Optical Myography-Based Sensing Methodology of Application of Random Loads to Muscles during Hand-Gripping Training.

Hand-gripping training is important for improving the fundamental functions of human physical activity. Bernstein's idea of "repetition without repetition" suggests that motor control function should be trained under changing states. The randomness level of load should be visualized for self-administered screening when repeating various training tasks under changing states. This study aims to develop a sensing methodology of random loads applied to both the agonist and antagonist skeletal muscles when performing physical tasks. We assumed that the time-variability and periodicity of the applied load appear in the time-series feature of muscle deformation data. In the experiment, 14 participants conducted the gripping tasks with a gripper, ball, balloon, Palm clenching, and paper. Crumpling pieces of paper (paper exercise) involves randomness because the resistance force of the paper changes depending on the shape and layers of the paper. Optical myography during gripping tasks was measured, and time-series features were analyzed. As a result, our system could detect the random movement of muscles during training.

Wearable EMG Measurement Device Using Polyurethane Foam for Motion Artifact Suppression.

We propose the use of a specially designed polyurethane foam with a plateau region in its mechanical characteristics-where stress remains nearly constant during deformation-between the electromyography (EMG) electrode and clothing to suppress motion artifacts in EMG measurement. Wearable EMG devices are receiving attention for monitoring muscle weakening due to aging. However, daily EMG measurement has been challenging due to motion artifacts caused by changes in the contact pressure between the bioelectrode and the skin. Therefore, this study aims to measure EMG signals in daily movement environments by controlling the contact pressure using polyurethane foam between the bioelectrode on the clothing and the skin. Through mechanical calculations and finite element method simulations of the polyurethane foam's effect, we clarified that the characteristics of the polyurethane foam significantly influence contact pressure control and that the contact pressure is adjustable through the polyurethane foam thickness. The optimization of the design successfully controlled the contact pressure between the bioelectrode and skin from 1.0 kPa to 2.0 kPa, effectively suppressing the motion artifact in EMG measurement.

Usefulness of diurnal variation of fractional exhaled nitric oxide for predicting early therapeutic response to asthma treatment.

OBJECTIVE: Fractional exhaled nitric oxide (FeNO) is considered to be an adjunct for asthma management, although its usefulness remains controversial. Therefore, it may be necessary for new approaches to use FeNO for asthma management. We evaluated whether diurnal variations of FeNO can predict response to asthma treatment. METHODS: This pilot study consisted of 22 uncontrolled asthmatics and 16 healthy subjects. FeNO and peak expiratory flow (PEF) were measured by themselves twice daily at home for three weeks (asthmatics) or two weeks (healthy subjects), and daily mean and diurnal variations of FeNO and PEF levels were calculated. In uncontrolled asthmatics, treatment was intensified a week after study entry, and then control status was reevaluated after three to four weeks. Asthmatics were then divided into two groups; good or poor responders. RESULTS: Diurnal variations of FeNO levels, as well as daily mean FeNO and PEF levels, in uncontrolled asthmatics before intensive treatment were significantly higher than those in healthy subjects, regardless of treatment response (p < 0.01). Furthermore, in the good responders, diurnal variations of FeNO levels were significantly decreased in the 1st week (p < 0.05) of intensive treatment, whereas the daily mean FeNO levels significantly dropped in the 2nd week (p < 0.05). In the poor responders, no such changes were observed in FeNO levels. In terms of PEF, only the daily mean levels were significantly elevated after the initiation of intensive treatment, regardless of treatment response. CONCLUSIONS: Diurnal variations of FeNO may contribute to predicting early therapeutic response to asthma treatment.

Urethane-Foam-Embedded Silicon Pressure Sensors including Stress-Concentration Packaging Structure for Driver Posture Monitoring.

