Fukuoka International University

Introduction: Frailty in older adults is a multidimensional condition that affects healthy life expectancy. Engagement in meaningful activities (MA) is thought to support healthy aging, but the specific relationship between satisfaction with MA and frailty remains underexplored. This study investigated the longitudinal association between satisfaction with MA and frailty (physical, social, and cognitive domains) in community-dwelling older adults. Method: A total of 231 community-dwelling older adults who completed a 2-year follow-up were analyzed. Frailty in each domain was assessed at baseline and at 1- and 2-years. Participants’ MA and satisfaction were obtained through face-to-face interviews. Mixed-effects logistic regression models were used to examine the longitudinal associations between satisfaction with MA and frailty status trajectories. Results: At follow-up, changes in physical frailty status were observed in most participants. Robust status was commonly maintained in the social and cognitive frailty domain. Participants’ MA primarily involved leisure, sports, and domestic activities. Mixed-effects logistic regression analysis showed that satisfaction with MA was significantly associated with physical frailty, even after adjusting for potential covariates (odds ratio 0.68; 95% confidence interval 0.45, 0.99, p = 0.045). However, this association was not significant for social or cognitive frailty. Conclusion: Satisfaction with MA was longitudinally associated with physical frailty, but not with social or cognitive frailty.

<title>Abstract</title> <bold>Objectives:</bold> To develop a revised version of the Professional Identity Scale for Physiotherapists and clarify core elements of professional identity among Japanese physiotherapists. <bold>Design:</bold> A nationwide cross-sectional web-based survey. <bold>Setting:</bold> The survey was conducted across 499 institutions employing physiotherapists in Japan. <bold>Participants:</bold> A total of 1 <bold/> 037 physiotherapists participated in the study (mean age = 32.3 years; 68.5% male, 31.0% female, and 0.5% unspecified gender). <bold>Main outcome measures:</bold> Primary outcome measures were the factor structure and internal consistency of the newly developed Professional Identity Scale for Physiotherapists. Secondary outcome measure included correlations between this scale and the Burnout Scale to assess criterion-related validity. <bold>Results:</bold> Exploratory factor analysis yielded a five-factor structure (“Development of and Contribution to the Professional Group,” “Practical Skills,” “Client-Centered Support,” “Sense of Adaptability,” and “Orientation Toward Contributing to Interprofessional Collaboration”) comprising 28 items, after excluding 9 items from the original 37-item version. Cronbach’s α coefficient ranged from 0.85 to 0.92 for the five factors, with an overall value of 0.96. Criterion-related validity was evidenced by significant correlations with the Burnout Scale: the total identity score was negatively correlated with emotional exhaustion ( <italic>r</italic> = -0.322, <italic>p</italic> &lt; 0.001) and depersonalization ( <italic>r</italic> = -0.281, <italic>p</italic> &lt; 0.001) and positively correlated with personal accomplishment ( <italic>r</italic> = 0.498, <italic>p</italic> &lt; 0.001). <bold>Conclusions:</bold> The revised Professional Identity Scale for Physiotherapists is a reliable and valid instrument for assessing professional identity among physiotherapists. It provides a practical framework for research and educational initiatives aimed at fostering professional identity and mitigating burnout. In addition, the scale may contribute to curriculum development, competency-based training, and international comparative studies focused on professional identity within the health professions.

