICCs) were used as relative within-day and between-day reliability of measurement. Absolute reliability was based on Bland-Altman analysis, standard error of measurement, and minimum detectable change., Results: The ICCs ranged from 0.76 to 0.95. As the results of the Bland-Altman analysis, all MTs and EIs included 0 in the 95% confidence interval of the mean difference., Discussion: Our results suggest that quadriceps ultrasound images have high reliability for MT and EI for all muscles. There were no systematic errors in both MT and EI., Conclusion: It might indicate that even novice examiners could obtain MT and EI measurements without systematic error after a few hours of practice., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Skeletal muscle mass and muscle strength are positively correlated, but the relationship between grip strength and global muscle strength is controversial. This study aimed to clarify the changes in site-specific skeletal muscle mass by age group and determine the relationship between site-specific, age-related changes in skeletal muscle mass and physical function in community-dwelling elderly people in Japan. The participants were divided into age groups of five-year intervals (65-69 years, 70-74 years, 75-79 years, and ≥80 years) and were also categorized by sex. The skeletal muscle mass of the upper limbs, lower limbs, and trunk was measured using multifrequency bioelectrical impedance analyzers (InBody 430 (Biospace Co., Ltd., Seoul, Korea) and InBody 470 (InBody Japan Inc., Tokyo, Japan)). For physical function assessment, we measured grip strength, quadriceps strength, sit-up count, sit-and-reach distance, and standing time on one leg with eyes open and performed the timed up and go (TUG) test. The results showed that skeletal muscle mass decreased with age regardless of sex at all measured sites. Furthermore, a partial correlation analysis adjusted for age, physical constitution, and the presence/absence of exercise habits revealed that the highest correlation was between skeletal muscle mass in all sites and grip strength. Thus, monitoring grip strength may be used as a representative of systemic skeletal mass even in Japanese people., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Iwase et al.)

The Erysipelothrix rhusiopathiae ERH&#95;1440 gene, which encodes CDP-glycerol:poly (glycerophosphate) glycerophosphotransferase, is conserved in serovar 1a strains. The gene is usually missing or truncated in other serovar strains and therefore has been used for PCR detection of serovar 1a strains. We have previously reported a rare case of an E. rhusiopathiae serovar 2 strain possessing an intact ERH&#95;1440. In this study, we analyzed three additional serovar 2 strains with an intact ERH&#95;1440 and developed a new PCR assay for the specific detection and differentiation of serovar 1a strains from these serovar 2 strains. PCR with primers designed based on serovar 1a-specific gene sequences upstream of ERH&#95;1440 showed 100% specificity for four hundred thirty Erysipelothrix strains isolated from extensive origins.

