Stability of ischial pressure with 3D thermoplastic elastomer cushion and the characteristics of four types of cushions in pressure redistribution.

Wheelchair cushions are recommended to be used with wheelchair and can protect the buttocks from pain and injury by relieving interface pressure for wheelchair users. However, further investigations are required for proper use in response to the development of new types of wheelchair cushions. The objective of this study was to evaluate physical characteristics of wheelchair cushions by comparing pressure redistributing effects of four types of cushions. The participants were 16 healthy adults who consented to participate in this study. A pressure mapping system (CONFORMat, Nitta Corp.) was used for the measurements. Pressure at ischium was measured immediately after the stabilization of the sitting posture and 10 minutes after. The pressure at ischium significantly decreased with any wheelchair cushions (P < 0.01). A significant negative correlation between body mass index and pressure at ischium was observed without a wheelchair cushion (r = - 0.70), however, the correlation disappeared upon use of a wheelchair cushion. The pressure at ischium increased over time with cushions of urethane, air, and urethane-air hybrid while that with the 3D thermoplastic elastomer cushion did not, and the change in the pressure was statistically less than that in other cushions (P < 0.01). Use of wheelchair cushions was effective in redistribution of the pressure at ischium, and the overtime change in the pressure depends on the type of used cushions.

Relationship between cleaning frequency and pressure ulcer healing time in older people receiving home care.

OBJECTIVE: The relationship between the healing time of pressure ulcers (PUs) and wound cleaning frequency among older people in homecare settings was investigated. METHOD: This single-centre, prospective cohort study was conducted from April 2018 to March 2019. Patients who used home-visit nursing services, had National Pressure Ulcer Advisory Panel classification stage 2 PUs, and had their wounds cleaned at least twice a week were enrolled in the study. Wound cleaning was performed using tap water and a weakly acidic cleanser. Participants were divided into two groups, determined by the frequency of wound cleaning (twice weekly versus ≥3 times weekly). Duration of PU healing and the increase in care insurance premiums were compared in both groups. RESULTS: A total of 12 patients were included in the study. The mean healing period of PUs cleaned ≥3 times per week (65.3±24.8 days) was significantly shorter than that of PUs cleaned twice a week (102.6±19.2 days; p<0.05). Furthermore, the increase in care insurance premiums for PUs cleaned ≥3 times per week (¥122,497±105,660 Yen per six months) was significantly lower than that for PUs cleaned twice a week (¥238,116±60,428 per six months) (p<0.05). CONCLUSION: Our results suggest that frequent cleaning of PUs by health professionals in homecare settings not only shorten PU healing period but also reduces care insurance premiums for PU care.

Facilitatory effect of low-pulse repetition frequency ultrasound on release of extracellular vesicles from cultured myotubes.

PURPOSE: Extracellular vesicles (EVs) serve as carriers of intracellular factors with therapeutic effects, including tissue regeneration and attenuation of inflammatory responses. The majority of EVs in vivo are derived from skeletal muscle, which is reported to have anti-inflammatory effects. While high-intensity pulsed ultrasound (US) irradiation has been shown to promote EV secretion from myotubes, the impact of pulse repetition frequency, a US parameter affecting pulse length, on EV release remains unclear. This study aimed to investigate the impact of pulse repetition frequency of US on the release of EVs from myotubes. METHODS: C2C12 myoblasts were used in this study. After differentiation into C2C12 myotubes, US was performed for 5 min at an intensity of 3.0 W/cm2, duty cycle of 20%, acoustic frequency of 1 MHz, and different pulse repetition frequencies (100 Hz, 10 Hz, or 1 Hz). After 12 h, EVs and cells were collected for subsequent analyses. RESULTS: US did not cause a reduction in cell viability across all US groups compared to the control. The concentration of EVs was significantly higher in all US groups compared to the control group. In particular, the highest increase was observed in the 1-Hz group on EV concentration as well as intracellular Ca2+ level. CONCLUSION: This study investigated the effect of three different pulse repetition frequencies of US on the release of EVs from cultured myotubes. It is concluded that a low-pulse repetition frequency of 1 Hz is the most effective for enhancing EV release from cultured myotubes with pulsed ultrasound.