Objectives: To develop an algorithm to assist in the diagnosis of glaucoma with concomitant retinal vein occlusion (RVO) and to compare its diagnostic accuracy with that of ophthalmology residents and specialists. Methods: Fundus photographs of eyes with RVO and those with both RVO and glaucoma were obtained from patients who visited the University of Yamanashi Hospital. All images were preprocessed through normalization and resized to 512 × 512 pixels to ensure uniformity before model training. The diagnostic accuracy of two algorithms—the Comprehensive Fundus Disease Diagnostic Artificial Intelligence Algorithm (CD-AI) and the Glaucoma Concomitant RVO Artificial Intelligence Algorithm (RVO-GLA AI)—was evaluated. CD-AI is a clinical decision support algorithm originally developed to detect eleven common fundus diseases, including glaucoma and RVO. RVO-GLA AI is a fine-tuned version of CD-AI that is specifically adapted to detect glaucoma with or without RVO. Fine-tuning was performed using 1234 images of glaucoma, 1233 images of nonglaucomatous conditions, including RVO, and 15 images of cases with both glaucoma and RVO. The number of comorbid cases was determined empirically by gradually adding glaucomatous eyes with concomitant RVO to the training set, and 15 images provided the best balance between sensitivity and specificity. Because the available number of such cases was limited, this small sample size may have influenced the stability of the performance estimates. For the final evaluation, both algorithms and all ophthalmologists assessed the same independent test dataset comprising 66 fundus images (16 eyes with glaucoma and RVO and 50 eyes with RVO alone). The diagnostic performance of both algorithms was compared with that of three first-year ophthalmology residents and three board-certified ophthalmologists. Results: CD-AI demonstrated high diagnostic accuracy (92.5%) in eyes with glaucoma alone. However, its sensitivity and specificity decreased to 0.375 and 1.0, respectively, in patients with concomitant RVO. In contrast, the RVO-GLA AI achieved an area under the curve (AUC) of 0.875, with a sensitivity of 0.87 and a specificity of 0.71. Across all the ophthalmologists, the average sensitivity was 0.63, and the specificity was 0.87. Specialists achieved a sensitivity of 0.80 and a specificity of 0.89, while residents had a sensitivity of 0.46 and a specificity of 0.85. Conclusions: An AI-based clinical decision support system specifically designed for glaucoma detection significantly improved diagnostic performance in eyes with combined RVO and glaucoma, achieving an accuracy comparable to that of ophthalmologists, even with a limited number of training cases.

To elucidate the features of plexin D1-immunoglobulin (Ig)G-associated neuropathic pain and its relationship to atopic myelitis (AM) in a nationwide Japanese survey. A preliminary survey questionnaire was sent to 1574 selected departments (neurology and pediatrics/pediatric neurology) to explore the numbers of AM and plexin D1-IgG-positive patients between 2018 and 2022. A secondary survey collected detailed patient data via a questionnaire. In the preliminary survey, 987 (62.7%) institutions responded, reporting 87 AM patients (49 women) and 11 plexin D1-IgG-positive non-AM patients (8 women). The secondary survey collected 71 AM (plexin D1-IgG-positive: 6/31) and 11 plexin D1-IgG-positive non-AM patients (83.7% recovery rate). In AM, paresthesia/dysesthesia was most frequently experienced (> 90%), followed by pain (> 70%). The underlying diseases in 17 plexin D1-IgG-positive patients, all of whom had neuropathic pain, were AM and small fiber neuropathy in 6 each, neuromyelitis optica spectrum disorder with aquaporin-4-IgG in 2, and painful trigeminal neuropathy, erythromelalgia, and multiple sclerosis in 1 each. When 14 plexin D1-IgG-positive patients (excluding 3 patients with established demyelinating diseases) were compared with 25 plexin D1-IgG-negative AM patients, onset ≥ 50 years old, pain at onset, and allodynia/erythromelalgia/facial pain during the entire disease course were significantly more common in the plexin D1-IgG-positive group. Conversely, atopic disorders and hyperIgEemia were associated with plexin D1-IgG-negative AM but not plexin D1-IgG-positive patients. Both AM and plexin D1-IgG-positive patients present long-standing neuropathic pain, whereas plexin D1-IgG is particularly associated with aged-onset neuropathic pain, allodynia, erythromelalgia, and facial pain, but not atopy.

Autonomic dysfunction is recognized as the central mechanism of orthostatic hypotension after microgravity exposure. Because the arterial baroreflex regulates arterial pressure (AP) via sympathetic nerve activity (SNA), we investigated the systematic baroreflex function under simulated microgravity by conducting an open‐loop analysis. We used Sprague–Dawley rats after hindlimb unloading (HU) for 2 weeks. We isolated the carotid sinuses from the systemic circulation, then changed intracarotid sinus pressure (CSP) stepwise and recorded SNA and AP responses. We compared CSP−AP (total loop), CSP−SNA (mechanoneural arc), and SNA−AP (neuromechanical arc) relations between control rats (n = 9) and HU rats (n = 7). The total loop gain at the operating point decreased significantly in HU rats compared with control rats (0.3 ± 0.4 vs. 1.1 ± 0.4 mmHg/mmHg, p < 0.05). In addition to the decrease in the mechanoneural arc gain at the operating point, the neuromechanical arc gain also decreased significantly in HU rats compared with control rats. A numerical simulation experiment showed a greater AP fall with a significant reduction of the total loop gain in response to hypotensive stress in HU rats. Thus, we conclude that simulated microgravity impairs baroreflex sympathetic regulation in the lower AP range, which may play an important role in the pathogenesis of orthostatic hypotension after microgravity exposure.

