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The Japan Society for the Study of Obesity recommends a weight loss of 3% of body weight over a period of 3-6 months. However, the effects of rapid weight loss on the body composition have not yet been adequately studied. Therefore, we observed the changes in the body composition induced by rapid weight loss and its effects on the pathophysiological mechanisms involved in obesity. The subjects were people with obesity admitted to our institution. The goal was to achieve a 3-5% body weight loss in the subjects by combining a carbohydrate-controlled therapeutic diet of 25-30 kcal/day per kg target body weight, exercise therapy, and pharmacotherapy. The body composition was measured at admission and at discharge by the dual bioelectrical impedance analysis. After 2 weeks, the participants' body weight decreased by 4.2%; the visceral fat area decreased by 16.7%, the subcutaneous fat area by 2.4%, and the lean area by 4.0%. The moderate weight loss, moderate energy restriction and adequate protein intake significantly reduced the visceral fat area while allowing the lean area to be preserved. Improvements were also noted in the peripheral white blood cell count and C-reactive protein level. However, no statistically significant changes in homeostasis model assessment for insulin resistance and the adiponectin level were noted. Regarding clinical parameters, improvements of the systolic and diastolic blood pressures, fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and degree of microalbuminuria were observed. Short-term comprehensive treatment produced beneficial body composition changes, and improvements in the pathophysiological mechanisms involved in obesity.

Background/Objectives : A 68-year-old man presented with progressive walking difficulty that developed into spastic paraplegia. This condition was a long-term consequence of a lightning strike injury sustained at the age of 22 years. His symptoms progressively deteriorated, eventually requiring double crutches for ambulation at approximately 40 years of age. A physical evaluation prior to hybrid assistive limb (HAL) training revealed a T10 level neurological injury and an American Spinal Cord Injury Association impairment scale grade D. Here, we aimed to evaluate the therapeutic effects of novel gait training with an HAL in this patient with chronic and progressive neural damage caused by a lightning strike. Methods : The HAL training program is composed of two sections. In the first section, one month of gait training with HAL was conducted across 10 sessions, with 2-3 sessions weekly. The second section followed 6 months later. A final evaluation was performed three months after the second section. Results : Electromyographic and kinematic evaluation showed that the HAL gait training inhibited abnormal antagonistic muscle activation in his lower extremities, especially after the first section. Our results collectively indicate that the repeated HAL gait training improved the gait pattern of this patient. Conclusions : Our results suggest that HAL gait training may improve the gait pattern in patients with delayed progressive spastic paraplegia, as observed in this case. In addition, a longer intervention period is recommended to facilitate better adaptation to HAL training. Hence, neurorehabilitation with an HAL could be an innovative treatment approach for delayed progressive spastic paraplegia.

Harmful algal blooms are responsible for economic, societal, and health issues worldwide. In Japan, heterogeneity concerning diarrhetic shellfish poisoning (DSP) events has been reported, with most occurrences in the northern region. Although the toxin profile of Dinophysis cells from the DSP outbreaks has been investigated, no statistical comparison has been conducted on total toxin (particulate and released) production using cultured strains. A comparative toxin analysis was done based on > 400 strains of Dinophysis fortii from Japan's southwestern and northern areas to investigate the heterogeneity in toxicity. Regardless of the origin, the toxin profile of all strains was dominated by PTX2. However, OA was the second most abundant toxin in the southwestern and DTX1 in the northern strains. For DTX1, the average concentrations in the north (330.54 ± 223.03 ng/mL) were significantly higher than in the southwest (5.85 ± 8.92 ng/mL). PTX2 also displayed significantly higher average concentrations in the north (384.51 ± 240.03 ng/mL) than in the southwest (122.66 ± 125.1 ng/mL). However, the northern strains had significantly lower levels of OA (6.74 ng/mL ± 13.53) than those from the southwest (34.86 ± 38.47 ng/mL). The total toxin yield in the northern strain cultures was about 56 times higher for DTX1, whereas OA content was 5 times lower, indicating significant differences in toxic potential in the strains from the two regions. The results of this toxin analysis contribute to the explanation of the geographical differences in DSP outbreaks associated with the blooms of D. fortii in Japan., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Wai Mun Lum reports financial support was provided by Japanese Society for the Promotion of Science. Sirje Sildever reports financial support was provided by Estonian Research Council. Satoshi Nagai reports financial support was provided by Japanese Society for the Promotion of Science. Corresponding author, Satoshi Nagai, is serving as an subject editor at the journal (Harmful Algae) to, which the manuscript was submitted If there are other authors, they 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 © 2025 Elsevier B.V. All rights reserved.)

Primary cardiac lymphoma is a rare disease with the potential to be fatal. This case reports a patient who developed primary cardiac lymphoma resulting in cardiac tamponade. Despite a compromised general condition, the lymphoma was diagnosed through a transvenous tumor biopsy. Chemotherapy led to significant improvement in the patient's condition. Malignant lymphoma can be treated with chemotherapy. Therefore, the performance of tumor biopsies even in patients with poor general condition enabled the initiation of treatment., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background/Objectives : Sarcopenic obesity adversely affects physical function and activities of daily living (ADL) in older individuals and patients undergoing rehabilitation. This condition is also common in individuals with spinal cord injury (SCI); however, its relationship with ADL in this group remains unclear. Hence, this study examined the association between sarcopenic obesity and ADL in individuals with SCI. Methods : This retrospective cross-sectional study identified sarcopenia using the low skeletal muscle mass index (SMI) and Asian Working Group for Sarcopenia reference values. Obesity was defined as a body fat percentage (%BF) exceeding 25% in men and 35% in women. Sarcopenic obesity was identified when both the sarcopenia and obesity criteria were met. The primary outcome, ADL, was measured using the Functional Independence Measure (FIM). Multiple linear regression models were used to analyze the associations among the SMI, %BF, and FIM scores, after adjusting for age, sex, lesion level, injury severity, comorbidities, and injury duration. Results : Of 82 participants (median age: 63.5 years; 18.3% women), 62.2% had sarcopenic obesity. Participants with sarcopenic obesity (54 vs. 69 points, p = 0.006) had significantly lower FIM motor scores than those without this condition. Multiple linear regression analysis revealed that SMI (β = 0.416, p < 0.001) and %BF (β = -0.325, p = 0.009) were independently associated with the FIM motor scores. Conclusions : Decreased SMI and increased %BF in patients with SCI were independently associated with decreased ADL independence. Routine body composition assessments are necessary for early detection and intervention in this population.