Niacin supplementation attenuates the regression of three-dimensional capillary architecture in unloaded female rat skeletal muscle.

Inactivity can lead to muscle atrophy and capillary regression in skeletal muscle. Niacin (NA), known for inducing hypermetabolism, may help prevent this capillary regression. In this study involving adult female Sprague-Dawley rats, the animals were randomly assigned to one of four groups: control (CON), hindlimb unloading (HU), NA, and HU with NA supplementation (HU + NA). For a period of 2 weeks, the rats in the HU and HU + NA groups underwent HU, while those in the NA and HU + NA groups received NA (750 mg/kg) twice daily through oral administration. The results demonstrated that HU lowered capillary number, luminal diameter, and capillary volume, as well as decreased succinate dehydrogenase activity, slow fiber composition, and PGC-1α expression within the soleus muscle. However, NA supplementation prevented these alterations in capillary structure due to unloading by stimulating PGC-1α factors and inhibiting mitochondrial dysfunction. Therefore, NA supplementation could serve as a potential therapeutic approach for preserving the capillary network and mitochondrial metabolism of muscle fibers during periods of inactivity.

Isthmin-1 promotes growth and progression of colorectal cancer through the interaction with EGFR and YBX-1.

While previous studies have indicated the involvement of Isthmin 1 (ISM1), a secreted protein, in cancer development, the precise mechanisms have remained elusive. In this study, we unveiled that ISM1 is significantly overexpressed in both the blood and tissue samples of colorectal cancer (CRC) patients, correlating with their poor prognosis. Functional experiments demonstrated that enforced ISM1 expression significantly enhances CRC proliferation, migration, invasion and tumor growth. Notably, our investigation reveals an interaction of ISM1 with epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase (RTK) family of CRC cells. The binding of ISM1 triggered EGFR activation and initiate downstream signaling pathways. Meanwhile, intracellular ISM1 interacted with Y-box binding protein 1 (YBX1), enhancing its transcriptional regulation on EGFR. Furthermore, our research uncovered the regulation of ISM1 expression by the hypoxia-inducible transcription factor HIF-1α in CRC cells. Mechanistically, we identified HIF-1α as a direct regulator of ISM1, binding to a hypoxia response element on its promoter. This novel mechanism illuminated potential therapeutic targets, offering insights into restraining HIF-1α/ISM1/EGFR-driven CRC progression and metastasis.

Dietary Intervention for Control of Clinical Symptom in Patients with Systemic Metal Allergy: A Single Center Randomized Controlled Clinical Study.

Patients with eczema with a systemic metal allergy, such as nickel (Ni), cobalt (Co), chromium (Cr), and tin (Sn), should pay attention to symptomatic exacerbation by excessive metal intake in food. However, dietary intervention for systemic metal allergy can be difficult. In this study, we evaluated the effect of dietary intervention by a registered dietitian on clinical symptoms in patients with a systemic metal allergy. Forty-four patients with cutaneous symptoms who were diagnosed with a metal allergy were randomly assigned to the dietary intervention group (DI group, n = 29) by a registered dietitian or the control group (C group, n = 15). The DI group was individually instructed by a registered dietitian how to implement a metal-restricted diet and then evaluated 1 month later. Dermatologists treated skin lesions of patients in both groups. Skin symptoms assessed by the Severity Scoring of Atopic Dermatitis (SCORAD) index, blood tests, and urinary metal excretion were evaluated. The DI group showed decreased Ni, Co, Cr, and Sn intake (all P ≤ 0.05), and an improved total SCORAD score, eczema area, erythema, edema/papulation, oozing/crust, excoriation, lichenization and dryness after 1 month of intervention compared with before the intervention (all P ≤ 0.05). However, the C group showed decreased Ni and Sn intake and an improved oozing/crust score (all P < 0.05). It showed the effective reduction of dietary metal intake controls dermatitis due to a metal allergy. In conclusion, dietary intervention by a registered dietitian is effective in improving skin symptoms with a reduction in metal intake.

