Effect of digital game intervention on cognitive functions in older adults: a multiple baseline single case experimental design study.

BACKGROUND: Residents in nursing homes are prone to cognitive decline affecting memory, visuospatial cognition, and executive functions. Cognitive decline can lead to dementia, necessitating prioritized intervention. METHODS: The current study aimed to investigate whether an intervention using a digital game was effective for preserving and improving the cognitive function of residents in nursing homes. An intervention study was conducted using a single-case AB design with multiple baselines. The participants in the study were five older adults aged 65 and over who do not play digital games regularly. The study ran for 15 weeks, including a baseline (phase A) and an intervention phase (phase B). Phase A had five baselines (5 to 9 weeks) with random participant assignment. In phase B, participants engaged in a digital game (Space Invaders) individually. Cognitive function was assessed as the outcome, measured using the Brain Assessment (performed on a tablet through the Internet) at 16 measurement points. Four of five participants (two female and two male) were included in the analysis, using visual inspection and Bayesian statistics with multi-level modeling. RESULTS: Visual inspection of the graphs revealed cognitive function score improvements after the intervention for most layers in terms of memory of numbers, memory of words, mental rotation test (visuospatial ability), and total scores in the Brain Assessment. These effects were also significant in the analysis by multi-level modeling. CONCLUSIONS: The results suggest that the use of digital games may be effective for preserving and improving cognitive function among residents of nursing home. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000048677; public title: Effect of a Digital Game Intervention for Cognitive Functions in Older People; registration date: August 30, 2022).

Associations Between Cognitive Function and Muscle Quality Among Community-Dwelling Older Adults: A Cross-Sectional Study.

OBJECTIVE: To investigate whether muscle quality is related to cognitive function in older adults living in the community. METHODS: The participants were 40 community-dwelling older adults without a diagnosis of dementia (mean age, 78.85 ± 6.40 years; 31 women). The dependent variable was the score on the mild cognitive impairment (MCI) index of the Japanese version of the Neurobehavioral Cognitive Status Examination Five (range: 0-6; higher scores indicate MCI or possible dementia). RESULTS: Multiple regression with Bayesian statistics was performed for analysis of muscle quality, as indicated by echo intensity (EI), with skeletal muscle mass index, gait speed, physical activity level, age, and sex as covariates. EI was significantly associated with the MCI index (expected a posterior = 0.04 [95% Bayesian confidence interval: 0.01, 0.07], t = 2.47, ß = 0.41, p = 0.019). CONCLUSIONS: The results suggest that EI may be related to the cognitive function of older adults living in the community. Future studies should examine whether focusing on EI can help prevent cognitive decline among older adults..

Association between muscle quality and nutritional status among community-dwelling older adults: A cross-sectional study.

Background: Decline in muscle quality is associated with poorer health in community-dwelling older adults. Although there is evidence that malnutrition is associated with the decline of muscle quality in older adults, few analyses have considered important factors related to muscle quality. Aim: The purpose of this study was to determine the relationship between muscle quality and nutritional status in community-dwelling older adults, taking into account muscle mass, muscle strength, and amount of physical activity. Methods: This was a cross-sectional study. Data were obtained from a health checkup program in Japan. Participants were older adults aged ≥65 years living in the community who participated in the health checkup program. The data collected were echo intensity, scores on the Global Leadership Initiative on Malnutrition criteria, skeletal muscle mass, grip strength, physical activity level, and demographic data. Multiple regression analysis was used to examine the association between muscle quality and nutritional status. Results: Data were analyzed for 50 participants (mean age 77.62 years, standard deviation 6.16 years, 78.0% women). Multiple regression analysis showed that nutritional status affected muscle quality even when various factors were taken into account (B = 6.95, ß = 0.31, p = 0.04, 95% confidence interval: 0.01-0.62). Conclusion: The observed association suggests that providing nutritional support for older adults living in the community may be a useful strategy to maintain muscle quality.