Background: We conducted a cross-sectional study to examine two-leg- and one-leg-type balance characteristics in athletes and explore factors related to their balance ability., Methods: A total of 213 participants, including athletes from various sports (gymnastics, boat racing, swimming, soccer, judo, and baseball) and non-athletes, were included (142 men, 71 women, average age 21.5 ± 2.1 years). Balance ability was classified into two-leg and one-leg types using the modified index of postural stability (mIPS) in a two-leg stance and the one-legged stance duration with eyes closed (OLS). Body composition, upper and lower limb strength, and lower limb sensation were also measured. To examine the balance characteristics of each sport, the mIPS and OLS were used as dependent variables in a multiple regression model with age, height, weight, and sex as independent variables., Results: The results showed a significantly higher mIPS in gymnastics (estimate: 0.22) and boat racing (0.14), and it was lower in swimming (-0.25). The OLS was significantly higher in soccer (16.98), judo (16.23), gymnastics (9.77), and baseball (9.12) and significantly lower in swimming (7.93). Additionally, the mIPS was independently associated with knee extension strength (0.12), sensory motor variables (-0.004), and height (-0.01). The OLS was associated with skeletal muscle mass (1.85) and height (-1.42)., Conclusions: In summary, gymnasts showed superior two-leg and one-leg balance; boat racers excelled in two-leg balance; swimmers showed inferior two-leg but better one-leg balance; and soccer, judo, and baseball athletes demonstrated superior one-leg balance. Additionally, the mIPS was associated with knee extensor strength, plantar pressure sensation, and height, whereas the OLS was associated with skeletal muscle mass and height.

The anisotropic electronic structure of MgB2C2 was studied using soft X-ray emission spectroscopy electron microscopes. MgB2C2 fragments were selected by examining C K-emission profiles. C and B K-emission and Mg L-emission spectra were obtained, revealing common and distinct structures that reflect the mixing of valence orbitals. Since the material is reported to have two-dimensional B-C honeycomb layers, the orientational dependence of these emission spectra was also examined. Experimental data were compared with theoretically calculated partial density of states of the valence bands of the material. The C K-emission profile showed an apparent orientational dependence, while the B K-emission exhibited minimal dependence. This difference originated from the different energy distributions of C-2pz and B-2pz components in the valence bands. The Mg L-emission intensity was very small, likely due to charge transfer from Mg atoms to B-N layers. The Mg L-emission profile showed a peak related to structures in C-K and B-K. An unexpected intensity was observed just above the valence bands, which also showed orientational dependence, possibly due to a small deviation from the ideal composition of Mg:B:C = 1:2:2., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background and Objectives : Bedridden patients are at a high risk of venous thromboembolism (VTE). Passive devices such as elastic compression stockings and intermittent pneumatic compression are common. Leg exercise apparatus (LEX) is an active device designed to prevent VTE by effectively contracting the soleus muscle and is therefore expected to be effective in preventing disuse of the lower limbs. However, few studies have been conducted on the kinematic properties of LEX. Therefore, this study aimed to compare the exercise characteristics of LEX with those of an ergometer, which is commonly used as a lower-limb exercise device, and examine its effect on the two domains of muscle activity and circulatory dynamics. Materials and Methods : This study used a crossover design in which each participant performed both exercises to evaluate the exercise characteristics of each device. Fifteen healthy adults performed exercises with LEX and an ergometer (Terasu Erugo, SDG Co., Ltd., Tokyo, Japan) for 5 min each and rested for 10 min after each exercise. Muscle activity was measured using surface electromyography (Clinical DTS, Noraxon, Scottsdale, AZ, USA), and circulatory dynamics were recorded using a non-invasive impedance cardiac output meter (Physioflow Enduro, Manatec Biomedical, Paris, France). The primary outcome was the mean percentage of maximum voluntary contraction (%MVC) of the soleus muscle during exercise. Results : The mean %MVC of the soleus muscle was significantly higher in the LEX group, whereas no significant differences were observed across the periods and sequences. Heart rate, stroke volume, and cardiac output increased during exercise and decreased thereafter; however, the differences between the devices were not significant. Conclusions : LEX may not only have a higher thromboprophylaxis effect, but also a higher effect on preventing muscle atrophy as a lower-extremity exercise device. Additionally, LEX could potentially be used safely in patients who need to be monitored for changes in circulatory dynamics.

Background and Objectives : The discharge destination of patients with advanced cancer correlates with their quality of life. Patients with bone metastases often undergo lifestyle changes owing to pain and activity limitations. However, there are few reports on factors related to the discharge destination of patients with bone metastases. This study aimed to elucidate the factors associated with the discharge destination of patients with bone metastases. Methods : This study included 278 patients diagnosed with bone metastases who were admitted to the University of Tsukuba Hospital between April 2015 and March 2020. This study examined discharge destination, occurrence of skeletal-related events (SREs), primary lesions, locations of bone metastases, functional ambulation categories (FAC), age, and length of hospital stay. A binomial logistic regression analysis was conducted to compare the home and non-home discharge groups. Results : Of the 278 patients, 142 were discharged to home, 89 were discharged to somewhere other than home (non-home), and 47 died. The discharge destination was associated with spinal cord compression (SCC) (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.35-8.43), hypercalcemia (OR 6.84, 95% CI 1.09-42.76), and FAC at admission (OR 0.45, 95% CI 0.35-0.58). The admission FAC cut-off value for discharge to home was determined to be 1.5 (area under the curve [AUC] 0.79, sensitivity 77.5%, specificity 68.5%). Conclusions : Factors associated with discharge destination were identified. The walking ability required for discharge to home was FAC 1.5, meaning that the patient needed one person to assist in preventing falls when walking on level ground. A cut-off value for FAC on admission for predicting outcomes was identified, suggesting the importance of gait ability assessment on admission.

Cancer is often accompanied by bone metastasis, which may lead to skeletal-related events (SREs), such as pain, hypercalcemia, pathological fractures, spinal cord compression, orthopedic surgical intervention, and palliative radiation directed at the bone. Herein, we report the case of a 75-year-old female patient diagnosed with diffuse large B-cell lymphoma (DLBCL) with bone metastasis and a pathological fracture of the right iliac bone. The management strategy and follow-up were determined by a multidisciplinary cancer board comprising physicians, physiatrists, orthopedic surgeons, radiologists, and rehabilitation therapists. A conservative approach was chosen, incorporating a bone-modifying agent and weight-bearing restrictions for the right leg, along with rehabilitation therapy and post-discharge support. A multidisciplinary rehabilitation approach for two months enabled the patient to walk independently upon discharge. She maintains her activities of daily living (ADL) for over six months after discharge without any skeletal issues. This case highlights the effectiveness of a multidisciplinary approach in managing bone metastasis or involvement in patients with lymphoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Watanabe et al.)