Pulsed ultrasound promotes secretion of anti-inflammatory extracellular vesicles from skeletal myotubes via elevation of intracellular calcium level.

The regulation of inflammatory responses is an important intervention in biological function and macrophages play an essential role during inflammation. Skeletal muscle is the largest organ in the human body and releases various factors which mediate anti-inflammatory/immune modulatory effects. Recently, the roles of extracellular vesicles (EVs) from a large variety of cells are reported. In particular, EVs released from skeletal muscle are attracting attention due to their therapeutic effects on dysfunctional organs and tissues. Also, ultrasound (US) promotes release of EVs from skeletal muscle. In this study, we investigated the output parameters and mechanisms of US-induced EV release enhancement and the potential of US-treated skeletal muscle-derived EVs in the regulation of inflammatory responses in macrophages. High-intensity US (3.0 W/cm2) irradiation increased EV secretion from C2C12 murine muscle cells via elevating intracellular Ca2+ level without negative effects. Moreover, US-induced EVs suppressed expression levels of pro-inflammatory factors in macrophages. miRNA sequencing analysis revealed that miR-206-3p and miR-378a-3p were especially abundant in skeletal myotube-derived EVs. In this study we demonstrated that high-intensity US promotes the release of anti-inflammatory EVs from skeletal myotubes and exert anti-inflammatory effects on macrophages.

Alternating current electromagnetic field exposure lessens intramyocellular lipid accumulation due to high-fat feeding via enhanced lipid metabolism in mice.

Long-term high-fat feeding results in intramyocellular lipid accumulation, leading to insulin resistance. Intramyocellular lipid accumulation is related to an energy imbalance between excess fat intake and fatty acid consumption. Alternating current electromagnetic field exposure has been shown to enhance mitochondrial metabolism in the liver and sperm. Therefore, we hypothesized that alternating current electromagnetic field exposure would ameliorate high-fat diet-induced intramyocellular lipid accumulation via activation of fatty acid consumption. C57BL/6J mice were either fed a normal diet (ND), a normal diet and exposed to an alternating current electromagnetic field (ND+EMF), a high-fat diet (HFD), or a high-fat diet and exposed to an alternating current electromagnetic field (HFD+EMF). Electromagnetic field exposure was administered 8 hrs/day for 16 weeks using an alternating current electromagnetic field device (max.180 mT, Hokoen, Utatsu, Japan). Tibialis anterior muscles were collected for measurement of intramyocellular lipids, AMPK phosphorylation, FAT/CD-36, and carnitine palmitoyltransferase (CPT)-1b protein expression levels. Intramyocellular lipid levels were lower in the HFD + EMF than in the HFD group. The levels of AMPK phosphorylation, FAT/CD-36, and CPT-1b protein levels were higher in the HFD + EMF than in the HFD group. These results indicate that alternating current electromagnetic field exposure decreases intramyocellular lipid accumulation via increased fat consumption.

Electrical stimulation facilitates NADPH production in pentose phosphate pathway and exerts an anti-inflammatory effect in macrophages.