Dupilumab improves eosinophilic otitis media associated with eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic otitis media (EOM) is a refractory condition associated with eosinophilic chronic rhinosinusitis and bronchial asthma. EOM is characterized by type-2 inflammation and is refractory to various treatments. We investigated the efficacy of dupilumab, interleukin-4 receptor alpha antagonist, for patients with EOM complicated by eosinophilic chronic rhinosinusitis (ECRS). METHODS: Between April 2017 and April 2022, we treated 124 patients with dupilumab for refractory CRS or bronchial asthma. Of these, 14 had EOM concurrently, and 10 of them who had been treated for >6 months were included in our study. We retrospectively evaluated the efficacy of dupilumab by the amount of systemic corticosteroid used, the frequency of exacerbations, severity score of EOM, computed tomography (CT) score of temporal bones, and pure tone audiometry. We also enrolled 8 EOM patients without dupilumab treatment as a control group. RESULTS: Dupilumab significantly improved the amount of systemic corticosteroid used and the frequency of exacerbation and compared with before dupilumab was used (p = 0.01 and <0.01, respectively). All patients could be weaned from systemic-corticosteroid therapy by 54 weeks of dupilumab use. The severity score of EOM and CT score for temporal bones were significantly lower than before the treatment (p = 0.01 and 0.01, respectively). Compared to the control group, the systemic corticosteroid used and severity scores were improved in the dupilumab group (p = 0.02 and < 0.01, respectively). CONCLUSIONS: Dupilumab could be used to wean patients from systemic corticosteroids with the improvement of severity score in EOM associated with ECRS and bronchial asthma.

Amyloid ß protein negatively regulates human platelet activation induced by thrombin receptor-activating protein.

Amyloid ß protein deposition in cerebral vessels, a characteristic of Alzheimer's disease, is a risk factor for intracerebral hemorrhage. Amyloid ß protein directly modulates human platelet function; however, the exact mechanism of action is unclear. Therefore, we investigated the effects of amyloid ß protein on human platelet activation using an aggregometer with laser scattering. Amyloid ß protein decreased platelet aggregation induced by thrombin receptor-activating protein, but not by collagen and ADP. Amyloid ß protein also suppressed platelet aggregation induced by SCP0237 and A3227. Platelet-derived growth factor-AB secretion and phosphorylated-heat shock protein 27 release by thrombin receptor-activating protein were inhibited by amyloid ß protein. Additionally, thrombin receptor-activating protein-induced phosphorylation of JNK and p38 MAP kinase was reduced by amyloid ß protein. Collectively, our results strongly suggest that amyloid ß protein negatively regulates protease-activated receptor-elicited human platelet activation. These findings may indicate a cause of intracerebral hemorrhage due to amyloid ß protein.

HSP90 inhibitors strengthen extracellular ATP-stimulated synthesis of interleukin-6 in osteoblasts: Amplification of p38 MAP kinase.