Objectives: For patients with hematological malignancy, triazole antifungal agents such as fluconazole (FLCZ), itraconazole (ITCZ), voriconazole (VRCZ), posaconazole (PSCZ) and isavuconazole (ISCZ) are often used for prophylaxis of deep mycosis. Since these azoles exhibit large pharmacokinetic variability, dose adjustment by therapeutic drug monitoring is recommended for some azoles. This study aimed to develop and validate a novel method for simultaneous determination of plasma concentrations of FLCZ, ITCZ, VRCZ, PSCZ, ISCZ and ITCZ-OH, an active metabolite of ITCZ, using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS)., Design & Methods: A high-throughput solid-phase extraction method using 96-well MCX µElution Plate was selected as the pretreatment procedure., Results: The calibration curves for FLCZ, ITCZ, ITCZ-OH, VRCZ, PSCZ and ISCZ showed good linearity (back-calculation of calibrators: relative error ≤ 15% [LLOQ: ≤ 20%]) over wide ranges of 100-100000, 20-20000, 40-40000, 20-20000, 5-5000 and 50-50000 ng/mL, respectively. The validation results of all six drugs fulfilled the criteria of the guidance for bioanalytical method validation of the US Food and Drug Administration for within-batch and batch-to-batch precision and accuracy. The extraction recovery rates were good at ≥ 74.9%, and almost no matrix effects were found for all the drugs. The trough (10 h post-dose in 1 patient on PSCZ) drug concentrations in patients with hematologic malignancy who received oral FLCZ, ITCZ, VRCZ or PSCZ were quantified using the method developed. The measurements for all samples were within the ranges of the calibration curves, demonstrating the feasibility of clinical application of the novel method., Conclusions: We have succeeded in developing a novel high-throughput method using UHPLC-MS/MS for simultaneous quantification of plasma concentrations of FLCZ, ITCZ, ITCZ-OH, VRCZ, PSCZ and ISCZ., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Pazopanib is widely used to treat renal cell carcinomas and soft tissue tumors in Japan. Although several reports demonstrated the usefulness of therapeutic drug monitoring (TDM) of pazopanib, those studies measured only total pazopanib concentration. For drugs with high protein binding rates such as pazopanib, measuring free concentrations may be clinically more useful than measuring total concentrations. In this study, we aimed to develop a high-throughput method for quantification of free pazopanib in human plasma using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Free pazopanib was separated by ultrafiltration. After a simple solid-phase extraction step using a 96-well plate, pazopanib was analyzed by UHPLC-MS/MS in positive electrospray ionization mode. The novel method fulfilled the requirements of the US Food and Drug Administration guidelines for assay validation, and the lower limit of quantification was 0.05 ng/mL. The calibration curve was linear over the concentration range of 0.05-50 ng/mL. The average recovery rate was 66.9 ± 2.1% (mean ± SD). The precision was below 7.02%, and accuracy was within 10.60% across all quality control levels. Matrix effect varied between 44.4% and 60.4%. This assay was successfully applied to measure trough free pazopanib concentrations in three patients treated with pazopanib for soft tissue tumors. We succeeded to develop a novel high-throughput UHPLC-MS/MS method for quantification of free pazopanib in human plasma. This method can be applied to TDM for patients receiving pazopanib in the clinical setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In Asia, including Japan, dementia incidence peaks in older adults over ≥75 years; it is therefore important to detect mild cognitive impairment (MCI), and prevent its onset in this age group. Our study hypothesized that physical and psychological status would be associated with MCI incidence among community-dwelling people aged 75 years and older. The study population comprised 291 such individuals. Participants with a Mini-Mental State Examination score of 28 or more were considered non-MCI, and those with a score of less than 28 and greater than 24 were considered to have MCI. Several other measures were also evaluated, including information about their current medical visits due to diseases, depressive symptom severity, various physical functions (trunk function, 30 s chair-stand test, one-legged stance test, timed up and go test time, 5 m walking time, grip strength, knee-extension strength, and toe-grip strength), and body composition (body fat and skeletal muscle mass). Participants suspected of having MCI had significantly shorter educational histories, higher rates of medical visits due to hypertension, and poorer balance abilities. The results suggest that these indices can be considered screening indicators for detecting MCI in people aged 75 years and older, which may be useful for planning intervention programs for this population.

Background: Although lenvatinib treatment has a favorable efficacy for unresectable hepatocellular carcinoma (HCC), it is associated with adverse events (AEs) that must be closely monitored and managed. Thrombocytopenia is one of the major AEs. The aim of this study was to clarify whether thrombocytopenia can be predicted by the plasma concentration of lenvatinib., Methods: This was a single-center retrospective observational study. Twenty-three patients with unresectable HCC and pharmacokinetics data at the initial lenvatinib administration between May 2018 and September 2020 at Oita University Hospital were enrolled. The AEs during the 4 weeks after the initiation of treatment were evaluated, and the correlations between the thrombocytopenia and the plasma concentration of lenvatinib were examined. Spearman's correlation was used to evaluate the correlation between two continuous variables., Results: The rate of platelet count decrease correlated with the maximum plasma concentration (C max ) (r = 0.65, P = 0.001), whereas it did not with the minimum plasma concentration (C min ) (r = 0.29, P = 0.206). After stepwise multiple linear regression analysis, the starting dose of lenvatinib and the serum albumin concentration were identified as independent explanatory variables. Next, a formula for predicting the C max using these two variables was created. The predicted C max was strongly correlated with the C max (r = 0.87, P < 0.0001) and the rate of platelet count decrease (r = 0.67, P = 0.001)., Conclusions: This study identified the usefulness of the drug C max to predict the rate of platelet count decrease within 4 weeks after the initiation of treatment. Although it is difficult to measure the plasma concentration of lenvatinib in community hospitals, the predicted C max is useful for predicting the rate of platelet count decrease with this treatment., Competing Interests: We have no financial relationships to disclose., (Copyright 2021, Endo et al.)

Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning 1,2 . However, it remains unclear how dopamine reward signals influence the entorhinal-hippocampal circuit, another brain network that is crucial for learning and memory 3-5 . Here, using cell-type-specific electrophysiological recording 6 , we show that dopamine signals from the ventral tegmental area and substantia nigra control the encoding of cue-reward association rules in layer 2a fan cells of the lateral entorhinal cortex (LEC). When mice learned novel olfactory cue-reward associations using a pre-learned association rule, spike representations of LEC fan cells grouped newly learned rewarded cues with a pre-learned rewarded cue, but separated them from a pre-learned unrewarded cue. Optogenetic inhibition of fan cells impaired the learning of new associations while sparing the retrieval of pre-learned memory. Using fibre photometry, we found that dopamine sends novelty-induced reward expectation signals to the LEC. Inhibition of LEC dopamine signals disrupted the associative encoding of fan cells and impaired learning performance. These results suggest that LEC fan cells represent a cognitive map of abstract task rules, and that LEC dopamine facilitates the incorporation of new memories into this map., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Lenvatinib is increasingly being selected as the first-line treatment for unresectable hepatocellular carcinoma (HCC) based on the results of the REFLECT trial. However, early discontinuation of lenvatinib because of adverse effects is a frequent occurrence. Hence, lenvatinib is a difficult drug for use in the clinical setting. One of the causes is that the dose of lenvatinib is mainly determined by body weight alone, despite high interindividual variability. To overcome this problem, a dosing regimen of lenvatinib based on a population pharmacokinetic (PPK) model for HCC patients is proposed. The aim of this study was to develop a high-throughput quantification method for lenvatinib using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) that can be applied to a PPK analysis of HCC patients in the future., Methods: After a simple solid-phase extraction step using a 96-well plate, lenvatinib was analyzed by UHPLC-MS/MS in a positive electrospray ionization mode., Results: The novel method fulfilled the requirements of the US Food and Drug Administration guidance on bioanalytical method validation. The calibration curve was linear over the 0.2-1000 ng/mL concentration range. The average recovery rate was 98.63 ± 4.55% (mean ± SD). The precision was below 6.05%, and the accuracy was within 12.96% for all quality control levels. The matrix effect varied between 103.33% and 134.61%. This assay was successfully applied to the measurement of plasma concentrations in 6 HCC patients receiving lenvatinib., Conclusions: A novel high-throughput UHPLC-MS/MS assay for quantification of lenvatinib in human plasma was successfully developed. This method can be applied to PPK analysis for patients receiving lenvatinib in the clinical setting., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Preserved ratio impaired spirometry (PRISm) is associated with an increased mortality rate; however, its characteristics have not been clearly identified in Japan. This cross-sectional study of community-dwelling older adults compared physical function between people with PRISm and those with no respiratory issues, from 2014 to 2019. We collected demographic data through interviews and measured respiratory and physical functions. We included 668 older adults (male, 23.5%; mean age, 72.8 ± 5.6 years); the prevalence of PRISm was 12%, while the prevalence of obstruction was 6.9%. Propensity score matching was used to identify control subjects with normal spirometry (n = 80) while minimizing the effects of confounders during comparisons with the PRISm population (n = 80). Compared with community-dwelling older adults with normal lung capacity, older adults with PRISm had a lower forced vital capacity (%FVC; 68.7 ± 9.1% vs. 92.5 ± 12.7%, p < 0.001), lower core muscle endurance (sit-up test: 6.7 ± 5.8 vs. 8.7 ± 6.0, p = 0.032), and a longer one-leg stance duration (52.4 ± 41.1 s vs. 36.4 ± 34.1 s, p = 0.008). In multivariable logistic regression, %FVC and increased one-leg stance were independent predictors of PRISm status. The prevalence of PRISm among community-dwelling elderly Japanese exceeds that of obstructive lung disease and is associated with reduced %FVC and better performance on balance testing., (© 2021. The Author(s).)