Macrophages play an important role as effector cells in innate immune system. Meanwhile, macrophages activated in a pro-inflammatory direction alter intracellular metabolism and damage intact tissues by increasing reactive oxygen species (ROS). Electrical stimulation (ES), a predominant physical agent to control metabolism in cells and tissues, has been reported to exert anti-inflammatory effect on immune cells. However, the mechanism underlying the anti-inflammatory effects by ES is unknown. This study aimed to investigate the effect of ES on metabolism in glycolytic-tricarboxylic acid cycle (TCA) cycle and inflammatory responses in macrophages. ES was performed on bone marrow-derived macrophages and followed by a stimulation with LPS. The inflammatory cytokine expression levels were analyzed by real-time polymerase chain reaction and ELISA. ROS production was analyzed by CellRox Green Reagent and metabolites by capillary electrophoresis-mass spectrometry. As a result, ES significantly reduced proinflammatory cytokine expression levels and ROS generation compared to the LPS group and increased glucose-1-phosphate, a metabolite of glycogen. ES also increased intermediate metabolites of the pentose phosphate pathway (PPP); ribulose-5-phosphate, rebose-5 phosphate, and nicotinamide adenine dinucleotide phosphate, a key factor of cellular antioxidation systems, as well as α-Ketoglutarate, an anti-oxidative metabolite in the TCA cycle. Our findings imply that ES enhanced NADPH production with enhancement of PPP, and also decreased oxidative stress and inflammatory responses in macrophages.

Soleus muscle contains a higher concentration of lipid metabolites than extensor digitorum longus in rats with lipopolysaccharide-induced acute muscle atrophy.

BACKGROUND & AIMS: Muscle atrophy is one of the most important and frequent problems for critically ill patients. The purpose of this study was to evaluate the effect of lipid mediators on acute muscle atrophy. Skeletal muscle fiber-specific analysis of lipid mediators in endotoxemic rats was therefore performed. METHODS: Male Wistar rats were intraperitoneally injected with lipopolysaccharide (LPS). Slow-twitch soleus muscle and fast-twitch extensor digitorum longus (EDL) muscle were harvested 0, 6, and 24 h after LPS injection. Lipid mediators were profiled using liquid chromatography-tandem mass spectrometry, and free fatty acid (FFA) concentrations were measured using gas chromatography-mass spectrometry. Muscles were weighed and their cross-sectional areas were evaluated. Expression levels of mRNAs encoding inflammatory cytokines, autophagy-related transcription factors, and members of the ubiquitin-proteasome system were measured using real-time PCR. RESULTS: Before LPS injection, the concentrations of all FFAs, including arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, and all measured lipid mediators were higher in soleus muscle than in EDL muscle, especially those of pro-inflammatory prostaglandin E2 (PGE2) and leukotriene B4. LPS injection, increased PGE2 and D2 and decreased FFAs in soleus muscle but did not change in EDL muscle. The concentrations of specialized pro-resolving mediators E-series hydroxy-eicosapentaenoic acid and D-series hydroxy-docosahexaenoic acid were higher in soleus muscle. Muscle cross-sectional area decreased and the expression level of atrogin-1 was upregulated in EDL muscle, but both were unchanged in soleus muscle. After LPS injection, a discrepancy involving an increased PGE2 concentration and decreased muscle atrophy was identified in this acute muscle atrophy model of critical illness. CONCLUSION: Concentrations of FFAs and lipid mediators were higher in soleus muscle than in EDL muscle, and LPS injection rapidly increased concentrations of pro-inflammatory lipid mediators. However, muscle atrophy with upregulation of autophagy-related transcription factors was observed in EDL muscle but not in soleus muscle.

Association between Patients' Body Mass Index and the Effect of Monophasic Pulsed Microcurrent Stimulation on Pressure Injury Healing.

This secondary analysis study aimed to detect individual variables that influence the efficacy of monophasic pulsed microcurrent on pressure injury healing. Eleven patients with pressure injuries showing delayed healing underwent a microcurrent stimulation period and a placebo period. We analyzed the correlation between the individual variables and the following three outcomes using monophasic pulsed microcurrent: the wound reduction rate in the electrical stimulation period, the reduction rate in the placebo period, and the difference between these two reduction rates. Furthermore, the patients were divided into two groups, one with a wound reduction rate of more than 10% and the other with less than 10%, and the relationship between each variable was compared. As a result, the wound reduction rate in the electrical stimulation period and the difference in the reduction rate between the two periods showed significant positive correlations with patients' body mass index. In addition, a significant difference was observed in the body mass index between subjects with a reduction rate of 10% or higher and those with a reduction rate of less than 10%. This study found a correlation between the effect of monophasic pulsed microcurrent for pressure injury healing and the level of patients' body mass index.

