Postural differences in the immediate effects of active exercise with compression therapy on lower limb lymphedema.

PURPOSE: Although regarded as an important treatment for lymphedema, the therapeutic effects of active exercise with compression therapy (AECT) are supported by little evidence. The purpose of this study was to determine the relative benefits of AECT with different postures for patients with lower limb lymphedema (LLL). METHODS: Eighteen women with LLL secondary to surgical treatment of gynecological cancer, completed (1) AECT in a seated position (seated AECT), (2) AECT in a supine position (supine AECT), and (3) compression-only therapy in a supine position (CT) in this randomized, controlled, crossover trial. AECT was performed on a bicycle ergometer while wearing elastic compression bandages. Each intervention was performed for 15 min, and the three conditions were separated by a 1-week washout period. Lower-limb volumes were evaluated using a PerometerTM sensor (Pero-system, Wuppertal, Germany), and symptom severity was assessed before and after each intervention using a visual analog scale (pain, heaviness) and palpation (pitting, stiffness). The effects of the interventions were estimated using linear mixed-effect models. RESULTS: The magnitude of limb volume decreases differed significantly among the interventions, with a greater decrease after supine AECT than after CT. Pre-intervention pitting severity and skin stiffness were significantly correlated with the magnitude of volume decrease after all interventions and after AECT in the supine position, respectively. CONCLUSIONS: Supine AECT using a bicycle ergometer has marked immediate effects to decrease the fluid volume of severe LLL. CLINICAL TRIAL REGISTRATION: UMIN clinical trial registry (UMIN-CTR; ID000020129) by CONSORT 2010, TRN R000023253, December 9, 2015.

Factors related to daily use of the paretic upper limb in patients with chronic hemiparetic stroke-A retrospective cross-sectional study.

AIMS: The present study aimed to determine factors associated with the frequency of paralyzed upper extremity (UE) use in chronic stroke patients with severe UE functional deficiency. METHODS: We retrospectively reviewed the medical records of 138 consecutive patients, and 117 was analyzed (median age, 55 [range, 18-85] years; median stroke duration, 24.5 [range, 7-302] months) with chronic hemiparetic stroke who were admitted to our hospital for intensive upper extremity rehabilitation. The mean Fugl-Meyer Assessment (FMA) UE score was 28.6. All of them are independent in their activity of daily living (ADL) and without remarkable cognitive deficits. Amount-of-use score of Motor Activity Log-14 (MAL-AOU) was applied as the index of daily use of affected UE. The following parameters were examined as the explanatory variables: demographics, proximal and distal sub-scores of FMA UE, Modified Ashworth Scale (MAS), and sensory function scores in the Stroke Impairment Assessment Set (SIAS). RESULTS: The median MAL-AOU score was 0.57 [range, 0.28-0.80]. Ordinal regression analysis revealed that FMA proximal, FMA distal, and SIAS sensory function (touch) were associated with AOU score of MAL-14 (Pseudo R-square = 0.460). CONCLUSION: Not only motor but also sensory function, especially tactile sensation, play a crucial role in the daily use of affected UE in chronic stroke patients with severe UE hemiparesis.

Effects of hybrid assistive neuromuscular dynamic stimulation therapy for hemiparesis after pediatric stroke: a feasibility trial.

BACKGROUND: Hybrid assistive neuromuscular dynamic stimulation (HANDS) therapy, consisting of a wrist-hand splint and an integrated volitional control electrical stimulator to stimulate the extensor digitorum communis, is effective for chronic hemiparesis after stroke in adults. We investigated the feasibility and effects of HANDS therapy for patients with pediatric stroke by performing a longitudinal study. METHODS: Twelve patients with chronic hemiparetic pediatric stroke (aged 14-38 years) wore the herapeutic device for 3 weeks. The device was active for 8 h during the daytime, and patients were instructed to use their paretic hand as much as possible. Upper extremity items of the Fugl-Meyer Motor Assessment Scale and the Stroke Impairment Assessment Set motor test were used to measure motor function and were compared before and after the intervention with the Wilcoxon signed rank test. RESULTS: All patients were fully compliant with the therapy with no adverse events. After the intervention, both treatment endpoints improved significantly (p < .05). The effect size for upper extremity items of the Fugl-Meyer Motor Assessment Scale was medium (d = 0.59). CONCLUSION: This preliminary study demonstrated the feasibility and effectiveness of HANDS therapy in patients with pediatric stroke.Implications for rehabilitationPediatric stroke is a very rare disease and patients are forced to live with sequelae in most of the rest of their lives.Hybrid assistive neuromuscular dynamic stimulation therapy is effective for upper limb paralysis of adult stroke.Hybrid assistive neuromuscular dynamic stimulation therapy was adaptable even for children, and improvement of upper limb paralysis was observed even in a relatively short period of intervention.

