Electrical Stimulation Intensity to Induce Sensory Reweighting Dynamics While Standing on Balance Board.

In human postural control, maladaptation of sensory reweighting to sudden environmental changes is one of the main causes of postural instability. Providing sensory cues for body motion by means of stimulation could induce the sensory reweighting dynamics. In this paper, we aimed to investigate the intensity level of electrical stimulation to induce sensory reweighting dynamics while standing on a balance board under three conditions: no stimulation (control), electrotactile stimulation (ETS) at a low-intensity level, and electrical muscle stimulation (EMS) at a high-intensity level. A total of 30 participants (ten for each condition) controlled their posture to keep the board horizontal in a balance-board task, which included a pre-test without stimulation, a stimulation test, and a post-test without stimulation. The EMS and ETS groups received electrical stimulation to the tibialis anterior or soleus muscles based on the board tilt. Before and after the balance-board task, participants performed static standing with their eyes open and also with their eyes closed to evaluate the visual reweighting. In the EMS group, the visual reweighting showed a strong negative correlation with the balance-board sway ratio between the pre- and stimulation tests, indicating that EMS induced a tendency that requires visual up-weighting to improve postural balance. However, there were no significant correlations between either parameter in the control and ETS groups. These results suggest that high-intensity electrical stimulation at the level of directly contracting muscles may be effective in reliably inducing sensory reweighting dynamics, while low-intensity electrical stimulation may be insufficient.Clinical relevance- These findings will be helpful for designing stimulus conditions to reliably induce the reweighting during balance training, and for establishing a new balance training method utilizing EMS to induce visual up-weighting.

The nucleotide-sensing Toll-Like Receptor 9/Toll-Like Receptor 7 system is a potential therapeutic target for IgA nephropathy.

The progression determinants of IgA nephropathy (IgAN) are still not fully elucidated. We have previously demonstrated that the mucosal activation of toll-like receptor (TLR) 9, which senses microbial unmethylated CpG DNA, influences progression by producing aberrantly glycosylated IgA. However, numerous recent reports of patients with IgAN presenting with gross hematuria after the mRNA vaccination for coronavirus disease 2019 suggest that the RNA-sensing system also exacerbates IgAN. Here, we investigated whether TLR7, which recognizes microbial RNA, is also involved in IgAN progression using a murine model and tonsil tissue from 53 patients with IgAN compared to samples from 40 patients with chronic tonsillitis and 12 patients with sleep apnea syndrome as controls. We nasally administered imiquimod, the ligand of TLR7, to IgAN-prone ddY mice and found that TLR7 stimulation elevated the serum levels of aberrantly glycosylated IgA and induced glomerular IgA depositions and proteinuria. Co-administered hydroxychloroquine, which inhibits TLRs, canceled the kidney injuries. In vitro, stimulating splenocytes from ddY mice with imiquimod increased interleukin-6 and aberrantly glycosylated IgA levels. The expression of TLR7 in the tonsils was elevated in patients with IgAN and positively correlated with that of a proliferation-inducing ligand (APRIL) involved in the production of aberrantly glycosylated IgA. Mechanistically, TLR7 stimulation enhanced the synthesis of aberrantly glycosylated IgA through the modulation of enzymes involved in the glycosylation of IgA. Thus, our findings suggest that nucleotide-sensing TLR9 and TLR7 play a crucial role in the pathogenesis of IgAN. Hence, nucleotide-sensing TLRs could be reasonably strong candidates for disease-specific therapeutic targets in IgAN.

Induced effects of electrical muscle stimulation and visual stimulation on visual sensory reweighting dynamics during standing on a balance board.

Providing instruction cues on body motions using stimulations has the potential to induce sensory reweighting dynamics. However, there are currently very few quantitative investigations on the difference in the induced effects on the sensory reweighting dynamics between stimulation methods. We therefore investigated the difference in the induced effects of electrical muscle stimulation (EMS) and visual sensory augmentation (visual SA) on sensory reweighting dynamics during standing on a balance board. Twenty healthy participants controlled their posture to maintain the board horizontally in the balance-board task, which included a pre-test without stimulation, a stimulation test, and a post-test without stimulation. The EMS group (n = 10) received EMS to the tibialis anterior or soleus muscle based on the board tilt. The visual SA group (n = 10) received visual stimuli via a front monitor based on the board tilt. We measured the height of the board marker and calculated the board sway. Before and after the balance-board task, the participants performed static standing with their eyes open and closed. We measured postural sway and calculated the visual reweighting. The visual reweighting showed a strong negative correlation with the balance board sway ratio between the pre- and stimulation tests in the EMS group and a strong positive correlation with that in the visual SA group. Moreover, for those who reduced the balance board sway in the stimulation test, the visual reweighting was significantly different between the stimulation methods, demonstrating that the induced effect on sensory reweighting dynamics is quantitatively different depending on which method is used. Our findings suggest that there is an appropriate stimulation method to change to the targeted sensory weights. Future investigations on the relationship between sensory reweighting dynamics and stimulation methods could contribute to the proposal and implementation of new training methods for learning to control the target weights.