Effect of Early Rehabilitation on Walking Independence and Health-Related Quality of Life in Patients With Chronic Foot Wounds: A Multicenter Randomized Clinical Trial.

Rehabilitation is usually provided to patients with chronic foot wounds (CFWs) after surgery. This study aimed to assess whether early postoperative rehabilitation could maintain walking independence in hospitalized patients with CFWs. This single-blind, randomized clinical trial was performed between September 10, 2018 and March 2019, involving 60 patients who underwent both surgical procedures and rehabilitation. Participants were randomly allocated into the early rehabilitation (EG, n = 30) or the control (CG, n = 30) groups. EG received early rehabilitation immediately after surgery, while CG received late rehabilitation after wound closure. Both groups received rehabilitation sessions 5 times per week until discharge. The primary outcome was walking independence, measured via Functional Independence Measure (FIM)-gait scores. Secondary outcomes included health-related quality of life (HRQoL) using EuroQol 5 dimensions 5-level (EQ-5D-5L) and the presence of rehabilitation-related adverse events, including dehiscence of wounds and falls. Differences in intervention timing effects were analyzed using nonparametric split-plot factorial design analysis, including Fisher's exact test, Mann-Whitney U test, and Wilcoxon signed-rank test (P < .05). Out of the 60 participants, 53 patients completed the discharge follow up. Three participants (10.0%) from the EG and 4 (13.3%) from the CG dropped out due to postoperative complications unrelated to rehabilitation intervention. No rehabilitation-related adverse events were found. Participants in the EG maintained greater FIM-gait scores during hospitalization than the CG (difference, -1; P = .0001), with a difference of 0 (P = .109) at discharge. EQ-5D-5L significantly improved in both groups (EG: difference, 0.13 [P = .014], CG: difference, 0.17 [P = .0074]). The EG intervention was associated more with maintaining walking independence at discharge than CG intervention. Postoperative rehabilitation improved HRQoL without adverse events, indicating that clinicians should recommend early rehabilitation for patients with CFW to enhance walking independence.

Proapoptotic effect of nonthermal pulsed ultrasound on prostate cancer cells in a nude mouse model.

BACKGROUND: Ultrasound (US) can induce cell injury, and we have previously reported that adjusting the pulse repetition frequency (PRF) of ultrasound output can induce prostate cancer cell destruction without causing a rise in the temperature of the irradiated area. In this study, we examined the mechanism of nonthermal ultrasound cell destruction, which was not fully clarified in our previous reports. METHODS: In vitro, we evaluated postirradiation cells immediately after treatment and examined membrane disruption by proliferation assay, LDH assay, and apoptosis assay. In vivo, we injected mice with human LNCaP and PC-3 prostate cancer cells and evaluated the therapeutic effects of US irradiation by H-E staining and immunostaining. RESULTS: Proliferation assays showed inhibition at 3 h postirradiation independently of PRF and cell line (p < 0.05). Quantitative assessment of apoptosis/necrosis by flow cytometry showed widely varying results depending on cell type. LNCaP showed an increase in late apoptosis at 0 h independent of PRF (p < 0.05), while PC-3 showed no significant difference at 0 h. The LDH assay showed an increase in LDH independent of PRF in LNCaP (p < 0.05 respectively), but no significant difference in PC-3. In vivo, tumor volume was compared and a significant reduction was observed at 10 Hz for LNCaP (p < 0.05) and 100 Hz for PC-3 (p < 0.001) at 3 weeks after the start of irradiation. The excised tumors were evaluated with Ki-67, Caspase-3, and CD-31 and showed a significant treatment effect independent of cell type and PRF (p < 0.001 respectively). CONCLUSION: Examining the mechanism behind the therapeutic effect of US irradiation revealed that the main effect was achieved by apoptosis induction rather than necrosis.