Heat shock protein 90 (HSP90) is expressed ubiquitously in a variety of cell types including osteoblasts. HSP90 acts as a key driver of proteostasis under pathophysiological conditions. Here, we investigated the involvement of HSP90 in extracellular ATP-stimulated interleukin (IL)-6 synthesis and HSP90 downstream signalling in osteoblast-like MC3T3-E1 cells. In osteoblasts, extracellular ATP stimulates the synthesis of IL-6, a bone-remodelling agent. Geldanamycin, 17-allylamino-17-demethoxy-geldanamycin (17-AAG) and onalespib, three different HSP90 inhibitors, amplified the ATP-stimulated IL-6 release. Geldanamycin increased IL-6 mRNA expression elicited by ATP. ATP enhanced the triiodothyronine-induced osteocalcin release, but HSP90 inhibitors suppressed the release. Extracellular ATP induced the phosphorylation of p44/p42 mitogen-activated protein kinase (MAPK), p38 MAPK, c-Jun N-terminal kinase (JNK), p70 S6 kinase, Akt, and myosin phosphatase-targeting subunit (MYPT), a Rho-kinase substrate. SB203580, an inhibitor of p38 MAPK, suppressed ATP-stimulated IL-6 release. Inhibitors of MEK1/2 (PD98059), JNK (SP600125), upstream kinase of p70 S6 kinase (rapamycin) and Akt (deguelin), all increased IL-6 release. Y27632, a Rho-kinase inhibitor, failed to affect the IL-6 release stimulated by ATP. Geldanamycin and 17-AAG both amplified ATP-induced p38 MAPK phosphorylation, although geldanamycin inhibited the phosphorylation of Akt induced by ATP. In addition, SB203580 significantly reduced the amplification by geldanamycin of the IL-6 release. Taken together, our results strongly suggest that HSP90 inhibitors up-regulate extracellular ATP-stimulated IL-6 synthesis via amplification of p38 MAPK activation in osteoblasts. SIGNIFICANCE OF THE STUDY: Heat shock protein 90 (HSP90) acts as a key driver of proteostasis under pathophysiological conditions in a variety of cell types. We have previously shown that HSP90 is expressed at high levels in osteoblast-like MC3T3-E1 cells, even in their quiescent state, consistent with HSP90 performing an important physiological function in osteoblasts. In the present study, we investigated whether HSP90 is implicated in extracellular ATP-induced interleukin (IL)-6 synthesis in osteoblast-like MC3T3-E1 cells. Our results strongly suggest that HSP90 inhibitors up-regulate extracellular ATP-stimulated IL-6 synthesis via amplification of p38 mitogen-activated protein kinase activation in osteoblasts.

Olive polyphenol reduces the collagen-elicited release of phosphorylated HSP27 from human platelets.

Hydroxytyrosol (HT) and oleuropein (OLE) are natural polyphenols found in extra virgin olive oil. Accumulating evidence indicates that ingestion of olive oil contributes to reduce the risk of cardiovascular diseases and stroke. It has been reported that HT and OLE inhibit human platelet aggregation. We have shown that collagen induces the phosphorylation of heat shock protein 27 (HSP27) in human platelets, resulting in the release of HSP27, an extracellular pro-inflammatory agent. In this study, we investigated the effects of HT and OLE on the collagen-stimulated human platelet activation. The PDGF-AB secretion and the soluble CD40 ligand (sCD40L) release by collagen were reduced by HT or OLE. HT and OLE significantly suppressed the phosphorylation of HSP27 and the release of phosphorylated-HSP27. These findings suggest that olive polyphenol reduces the collagen-stimulated phosphorylation of HSP27 in human platelets and the release. Our results may provide a novel anti- inflammatory effect of olive polyphenol.

Enhancement by HSP90 inhibitor of PGD2-stimulated HSP27 induction in osteoblasts: Suppression of SAPK/JNK and p38 MAP kinase.

Heat shock protein (HSP) 90 that is ubiquitously expressed in various tissues is a major molecular chaperone. We have previously demonstrated that prostaglandin D2 (PGD2), a bone remodeling factor, elicits the expression of HSP27, a small HSP, through stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of HSP90 in the PGD2-stimulated HSP27 induction and the underlying mechanism in MC3T3-E1 cells. Onalespib, an inhibitor of HSP90, significantly enhanced the PGD2-stimulated HSP27 induction. In addition, geldanamycin, another HSP90 inhibitor, potentiated the HSP27 induction. Both onalespib and geldanamycin markedly amplified the PGD2-induced phosphorylation of SAPK/JNK and p38 MAP kinase. SP600125, an inhibitor of SAPK/JNK, and SB203580, an inhibitor of p38 MAP kinase, suppressed the amplification by onalespib of the PGD2-stimulated HSP27 induction. These results strongly suggest that HSP90 plays a negative role in the HSP27 induction stimulated by PGD2 in osteoblasts, and that the inhibitory effect of HSP90 is mediated through the regulation of SAPK/JNK and p38 MAP kinase.

Exploring the factor on sensory motor function of upper limb associated with executive function in communitydwelling older adults.