We propose urethane-foam-embedded silicon pressure sensors, including a stress-concentration packaging structure, for integration into a car seat to monitor the driver's cognitive state, posture, and driving behavior. The technical challenges of embedding silicon pressure sensors in urethane foam are low sensitivity due to stress dispersion of the urethane foam and non-linear sensor response caused by the non-uniform deformation of the foam. Thus, the proposed package structure includes a cover to concentrate the force applied over the urethane foam and frame to eliminate this non-linear stress because the outer edge of the cover receives large non-linear stress concentration caused by the geometric non-linearity of the uneven height of the sensor package and ground substrate. With this package structure, the pressure sensitivity of the sensors ranges from 0 to 10 kPa. The sensors also have high linearity with a root mean squared error of 0.049 N in the linear regression of the relationship between applied pressure and sensor output, and the optimal frame width is more than 2 mm. Finally, a prototype 3 × 3 sensor array included in the proposed package structure detects body movements, which will enable the development of sensor-integrated car seats.

Mitochondrial replacement by genome transfer in human oocytes: Efficacy, concerns, and legality.

BACKGROUND: Pathogenic mitochondrial (mt)DNA mutations, which often cause life-threatening disorders, are maternally inherited via the cytoplasm of oocytes. Mitochondrial replacement therapy (MRT) is expected to prevent second-generation transmission of mtDNA mutations. However, MRT may affect the function of respiratory chain complexes comprised of both nuclear and mitochondrial proteins. METHODS: Based on the literature and current regulatory guidelines (especially in Japan), we analyzed and reviewed the recent developments in human models of MRT. MAIN FINDINGS: MRT does not compromise pre-implantation development or stem cell isolation. Mitochondrial function in stem cells after MRT is also normal. Although mtDNA carryover is usually less than 0.5%, even low levels of heteroplasmy can affect the stability of the mtDNA genotype, and directional or stochastic mtDNA drift occurs in a subset of stem cell lines (mtDNA genetic drift). MRT could prevent serious genetic disorders from being passed on to the offspring. However, it should be noted that this technique currently poses significant risks for use in embryos designed for implantation. CONCLUSION: The maternal genome is fundamentally compatible with different mitochondrial genotypes, and vertical inheritance is not required for normal mitochondrial function. Unresolved questions regarding mtDNA genetic drift can be addressed by basic research using MRT.

Generation of mouse iPS cells using an inducible expression of transgenes via the cumate gene-switch.

We applied an inducible gene expression system that utilizes the p-cmt operon, the cumate gene-switch, to generate mouse induced pluripotent stem (iPS) cells. Mouse embryonic fibroblast (MEF) E6E7-MEF cells were transfected with a single cumate gene-switch vector enabling concomitant expression of Oct4, Sox2, c-Myc, Klf4, and Gfp. Then, the cells were cultured with cumate, a monoterpene. An increase in colonies positive for alkaline phosphatase activity was observed dose-dependently with cumate. In the absence of cumate, the expression of GFP, a marker for transgene expression, was undetectable in tightly aggregated iPS cell-like colonies with endogenous expression of NANOG and OCT4. From primary MEFs using the cumate gene-switch, we also isolated iPS cells expressing endogenous NANOG, OCT4, SOX2, KLF4, and SSEA1 with hypo-methylated genomic promoter regions of endogenous Nanog and Oct4. In embryoid bodies with the progression of differentiation, expression of markers for all three germ layers was detected, and contracting cardiomyocytes were observed. Overall, we suggest that the cumate gene-switch is applicable for the generation of mouse iPS cells. The cumate gene-switch in combination with other inducible systems, such as the tet system, may provide useful approaches for analyzing the roles of transgenes underlying the establishment of iPS cells.

Comparison of fractional exhaled nitric oxide levels measured by different analyzers produced by different manufacturers.