Skeletal myotube-derived extracellular vesicles enhance itaconate production and attenuate inflammatory responses of macrophages.

Introduction: Macrophages play an important role in the innate immunity. While macrophage inflammation is necessary for biological defense, it must be appropriately controlled. Extracellular vesicles (EVs) are small vesicles released from all types of cells and play a central role in intercellular communication. Skeletal muscle has been suggested to release anti-inflammatory factors, but the effect of myotube-derived EVs on macrophages is unknown. As an anti-inflammatory mechanism of macrophages, the immune responsive gene 1 (IRG1)-itaconate pathway is essential. In this study, we show that skeletal muscle-derived EVs suppress macrophage inflammatory responses, upregulating the IRG1-itaconate pathway. Methods: C2C12 myoblasts were differentiated into myotubes and EVs were extracted by ultracentrifugation. Skeletal myotube-derived EVs were administered to mouse bone marrow-derived macrophages, then lipopolysaccharide (LPS) stimulation was performed and inflammatory cytokine expression was measured by RT-qPCR. Metabolite abundance in macrophages after addition of EVs was measured by CE/MS, and IRG1 expression was measured by RT-PCR. Furthermore, RNA-seq analysis was performed on macrophages after EV treatment. Results: EVs attenuated the expression of LPS-induced pro-inflammatory factors in macrophages. Itaconate abundance and IRG1 expression were significantly increased in the EV-treated group. RNA-seq analysis revealed activation of the PI3K-Akt and JAK-STAT pathways in macrophages after EV treatment. The most abundant miRNA in myotube EVs was miR-206-3p, followed by miR-378a-3p, miR-30d-5p, and miR-21a-5p. Discussion: Skeletal myotube EVs are supposed to increase the production of itaconate via upregulation of IRG1 expression and exhibited an anti-inflammatory effect in macrophages. This anti-inflammatory effect was suggested to involve the PI3K-Akt and JAK-STAT pathways. The miRNA profiles within EVs implied that miR-206-3p, miR-378a-3p, miR-30d-5p, and miR-21a-5p may be responsible for the anti-inflammatory effects of the EVs. In summary, in this study we showed that myotube-derived EVs prevent macrophage inflammatory responses by activating the IRG1-itaconate pathway.

Mild Hyperbaric Oxygen Exposure Enhances Peripheral Circulatory Natural Killer Cells in Healthy Young Women.

Mild hyperbaric oxygen (HBO) enhances oxygen absorption in blood, relieving fatigue without causing oxidative stress. The benefits of mild HBO have been recognized in the treatment of lifestyle-related diseases and hypertension, but no research has been conducted on its effects on immunity. The aim of the present study is to investigate the effect of mild HBO on natural killer (NK) cells and cytokines in healthy young women. This crossover randomized control trial was conducted with 16 healthy young women. Participants were randomly exposed to normobaric oxygen (NBO; 1.0 atmospheres absolute (ATA), 20.8% oxygen) and mild HBO conditions (1.4 ATA, 35-40% oxygen, injected 18L oxygen per minute) in a hyperbaric oxygen chamber for 70 min. Heart rate, parasympathetic activity, NK cell count, interleukin (IL)-6, IL-12p70 and derivatives of reactive oxygen metabolites (d-ROMs) were measured before and after both exposures. In the NBO condition, parasympathetic activity remained unchanged, whereas after mild HBO exposure, parasympathetic activity was significantly increased. NK cells remained unchanged after NBO exposure, while NK cells were increased after exposure to mild HBO. Exposure to mild HBO did not increase d-ROM values, IL-6 and IL-12p70 protein levels. These findings suggest that exposure to mild HBO can be a useful protocol to increase NK cells by regulating parasympathetic activity via increasing oxygen delivery.

