TLR2-Dependent Induction of IL-10 and Foxp3+CD25+CD4+ Regulatory T Cells Prevents Effective Anti-Tumor Immunity Induced by Pam2 Lipopeptides In Vivo

16 S-[2,3-bis(palmitoyl)propyl]cysteine (Pam2) lipopeptides act as toll-like receptor (TLR)2/6 ligands and activate natural killer (NK) cells and dendritic cells (DCs) to produce inflammatory cytokines and cytotoxic NK activity in vitro. However, in this study, we found that systemic injection of Pam2 lipopeptides was not effective for the suppression of NK-sensitive B16 melanomas in vivo. When we investigated the immune suppressive mechanisms, systemic injection of Pam2 lipopeptides induced IL-10 in a TLR2-dependent manner. The Pam2 lipopeptides increased the frequencies of Foxp3+CD4+ regulatory T (T reg) cells in a TLR2- and IL-10- dependent manner. The T reg cells from Pam2-lipopeptide injected mice maintained suppressor activity. Pam2 lipopeptides, plus the depletion of T reg with an anti-CD25 monoclonal antibody, improved tumor growth compared with Pam2 lipopeptides alone. In conclusion, our data suggested that systemic treatment of Pam2 lipopeptides promoted IL-10 production and T reg function, which suppressed the effective induction of anti-tumor immunity in vivo. It is necessary to develop an adjuvant that does not promote IL-10 and T reg function in vivo for the future establishment of an anti-cancer vaccine

The Effect of a Portable Electrical Muscle Stimulation Device at Home on Muscle Strength and Activation Patterns in Locomotive Syndrome Patients: A Randomized Control Trial

The aim of the present study was to quantify the effect of electrical muscle stimulation (EMS) intervention using a portable device on muscle strength and activation patterns in locomotive syndrome. Nineteen women were randomly assigned to the intervention group (n = 10; age = 71–82 years) and control group (n = 9; age = 70–84 years). Participants in the intervention group used a portable EMS device to stimulate the bilateral quadriceps muscles for 8 weeks (23 min/5 days/week). To understand the effects of EMS, the following measurements were made at baseline, 8 weeks, and 12 weeks: locomotive syndrome assessment score, knee extensor strength, vastus lateralis muscle activation patterns during a maximal isometric knee extension contraction using multi-channel surface electromyography, and muscle thickness. The locomotive syndrome assessment, muscle strength, muscle thickness, and muscle activity patterns in the intervention group were significantly different to control after 8 weeks (p \u3c 0.05). However, these results were not sustained at 12 weeks. EMS increased locomotor assessment scores, which were accompanied by enhanced muscle strength, increased muscle thickness, and changes in muscle activation patterns in locomotive syndrome patients. These results suggest that EMS is potentially useful for improving muscle neural activation and force output in locomotive syndrome

Laterality of the Activation of the Vastus Lateralis Muscle in Females with Parkinson\u27s Disease during the Medication State Compared with Healthy Controls

This study quantified the laterality of motor unit activation properties in females with Parkinson’s disease during force production (low to high-intensity contraction) using high-density surface electromyography. Sixteen females with Parkinson’s disease (age = ± 7.6 years, disease duration = 4.9 ± 5.1 years) and 14 healthy female subjects (age = 68.6 ± 3.6 years) performed submaximal ramp-up contractions during isometric knee extension. High-density surface electromyography signals were recorded from both vastus lateralis muscles. The level of heterogeneity was calculated in the spatial distribution patterns of the high-density surface electromyography signals to determine the modified entropy, coefficient of variation of the root mean square and correlation coefficient to evaluate motor unit activation properties. Pearson’s correlation coefficients were calculated to examine the relationships between disease severity and the root mean square and electromyography variables. The root mean square value and heterogeneity were significantly higher and lower on the more-affected side in females with Parkinson’s disease than on the contralateral side in females with Parkinson’s disease or either side in control subjects (p \u3c 0.05). Females with Parkinson’s disease that exhibited temporal changes of spatial motor unit activation properties showed significant laterality when compared to healthy control subjects in both the low and high-intensity contractions. Moderate-to-strong correlations were observed between disease severity and root mean square and electromyography variables in females with Parkinson’s disease (r\u3e 0.6, p \u3c 0.001). The laterality of motor unit activation properties was compared between the subjects with Parkinson’s disease and the control subjects. The findings suggest that females with Parkinson’s disease have asymmetrical motor unit activation properties, independent of the magnitude of force production