Background and Objective: Opening wedge high tibial osteotomy (OWHTO) influences the knee extensor mechanism, the range of passive motion of knee extension and persistent quadriceps, and anterior knee pain and weakness. Rehabilitation should focus on quadriceps strength and improving joint mobility. The single-joint hybrid assistive limb device (HAL-SJ) is a wearable exoskeleton cyborg. In this study, we investigated the feasibility and safety of HAL-SJ training after the early postoperative period following OWHTO and whether the use of this device can improve functional outcomes, including knee muscle extensor strength and knee extension range of motion without knee pain., Methods: Patients who had been diagnosed with knee osteoarthritis and had undergone OWHTO were assessed for eligibility in this prospective trial conducted at our institution between June 2015 and November 2020. The participants were split into two groups, i.e., 10 patients in the hybrid assistive limb (HAL) group and eight patients in the control group. We initiated HAL-SJ therapy on postoperative day 8 and continued it until the patient's discharge. During the hospitalization period, patients engaged in HAL-SJ-assisted knee extension exercises. This exercise routine encompassed five sets, each comprising 10 repetitions, and was conducted twice a week. We conducted assessments aimed at detecting any potential adverse events that could be linked to HAL training. Assessment of the knee extension angle via the visual analog scale (VAS) and strength assessments using a hand-held dynamometer (HHD) were conducted. To compare clinical outcomes before and after OWHTO, knee extension angle, the VAS, HHD, Japanese Orthopaedics Association (JOA) score, and the Japanese Knee Osteoarthritis Measure (JKOM) were assessed at four distinct time points., Results: No adverse events were observed during the study. The assessment of clinical outcomes before and after OWHTO demonstrated a gradual improvement in outcomes., Conclusion: The single-joint hybrid assistive limb device in patients who underwent OWHTO appears to be potentially safe. It contributed to enhanced muscle activity efficiency by reducing knee pain and improving knee extension angles in the early postoperative phase., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Soma et al.)

Background and Objectives: Sarcopenia is characterized by a decline in skeletal muscle mass, strength, and function and is associated with advancing age. This condition has been suggested as a factor that negatively influences the functional outcomes of patients with hip fractures. However, the association between sarcopenia and balance impairment in patients undergoing inpatient rehabilitation after hip fractures remains unclear. In this retrospective cohort study, we aimed to investigate the impact of sarcopenia on balance outcomes in patients undergoing inpatient rehabilitation following hip fractures. Materials and Methods: Baseline sarcopenia was diagnosed using skeletal muscle mass index and handgrip strength, with cut-off values recommended by the Asian Working Group for Sarcopenia. The primary outcome was balance, which was assessed using the Berg Balance Scale (BBS) at the time of discharge. A multiple linear regression model analyzed the association between sarcopenia and balance. The model was adjusted for age, sex, comorbidities, and cognitive function. Results: Among the 62 patients (mean age: 78.2; sex: 75.8% women), 24.2% had sarcopenia. Patients with sarcopenia had significantly lower BBS scores than did those without sarcopenia (41 vs. 49 points, p = 0.004). Multiple linear regression analysis revealed that baseline sarcopenia was independently associated with BBS scores at discharge (β = -0.282, p = 0.038). Conclusions: Following inpatient rehabilitation, patients with baseline sarcopenia had inferior balance outcomes than did those without sarcopenia at discharge. Sarcopenia should be assessed on admission to consider and provide additional care for those with a higher risk of poor functional outcomes. More studies are needed to investigate the association between sarcopenia and functional outcomes, examine the impact of sarcopenia treatment on these outcomes, and reduce the risk of recurrent falls and fractures in patients with hip fractures., Competing Interests: The authors declare no conflicts of interest.

Myoelectric hands are beneficial tools in the daily activities of people with upper-limb deficiencies. Because traditional myoelectric hands rely on detecting muscle activity in residual limbs, they are not suitable for individuals with short stumps or paralyzed limbs. Therefore, we developed a novel electric prosthetic hand that functions without myoelectricity, utilizing wearable wireless sensor technology for control. As a preliminary evaluation, our prototype hand with wireless button sensors was compared with a conventional myoelectric hand (Ottobock). Ten healthy therapists were enrolled in this study. The hands were fixed to their forearms, myoelectric hand muscle activity sensors were attached to the wrist extensor and flexor muscles, and wireless button sensors for the prostheses were attached to each user's trunk. Clinical evaluations were performed using the Simple Test for Evaluating Hand Function and the Action Research Arm Test. The fatigue degree was evaluated using the modified Borg scale before and after the tests. While no statistically significant differences were observed between the two hands across the tests, the change in the Borg scale was notably smaller for our prosthetic hand ( p = 0.045). Compared with the Ottobock hand, the proposed hand prosthesis has potential for widespread applications in people with upper-limb deficiencies.