Effect of Partial Foot Amputation Level on Gait Independence in Patients With Chronic Lower Extremity Wounds: A Retrospective Analysis of a Japanese Multicenter Database.

Partial foot amputation (PFA) is generally planned to minimize the amputation level; nonetheless, the effect of PFA levels on gait independence in amputees remains unclear. This study aimed to investigate the impact of PFA levels of the forefoot on gait independence in patients with chronic lower extremity (LE) wounds. This multicenter retrospective cohort study included 232 hospitalized Japanese patients treated and rehabilitated for chronic LE wounds. A multivariate analysis based on PFA levels was conducted for gait independence at discharge, with age and comorbidities as independent variables. Patients with Lisfranc amputation had significantly less independent gait than patients with more distal amputation and those without amputation (<22% vs >40%; P = .027; Fisher's exact test). Logistic regression analysis revealed that Lisfranc amputation (odds ratio [OR]: 0.257, P = .047), age (OR: 0.559, P = .043), and chronic limb-threatening ischemia (OR: 0.450, P = .010) were independent factors associated with gait independence. Additionally, the regression model confirmed discrimination performance using the C index (0.691, P < .001) with receiver operating characteristic analysis. In patients with chronic LE wounds undergoing PFA, Lisfranc amputation was negatively associated with gait independence.

Acute Effects of Combination Therapy by Triceps Surae Stretching and Electrical Stimulation to the Tibialis Anterior on Medial Forefoot Plantar Pressure During Gait in Patients With Diabetes Mellitus.

High plantar flexor moment and limited ankle mobility are known to cause high plantar pressure under the forefoot. Stretching is an effective physical therapy for the limited ankle range of motion (ROM), and electrical stimulation is used to regulate the activity of antagonistic muscle via the action of reciprocal inhibition. Additionally, stretching paired with electrical stimulation has been reported to improve the limited ROM significantly. This study aims to investigate the influences of stretching on triceps surae (STR), electrical stimulation to tibialis anterior (ES), and the combination (ES+STR) on the ROM, kinematic parameters, and plantar pressure distribution during gait in patients with diabetes mellitus. Planter pressure and other parameters were measured before and after the intervention of ES, STR, ES+STR, or the rest sitting on the bed (CON) for 10 min. Pressure time integral under the medial forefoot decreased in the ES+STR compared to CON (P< .05). Interestingly, ES+STR increased passive and dynamic ROM on ankle dorsiflexion during gait and increased the lateral center of pressure excursion (P < .05). Furthermore, these changes were followed by decreased contact duration under the medial forefoot (P < .05). The combined therapy improves ankle mobility during gait and reduces the contact duration and the plantar pressure under the medial forefoot in patients with diabetes mellitus.

Brazilian Propolis Intake Decreases Body Fat Mass and Oxidative Stress in Community-Dwelling Elderly Females: A Randomized Placebo-Controlled Trial.

This study aimed to investigate the effects of Brazilian propolis on body fat mass and levels of adiponectin and reactive oxygen species among community-dwelling elderly females. This was a double-blind randomized placebo-controlled trial. Altogether, 78 females aged 66-84 years were randomly assigned to the propolis (PRO; n = 39) or placebo (PLA; n = 39) group. For 12 weeks, the PRO group were given three capsules containing 227 mg of propolis twice a day. Meanwhile, the PLA group were given daily placebo capsules. Of 78 participants, 53 (PLA group: n = 28, PRO group: n = 25) completed the study. Although no changes were observed in absolute or relative fat mass in the PLA group, they showed a significant decline in the PRO group. The level of serum adiponectin in the PLA group did not change, although that of the PRO group significantly increased. The level of d-ROMs in the PLA group significantly increased, whereas that of the PRO group significantly decreased. The serum SOD activity in the PLA group significantly decreased, whereas that of the PRO group tended to increase. These results suggest that propolis supplementation may decrease body fat mass and oxidative stress among community-dwelling elderly females.