Objective: Fractional exhaled nitric oxide (FeNO) is widely used as a biomarker of allergic airway inflammation. At present, both stationary chemiluminescence and portable electrochemical analyzers produced by different manufacturers are available. However, it remains debatable whether those analyzers are comparable to each other. We compare FeNO levels obtained by different analyzers.Methods: For the first study, 153 subjects were enrolled to compare differences in FeNO levels measured using three analyzers (NA623NP®, NObreath®, and NIOX MINO®) which were produced by different manufacturers. For the second study, 30 subjects were recruited to compare FeNO levels obtained by the two analyzers (NIOX MINO® and NIOX VERO®) produced by the same manufacturer. FeNO was measured twice using each analyzer in random order.Results: FeNO levels obtained using the NIOX MINO® and NObreath® were more variable than those measured using the NA623NP®. There were strong positive correlations in FeNO levels measured by the NA623NP®, NIOX MINO®, and NObreath® (p < 0.001). The NA623NP® and NIOX MINO® provided the highest and lowest FeNO levels, respectively; whereas, those obtained by NObreath® were intermediate. No significant differences were observed in FeNO levels obtained using the NIOX MINO® and NIOX VERO®.Conclusions: FeNO levels measured by the NIOX MINO® and NIOX VERO®, both of which were produced by the same manufacturer, have comparability. However, significant differences in FeNO levels exist when measured by analyzers manufactured by different manufacturers. This should be taken into account for FeNO measurement.

The impact of parental unaffected allele combination on the diagnostic outcome in the preimplantation genetic testing for myotonic dystrophy type 1 in Japanese ancestry.

PURPOSE: The objective is to clarify the practical problem of the preimplantation genetic testing (PGT) for myotonic dystrophy type 1 (DM1) in Japanese subjects. METHODS: For the 32 couples who consented to participate in PGT for DM1, CTG repeats number on the unaffected alleles was analyzed. Based on the allele combination, they were classified into 3 groups by the number of diagnostic allelic pattern; "full informative," "semi informative," and "noninformative." According to the Japan Society of Obstetrics and Gynecology (JSOG) principle, PGT was performed using the direct diagnosis to the 288 embryos from the 17 couples who received the ethical approval from both our institution and JSOG. RESULTS: In the 32 couples, the frequency of CTG repeats on the unaffected alleles showed bimodal distribution. The "full informative," "semi informative," and "noninformative" couples accounted for 46.9% (15/32 couples), 46.9% (15/32 couples) and 6.2% (2/32 couples), respectively. The transferable embryos accounted for 28.9% (33/114 embryos) in the "full informative" couples, although it was limited to 12.6% (22/174 embryos) in the "semi informative" couples. CONCLUSION: The loss of unaffected embryos which cannot be diagnosed as transferable was a clinically major problem and implied an increase in oocyte retrieval, especially for "semi informative" couples.

The clinical role of fractional exhaled nitric oxide in asthma control.

BACKGROUND: The potential role and characteristics of fractional exhaled nitric oxide (FeNO) remain unclear in the treatment of asthma. OBJECTIVE: To explore the clinical role of FeNO in asthmatic treatment. METHODS: We evaluated whether the mean or change of FeNO levels in the treatment period is associated with other conventional control parameters and predicted some clinical outcomes of asthma. We retrospectively analyzed the mean and percentage change of FeNO levels in the first 5 measurements at our hospital. RESULTS: The study found a significantly strong correlation between FeNO level at diagnosis and the largest changes of FeNO values from diagnosis. No significant correlations were observed between FeNO levels and other parameters (Asthma Control Test [ACT] score or forced expiratory volume in one second [FEV1]) in mean and percentage change of values under treatment of asthma; however, significant positive correlations were found between ACT scores and FEV1. The mean FeNO level revealed a significant negative correlation with an annual change in FEV1 in individuals with asthma who were followed up for more than 2 years. Both the mean ACT score and percent predicted FEV1 revealed a significant negative correlation with occasional use of systemic corticosteroids. CONCLUSION: During conventional treatment of asthma, the largest changes of FeNO values from diagnosis were strongly correlated with FeNO levels at diagnosis. As for the unlikely conventional parameters, no significant associations were observed between FeNO levels and deterioration of asthma during the treatment periods. An elevated mean FeNO level may be a marker of decreased lung function in individuals with asthma.