Background: Pazopanib is widely used to treat renal cell carcinomas and soft tissue tumors in Japan. Pazopanib has significant therapeutic efficacy but it is associated with frequent severe adverse effects. Therapeutic drug monitoring (TDM) may help to prevent adverse effects. A more convenient and rapid pazopanib assay is desirable for the application of TDM in clinical settings. In this study, the authors developed a high-throughput method for quantifying pazopanib in human plasma using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)., Methods: After a simple solid-phase extraction step using a 96-well plate, pazopanib was analyzed by UHPLC-MS/MS in the positive electrospray ionization mode., Results: The novel method fulfilled the requirements of the US Food and Drug Administration and the European Medicines Agency guidelines for assay validation, and the lower limit of quantification was 0.5 mcg/mL. The calibration curves were linear over the concentration range of 0.5-100 mcg/mL. The average recovery rate was 102.0% ± 3.9% (mean ± SD). The precision was below 5.0%, and the accuracy was within 12.0% for all quality control levels. Matrix effect varied between 90.9% and 97.1%. This assay was successfully applied to TDM of pazopanib trough concentrations in 3 patients treated with the drug for soft tissue tumors., Conclusions: The authors succeeded in developing a novel high-throughput UHPLC-MS/MS method for quantifying pazopanib in human plasma. This method can be applied to TDM of patients receiving pazopanib in clinical settings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The regulation of glutamate receptor localization is critical for development and synaptic plasticity in the central nervous system. Conventional biochemical and molecular biological approaches have been widely used to analyze glutamate receptor trafficking, especially for α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate-type glutamate receptors (AMPARs). However, conflicting findings have been reported because of a lack of useful tools for analyzing endogenous AMPARs. Here, we develop a method for the rapid and selective labeling of AMPARs with chemical probes, by combining affinity-based protein labeling and bioorthogonal click chemistry under physiological temperature in culture medium. This method allows us to quantify AMPAR distribution and trafficking, which reveals some unique features of AMPARs, such as a long lifetime and a rapid recycling in neurons. This method is also successfully expanded to selectively label N-methyl-D-aspartate-type glutamate receptors. Thus, bioorthogonal two-step labeling may be a versatile tool for investigating the physiological and pathophysiological roles of glutamate receptors in neurons.

Combination therapy of tegafur/uracil (UFT) and leucovorin (LV) is widely used to treat colorectal cancers. Although this therapy has a significant therapeutic effect, severe adverse effects occur frequently. Therapeutic drug monitoring (TDM) may help to prevent adverse effects. A useful assay that can quantitate plasma levels of 5-FU, uracil, and tegafur simultaneously for TDM has been desired, but such a method is not currently available. In this study, we aimed to develop a sensitive method for simultaneous quantification of 5-FU, uracil, and tegafur in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). After preparing plasma samples by protein precipitation and liquid extraction, 5-FU, uracil, and tegafur were analyzed by UPLC-MS/MS in negative electrospray ionization mode. Validation was performed according to US Food and Drugs Administration guidance. The calibration curves were linear over concentration ranges of 2-500 ng/mL for 5-FU, 20-5000 ng/mL for uracil, and 200-50,000 ng/mL for tegafur. The corresponding average recovery rates were 79.9, 80.9, and 87.8%. The method provides accuracy within 11.6% and precision below 13.3% for all three analytes. Matrix effects of 5-FU, uracil, and tegafur were higher than 43.5, 84.9, and 100.2%, respectively. This assay was successfully applied to assess the time courses of plasma 5-FU, uracil, and tegafur concentrations in two patients with colorectal liver metastasis who received UFT/LV therapy after hepatectomy. In conclusion, we succeeded to develop a sensitive and robust UPLC-MS/MS method for simultaneous quantification of 5-FU, uracil, and tegafur in human plasma. This method is potentially useful for TDM in patients receiving UFT/LV combination therapy.