Background: Abdominal aortic aneurysm (AAA) is an arterial disease characterized by dilatation of the aortic wall. It has been suggested that neutrophil counts and neutrophil elastase activity are associated with AAA. We investigated whether a neutrophil elastase (NE) inhibitor, sivelestat (Siv), had a protective effect against angiotensin II (AngII)-induced AAAs., Methods: Male apolipoprotein E-deficient mice were assigned into three groups: Vehicle + saline, AngII + saline, and AngII + Siv. All mice were administered intraperitoneally with either Siv or vehicle twice daily after AngII infusion., Results: In the 4-week AngII infusion study, plasma NE concentration (P = 0.041) and its activity (P = 0.011) were elevated by AngII. These increases were attenuated by Siv (concentration:P = 0.010, activity:P = 0.027). Further, plasma elastase activity was closely correlated with aortic width (R = 0.6976, P < 0.001). In the 1-week AngII infusion study, plasma and tissue elastase activity increased by AngII (plasma:P = 0.034, tissue:P < 0.001), but were reduced by Siv (plasma:P = 0.014, tissue:P = 0.024). AngII increased aortic width (P = 0.011) but was attenuated by co-administration of Siv (P = 0.022). Moreover, Siv decreased the incidence of AAAs (P = 0.009). Elastin fragmentation induced by AngII was reduced by Siv. Many inflammatory cells that were either CD68 or Gr-1 positive were observed in the AngII + saline group, whereas few inflammatory cells were accumulated in the AngII + Siv group. MMP-2 and MMP-9 were enhanced by AngII, but were reduced by Siv. In vitro, MMP-2 activity was induced by human NE (medium:P < 0.001, cells:P = 0.001), which was attenuated by co-incubation of Siv in medium (P < 0.001) and protein of human aortic smooth muscle cells (P = 0.001)., Conclusions: Siv attenuated AngII-induced AAA through the inhibition of NE., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Resistance training is considered the most effective intervention for increasing older people's muscle mass and strength. Thus, we created the Sukubara®, a self-administered training system (squat + balance training) that incorporates a new low-load exercise. In this study, we hypothesize that introducing Sukubara will positively affect skeletal muscle mass and physical function. A preliminary verification was carried out on healthy, non-elderly participants who were recruited from the hospital staff. Participants were randomly assigned to two groups for a 12-week intervention: the resistance training group (R group) that performed the Sukubara exercise program and the control group (C group) that did not. This study's primary end¬point was a change in skeletal muscle mass, while the secondary endpoints were knee extension strength and one-leg standing time with eyes closed. An analysis of the 18 participants (R group = 8; C group = 10) was performed. Results showed that skeletal muscle mass, knee extension strength, and one-leg standing time were significantly improved or tended to be significantly higher in the R group than in the C group. Our study concluded that, by incorporating low-load exercise, Sukubara resulted in muscle hypertrophy and improved physical function.

Background: This study investigated the association between obesity and short-term patient-reported outcomes after total knee arthroplasty (TKA). Methods: The primary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index's (WOMAC) pain and function scores. Data were collected preoperatively and 2 and 4 weeks after surgery. Patients were stratified into three groups based on body mass index (BMI): normal weight (BMI < 24.99 kg/m 2 ), overweight (25 ≤ BMI < 29.99 kg/m 2 ), and obese (BMI ≥ 30 kg/m 2 ). The associations between BMI and the WOMAC pain and function scores were assessed using generalized linear mixed models. Results: Among the 102 patients (median age: 75.0, women [85.3%]), 29.4%, 48.0%, and 22.5% were normal weight, overweight, and obese, respectively. The mean pain and function scores at baseline were similar across the BMI-stratified groups ( p = 0.727 and 0.277, respectively). The pain score significantly improved 2 weeks post-surgery ( p = 0.001). The function score improved significantly 4 weeks post-surgery ( p < 0.001). The group and group-by-time interaction effects lacked statistical significance. Conclusions: All patients statistically and clinically showed relevant pain reduction and functional improvement shortly after TKA, irrespective of their obesity status. These data may help healthcare professionals discuss the expectations of pain amelioration and functional improvement with TKA candidates.

This study examined whether SUKUBARA ® , a remotely managed training system that we developed, could improve skeletal muscle mass and muscle strength in community-dwelling older adults. SUKUBARA ® is a composite exercise program that combines lower-load resistance training and balance exercises. Participants were instructed to exercise while watching individually assigned videos on YouTube, such that the research administrators could verify the viewing records of each participant. Fifteen participants (69 ± 4 years) were randomly assigned to the intervention (eight participants; the RT group) or the control group (seven participants; the CO group). The primary endpoint was a change in fat-free mass (FFM; kg), whereas the secondary endpoints included a change in knee extension strength (KES; Nm/kg). Correlation analyses were conducted to examine the relationship between FFM and KES. During the 12-week intervention period, significant differences were observed between the RT and CO groups in the changes in FFM (0.5 ± 0.5 vs. -0.1 ± 0.5) and KES (0.20 ± 0.22 vs. 0.02 ± 0.13), and significant positive correlations were found between the changes. Thus, SUKUBARA ® -based interventions have the potential to improve muscle hypertrophy and enhance muscle strength among community-dwelling older adults. Thus, SUKUBARA ® -based interventions show promise in improving muscle hypertrophy and enhance muscle strength among community-dwelling older adults. However, appropriately powered future research is needed to replicate these findings.

Bilateral adrenal infarction is an extremely rare disease, and it has been reported that some coagulation abnormalities, including essential thrombocythemia (ET), exist in the background. We herein report a 76-year-old patient in whom the platelet count had been in the normal range at the onset of adrenal infarction but subsequently increased to 102×10 4 /μL at 7 months later, leading to the diagnosis of JAK2V617F-positive ET. As the presence of the JAK2V617F mutation increases the risk of thrombosis, Janus kinase 2 (JAK2) genetic testing should be considered in some cases of nonspecific unknown thrombosis, even if there are no obvious hematological findings, such as clonal hematopoiesis of indeterminate potential (CHIP).

Competing Interests: The authors declare that they have no conflict of interest.