Exercise, such as cardiovascular fitness training, has been shown to have utility in improving executive function but is difficult for older adults with low mobility to perform. Accordingly, there is interest in the development of regimens other than high mobility exercises for older adults with low mobility. The aim of the present study was to evaluate the association between sensory motor function of the upper limb and executive function in community-dwelling older adults. A cross-sectional study was conducted in 57 right-handed, independent, community-dwelling older adults. Sensory motor function of upper limb, including range of motion, strength, sensation, finger dexterity, and comprehensive hand function was measured in both hands. Executive function was assessed using the Delta Trail Making Test. Multiple regression analysis indicated the finger dexterity of the non-dominant hand as independently associated with executive function (ß = -0.414, P < 0.001). The findings of the present study may facilitate the development of exercise regimens for improving executive function that are more suitable for older adults with limited physical fitness levels. As this was a cross-sectional study, further studies are required to validate the efficacy of non-dominant finger dexterity training for improving executive function in older adults.

Factors affecting the discharge destination of hip fracture patients who live alone and have been admitted to an inpatient rehabilitation unit.

[Purpose] (1) The aim of this study was to examine relations between clinical and functional assessment and discharge destination and (2) to identify the optimal cutoff point for estimating discharge to home after inpatient rehabilitation. [Subjects] The subjects were 54 hip fracture patients (15 males, 39 females; mean age 81.3 ± 7.4 years) living alone. [Methods] The patients were classified into two groups: those discharged to home and those admitted to an institution. Age, gender, side of fracture, fracture type, number of comorbidities, Functional Independence Measure motor score, and Functional Independence Measure cognitive score were compared between groups. Multiple logistic regression analysis was conducted with discharge to home as the dependent variable and age, gender, side of fracture, fracture type, number of comorbidities, Functional Independence Measure motor score, and Functional Independence Measure cognitive score as independent variables. A receiver operating characteristic curve analysis was used to identify a cutoff point for classification of the patients into the two groups. [Results] Multiple logistic regression analysis showed that the Functional Independence Measure cognitive score was a significant variable affecting the discharge destination. The receiver operating characteristic curve analysis revealed that discharge to home was predicted accurately by a Functional Independence Measure cognitive score of 23.5. [Conclusion] Information from this study is expected to be useful for determining discharge plans and for the setting of treatment goals.

A case of recurrent chronic eosinophilic pneumonia after switching from benralizumab to dupilumab.

Dupilumab inhibits interleukin-4Rα and suppresses type 2 inflammation. Careful administration of dupilumab is required because it increases the blood eosinophil count secondary to a decrease in local eosinophil counts, sometimes resulting in eosinophilic complications. We herein report a case of recurrent chronic eosinophilic pneumonia after switching from benralizumab to dupilumab. A 54-year-old man with a history of eosinophilic pneumonia presented to our hospital with symptoms of cough, fever, and phlegm production six months after beginning dupilumab administration for recurrent chronic rhinosinusitis. When using dupilumab, it is essential to carefully monitor patients' eosinophil trends and pulmonary symptoms.

Clinical characteristics in Japanese patients with chronic rhinosinusitis who underwent endoscopic sinus surgery.

OBJECTIVE: There is heterogeneity in the pathophysiology of chronic rhinosinusitis (CRS). Obtaining a detailed understanding of patient profiles in specific regions can provide valuable information not only for clinical practice but also future research plans. The aim of this study was to investigate the characteristics of patients who underwent endoscopic sinus surgery (ESS) for CRS. METHODS: This retrospective, single-center study examined the features of 453 patients with CRS who underwent ESS in the Tokyo area of Japan. The study evaluated various factors in patients with CRS including sex and age, the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, the recurrence rate of CRS, comorbidities of asthma and/or allergic diseases, and IgE sensitization to 12 inhaled allergens. RESULTS: Age-related declines in the sensitization rate to inhaled allergens were observed, and the most notable age-related decrease in specific IgE antibodies was observed for house dust mites (HDM) (p = 8.3 × 10-7). Sensitization to HDM, cat dander, and various types of fungi, including Aspergillus, was frequently observed in the CRS with asthma group, with rates of 54%, 17%, and 17%, respectively. We found that 23% of the patients had recurrence. In the recurrence group, the positive rates of specific IgE antibodies for birch and cat dander were significantly higher than in the no recurrence group. Bronchial asthma was identified as an important factor for recurrence. Among male patients, the recurrence group was younger than the no-recurrence group (p = 0.0032). Severe eosinophilic CRS (ECRS) showed early recurrence after surgery, with over the half of the patients experiencing at least one recurrence within 2 years post-surgery. Among patients with ECRS, the recurrence rate for females was 1.92 times higher than for males. CONCLUSION: Our study revealed the influences of age and sex on various clinical phenotypes of CRS patients undergoing ESS. There was a high sensitization rate to cat dander in both the recurrence and asthma groups. Further research on diverse disease etiologies is necessary to improve therapeutic strategies for patients with CRS.