cnm-positive Streptococcus mutans is associated with galactose-deficient IgA in patients with IgA nephropathy.

The presence of Streptococcus mutans expressing Cnm protein encoded by cnm (cnm-positive S. mutans) in the oral cavity is associated with immunoglobulin A (IgA) nephropathy (IgAN). However, the precise mechanism by which cnm-positive S. mutans is involved in the pathogenesis of IgAN remains unclear. The present study evaluated glomerular galactose-deficient IgA1 (Gd-IgA1) to clarify the association between the presence of cnm-positive S. mutans and glomerular Gd-IgA1 in patients with IgAN. The presence of S. mutans and cnm-positive S. mutans was evaluated by polymerase chain reaction in saliva specimens from 74 patients with IgAN or IgA vasculitis. Immunofluorescent staining of IgA and Gd-IgA1 using KM55 antibody in clinical glomerular tissues was then performed. There was no significant association between the glomerular staining intensity of IgA and the positive rate of S. mutans. However, there was a significant association between the glomerular staining intensity of IgA and the positive rate of cnm-positive S. mutans (P < 0.05). There was also a significant association between the glomerular staining intensity of Gd-IgA1 (KM55) and the positive rate of cnm-positive S. mutans (P < 0.05). The glomerular staining intensity of Gd-IgA1 (KM55) was not associated with the positive rate of S. mutans. These results suggest that cnm-positive S. mutans in the oral cavity is associated with the pathogenesis of Gd-IgA1 in patients with IgAN.

Mucosal Immune System Dysregulation in the Pathogenesis of IgA Nephropathy.

The mucosal immune system, via a dynamic immune network, serves as the first line of defense against exogenous antigens. Mucosal immune system dysregulation is closely associated with the pathogenesis of immunoglobulin A nephropathy (IgAN), as illustrated by IgAN having the clinical feature of gross hematuria, often concurrent with mucosal infections. Notably, previous studies have demonstrated the efficacy of tonsillectomy and found that a targeted-release formulation of budesonide reduced proteinuria in patients with IgAN. However, it remains unclear how exogenous antigens interact with the mucosal immune system to induce or exacerbate IgAN. Thus, in this review, we focus on the dysregulation of mucosal immune response in the pathogenesis of IgAN.

Force Control on Fingertip Using EMS to Maintain Light Touch.

Light touch on a rigid surface with minimal force below a specific threshold reduces postural sway by providing additional sensory cues from the fingertips. The feasibility of maintaining light touch depends on subject characteristics and task difficulty. Therefore, we introduce a method of maintaining light touch by using electrical muscle stimulation (EMS). We applied it in a single-leg standing task involving healthy adult subjects. The subjects stood upright in a single-leg stance on a firm surface and on foam rubber (FR), respectively, under three conditions: no touch (NT, NT-FR), light touch without EMS (LT, LT-FR), and light touch in which EMS was applied based on the contact force (LT-EMS, LT-EMS-FR). The results showed that the force control by EMS helped maintain light touch and reduce postural sway compared with the no-touch condition. The amplitude of postural sway under the touch condition with EMS was equivalent to that under the touch condition without EMS.

Correction of Electrode ID Configuration based on Distribution of Surface EMG Features.

Surface EMG (sEMG) signals are useful for estimating the motion or exercise of users. Wireless-type sensor electrodes, which are placed on multiple parts of the body and send the measured signals to a server, have recently become commercially available. With many estimation algorithms, the relationships between the sensor IDs and the body parts they are placed on (ID configuration) are expected to be fixed between the calibration and estimation phases. If the ID configuration is changed after the calibration phase, the estimation accuracy tends to dramatically decrease. Since it is inconvenient for users to check the ID configuration every time, we developed a method to correct the electrode ID configuration on the basis of the distribution of sEMG features. Using open data, we investigated the feasibility of our method by shuffling the order of sEMG signals. The results showed that the method was able to correct the ID configuration and restore the estimation accuracy to close to that of the calibration.