Aims: We aimed to verify the usefulness of targeted next-generation sequencing (NGS) technology for diagnosing monogenic diabetes in a single center., Methods: We designed an amplicon-based NGS panel targeting 34 genes associated with known monogenic diabetes and performed resequencing in 56 patients with autoantibody-negative diabetes mellitus diagnosed at < 50 years who had not been highly obese. By bioinformatic analysis, we filtered significant variants based on allele frequency (< 0.005 in East Asians) and functional prediction. We estimated the pathogenicity of each variant upon considering the family history., Results: Overall, 16 candidate causative variants were identified in 16 patients. Among them, two previously known heterozygous nonsynonymous single-nucleotide variants associated with monogenic diabetes were confirmed as causative variants: one each in the GCK and WFS1 genes. The former was found in two independent diabetes-affected families. Two novel putatively deleterious heterozygous variants were also assumed to be causative from the family history: one frameshift and one nonsynonymous single-nucleotide variant in the HNF4A gene. Twelve variants remained as candidates associated with the development of diabetes., Conclusion: Targeted NGS panel testing was useful to diagnose various forms of monogenic diabetes in combination with familial analysis, but additional ingenuity would be needed for practice., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00669-3., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Japan Diabetes Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: The wearable cyborg Hybrid Assistive Limb (HAL) is the world's first cyborg-type wearable robotic device, and it assists the user's voluntary movements and facilitates muscle activities. However, since the minimum height required for using the HAL is 150 cm, a smaller HAL (2S size) has been newly developed for pediatric use. This study aimed to (1) examine the feasibility and safety of a protocol for treatments with HAL (2S size) in pediatric patients and (2) explore the optimal method for assessing the efficacy of HAL., Methods: This clinical study included seven pediatric patients with postural and motor function disorders, who received 8-12 sessions of smaller HAL (2S size) treatment. The primary outcome was the Gross Motor Function Measure-88 (GMFM-88). The secondary outcomes were GMFM-66, 10-m walk test, 2- and 6-min walking distances, Canadian Occupational Performance Measure (COPM), a post-treatment questionnaire, adverse events, and device failures. Statistical analyses were performed using the paired samples t -test or Wilcoxon signed-rank test., Results: All participants completed the study protocol with no serious adverse events. GMFM-88 improved from 65.51 ± 21.97 to 66.72 ± 22.28 ( p  = 0.07). The improvements in the secondary outcomes were as follows: GMFM-66, 53.63 ± 11.94 to 54.96 ± 12.31, p  = 0.04; step length, 0.32 ± 0.16 to 0.34 ± 0.16, p  = 0.25; 2-MWD, 59.1 ± 57.0 to 62.8 ± 63.3, p  = 0.54; COPM performance score, 3.7 ± 2.0 to 5.3 ± 1.9, p  = 0.06; COPM satisfaction score, 3.3 ± 2.1 to 5.1 ± 2.1, p  = 0.04., Discussion: In this exploratory study, we applied a new size of wearable cyborg HAL (2S size), to children with central nervous system disorders. We evaluated its safety, feasibility, and identified an optimal assessment method for multiple treatments. All participants completed the protocol with no serious adverse events. This study suggested that the GMFM would be an optimal assessment tool for validation trials of HAL (2S size) treatment in pediatric patients with posture and motor function disorders., Competing Interests: HKaw, AkM, and YSa are shareholders and directors in Cyberdyne Inc., which manufactures Wearable Cyborg HAL, and YSa is the CEO of CYBERDYNE. CYBERDYNE was not involved in the study design, data collection, analysis, writing, or submission of this article. The remaining 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 © 2023 Takahashi, Mizukami, Watanabe, Kuroda, Shimizu, Nakajima, Mutsuzaki, Kamada, Tokeji, Hada, Koseki, Yoshikawa, Nakayama, Iwasaki, Kawamoto, Sankai, Yamazaki, Matsumura and Marushima.)

Pseudoinvasion is a phenomenon in which adenomatous tissue deviates into the submucosa with the mucosal lamina propria in colorectal epithelial tumors. A relatively large, stalked, neoplastic lesion of the sigmoid colon is considered at high risk of pseudoinvasion. A few reports have described endoscopic mucosal resection or polypectomy for colorectal tumors with pseudoinvasion, but the vertical margins were not sufficiently assessed. Because a positive margin can be a risk factor for recurrence, endoscopic treatment for pseudoinvasion should be carefully considered. We herein report a case in which even endoscopic submucosal dissection (ESD) was not adequate for curative resection of pseudoinvasion in early colorectal cancer. The endoscopic findings of a 25-mm Type 0-Is lesion in the sigmoid colon suggested a low possibility of carcinoma invasion into the deep submucosa. Although ESD was considered to be indicated in this case, laparoscopic sigmoid colon resection was eventually performed because we observed a broadly pulled muscle layer and an almost undetectable submucosal layer during ESD. The surgical specimen showed that the tumor glands of pseudoinvasion existed beyond the planned ESD dissection line, indicating that the vertical margin would have been positive if we had continued ESD. Whether pseudoinvasion was associated with the infeasibility of ESD remains unclear. This case indicates that diagnosing the presence and depth of pseudoinvasion by magnified endoscopy with narrow-band imaging is challenging and that preoperative examinations, such as endoscopic ultrasound, may be needed for a tumor with a high risk of pseudoinvasion., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Stroke rehabilitation with mechanical assistance improves outcomes by facilitating repetition and relieving the care burden of therapy staff. Here, we tested the Medical Care Pit (MCP) walking assistance training device in the rehabilitation of eight acute stroke patients (median age 60.7 ± 16.3 years) who had recently suffered ischemic (three) or hemorrhagic (five) stroke (14.1 ± 6.5 days). Patients received standard rehabilitation approximately 5 days per week (weekdays only), plus MCP therapy twice a week, totaling four MCP sessions over 2 weeks. Fugl-Meyer Assessment-Lower Extremities (FMA-LE), Functional Ambulation Category (FAC), and other gait-associated parameters were measured. Over the 10.5 ± 1.6 days of therapy, MCP qualitatively assisted in gait analysis and real-time patient feedback while independent walking scores significantly improved (FAC 2.2 ± 0.8 to 3.1 ± 1.3, p = 0.020). FMA-LE scores also slightly improved but not to significance ( p = 0.106). Objective burden on patients, as measured by modified Borg scale, was significantly improved (2.7 ± 1.6 to 2.0 ± 1.6, p = 0.014). In terms of questionnaires, anxiety scores for the physical therapist regarding gait training and falling with MCP significantly decreased (3.8 ± 2.3 to 1.0 ± 1.6; p = 0.027 and 3.1 ± 2.2 to 0.8 ± 1.3; p = 0.045) from the first to fourth sessions. Taken together, MCP, in addition to the usual rehabilitation program, was effective in gait rehabilitation for independent walking and relieved burdens on the patients. Such walking support systems may be an important part of acute stroke rehabilitation.

Studies on the effects of training confinement on athletes with physical impairments are limited. Hence, in this retrospective cohort study, we aimed to investigate the impact of prolonged cessation of organized team training due to the coronavirus disease 2019 pandemic on the body composition of elite female Japanese basketball athletes. Fourteen female wheelchair basketball athletes (aged ≥20 years) were enrolled. The primary outcomes were lean and adipose indices measured using whole-body dual-energy X-ray absorptiometry. The impact of prolonged organized team training cessation on body composition was investigated by comparing the body composition at baseline and post-training confinement. A reduced whole-body lean mass ( p = 0.038) and percent lean mass ( p = 0.022), as well as an increased percent body fat ( p = 0.035), were observed after the confinement period. The regional analysis revealed reduced percent lean and increased percent fat masses in the trunk ( p = 0.015 and p = 0.026, respectively) and upper limbs ( p = 0.036 and p = 0.048, respectively). In conclusion, prolonged organized team training cessation reduced lean mass and increased body fat percentage, primarily in the trunk and upper limbs. Individualized training programs targeting these body regions should be implemented to improve body composition and physical conditions in athletes during and after prolonged cessation of organized team training.