Relationship between Phase Angle and Physical Activity Intensity among Community-Dwelling Older Adults in Japan: A Cross-Sectional Study.

This cross-sectional study aimed to determine the association between phase angle (PhA) and physical activity intensity in community-dwelling older Japanese adults. The intensity and time of physical activity for predicting high PhA were also examined. This study involved 67 community-dwelling older adults (mean age: 78.3 ± 5.5; female: 83.6%). We measured the physical activity and body composition of the participants. Physical activity was measured using a triaxial accelerometer, and light-intensity physical activity (LPA) and moderate-to-vigorous intensity physical activity (MVPA) hours per day were calculated from the results. Body composition was measured using Inbody S10, and the PhA was calculated from the measurements of the right side of the body. Bayesian statistical modeling revealed an association between PhA and MVPA (ß = 0.256; p = 0.022; 95% Bayesian confidence interval [CI] = 0.001, 0.012), but not LPA (ß = -0.113; p = 0.341; 95% Bayesian CI = -0.002, 0.001), even after adjustment for confounders. The cutoff value of MVPA predicting high PhA, calculated by the receiver operator characteristic curve, was 19.7 min/d (sensitivity = 0.906; specificity = 0.429). These results can be used to develop strategies to increase PhA in older adults and suggest that MVPA is important in this population.

Appetite and family and friends network among community-dwelling older adults: A cross-sectional study.

OBJECTIVES: The aim of this study was to investigate the stronger correlate of appetite-family or friend networks-in community-dwelling older adults, given that undernutrition can impair physical function, increase mortality, and be influenced by social networks. METHODS: A cross-sectional study was conducted in Kasugai City, Aichi Prefecture, and Nara City, Nara Prefecture, Japan, between August 2019 and March 2023. The analysis included 119 participants (women: 79%, mean age: 76.5 ± 5.6 y). A multiple regression analysis was performed, using the scores from the Japanese version of the Simplified Nutritional Appetite Questionnaire (SNAQ-J) as the dependent variable and family network and friend network as the independent variables. The analysis included social participation, living alone status, sex, age, body mass index, skeletal muscle mass index, grip strength, walking speed, and the Japanese version of the 15 Geriatric Depression Scale score as covariates to examine their relationship with appetite. RESULTS: The mean value of the SNAQ-J score of the participants was 15.4 ± 1.2. Seven participants (6%) had a loss of appetite. Family network was significantly associated with appetite (B = 0.121, ß = 0.266, P <0.05; 95% condidence interval [CI], 0.030-0.212). In the single regression analysis, the friend network was significantly associated with the total score of the SNAQ-J (B = 0.115, P <0.001; 95% CI, 0.052-0.177); however, this association was not observed in the multiple regression analysis (B = 0.002, ß = 0.006, P = 0.954; 95% CI, -0.074-0.078). CONCLUSION: Appetite was associated with family networks. Among social networks, focusing on family networks may help prevent the loss of appetite in older adults in Japan.

Type of skin eruption is an independent prognostic indicator for adult T-cell leukemia/lymphoma.