ZEB1 expression is a potential indicator of invasive endometriosis.

INTRODUCTION: Although endometriosis is a benign disease, it shares some features with cancers, such as invasiveness and the potential to metastasize. This study sought to investigate the epithelial-mesenchymal transition status in human endometriotic lesions. MATERIAL AND METHODS: Thirteen endometriosis patients and 10 control women without endometriosis undergoing surgery for benign indications were recruited. We examined the expression of E-cadherin, vimentin, and epithelial-mesenchymal transition-induced transcriptional factors, such as Snail and ZEB1, by immunohistochemistry. We evaluated the expression of each marker in epithelial cells of both endometriotic lesions (ovarian endometrioma, deep infiltrating endometriosis, adenomyosis) and normal endometria. The correlation between ZEB1 expression and serum level of CA125 was also investigated. RESULTS: Immunohistochemical analysis revealed that although E-cadherin, vimentin, and Snail were expressed in epithelia of normal endometria and endometriotic lesions, ZEB1 expression was only expressed in epithelia of endometriotic lesions. Additionally, ZEB1 was most frequently observed in epithelial cells of invasive endometriosis. The endometriosis patients with high serum CA125 level were more likely to have ZEB1-positive lesions. CONCLUSIONS: This is the first observation of ZEB1 expression in epithelial cells of benign disease. The preferential expression of ZEB1 in epithelial cells of endometriotic lesions suggests that these cells may have, at least in part, a higher level of mesenchymal features possibly via ZEB1-driven epithelial-mesenchymal transition than normal endometria and that ZEB1 can be a potential indicator of invasiveness or severity of endometriosis.

Pregnancy Outcomes After Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer: A 13-Year Experience in a Single Tertiary-Care Center.

OBJECTIVE: To investigate pregnancy outcomes in women after abdominal radical trachelectomy (RT) for early-stage cervical cancer. METHODS: The patients' background, fertility, and pregnancy outcomes were reviewed in a total of 61 pregnancies in 48 of 172 women who underwent abdominal RT at Keio University Hospital between September 2002 and December 2013. RESULTS: There were 5 women with stage IA1, 2 with stage IA2, and 41 with stage IB1. Histological types were as follows: squamous cell carcinoma (n = 36), adenocarcinoma (n = 10), and adenosquamous cell carcinoma (n = 2). The pregnancy rate of women attempting to conceive after abdominal RT was 44% (48/109). The mean ± SD duration from abdominal RT to conception was 3.1 ± 1.9 years. Of 61 pregnancies, 42 pregnancies were achieved by fertility treatment (in vitro fertilization-embryo transfer, 39; intrauterine insemination, 3). After excluding one pregnancy without detailed clinical information, there were 42 live births (5 in 22-27 weeks, 11 in 28-33weeks, 20 in 34-36 weeks, and 6 in 37-38 weeks), 13 miscarriages, and 5 ongoing pregnancies. While there were 10 first trimester miscarriages, 3 pregnancies ended in the second trimester owing to chorioamnionitis. The mean gestational age at birth was 33 weeks of pregnancy. Thirty-seven neonates were appropriate-for-date, and one was small-for-date. Six pregnancies exhibited massive bleeding from the residual cervix in the late pregnancy. Preterm birth less than 34 weeks of pregnancy was related to premature rupture of the membrane (P < 0.05). Chorioamnionitis was evident in 9 of 11 pregnancies with preterm premature rupture of the membrane followed by birth at less than 34 weeks of pregnancy. No parturients exhibited lochiometra and endometritis postpartum. CONCLUSIONS: Abdominal RT provided favorable pregnancy outcomes, and fertility treatment could be advantageous to conception. Massive bleeding from the residual cervix as well as ascending infection might be characteristic features during pregnancy after abdominal RT.

Exhaled nitric oxide and inducible nitric oxide synthase gene polymorphism in Japanese asthmatics.