Competing Interests: None disclosed.

Background: The volume of the hippocampus and its subfields is known to be affected by aging, disease, and physical training. In regard to training, the differential effects of aerobic exercise and dance training on the subfield volume suggest that balance function may be involved. However, the relationship between balance function and the volume of the hippocampus and its subfields remains unclear., Methods: Subjects were 30 cognitively intact individuals. They underwent balance tests, cognitive tests and structural MRI scans. The balance index measured was the index of postural stability (IPS) under a visual block condition and/or a proprioception block condition. MR images acquired using a 3-tesla system and three-dimensional T1-weighted images were segmented in the hippocampal subfield with Freesurfer 6.0.0. The relationship between the IPS and hippocampal volume was evaluated., Results: A positive correlation was observed only between the IPS closed eyes/soft surface condition and whole hippocampal volume ratio. In the subfields, positive correlations were found between the IPS and molecular layer of the hippocampus, granule cell layer of the dentate gyrus (GC-ML-DG), and cornu ammonis areas (CA)3 and CA4. These correlations were stronger under the closed eyes/soft surface condition than under the other conditions., Conclusions: A correlation between balance function and the volume of the hippocampus and subfields was found in healthy elderly subjects. The balance function may be involved in the volume of the whole hippocampus and specific subfields. The IPS closed eyes/soft surface condition is considered to reflect vestibular function. Thus, IPS may be useful in evaluations of the relationship between the vestibular system function via the hippocampus and balance., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Mild cognitive impairment (MCI) is not just a prodrome to dementia, but a very important intervention point to prevent dementia caused by Alzheimer's disease (AD). It has long been known that people with AD have a higher frequency of falls with some gait instability. Recent evidence suggests that vestibular impairment is disproportionately prevalent among individuals with MCI and dementia due to AD. Therefore, we hypothesized that the measurement of balance capability is helpful to identify individuals with MCI., Methods: First, we developed a useful method to evaluate balance capability as well as vestibular function using Nintendo Wii balance board as a stabilometer and foam rubber on it. Then, 49 healthy volunteers aged from 56 to 75 with no clinically apparent cognitive impairment were recruited and the association between their balance capability and cognitive function was examined. Cognitive functions were assessed by MoCA, MMSE, CDR, and TMT-A and -B tests., Results: The new balance capability indicator, termed visual dependency index of postural stability (VPS), was highly associated with cognitive impairment assessed by MoCA, and the area under the receiver operating characteristic (ROC) curve was more than 0.8, demonstrating high sensitivity and specificity (app. 80% and 60%, respectively)., Conclusions: Early evidence suggests that VPS measured using Nintendo Wii balance board as a stabilometer helps identify individuals with MCI at an early and preclinical stage with high sensitivity, establishing a useful method to screen MCI., (© 2023. The Author(s).)

Upper extremity dysfunction after stroke affects quality of life. Focusing on the shoulder joint, we investigated the safety and effectiveness of rehabilitation using a shoulder joint hybrid assistive limb (HAL). Eight patients with chronic stroke and upper extremity functional disability were enrolled and used a shoulder joint HAL, which assisted shoulder movement based on the user's intention, through myoelectric activation of the shoulder flexor. Ten training sessions of 30-40 min each were performed to assist voluntary movement of upper limb elevation on the affected side through triggering the deltoid muscle. All patients completed the interventions without shoulder pain. Surface electromyography evaluation indicated post-intervention improvement in coordinated movement of the affected upper extremity. Significant improvements in voluntary and passive shoulder joint range of motion were obtained after the intervention, suggesting improvement in shoulder muscle strength. A significant decrease in the modified Ashworth scale and improvements in functional scores in the upper limb were also observed. Along with safe use for our study patients, the shoulder HAL provided appropriate motor learning benefits. Improvements in shoulder joint function and whole upper limb function were observed, suggesting that HAL could be an optimal treatment method.

This study aims to investigate the prevalence of sarcopenic obesity and factors influencing body composition in persons with spinal cord injury (SCI) in Japan. Adults with SCI aged ≥ 20 years who underwent whole-body dual-energy X-ray absorptiometry between 2016 and 2022 were retrospectively analyzed. Data from 97 patients were examined. The primary outcome was appendicular skeletal muscle mass (ASM). Multiple linear regression analysis was conducted to assess factors influencing the lean and adipose indices in persons with SCI. Sarcopenia, obesity, and sarcopenic obesity were prevalent in 76%, 85%, and 64% of patients, respectively. Multivariate linear regression analysis revealed that sex (β = 0.34, p < 0.001), lesion level (β = 0.25, p = 0.007), severity (β = 0.20, p = 0.043), and ability to walk (β = 0.29, p = 0.006) were independently associated with ASM. Sex (β = −0.63, p < 0.001) was independently associated with percent body fat. In conclusion, sarcopenia, obesity, and sarcopenic obesity were prevalent among patients with SCI in Japan. Female sex, tetraplegia, motor-complete injury, and inability to walk were risk factors for sarcopenia, whereas female sex was a risk factor for obesity in persons with SCI. A routine monitoring of body composition is necessary, especially among those with multiple risk factors, to identify individuals in need of preventive and therapeutic interventions.