T2-weighted short-tau-inversion-recovery imaging reflects disease activity of cardiac sarcoidosis.

OBJECTIVE: We investigated the diagnostic performance of semi-quantitative hyperintensity on T2-weighted short-tau-inversion-recovery black-blood (T2W-STIR-BB) images in identifying active cardiac sarcoidosis (CS) in patients, and compared it with that of 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). METHODS: This retrospective study included 40 steroid-naive patients (age 63.1±12.9 years, 20 men) diagnosed with CS who underwent both cardiac MRI and FDG-PET imaging. Active CS cases were defined as satisfying at least one of the following criteria for conventional indices: exacerbation of ventricular arrhythmia, newly identified advanced atrioventricular block, greater than 5% decrease in left ventricular ejection fraction on echocardiography, positive finding on gallium-scintigraphy or elevated levels of sarcoidosis-related serum biomarkers. T2W-STIR-BB images were semi-quantitatively analysed using a myocardium-to-spleen ratio (MSR). The diagnostic performance of T2W-STIR-BB and FDG-PET imaging for detecting active CS was investigated. RESULTS: Thirty-three patients satisfied at least one criterion and were considered as having active CS. Thirty patients (75%) tested positive with T2W-STIR-BB imaging, and 25 patients (63%) tested positive with FDG-PET. The sensitivity, specificity, accuracy, and positive and negative predictive values for identifying active CS by semi-quantitative MSR on T2W-STIR-BB images were 79%, 43%, 73%, 87% and 30%, respectively. These results were statistically comparable to those of FDG-PET (70%, 71%, 70%, 92% and 33%, respectively). CONCLUSIONS: When using conventional diagnostic indices for active CS as the gold standard, T2W-STIR-BB imaging demonstrated comparable diagnostic performance to that of FDG-PET. The semi-quantitative analysis of high signal intensity on T2W-STIR-BB images using MSR was useful for detection of active CS.

Sock-Type Wearable Sensor for Estimating Lower Leg Muscle Activity Using Distal EMG Signals.

Lower leg muscle activity contributes to body control; thus, monitoring lower leg muscle activity is beneficial to understand the body condition and prevent accidents such as falls. Amplitude features such as the mean absolute values of electromyography (EMG) are used widely for monitoring muscle activity. Garment-type EMG measurement systems use electrodes and they enable us to monitor muscle activity in daily life without any specific knowledge and the installation for electrode placement. However, garment-type measurement systems require a high compression area around the electrodes to prevent electrode displacement. This makes it difficult for users to wear such measurement systems. A less restraining wearable system, wherein the electrodes are placed around the ankle, is realized for target muscles widely distributed around the shank. The signals obtained from around the ankle are propagated biosignals from several muscles, and are referred to as distal EMG signals. Our objective is to develop a sock-type wearable sensor for estimating lower leg muscle activity using distal EMG signals. We propose a signal processing method based on multiple bandpass filters from the perspectives of noise separation and feature augmentation. We conducted an experiment for designing the hardware configuration, and three other experiments for evaluating the estimation accuracy and dependability of muscle activity analysis. Compared to the baseline based on a 20-500 Hz bandpass filter, the results indicated that the proposed system estimates muscle activity with higher accuracy. Experimental results suggest that lower leg muscle activity can be estimated using distal EMG signals.

Lower Limb Muscle Activity Control by using Jamming Footwear.

To change the lower limb muscle activities while walking, we propose a muscle activity controlling system that dynamically changes shoe insoles. We conducted a preliminary experiment on a prototype system to determine the system's validity. In this experiment, we analyzed how tibialis anterior and gastrocnemius muscle might change their activities depending on each insole condition. The results lead us to conclude that our system may affect changes in the duration percentage of tibialis anterior muscle activation when we change the heel part shape, and that it may change the maximum amplitude of gastrocnemius muscle activation when we change the arch part shape and hardness.

R-R Interval Outlier Exclusion Method Based on Statistical ECG Values Targeting HRV Analysis Using Wearable ECG Devices.

This paper describes an R-R Interval (RRI) outlier exclusion method that can exclude RRI outliers including misdetected R waves caused by artifacts, which are frequently observed when using wearable electrocardiogram (ECG) devices. The method distinguishes targeted misdetected R waves based on statistical ECG values that can reflect the occurrence of artifacts, and annotates all detected R waves with those results for evaluating RRI measurement status. Experimental results confirmed that the proposed method is effective to improve the accuracy of both time and frequency domain measures of heart rate variability than the conventional one.