Immediate Effects of Weight-Bearing Calf Stretching on Ankle Dorsiflexion Range of Motion and Plantar Pressure During Gait in Patients with Diabetes Mellitus.

High plantar pressure is a risk factor for diabetic foot ulcers, and it is known that restriction of ankle dorsiflexion range of motion (ROM) causes high plantar pressure. Stretching is a non-invasive and general means to improve ROM; however, the effect of stretching on the ROM and plantar pressure has not been clarified in patients with diabetes mellitus. We aimed to study the effects of intermittent weight-bearing stretching on ankle dorsiflexion ROM and plantar pressure during gait in patients with diabetes mellitus. Seven patients with diabetes mellitus participated, and their triceps surae was stretched using weight-bearing stretching with a stretch board. Five minutes of stretching was performed 4 times with a rest interval of 30 s. Ankle dorsiflexion ROM was measured with the knee flexed and extended. Peak pressure and pressure-time integral during gait were measured and calculated for the rearfoot, midfoot, forefoot, and total plantar surface before and after stretching. Ankle dorsiflexion ROM with the knee extended or bent increased significantly after stretching (P < .05). Peak pressure and the pressure-time integral decreased significantly, especially in the forefoot (P < .01), and these also decreased significantly in the total plantar surface (P < .05). The duration of foot-flat decreased after stretching (P < .05). Weight-bearing stretching improved ankle dorsiflexion ROM and reduced plantar pressure during gait. These results suggest that weight-bearing calf stretching may be an effective means to prevent and treat diabetic foot ulcers.

Combined Treatment with Ultrasound and Immune Checkpoint Inhibitors for Prostate Cancer.

Background: Ultrasound (US) is mostly used for diagnostic purpose but could be used for cancer treatments with a US intensity or frequency fitted to such a purpose. Prostate cancer (PC) has the highest prevalence in the urological field, but indications for immune checkpoint inhibitors (ICIs) for PC are limited to very few cases. In this study, we compared the antitumor effect of US irradiation alone with the combined use of US and ICIs in vitro and in vivo. Methods: PC cell line TRAMP-C2 cells were used in our experiments. TRAMP-C2 cells were irradiated with US with pulse repeated frequencies (PRF) of 1, 10, and 100 Hz. Cell proliferation was evaluated by MTS assay and apoptotic cells were analyzed using flow cytometry. To verify the antitumor effect of US irradiation on PC in vivo, we conducted animal experiments using mice. TRAMP-C2-bearing mice were irradiated with US with PRF of 10 and 100 Hz. Three weeks after the start of US irradiation, anti-PD-1 antibody was administered to the mice. Finally, mice were sacrificed and tumors were collected. Immunohistochemical (IHC) analyses were assessed for cleaved caspase-3 and CD3 in tumor cell extracts. Results: Cell proliferation assays showed that 1 and 10 Hz US significantly inhibited cell survival (p < 0.0001). In addition, US irradiation induced apoptosis at 1, 10, and 100 Hz (p = 0.0129, p = 0.0150, and p = 0.0017, respectively). In animal experiments, a significant tumor growth inhibitory effect was observed at 10 and 100 Hz, and 100 Hz + ICIs (p < 0.05, respectively). Hematoxylin−eosin (H−E) staining showed a significant increase in the necrotic area of the tumor at 100 Hz and 100 Hz + ICIs (p < 0.05, respectively). In addition, under IHC staining the expression level of cleaved caspase-3 and the number of CD3-positive cells increased at 100 Hz (p < 0.05, respectively). Conclusion: US irradiation induced apoptosis in cells and reduced cell viability. In vivo tumor growth was suppressed by combined treatment with US irradiation and ICIs. Further research on immune system activation will lead to less invasive and more efficient treatments for PC.