Few studies have examined the effects of health literacy on people at risk of developing dementia; its effects on the pathogenesis of subjective cognitive decline (SCD) are particularly unclear. This study aimed to clarify the relationship between health literacy and SCD in a population of healthy community-dwelling older adults. SCD status was assessed using the Cognitive Function domain of the Kihon Checklist (KCL-CF). Health literacy, in turn, was evaluated using the Communicative and Critical Health Literacy (CCHL) scale. Global cognitive function and depressive symptoms were evaluated using the Mini-Mental State Examination (MMSE) and a five-item version of the Geriatric Depression Scale (GDS-5), respectively. Participants who were suspected of having SCD were significantly older than their non-SCD peers, and scored significantly worse on the CCHL, MMSE, and GDS-5. In addition, SCD status was found to be associated with CCHL and GDS-5 scores, as well as age, according to a logistic regression analysis. These findings suggest that low health literacy is linked to SCD morbidity in healthy community-dwelling older adults and should prove useful in the planning of dementia prevention and intervention programs for this population.

Occupational therapy often uses craft activities as therapeutic tools, but their therapeutic effectiveness has not yet been adequately demonstrated. The aim of this study was to examine changes in frontal midline theta rhythm (Fmθ) and autonomic nervous responses during craft activities, and to explore the physiological mechanisms underlying the therapeutic effectiveness of occupational therapy. To achieve this, we employed a simple craft activity as a task to induce Fmθ and performed simultaneous EEG and ECG recordings. For participants in which Fmθ activities were provoked, parasympathetic and sympathetic activities were evaluated during the appearance of Fmθ and rest periods using the Lorenz plot analysis. Both parasympathetic and sympathetic indices increased with the appearance of Fmθ compared to during resting periods. This suggests that a relaxed-concentration state is achieved by concentrating on craft activities. Furthermore, the appearance of Fmθ positively correlated with parasympathetic activity, and theta band activity in the frontal area were associated with sympathetic activity. This suggests that there is a close relationship between cardiac autonomic function and Fmθ activity., 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., (Copyright © 2020 Shiraiwa, Yamada, Nishida and Toichi.)

We studied wing pattern characters to distinguish closely related sympatric species Papilio zelicaon Lucas, 1852 and Papilio polyxenes Fabricius, 1775 in Southern California, and developed a morphometric method based on the ventral black postmedian band. Application of this method to the holotype of Papilio [Zolicaon variety] Coloro W. G. Wright, 1905, the name currently applied to the P. polyxenes populations, revealed that it is a P. zelicaon specimen. The name for western US polyxenes subspecies thus becomes Papilio polyxenes rudkini (F. R. Chermock, 1981), reinstated status, and we place coloro as a junior subjective synonym of P. zelicaon. Furthermore, we sequenced mitochondrial DNA COI barcodes of rudkini and coloro holotypes and compared them with those of polyxenes and zelicaon specimens, confirming rudkini as polyxenes and coloro as zelicaon.

We previously developed a multiplex PCR assay for the differentiation of serovar 1a, 1b, 2 and 5 strains of Erysipelothrix rhusiopathiae. In this study, we analyzed the serovar-defining chromosomal region of a serovar 2 swine isolate, which was PCR-positive for both serovars 1a and 2 by the multiplex PCR assay. Genetic analysis of the chromosomal region revealed that, as in serovar 1a strains, the ERH&#95;1440 gene, which is usually truncated or missing in serovar 2 strains, was intact in this strain. This paper first shows an E. rhusiopathiae serovar 2 strain possessing an intact ERH&#95;1440 gene and suggests that care may be needed when determining the serovar of such rare strains by PCR assay.