BACKGROUND: Inducible nitric oxide synthase (iNOS) induced by inflammatory cytokines and iNOS activity in bronchial epithelial cells is a major determinant of fractional exhaled nitric oxide (FeNO) levels. The aim of this study was to investigate the association of iNOS promoter gene polymorphisms and FeNO levels in Japanese asthmatics before the introduction of asthma treatment. METHODS: Asthmatics were recruited from Fukushima Medical University Hospital. Genotyping of the pentanucleotide repeat (CCTTT)n and seven previously detected single nucleotide polymorphisms (SNPs) in the iNOS promoter lesion was performed. The relationships between the genotypes and FeNO levels before the introduction of asthma treatment were compared. RESULTS: In 91 asthmatics, the number of microsatellite repeats ranged from 9 to 20 and showed a bimodal distribution. According to this distribution, asthmatics were divided into two groups: genotypes with at least one long allele with more than 14 repeats (L/s or L/L) and genotypes with both short alleles with 14 or fewer repeats (s/s). No significant differences were observed in each parameter between the two groups. The mean FeNO level before treatment was significantly higher in the L/s or L/L subjects than in the s/s subjects. After treatment, the lowest FeNO level did not differ between the two groups. Three SNPs detected in the Japanese subjects were not associated with FeNO levels. CONCLUSIONS: The number of CCTTT repeats in the iNOS promoter region was associated with FeNO levels in asthmatics before treatment, suggesting the importance of iNOS genotype in the clinical application of FeNO for asthmatics.

Serum Syndecan-4 as a Possible Biomarker in Patients With Acute Pneumonia.

BACKGROUND: Syndecan-4 is a transmembrane heparan sulfate proteoglycan expressed in a variety of cells, and glycosaminoglycan side chains of syndecan-4 bind to several proteins, suggesting several biological functions. However, the role of syndecan-4 in acute bacterial pneumonia has not yet been elucidated. METHODS: Serum syndecan-4 levels were measured in patients with acute pneumonia, and the relationships between serum syndecan-4 levels and clinical parameters were analyzed. Next, we treated wild-type and syndecan-4-deficient mice with Streptococcus pneumoniae intranasally and analyzed the phenotype of syndecan-4-deficient mice. RESULTS: In the patients with acute pneumonia, serum syndecan-4 levels were significantly higher than in the healthy volunteers and correlated negatively with the pneumonia severity score. In addition, in patients who improved with short-term antibiotic therapy, serum syndecan-4 levels were higher on admission and gradually increased during antibiotic therapy. Furthermore, in syndecan-4-deficient mice, the survival rate was significantly worse, and total neutrophil counts in bronchoalveolar lavage fluid, bacterial counts in blood, and plasma levels of inflammatory cytokines were significantly higher than in wild-type mice. CONCLUSIONS: These results suggest that syndecan-4 has an anti-inflammatory function in acute pneumonia and could serve as a useful biomarker in these patients.

Successful treatment of atypical cesarean scar defect using endoscopic surgery.

BACKGROUND: Cesarean scar syndrome results from a postoperative defect of the uterine isthmus, also known as an isthmocele. Patients present with gynecological symptoms, such as abnormal genital bleeding or infertility, after cesarean delivery. Although the cesarean rate is increasing worldwide, this syndrome is not widely known. CASE PRESENTATION: A 43-year-old G2P1 Japanese woman with atypical cesarean scar syndrome had a 3-year history of secondary infertility and postmenstrual brown discharge. Laparoscopic and hysteroscopic exploration revealed a cesarean scar defect connected to a small cavity in the myometrium: this was not an endometrial cavity or a uterine diverticulum. After endoscopic excision of the cavity, the brown discharge resolved, and the patient achieved ongoing pregnancy on her third attempt at intrauterine insemination. CONCLUSION: Consensus is still lacking regarding the diagnosis and treatment of cesarean scar defect. However, the gynecologists should be aware that cesarean scar syndrome can have scar defects forming cavities of unusual shapes and features. Surgical correction of these defects will often improve postmenstrual bleeding and subfertility in these cases.