Pituitary apoplexy is an uncommon syndrome that often results in spontaneous hemorrhage or infarction of pituitary tumors or glands. We previously reported pituitary apoplexy occurred most frequently in nonfunctional pituitary adenomas among all types of pituitary incidentalomas. In the present study, we aimed to investigate the characteristics of pituitary apoplexy in patients with incidental nonfunctional pituitary adenomas. 65 patients with pituitary incidentaloma were enrolled. All patients underwent clinical/endocrinological/pathological investigations. As a result, 33 patients were diagnosed with nonfunctional pituitary adenomas. Of these, 12.1% of patients had pituitary apoplexy. There was no difference in tumor diameter, age, or sex between the apoplexy and the non-apoplexy groups. However, the liver enzymes aspartate transaminase and alanine aminotransferase were significantly higher, and plasma sodium and chloride levels were significantly lower in the apoplexy group than in the non-apoplexy group (each P < .05). In addition, low-density lipoprotein-cholesterol was significantly higher in the apoplexy group than in the non-apoplexy group (P < .05). Besides, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin deficiencies were significantly more frequent in the apoplexy group than in the non-apoplexy group (each P < .05), and growth hormone and adrenocorticotropic hormone deficiencies were more frequent in the apoplexy group than in the non-apoplexy group (P = .09 and.08, respectively). Furthermore, tumor diameter was not associated with pituitary apoplexy, whereas thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone deficiencies were significantly associated with the apoplexy group (each P < .05). Hence, the present study indicated that pituitary apoplexy could not be related to tumor diameter. Moreover, hormonal deficiencies, hepatic dysfunction, hyponatremia or hypochloremia, and dyslipidemia might be indicators of pituitary apoplexy. There could be the possibility the treatment for dyslipidemia prevents pituitary apoplexy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sensory ataxia due to posterior cord syndrome is a relevant, disabling condition in nontraumatic spinal cord dysfunction. Ataxic gait is a common symptom of sensory ataxia that restricts activities of daily living. A 70-year-old woman with severe sensory disturbance was diagnosed with intradural extramedullary spinal cord tumors found in the thoracic spine region (T8). Surgical management of the tumors was performed. The patient received gait training 20 days after surgery (postoperative acute phase) using a hybrid assistive limb (HAL). HAL is a wearable exoskeleton cyborg that provides real-time assistance to an individual for walking and limb movements through actuators mounted on the bilateral hip and knee joints. Walking ability was assessed using the 10 m walking test, which included evaluating walking speed, step length, and cadence in every session. To evaluate the immediate effects of HAL training, walking speed and step length were measured before and after the training in each session. During the 10 m walking test, gait kinematics and lower muscle activity were recorded using a motion capture system and wireless surface electromyography before the first session and after completion of all HAL sessions. After the HAL training sessions, improvement in the patient’s gait performance was observed in the gait joint angles and muscle activity of the lower limb. After 10 training sessions, we observed the following changes from baseline: walking speed (from 0.16 m/s to 0.3 m/s), step length (from 0.19 m to 0.37 m), and cadence (from 50.9 steps/min to 49.1 steps/min). The average standard deviations of the knee (from right, 7.31; left, 6.75; to right, 2.93; p < 0.01, left, 2.63; p < 0.01) and ankle joints (from right, 6.98; left, 5.40; to right, 2.39; p < 0.01, left, 2.18; p < 0.01) were significantly decreased. Additionally, walking speed and step length improved immediately after completing all the HAL training sessions. This suggests that HAL gait training might be a suitable physical rehabilitation program for patients with sensory ataxia causing dysfunctional movement of the lower limb.

Shoulder elevation, defined here as arm raising, being essential for activities of daily living, dysfunctions represent a substantial burden in patients' lives. Owing to the complexity of the shoulder joint, the tightly coordinated muscular activity is a fundamental component, and neuromuscular impairments have devastating effects. A single-joint shoulder type version of the Hybrid Assistive Limb (HAL) allowing motion assistance based on the intention of the user via myoelectric activation has recently been developed, and its safety was demonstrated for shoulder rehabilitation. Yet, little is known about the physiological effects of the device. This study aims to monitor the changes in muscle activity and motion during shoulder HAL rehabilitation in several patients suffering from shoulder elevation dysfunction from cervical radicular origin. 8 patients (6 males, 2 females, mean age 62.4 ± 9.3 years old) with weakness of the deltoid muscle resulting from a damage to the C5 nerve root underwent HAL-assisted rehabilitation. We combined surface electromyography and three-dimensional motion capture to record muscular activity and kinematics. All participants showed functional recovery, with improvements in their Manual Muscle Testing (MMT) scores and range of motion (ROM). During training, HAL decreased the activity of deltoid and trapezius, significantly more for the latter, as well as the coactivation of both muscles. We also report a reduction of the characteristic shrugging compensatory motion which is an obstacle to functional recovery. This reduction was notably demonstrated by a stronger reliance on the deltoid rather than the trapezius, indicating a muscle coordination tending toward a pattern similar to healthy individuals. Altogether, the results of the evaluation of motion and muscular changes hint toward a functional recovery in acute, and chronic shoulder impairments from cervical radicular origin following shoulder HAL rehabilitation training and provide information on the physiological effect of the device., Competing Interests: YSa was the C.E.O., shareholder, and director of CYBERDYNE Inc., which produces the robot suit HAL. CYBERDYNE was not involved in the study design, data collection, analysis, writing, or submission of this article. The remaining 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 © 2022 Lafitte, Kadone, Kubota, Shimizu, Tan, Koda, Hada, Sankai, Suzuki and Yamazaki.)

Although branched-chain amino acids (BCAA) are known to stimulate myofibrillar protein synthesis and affect insulin signaling and kynurenine metabolism (the latter being a metabolite of tryptophan associated with depression and dementia), the effects of BCAA supplementation on type 2 diabetes (T2D) are not clear. Therefore, a 24-week, prospective randomized open blinded-endpoint trial was conducted to evaluate the effects of supplementation of 8 g of BCAA or 7.5 g of soy protein on skeletal muscle and glycemic control as well as adverse events in elderly individuals with T2D. Thirty-six participants were randomly assigned to the BCAA group ( n = 21) and the soy protein group ( n = 15). Skeletal muscle mass and HbA1c, which were primary endpoints, did not change over time or differ between groups. However, knee extension muscle strength was significantly increased in the soy protein group and showed a tendency to increase in the BCAA group. Homeostasis model assessment for insulin resistance did not significantly change during the trial. Depressive symptoms were significantly improved in the BCAA group but the difference between groups was not significant. Results suggested that BCAA supplementation may not affect skeletal muscle mass and glycemic control and may improve depressive symptoms in elderly individuals with T2D.

Introduction: Coronary artery disease (CAD) is the most frequent cause of out-of-hospital cardiac arrest (OHCA). Nevertheless, there have been limited studies focusing on the impact of lesion complexity on resuscitated CAD patients. The purpose of the present study was to investigate the association between coronary lesion complexity and the mortality of CAD patients after OHCA., Methods: From pooled database of two centers, which comprised 706 successfully resuscitated OHCA patients, 172 patients undergoing coronary angiography were retrospectively investigated. A total of 148 patients exhibited coronary stenosis on angiogram and were included in the final analysis. Baseline characteristics, pre-and post-hospital care, general status after resuscitation and angiographical findings were compared between the patients who deceased within 30 days and those who survived and the predictors of 30-day mortality were determined., Results: Ninety-four patients (63.5%) survived at 30 days. Bystander cardiopulmonary resuscitation (CPR) (Odds ratio (OR) 0.36; 95% confidence interval (CI) 0.14-0.96; P = 0.041), revascularization of coronary stenosis (OR 0.15; 95% CI 0.19-0.86; P < 0.001), GRACE risk score (OR 1.04; 95% CI 1.02-1.05; P < 0.001) and SYNTAX score (OR 1.07; 95% CI 1.01-1.13; P = 0.025) were independent predictors of 30-day mortality. As multiple predictors such as bystander CPR, GRACE score and SYNTAX score were combined, the 30-day mortality gradually deteriorated., Conclusions: In addition to bystander CPR, GRACE score and revascularization, SYNTAX score independently predicted 30-day mortality of CAD patients after OHCA., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Competing Interests: Declaration of Competing Interest None.