Cutaneous involvement is seen in ~ 50% of adult T-cell leukemia/lymphoma (ATLL) patients. We investigated the association between skin eruption type and prognosis in 119 ATLL patients. ATLL eruptions were categorized into patch (6.7%), plaque (26.9%), multipapular (19.3%), nodulotumoral (38.7%), erythrodermic (4.2%), and purpuric (4.2%) types. When the T stage of the tumor-node-metastasis-blood (TNMB) classification of mycosis fungoides/Sézary syndrome was applied to ATLL staging, 16.0% were T1, 17.7% T2, 38.7% T3, and 4.2% T4, and the remaining 23.5% were of the multipapular and purpuric types. For the patch type, the mean survival time (median survival time could not be estimated) was 188.4 months. The median survival times (in months) for the remaining types were as follows: plaque, 114.9; multipapular, 17.3; nodulotumoral, 17.3; erythrodermic, 3.0; and purpuric, 4.4. Kaplan-Meier curves of overall survival showed that the erythrodermic type had the poorest prognosis, followed by the nodulotumoral and multipapular types. The patch and plaque types were associated with better survival rates. Multivariate analysis demonstrated that the hazard ratios of the erythrodermic and nodulotumoral types were significantly higher than that of the patch type, and that the eruption type is an independent prognostic factor for ATLL. The overall survival was worse as the T stage became more advanced: the multipapular type and T2 were comparable, and the purpuric type had a significantly poorer prognosis than T1.

[Verification of the hygienic hypothesis by evaluating the regional incidence of eosinophilic pustular folliculitis].

Eosinophilic pustular folliculitis (EPF) is a disorder associated with a high expression of interleukin-5 by T helper 2 cells. Treatment involving T helper 1 (Th1) modulation has been shown to be effective. We report that the occurrence of Bowen's disease in the medical care zone of the University of Occupational and Environmental Health in the Kitakyushu industrial area is more frequent in Yahatahigashi-ku, Yahatanishi-ku, and Wakamatsu-ku than in Tobata-ku, Kokurakita-ku, and Kokuraminamiku. We also show that these cases are more common in the regions with steel- and coal-related industries, which is suggestive of a higher rate of Th1 modulation associated with these occupations. Similarly, the incidence of EPF per unit population was found to be high in Tobata-ku and low in Yahatahigashi-ku, which indicates that EPF is a typical disease of hygiene hypothesis.

Relationships between Loneliness and Occupational Dysfunction in Community-Dwelling Older Adults: A Cross-Sectional Study.

The study explored cross-sectional associations between loneliness and occupational dysfunction in community-dwelling older adults. Seventy-four older adults (12 men and 62 women; mean age 73.9 ± 8.3 years) completed a questionnaire survey that included the Japanese version of the UCLA Loneliness Scale Version 3 and the Classification and Assessment of Occupational Dysfunction (CAOD). Bayesian statistical modeling was used for a more stable estimation given the small sample. For model selection, we assumed a univariate analysis model of the CAOD (Model 1); a multivariate analysis model, including confounding factors in Model 1 (Model 2); and a multivariate analysis model, including random effects in Model 2 (Model 3). The best model was selected by comparing the widely applicable information criterion (WAIC) and the widely applicable Bayesian information criterion (WBIC) for each model. Bayesian statistics with the dependent variable as "loneliness" showed that the best model used "occupational dysfunction" as the independent variable and included confounding factors and random effects (WAIC = 474.5 and WBIC = 213.1). The best model identified an association between occupational dysfunction and loneliness (odds ratio [OR] = 2.363; 95% Bayesian confidence interval [CI] = 1.105-5.259). This study highlights the role of occupational dysfunction in addition to the risks and related factors reported to date when dealing with loneliness. Therapists could help older adults cope with loneliness by supporting their social participation and improving their occupational dysfunction.

Effect of acute high-intensity intermittent exercise on serum brain-derived neurotrophic factor concentrations.