TRIM48 is a human-specific tripartite motif (TRIM) family protein with E3 ubiquitin ligase activity that plays a significant role in the oxidative stress response and tumor suppression. However, the mechanisms regulating TRIM48 expression remain unknown. In this study, we demonstrate that TRIM48 is targeted for ubiquitination-dependent degradation by S-phase kinase-associated protein 1 (Skp1)-Cullin1 (Cul1)-F-box protein (SCF) ubiquitin ligase complex, containing F-box protein 22 (FBXO22) as a substrate recognition subunit. We found that TRIM48 is a rapid turnover protein, as evidenced by the fast and drastic decrease in its protein expression level in the presence of a protein synthesis inhibitor cycloheximide, which was suppressed by knocking down either Skp1, Cul1 or FBXO22. Exogenous FBXO22 expression promoted K48-linked polyubiquitination and degradation of TRIM48. FBXO22 deficiency accelerated oxidative stress-induced activation of apoptosis signal-regulating kinase 1 (ASK1) and cell death, which was reversed by additional TRIM48 knockdown. Collectively, our findings identify the FBXO22 SCF complex as a key negative regulator of TRIM48-driven ASK1-activation and cell death under oxidative stress. The dysregulation of this axis may underlie human-specific pathologies, such as tumorigenesis and oxidative stress-associated disorders, highlighting its potential as a target for novel therapeutic interventions.

Septic cardiomyopathy, one manifestation of multiple organ dysfunction syndrome, is a challenging complication in sepsis, and cytopathic hypoxia has been proposed to have a key role in the pathophysiology of multiple organ dysfunction syndrome. However, the underlying mechanisms remain unknown. Here, we show that upregulation of hypoxia-inducible factor-1α (HIF-1α) in cardiomyocytes following lipopolysaccharide (LPS) treatment suppresses mitochondrial respiration via inducible nitric oxide synthase-dependent nitric oxide, leading to cytopathic hypoxia. Cardiac-specific heterozygous deletion of HIF-1α ameliorates mitochondrial and contractile dysfunction in a mouse model of septic cardiomyopathy. Mechanistically, nuclear factor-κB (NF-κB)-mediated upregulation of cyclooxygenase 2 (COX2) and secretory phospholipases A2 (sPLA2) enhances HIF-1α expression following LPS exposure, whereas their inhibition prevents LPS-induced HIF-1α upregulation, cytopathic hypoxia and contractile dysfunction. In addition, phospholipid metabolites (prostaglandins and lysophospholipids/free fatty acids, respectively) stabilize HIF-1α via protein kinase A activation. These findings highlight a crucial role of excessive HIF-1α, driven by LPS-enhanced phospholipid metabolism, in septic cardiomyopathy through induction of cytopathic hypoxia.

ABSTRACT Objectives Participating in religious activities benefits older adults’ mental health; however, the effects of grave visitation, a significant religious practice in Japan, on older adults’ mental health remain unclear. Therefore, this study examined the relationship between grave visitation frequency and depressive symptoms. Methods A prospective cohort study of 273 community-dwelling older adults in Japan was conducted with baseline (2018) and follow-up (2022) assessments. Participants were categorized by visitation frequency: more or less than once a week. Changes in visitation frequency were classified as continued high, decreased, continued low, or increased. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15). Multivariable linear regressions were used to examine the association between visitation and depressive symptoms. Results Lower visitation at baseline was associated with worse GDS-15 scores in the follow-up. Those with decreased or continued low visitation had significantly worse depressive symptoms. After adjusting for baseline GDS-15 scores and covariates, the decreased group had significantly worse depressive symptoms than the continued high group. Conclusions The findings indicate that changes in grave visitation frequency are significantly associated with depressive symptoms. Clinical Implications Supporting older adults’ access to grave visitation through transportation or community programs may help maintain their well-being and emotional health.