Background: The aim of the study was to define whether edaravone, a free-radical scavenger, influenced angiotensin II (AngII)-induced atherosclerosis and abdominal aortic aneurysms (AAAs) formation., Methods: Male apolipoprotein E-deficient mice (8-12 weeks old) were fed with a normal diet for 5 weeks. Either edaravone (10 mg/kg/day) or vehicle was injected intraperitoneally for 5 weeks. After 1 week of injections, mice were infused subcutaneously with either AngII (1000 ng/kg/min, n = 16-17 per group) or saline ( n = 5 per group) by osmotic minipumps for 4 weeks., Results: AngII increased systolic blood pressure equivalently in mice administered with either edaravone or saline. Edaravone had no effect on plasma total cholesterol concentrations and body weights. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas and en face atherosclerosis but was significantly attenuated by edaravone administration. Edaravone also reduced the incidence of AngII-induced AAAs. In addition, edaravone diminished AngII-induced aortic MMP-2 activation. Quantitative RT-PCR revealed that edaravone ameliorated mRNA abundance of aortic MCP-1 and IL-1β. Immunostaining demonstrated that edaravone attenuated oxidative stress and macrophage accumulation in the aorta. Furthermore, edaravone administration suppressed thioglycolate-induced mice peritoneal macrophages (MPMs) accumulation and mRNA abundance of MCP-1 in MPMs in male apolipoprotein E-deficient mice. In vitro, edaravone reduced LPS-induced mRNA abundance of MCP-1 in MPMs., Conclusions: Edaravone attenuated AngII-induced AAAs and atherosclerosis in male apolipoprotein E-deficient mice via anti-oxidative action and anti-inflammatory effect.

Cardiac fibrosis is characterized by the net accumulation of extracellular matrix in the myocardium and is an integral component of most pathological cardiac conditions. Cilostazol, a selective inhibitor of phosphodiesterase type III with anti-platelet, anti-mitogenic, and vasodilating properties, is widely used to treat the ischemic symptoms of peripheral vascular disease. Here, we investigated whether cilostazol has a protective effect against Angiotensin II (AngII)-induced cardiac fibrosis. Male apolipoprotein E-deficient mice were fed either a normal diet or a diet containing cilostazol (0.1% wt/wt). After 1 week of diet consumption, the mice were infused with saline or AngII (1000 ng kg−1 min−1) for 28 days. AngII infusion increased heart/body weight ratio (p < 0.05), perivascular fibrosis (p < 0.05), and interstitial cardiac fibrosis (p < 0.0001), but were significantly attenuated by cilostazol treatment (p < 0.05, respectively). Cilostazol also reduced AngII-induced increases in fibrotic and inflammatory gene expression (p < 0.05, respectively). Furthermore, cilostazol attenuated both protein and mRNA abundance of osteopontin induced by AngII in vivo. In cultured human cardiac myocytes, cilostazol reduced mRNA expression of AngII-induced osteopontin in dose-dependent manner. This reduction was mimicked by forskolin treatment but was cancelled by co-treatment of H-89. Cilostazol attenuates AngII-induced cardiac fibrosis in mice through activation of the cAMP−PKA pathway.

Background: This study aimed to compare the usefulness of arterial stiffness parameters, cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV), for evaluating arterial damage and risk of cardiovascular disease (CVD) in subjects with diabetes., Methods: The study subjects were 277 patients with type 1 or type 2 diabetes. All subjects were evaluated for vascular stiffness using CAVI (n = 154) or baPWV (n = 123). Carotid intima-media thickness (IMT) and the Suita score were also measured because these are established risk factors for future CVD. Associations of both CAVI and baPWV with these established parameters were evaluated in all subjects, and then in 174 subjects with adjustment for covariates by using propensity score matching., Results: In all subjects, CAVI and baPWV correlated significantly with both IMT (r = 0.462, P < 0.001, and r = 0.212, P = 0.019, respectively) and the Suita score (r = 0.573, P < 0.001, and r = 0.373, P < 0.001, respectively). The correlation between CAVI and IMT was more significant than that between baPWV and IMT (Z = 2.33, P = 0.020). Similarly, the correlation between CAVI and the Suita score was more significant than that between baPWV and the Suita score (Z = 2.13, P = 0.033). After adjustment by propensity score matching, significant correlations between CAVI and IMT (r = 0.432 P < 0.001) and between CAVI and the Suita score (r = 0.544, P < 0.001) were preserved, though only the association between baPWV and the Suita score was significant (r = 0.289, P = 0.007) while that between baPWV and IMT showed no significance. Again, CAVI showed a significant association with the Suita score than baPWV (Z = 2.02, P = 0.043)., Conclusions: CAVI is more closely associated than baPWV with arterial damage and risk of CVD in patients with diabetes., (© 2022. The Author(s).)

We aimed to investigate the status of falls and to identify important risk factors for falls in persons with type 2 diabetes (T2D) including the non-elderly. Participants were 316 persons with T2D who were assessed for medical history, laboratory data and physical capabilities during hospitalization and given a questionnaire on falls one year after discharge. Two different statistical models, logistic regression and random forest classifier, were used to identify the important predictors of falls. The response rate to the survey was 72%; of the 226 respondents, there were 129 males and 97 females (median age 62 years). The fall rate during the first year after discharge was 19%. Logistic regression revealed that knee extension strength, fasting C-peptide (F-CPR) level and dorsiflexion strength were independent predictors of falls. The random forest classifier placed grip strength, F-CPR, knee extension strength, dorsiflexion strength and proliferative diabetic retinopathy among the 5 most important variables for falls. Lower extremity muscle weakness, elevated F-CPR levels and reduced grip strength were shown to be important risk factors for falls in T2D. Analysis by random forest can identify new risk factors for falls in addition to logistic regression., (© 2022. The Author(s).)