Detection of Salivary miRNAs That Predict Chronic Periodontitis Progression: A Cohort Study

The aim of this two-year cohort study was to investigate salivary microRNAs (miRNAs) that predict periodontitis progression. A total of 120 patients who underwent supportive periodontal therapy were recruited. Unstimulated whole saliva was collected at baseline. Two years later, 44 patients were followed up (median age, 67.1 years) and divided into two groups: progression group (n = 22), with one or more sites with clinical attachment level (CAL) progression (>3 mm compared with baseline) or tooth extraction due to periodontitis progression; and the control group (n = 22), which did not exhibit CAL progression. In the microarray analysis of salivary miRNAs, hsa-miR-5571-5p, hsa-miR-17-3p, hsa-let-7f-5p, hsa-miR-4724-3p, hsa-miR-99a-5p, hsa-miR-200a-3p, hsa-miR-28-5p, hsa-miR-320d, and hsa-miR-31-5p showed fold change values = 2.0 in the progression group compared with the control group (p 0.7, indicating fair discrimination power. The expressions of salivary hsa-miR-5571-5p, hsa-let-7f-5p, hsa-miR-99a-5p, hsa-miR-28-5p, and hsa-miR-320d were associated with periodontitis progression in patients with chronic periodontitis. These salivary miRNAs may be new biomarkers for progression of periodontitis, and monitoring them may contribute to new diagnostics and precision medicine for periodontitis

A novel homozygous variant of the thrombomodulin gene causes a hereditary bleeding disorder

ArticleBlood Advances. 5(19): 3830-3838 (2021)journal articl

Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models

Objectives. It is still not clear how the intravesical instillation of drugs affects rat urinary frequency. This study aimed to examine the dynamics of intravesical treatments' treatment effect on rat urinary frequency models by real-time and extended monitoring using a novel continuous urination monitoring system. Methods. Nine eleven-week-old female Wistar rats were divided into three groups to receive intravesical instillation of 0.1% acetic acid (AA), 1.0% AA, or phosphate-buffered saline (PBS). Thirty minutes later, these drugs were voided, and rats were moved to a continuous urination monitoring system, UM-100. UM-100 monitored rat urination quantitatively and continuously for 24 hours. Rats were then euthanized, and histopathologic examinations using a damage score validated the severity of bladder inflammation. We used nine additional rats to determine the treatment effect of various drugs against the urinary frequency. These rats were also treated with 1.0% AA in the same way and divided into three groups (n = 3 each) to receive intravesical instillation of lidocaine, silver nitrate (AgNO3), or dimethyl sulfoxide (DMSO), respectively. Thirty minutes later, rats were catheterized again and moved to the UM-100, and their voiding was monitored for 24 hours. Results. Intravesical instillation of AA increased the urinary frequency and decreased the mean voided volume (VV) in a concentration-dependent manner, with statistical significance at a concentration of 1.0% (urinary frequency; p = 0.0007 , mean VV; p = 0.0032 , respectively) compared with PBS. Histopathological analysis of these models demonstrated a significantly higher damage score of bladder mucosa in both 0.1% AA and 1.0% AA compared with PBS, with the severity in concordance with the clinical severity of urinary frequency (0.1% AA: p < 0.0001 , 1.0% AA: p < 0.0001 ). Moreover, intravesical instillation of lidocaine, AgNO3, and DMSO decreased the urinary frequency. Continuous monitoring with UM-100 also demonstrated that the treatment effect of these intravesically instilled drugs occurred only at night. Conclusions. The extended monitoring of rat urination by UM-100 revealed a significant fluctuation in the treatment effect of intravesically instilled drugs between day and night. These findings may help establish novel therapies for urinary frequency

The Effect of a Portable Electrical Muscle Stimulation on Brain-Derived Neurotrophic Factor in Elderly People: Three Case Studies

金沢大学理工研究域フロンティア工学系Brain-derived neurotrophic factor (BDNF), which plays an important role in cognitive and nerve function, is released from skeletal muscle cells into the blood by muscle contractions and/or electrical muscle stimulation (EMS). However, the influence of EMS administered by a portable device on BDNF is unclear. The purpose of this case report was to quantify the influence of EMS administered by a portable device on BDNF and physical function. Three elderly people (age, 69.7 ± 1.5 years) were included in the present study. The participants used a portable EMS device to stimulate the bilateral quadriceps muscles for 8 weeks (23 min for 5 days/week). To determine the effects of EMS, the following parameters were assessed at baseline, 8 weeks, and 12 weeks (follow-up): knee extensor strength, muscle mass of the lower limb, Berg balance score, and blood BDNF level. All outcomes improved after the EMS intervention, but the improvements did not persist for 12 weeks. These findings suggest that portable EMS is potentially useful for improving the blood BDNF level and physical function