BACKGROUND: This study aimed to examine changes in serum brain-derived neurotrophic factor (BDNF) concentrations after exhaustive high-intensity intermittent exercise (HIIE) and non-exhaustive HIIE, and to compare the two conditions. METHODS: Eight healthy male college students (age: 22±1 year) participated in exhaustive (sets: 6-7) and non-exhaustive (sets: 5) HIIE. In both conditions, participants repeated sets of 20 seconds of exercise at 170% V̇O2max with 10 seconds of rest between sets. Serum BDNF was measured 8 times in each condition: 30 minutes after resting, 10 minutes after sitting, immediately after HIIE, and 5, 10, 30, 60, and 90 minutes after main exercise. Changes in serum BDNF concentrations over time and between measurement points in both conditions were measured using a two-way repeated measures ANOVA. RESULTS: Serum BDNF concentrations were measured, revealing significant interaction between two factors (conditions and measurement points) (F=3.482, P=0.027). In the exhaustive HIIE, there were significant increases at 5 minutes (P<0.01) and 10 minutes (P<0.01) after exercise compared to after resting. In the non-exhaustive HIIE, there was a significant increase immediately after (P<0.01) and 5 minutes after (P<0.01) exercise compared to resting. Comparison of the serum BDNF concentrations at each measurement point showed a significant difference at 10 minutes after exercise, with significantly higher values for the exhaustive HIIE condition (P<0.01, r=0.60). CONCLUSIONS: Exhaustive and non-exhaustive HIIE are time-efficient exercises that increase serum BDNF concentrations in healthy adults.

Tramadol regulates the activation of human platelets via Rac but not Rho/Rho-kinase.

Tramadol is a useful analgesic which acts as a serotonin and noradrenaline reuptake inhibitor in addition to µ-opioid receptor agonist. Cytoplasmic serotonin modulates the small GTPase activity through serotonylation, which is closely related to the human platelet activation. We recently reported that the combination of subthreshold collagen and CXCL12 synergistically activates human platelets. We herein investigated the effect and the mechanism of tramadol on the synergistic effect. Tramadol attenuated the synergistically stimulated platelet aggregation (300 µM of tramadol, 64.3% decrease, p<0.05). Not morphine or reboxetine, but duloxetine, fluvoxamine and sertraline attenuated the synergistic effect of the combination on the platelet aggregation (30 µM of fluvoxamine, 67.3% decrease, p<0.05; 30 µM of sertraline, 67.8% decrease, p<0.05). The geranylgeranyltransferase inhibitor GGTI-286 attenuated the aggregation of synergistically stimulated platelet (50 µM of GGTI-286, 80.8% decrease, p<0.05), in which GTP-binding Rac was increased. The Rac1-GEF interaction inhibitor NSC23766 suppressed the platelet activation and the phosphorylation of p38 MAPK and HSP27 induced by the combination of collagen and CXCL12. Tramadol and fluvoxamine almost completely attenuated the levels of GTP-binding Rac and the phosphorylation of both p38 MAPK and HSP27 stimulated by the combination. Suppression of the platelet aggregation after the duloxetine administration was observed in 2 of 5 patients in pain clinic. These results suggest that tramadol negatively regulates the combination of subthreshold collagen and CXCL12-induced platelet activation via Rac upstream of p38 MAPK.

Relationship between Empowerment and Functioning and Disability in Older Japanese Patients: A Covariance Structure Analysis.

In the present study, 151 Japanese older adults aged over 65 years and admitted to recovery-phase rehabilitation facilities were enrolled to investigate the relationship between empowerment and contextual factors, functioning and disability, with structural equation modeling (SEM). The analysis included 151 patients aged 81.75 ± 7.15 years, including 54 males (35.76%) and 97 females (64.24%). The results of the SEM analysis showed that role presence (ß = 0.45, p < 0.01) and family structure (ß = 0.18, p = 0.02) significantly impacted empowerment. In addition, the results showed that patient empowerment positively impacted physical activity (ß = 0.25, p < 0.01) and psychosomatic functions and abilities (ß = 0.36, p < 0.01). Furthermore, the goodness-of-fit of the model hypothesized in this study was shown to have explanatory power. This study showed that empowerment contributed to the prevention of physical inactivity and confinement among Japanese older patients. In other words, the study provided evidence for the importance of empowerment-based program planning in the practice of person-centered care aimed at promoting the health and discharge of older patients in Japan.