Consideration of Calculation Process Assuming Heart Rate Variability Analysis Using Wearable ECG Devices.

Since many shirt-type wearable electrocardiogram (ECG) devices employ shirt-embedded dry electrodes that are easily affected by the daily activities of users, measured ECG often includes noise or artifacts. Experiments confirmed that a desirable HRV calculation process assuming these wearable ECG devices is a combination of accurate R wave detection, RRI outlier exclusion and missing RRI complement methods.

Reliability evaluation of R-R interval measurement status for time domain heart rate variability analysis with wearable ECG devices.

Electrocardiograms (ECGs) captured by wearable ECG devices easily contain artifacts because of measurement faults. Since the frequency characteristics of artifacts are quite similar to those of R waves, it may result in R-R interval (RRI) miscalculations. To enable accurate heart rate variability (HRV) analysis in daily life, this paper proposes a method to reliably evaluate RRI measurement status, one that uses the electric potential characteristics of the QRS complex. Initial evaluation results show that it has the potential to distinguish miscalculated RRIs. Also proposed is a new RRI outlier exclusion method that uses the aforementioned method. Time domain measures of HRV derived from the proposed RRI outlier exclusion method are found to be more accurate than those derived from the conventional one.

An analysis method for wearable electrocardiogram measurement based on non-orthogonal complex wavelet expansion.

An analysis method for wearable electrocardiogram (ECG) measurement is proposed, which is based on the non-orthogonal complex wavelet expansion. The standard continuous wavelet transform performs the signal filtering that corresponds to the orthogonal projection of the ECG signal onto each of the non-orthogonal wavelets. This causes feature leakage from the neighboring wavelet filterbanks and degrades the detection accuracy of the QRS complexes or T waves, even though the wavelets whose waveforms fit to the morphologies of the ECG signals are chosen. The proposed method involves a different signal filtering that corresponds to the non-orthogonal projection of the signal onto each wavelet so that the filter outputs can be the expansion coefficients of the wavelets to approximate the ECG signal. The concept of our proposed method is supported by simulation results.

Characterizing muscular activities using non-negative matrix factorization from EMG channels for driver swings in golf.

The goal of this study is to propose a data driven approach method to characterize muscular activities of complex actions in sports such as golf from a lot of EMG channels. Two problems occur in a many channel measurement. The first problem is that it takes a lot of time to check the many channel data because of combinatorial explosion. The second problem is that it is difficult to understand muscle activities related with complex actions. To solve these problems, we propose an analysis method of multi EMG channels using Non-negative Matrix Factorization and adopt the method to driver swings in golf. We measured 26 EMG channels about 4 professional coaches of golf. The results show that the proposed method detected 9 muscle synergies and the activation of each synergy were mostly fitted by sigmoid curve (R2=0.85).

FOXP3(+) regulatory and TIA-1(+) cytotoxic T lymphocytes in HIV-associated Hodgkin lymphoma.

Human immunodeficiency virus (HIV) infects CD4(+) lymphocytes, leading to a development of malignant lymphomas, such as HIV-associated Hodgkin Lymphoma (HIV-HL). This study aimed to assess the differences in cellular composition of the inflammatory reactive background of HIV-HLs. We examined infiltrating T lymphocytes, specifically regulatory T cells, cytotoxic cells, Epstein-Barr virus (EBV) related antigens and HIV-receptor CCR5. In all HIV-HL cases, Hodgkin and Reed-Sternberg (HRS) cells showed EBER1 expression, LMP-1 staining positivity and EBNA-2 staining negativity, except for one case which showed LMP-1 staining negativity. Our histological findings indicate the percentage of CD8(+) , TIA-1(+) lymphocytes was significantly higher in HIV-HL than in non-HIV-HL cases (P < 0.05). On the other hand, the percentage of CD4(+) , FOXP3(+) lymphocytes was significantly lower in HIV-HL than in non-HIV-HL cases (P < 0.05) but present. The percentage of CCR5(+) lymphocytes was significantly lower in HIV-HL than in non-HIV-HL cases (P < 0.05). Usually, CD4(+) and CCR5(+) lymphocytes are reported to be rarely detected in HIV-associated non-Hodgkin lymphomas, but the presence of CD4(+) and/or FOXP3(+) lymphocytes may be implicated in the pathogenesis of HL. In addition, although additional CD8(+) lymphocytes are probably not EBV-LMP specific cytotoxic T-cells, these lymphocytes may also well be involved in the pathogenesis of HIV-HL.