A statistical study on malignant melanoma over the past 12 years in Fukui University Hospital.

BACKGROUND: The survival rate of patients with malignant melanoma is still low, and there is no established chemotherapeutic method. With the appearance of molecular targeted drugs, improvement in the survival rate can be expected. However, at present, malignant melanoma remains a disease associated with one of the poorest prognoses. MATERIALS AND METHODS: We analyzed a total of 51 cases of malignant melanoma who were treated at the Department of Dermatology, University of Fukui from September 2001 to May 2013. RESULTS: The survival rate was significantly lower in patients aged ≥65 years. The 5-year survival rate was 100 % for Stage 0/I, 79.59 % for Stage II, and 52 % for Stage III. The incidence of lymph node metastasis was highest in nodular melanoma, and zero in lentigo maligna melanoma. There was a significantly high risk of lymph node metastasis in the presence of ulceration. There was no association between incisional biopsy and lymph node metastasis. CONCLUSIONS: Although the data were obtained in only one institution and the number of cases was limited in this study, the results are close to previous international data.

Usefulness of CT-lymphography in sentinel lymph node navigation.

BACKGROUND: There are many methods for sentinel lymph node (SLN) navigation. The methods using radioisotopes and blue dyes are performed mainly for the identification of SLN. Our current method for SLN biopsy is a combination of three techniques with 99mTc-phytate, patent blue V dye, and preoperative CT-lymphography (CTLG). PATIENTS AND METHODS: Iomeprol (Iomeron®) as a water-soluble contrast agent is diluted twofold with 1 % lidocaine and intradermally injected into a few sites (2-5 ml at each site) around the tumor. After the injection, CT imaging is performed using a 64-row MDCT system (Siemens SOMATOM Definition AS+). We performed CTLG in 34 patients (16 men, 18 women) between September 2008 and March 2013. RESULTS: CTLG clearly visualized the SLN and the lymphatic drainage in 21 out of 34 patients. CONCLUSIONS: We can detect the SLN and lymphatic flow near to tumors without shine-through effect, especially in the head and neck regions. It is thought that CTLG may be useful to determine the range of lymph node dissection.

[Influence of documenting lunch menu details on subsequent snack intake].

In this study we examined the effect on subsequent snack intake of having participants document their lunch menus. In Experiment 1, we asked all participants to have lunch as usual. However, some were instructed to document their lunch menus before eating. These participants demonstrated lower snack intake than control condition participants who had not documented their lunch menus. In Experiment 2, participants in both groups ate snacks freely while viewing TV, which functioned as a stimulus interfering with recall of lunch menus. There was no difference in snack intake between participants who had documented their lunch menus and those who had not.

Antibiotic treatment for patients with exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Although respiratory tract infection is a significant factor that triggers exacerbation of chronic obstructive pulmonary disease (COPD), the benefit of antibiotics for patients with COPD exacerbation remains controversial. It is necessary to evaluate the efficacy and safety of antibiotics versus placebo in such patients. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials of antibiotics versus placebo for the treatment of COPD exacerbation, and compared the frequencies of treatment failure, mortality, and adverse events between patients treated with antibiotics and those treated with placebo. RESULTS: A total of six studies were included in this meta-analysis. The frequency of treatment failure was significantly lower in the antibiotic-treated patients compared to the placebo-treated patients (odds ratios [OR] 0.50, 95% confidence intervals [CI] 0.35-0.71, p = 0.0001). There was no significant difference between the two groups in mortality (OR 0.44, 95% CI 0.05-3.76, p = 0.45) or frequency of adverse events (OR 1.05, 95% CI 0.75-1.48, p = 0.78). CONCLUSION: In the current systematic review and meta-analysis, we found that antibiotics were superior to placebo in patients with exacerbated COPD, as shown by the lower treatment failure rate.