Erysipelothrix rhusiopathiae is a zoonotic pathogen that causes erysipelas in a variety of animals. In humans, in contrast to the cutaneous form called erysipeloid, which is an occupational disease and common in individuals who handle raw meat and fish, invasive systemic infections are unusual. E. rhusiopathiae expresses an immunogenic surface protein, Spa (surface protective antigen), which is involved in virulence. Among the antigenically different Spa proteins (SpaA, B and C), which are mostly associated with serovars, SpaA is by far the most prevalent in E. rhusiopathiae isolates from diseased animals. However, the Spa type has not been examined for human isolates, and it is unknown whether SpaB- or SpaC-possessing isolates can cause disease in humans. A Gram-positive, rod-shaped bacterium isolated from a case of human pyogenic spondylitis was analysed. The bacterium was identified as E. rhusiopathiae by a routine biochemical test and MS, and ultimately confirmed by an E. rhusiopathiae -specific PCR assay. Spa typing by sequencing revealed the SpaB type, and the serovar of the strain was identified as untypeable by a conventional agar gel precipitation test, but determined to be serovar 6 by a serotyping PCR assay. Sequence analysis of the serovar-defining chromosomal region revealed that the isolate displayed the same gene organization as the serovar 6 reference strain, but the region was disrupted by an insertion sequence element, suggesting that the isolate originated from a serovar 6 strain. These results highlight that unusual, spaB -possessing E. rhusiopathiae strains can potentially pose serious risks to humans.

The association between gait speed, a vital health outcome in older adults, and health literacy, an important health promotion aspect, is unclear. This study examined the relationship of gait speed with health literacy, physical function, and cognitive function in community-dwelling older adults. The subjects were 240 older adults (52 men, mean age 73.8 ± 6.0 years). Gender, age, and education were self-reported, while height and weight were measured directly. Health literacy was evaluated using Communicative and Critical Health Literacy (CCHL). Grip strength, knee extension strength, toe-grip strength, sit-up test, sit-and-reach test, one-leg stance test time, 30-s chair-stand test (CS-30), and normal gait speed were measured. Subjects were divided into two groups based on normal gait speed-fast (speed ≥ 1.3 m/s) and slow (<1.3 m/s). In the logistic regression analysis, the dependent variable was normal gait speed (fast/slow). Four logistic regression models were utilized to determine whether health literacy affects gait speed. Height and CCHL were found to independently affect gait speed. That health literacy influences gait speed is a new discovery.

Subjective cognitive decline (SCD) is complex and not well understood, especially among Japanese people. In the present study, we aimed to elucidate the relationships of subjective and objective mental and physical function with SCD among older community-dwelling Japanese adults. SCD was evaluated using the Kihon Checklist: Cognitive Function. Other parameters were evaluated using the Mini-Mental State Examination (MMSE) and the five-item version of the Geriatric Depression Scale (GDS-5), for an objective mental function other than SCD. A timed up-and-go test (TUG) and knee extension strength were used to test objective physical function, and the Mental Component Summary (MCS) and Physical Component Summary (PCS) in the Health-Related Quality of Life survey eight-item short form (SF-8) were used for subjective mental and physical functions. The results of the MMSE, GDS-5, TUG, knee extension strength, and MCS were significantly worse in the SCD group. In addition, logistic regression analysis showed that GDS-5 and MCS were associated with SCD onset. Depressive symptoms and decreased subjective mental function contribute to SCD among community-dwelling Japanese adults. These findings will be useful for planning dementia prevention and intervention programs for older Japanese adults.