Total knee arthroplasty (TKA) is a common intervention for treating end-stage knee osteoarthritis (OA). Postoperatively, altered biomechanics may increase the risk of OA progression in the contralateral knee. Knee adduction moment (KAM) is a key indicator of medial knee joint loading and is associated with OA progression. Walking aids are often prescribed to reduce joint stress during walking; however, their comparative effects on KAM in patients undergoing TKA remain unclear. This study aimed to evaluate the effects of different walking aids (double canes [D-canes], rollators without forearm support [rollators], and rollators with forearm support [F-rollators]) on KAM peak and impulse in both the operated and contralateral knees of patients after TKA using gait analysis. A cross-sectional study was conducted on eight women who underwent unilateral TKA. Participants walked under four conditions: no aid, D-canes, rollators, and F-rollators. A three-dimensional motion capture system measured the lower limb kinematics and kinetics. The primary outcomes were KAM peak and impulse for both knees. Secondary outcomes included ground reaction force in the vertical direction (GRF Z), forward trunk tilt angle, and lower limb joint angles. A two-way repeated-measures measures analysis of variance (ANOVA) was used for statistical comparisons. Walking aids significantly reduced the KAM peak and impulse in both the operated and contralateral knees compared with unaided walking (P < 0.001). In the operated knee, the KAM peak decreased by approximately 20% with all aids, whereas in the contralateral knee, reductions were 6% for D-canes, 16% for rollators, and 24% for F-rollators. Rollators and F-rollators more effectively reduced contralateral knee loading than D-canes (P < 0.001). A significant negative correlation was found between trunk forward tilt angle and GRF Z (ρ= -0.74, P < 0.001), suggesting that increased forward lean with rollators and F-rollators enhanced lower limb offloading. No significant changes were observed in knee varus angle or walking speed across conditions. Walking aids, particularly F-rollators, effectively reduce KAM and offload the contralateral knee in patients after TKA. These findings suggest potential benefits for patients at risk of OA progression in non-operated knees.

Heart failure with preserved ejection fraction (HFpEF), characterized by cardiac hypertrophy and diastolic dysfunction, is increasing worldwide. Goreisan (GRS) is a traditional herbal formulation; its component attenuates cardiomyocyte hypertrophy. This study aimed to investigate the effect of GRS on the pathophysiology of HFpEF. Administration of a high fat diet (HFD, 60% fat) and N-nitro-L-arginine methylester (L-NAME, 0.5 g/L in drinking water) increased heart and lung weights in C57BL/6 mice and GRS (5.9 mg/kcal) reduced them without changes in blood pressure. GRS attenuated HFD/L-NAME-induced increases in left ventricular wall thickness and E/A and E/E’, indices of diastolic dysfunction. GRS decreased cardiomyocyte cross-sectional area in HFD/L-NAME-treated mice. Mechanistically, it suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), in HFD/L-NAME-treated hearts. In addition, liquid chromatography/mass spectrometry demonstrated that HFD/L-NAME decreased and GRS increased 73 proteins in the heart. Among them, GRS prevented HFD/L-NAME-induced decrease in inhibitor of β-catenin and T-cell factor (ICAT), a negative regulator of cardiac hypertrophy. Consistently, β-catenin, an ICAT target, exhibited the opposite change. In in vitro experiments, GRS directly decreased β-catenin in isoproterenol (ISO)-treated cardiomyocytes, accompanied by a decrease in cardiomyocyte surface area. Overexpression of ICAT also suppressed ISO-induced increases in β-catenin, phosphorylated ERK, and cardiomyocyte surface area. Among GRS ingredients, cinnamaldehyde and alisol B 23-acetate attenuated ISO-induced increases in β-catenin and cardiomyocyte surface area. In conclusion, GRS attenuates cardiac hypertrophy and diastolic dysfunction via ICAT-β-catenin/ERK axis. GRS is a potential herbal formulation for the treatment of HFpEF.