Electromechanical characterization and kinetic energy harvesting of piezoelectric nanocomposites reinforced with glass fibers

Piezoelectric composites are a significant research field because of their excellent mechanical flexibility and sufficient stress-induced voltage. Furthermore, due to the widespread use of the Internet of Things (IoT) in recent years, small-sized piezoelectric composites have attracted a lot of attention. Also, there is an urgent need to develop evaluation methods for these composites. This paper evaluates the piezoelectric and mechanical properties of potassium sodium niobate (KNN)-epoxy and KNN-glass fiber-reinforced polymer (GFRP) composites using a modified small punch (MSP) and nanoindentation tests in addition to d33 measurements. An analytical solution for the piezoelectric composite thin plate under bending was obtained for the determination of the bending properties. Due to the glass fiber inclusion, the bending strength increased by about four times, and Young's modulus in the length direction increased by approximately two times (more than that of the KNN-epoxy); however, in the thickness direction, Young's modulus decreased by less than half. An impact energy harvesting test was then performed on the KNN-epoxy and KNN-GFRP composites. As a result, the output voltage of KNN-GFRP was larger than that of KNN-epoxy. Also, the output voltage was about 2.4 V with a compressive stress of 0.2 MPa, although the presence of the glass fibers decreased the piezoelectric constants. Finally, damped flexural vibration energy harvesting test was carried out on the KNN-epoxy and KNN-GFRP composites. The KNN-epoxy was broken during the test, however KNN-GFRP composite with a load resistance of 10 MΩ generated 35 nJ of energy. Overall, through this work, we succeeded in developing piezoelectric energy harvesting composite materials that can withstand impact and bending vibration using glass fibers and also established a method for evaluating the electromechanical properties with small test specimen

Virtual Human Generative Model: Masked Modeling Approach for Learning Human Characteristics

Identifying the relationship between healthcare attributes, lifestyles, and personality is vital for understanding and improving physical and mental conditions. Machine learning approaches are promising for modeling their relationships and offering actionable suggestions. In this paper, we propose Virtual Human Generative Model (VHGM), a machine learning model for estimating attributes about healthcare, lifestyles, and personalities. VHGM is a deep generative model trained with masked modeling to learn the joint distribution of attributes conditioned on known ones. Using heterogeneous tabular datasets, VHGM learns more than 1,800 attributes efficiently. We numerically evaluate the performance of VHGM and its training techniques. As a proof-of-concept of VHGM, we present several applications demonstrating user scenarios, such as virtual measurements of healthcare attributes and hypothesis verifications of lifestyles.Comment: 14 pages, 4 figure

Long-term ureteroscopic management of upper tract urothelial carcinoma: 28-year single-centre experience

Background Long-term survival outcomes of patients who undergo endoscopic management of non-invasive upper tract urothelial carcinoma remain uncertain. The longest mean follow-up period in previous studies was 6.1 years. This study reports the long-term outcomes of patients with upper tract urothelial carcinoma who underwent ureteroscopic ablation at a single institution over a 28-year period. Methods We identified all patients who underwent ureteroscopic management of upper tract urothelial carcinoma as their primary treatment at our institution between January 1991 and April 2011. Survival outcomes, including overall survival, cancer-specific survival, upper-tract recurrence-free survival and renal unit survival, were estimated using Kaplan−Meier methodology. Results A total of 15 patients underwent endoscopic management, with a mean age at diagnosis of 66 years. All patients underwent ureteroscopy, and biopsy-confirmed pathology was obtained. Median (range; mean) follow-up was 11.7 (2.3–20.9, 11.9) years. Upper tract recurrence occurred in 87% (n = 13) of patients. Twenty percent (n = 3) of patients proceeded to nephroureterectomy. The estimated cancer-specific survival rate was 93% at 5, 10, 15 and 20 years. Estimated overall survival rates were 86, 80, 54 and 20% at 5, 10, 15 and 20 years. Only one patient experienced cancer-specific mortality. The estimated mean and median overall survival times were 14.5 and 16.6 years, respectively. The estimated mean cancer-specific survival time was not reached. Conclusions Although upper tract recurrence is common, endoscopic management of non-invasive upper tract urothelial carcinoma provides a 90% cancer-specific survival rate at 20 years in selected patients