Regression of rectal mucosa-associated lymphoid tissue (MALT) lymphoma after antibiotic treatments.

Only a few reports have described regression of rectal mucosa-associated lymphoid tissue (MALT) lymphoma after antibiotic treatment are generally found to be successful for gastric tumors. We examined eight rectal MALT lymphomas treated with antibiotic treatments to determine whether they regressed after treatment. We also discuss the relationship between rectal MALT lymphomas and MALT1 gene genetic abnormalities. Eight patients who had undergone antibiotic treatments were followed up with colonoscopy after initiation of the treatment. In five of the eight cases (63%) endoscopic examination showed that the rectal tumor had disappeared, which was confirmed histologically. Polymerase chain reaction for immunoglobulin heavy chain identified a monoclonal band in seven of eight cases (88%). Of the eight cases analyzed with fluorescence in situ hybridization (FISH) for MALT1 translocation, two demonstrated MALT1 gene genetic abnormality. These cases tended to be resistant to antibiotic treatment. Investigation and analysis of a large number of rectal MALT lymphomas are needed to establish suitable standards for antibiotic treatment.

Ratio of M2 macrophage expression is closely associated with poor prognosis for Angioimmunoblastic T-cell lymphoma (AITL).

Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma characterized by systemic disease with polymorphous infiltrate including macrophages. Although many studies of tumor-associated macrophage (TAM) populations in various malignant tumors have been published, only a few have dealt with activation of macrophage phenotypes such as M1 and M2 in tumor tissue. Because M2 macrophages highly express CD163, we suspected that CD163 may be a useful marker for identification of activation of macrophage phenotypes in AITL. We performed a retrospective study of immunohistochemical expression using two markers for macrophages [CD68 (PG-M1), CD163] and of the correlation of these expressions with overall survival of 42 AITL patients. The number of CD68-positive cells in AITL tissues did not correlate with overall survival (P= 0.59), whereas the number of CD163-positive cells and overall survival correlated to some extent (P= 0.08). Meanwhile, a higher ratio of CD163-positive to CD68-positive cells in AITL significantly correlated with worse overall survival (P= 0.036). Considering that this ratio reflects the proportion of macrophages polarized to the M2 phenotype, our findings indicate that activation of macrophages towards the M2 phenotype correlates with worse prognosis. Our findings indicate that the ratio of M2 macrophages expressed may be a useful marker for prognosis of AITL.

Mantle cell lymphoma shows three morphological evolutions of classical, intermediate, and aggressive forms, which occur in parallel with increased labeling index of cyclin D1 and Ki-67.

Although the 2008 World Health Organization classification defines two subtypes of mantle cell lymphoma (MCL), classical and aggressive, we often encounter MCL with both features in the same site. We named this feature "MCL with focal aggressive form (intermediate MCL)". In the present study, we reclassified 237 patients with cyclin D1 (CCND1)-positive MCL on the basis of the concept of intermediate MCL, and analyzed the correlation of this reclassification with immunohistochemical detection of CCND1, Ki-67, p53, p27(Kip1), and p21(WAF/Cip1). The median overall survival was 77, 31, and 18 months for classical, intermediate, and aggressive MCL, respectively, showing a statistically significant difference (P < 0.0001). The expression levels of CCND1, Ki-67, p53, and p21(WAF/Cip1) in aggressive MCL (mean 80.1 +/- 27.8%, 73.7 +/- 28.9%, 31.0 +/- 69.0%, and 10.4 +/- 24.8%, respectively) were higher than those in classical MCL (mean 58.1 +/- 36.7%, 25.2 +/- 25.5%, 6.5 +/- 24.3%, and 2.5 +/- 13.0%, respectively) and intermediate MCL (mean 75.7 +/- 31.4%, 30.8 +/- 33.3%, 21.0 +/- 57.4%, and 4.8 +/- 16.5%, respectively). Significantly different levels of Ki-67 and p21(WAF/Cip1) were only recognized between intermediate and aggressive (P < 0.05 and P < 0.0001, respectively), whereas those of CCND1 and p53 were only between classical and intermediate (P < 0.0001 and P < 0.05, respectively). There were no significant differences in p27(Kip1) among the three groups. The subsequent discriminant analysis with independent prognostic factors clearly demonstrated that the morphological evolution of MCL occurs in parallel with increased labeling index of CCND1 and Ki-67. The diagnosis of intermediate MCL thus proved to be of major significance and should enable the design of more tailored therapies.