This study aimed to investigate the characteristics of skeletal muscle mass, muscle strength, and physical performance among community-dwelling older women. Data were collected from 306 older adults, and the data of 214 older women were included in the final analysis. Participants' calcaneus bone mass was measured using ultrasonography. Based on their T-scores, participants were divided into the following three groups: normal (T-score > -1), low (-2.5 < T-score ≤ -1), and very low (T-score ≤ -2.5) bone mass. Further, participants' skeletal muscle mass, muscle strength (grip and knee extension strength), and physical performance [gait speed and timed up and go (TUG)] were measured. Arm skeletal muscle index (SMI, skeletal muscle mass/height 2 ), leg SMI, and appendicular SMI in the very low bone mass group were low compared to those of the low bone mass group ( p = 0.034, p = 0.011, and p = 0.009, respectively). Grip and knee extension strength, gait speed, and TUG were not significantly different between the groups. These findings suggest that older women with low bone density had decreased skeletal muscle mass. Therefore, maintaining or improving skeletal muscle mass may prevent low bone mass.

Protein analysis under biological conditions is now regarded as indispensable for understanding the structure and function of proteins, in addition to in vitro studies using purified target proteins. Because there are many molecules other than the protein-of-interest (POI) under live cell conditions, selective labeling of a POI is critical to distinguish the POI from other proteins for precise analysis. Protein labeling strategies utilizing genetically encoded tags have been used in POI modification in the complex environment of live cells. However, genetic manipulation may often induce overexpression of the POI and/or perturb the cellular context, resulting in unexpected artifacts in the protein analysis. Alternatively, recent progress in chemical biology has produced two major chemical approaches for analyzing endogenous proteins under native conditions. In this review, we summarize these techniques that utilize either protein-selective chemical labeling or proteome-directed chemical modification., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Walking motor imagery ability is thought to be associated with a fear of falling; however, no studies have compared fall risk and motor imagery ability. This study aimed to ascertain the time difference between imagined and physical walking in older adults at low and high risks of falling. Motor imagery ability was assessed using mental chronometry, which measures the imagined time required for movement. Participants included 31 older adults classified as having a high ( n = 15) or low ( n = 16) risk of falling based on single leg stance time. The time required for imagined and physical walking was measured using 5 m long walkways with three different widths (15, 25, and 50 cm), and the temporal errors (absolute and constant error) were compared. Physical walking time was significantly longer in the high-risk group than in the low-risk group for the 15 and 25 cm wide walkways. The absolute error between the imagined and physical walking times was significantly larger in the high-risk group than in the low-risk group for the 15 and 25 cm wide walkways. There was also a significant difference in the constant error between the high- and low-risk groups between the imagined and physical walking times for all three walkways. Older adults who may be at a higher risk of falling showed longer walking times during action execution but overestimated their performance (i.e., they believe they would be faster) during motor imagery. Therefore, the time difference between imagined and physical walking could, in part, be useful as a tool for assessing fall risk based on motor imagery.

Studies involving the 30 second chair-stand test (CS-30) have shown that subjects' movements can vary during the test, and that these variations may follow several patterns. The present study aimed to define these different patterns and their respective incidences among a population of community-dwelling older adults in Japan. We also investigated, among the patterns identified, potential associations with physical and mental characteristics. The study population comprised 202 community-dwelling older adults. Subjects were classified into four groups based on how their CS-30 performance (defined through sit-stand-sit cycle count) changed over three successive 10 second segments: "steady-goers," "fluctuators," "decelerators," and "accelerators." Several other measures were also evaluated, including sit-up count, knee-extension strength, toe-grip strength, and Mini-Mental State Examination score. We found that steady-goers and decelerators comprised 70% of the sample. Fluctuators and steady-goers showed comparable physical function. Decelerators exhibited significant correlations between CS-30 score (total cycles) and tasks involving persistence and repetitive actions ( p < 0.05). In addition, accelerators showed significantly stronger knee extension than steady-goers ( p < 0.01). Differences in temporal patterns of CS-30 performance corresponded to differences in certain dimensions of physical and mental function. Our findings may be useful for planning and evaluating intervention programs aimed at long-term-care prevention among community-dwelling older adults., Competing Interests: The authors have no conflicts of interest to declare.