Validity and Reliability of the Semmes-Weinstein Monofilament Test and the Thumb Localizing Test in Patients With Stroke.

Background: Somatosensory impairment is common in patients who have had a stroke and can affect their motor function and activities of daily living (ADL). Therefore, detecting and treating somatosensory impairments properly is considered to be very important, and various examinations have been developed. However, the reliability and validity of few of them have been verified due to differences in the procedure of each examiner or poor quantification by the examination itself. Objective: We hypothesized that, with fixed procedures two convenient clinical examinations, the Semmes-Weinstein Monofilament Test (SWMT) and the Thumb Localizing Test (TLT), could provide reliable assessments of light touch sensation and proprioception. The purpose of this study was to verify the reliability and validity of these two examinations as indices of somatosensory impairment of the upper extremity (UE) in patients with chronic post-stroke hemiparesis. Methods: Fifty patients with chronic stroke (median time after onset of stroke, 848 [474-1708] days, mean age 57 [standard deviation 14] years) were enrolled at Keio University Hospital from 2017 to 2018. Examiners learned the original method of the SWMT and the TLT rigorously and shared it with each other. The TLT procedure was partially modified by dividing the location of the patient's thumb into four spaces. Two examiners evaluated the SWMT and the TLT for 2 days, and intra-rater and inter-rater reliabilities were calculated using weighted kappa statistics. In addition to this, the evaluator size score of the SWMT was assessed with Bland-Altman analysis to evaluate systematic bias. The Stroke Impairment Assessment Set (SIAS) sensory items were used to assess validity, and Spearman's rank correlation coefficients were calculated. Results: Intra/inter-rater agreements of the SWMT grade score were 0.89 (thumb, 95%CI: 0.83-0.95)/ 0.75 (0.60-0.91) and 0.80 (index finger, 0.67-0.93)/0.79 (0.66-0.92), and of the TLT they were 0.83 (navel level proximal space, 0.71-0.95)/ 0.83 (0.73-0.92), 0.90 (navel level distal space, 0.85-0.96)/ 0.80 (0.69-0.90), 0.80 (shoulder level proximal space, 0.68-0.92)/ 0.77 (0.65-0.89), and 0.87 (shoulder level distal space, 0.80-0.93)/ 0.80 (0.68-0.92) (P < 0.001, each item). All of them showed substantial agreement, but the MDC of the SWMT evaluator size was 1.28 to 1.79 in the inter-rater test and 1.94-2.06 in the intra-rater test. The SWMT grade score showed a strong correlation with the SIAS light touch sensation item (r = 0.65, p < 0.001), as did the TLT with the SIAS position sense item (r = -0.70-0.62, p < 0.001 each space). Conclusions: The reliability and validity of the SWMT and the TLT were verified. These tests can be used as reliable sensory examinations of the UE in patients with chronic stroke, and especially for the SWMT, it is more reliable for screening.

Estimating nutrition intake status of community-dwelling elderly people requiring care in disaster settings: A preliminary cross-sectional survey.

OBJECTIVE: There are a lack of disaster preparedness measures that target populations with dysphagia. In particular, disaster response plans frequently overlook differences in textures between emergency foods and regularly consumed foods. The aim of this study was to estimate the number of community-dwelling elderly care recipients requiring specific food preparations, including the population at risk of aspiration when solely consuming common emergency foods. DESIGN: A cross-sectional study. PATIENTS: Community-dwelling elderly care recipients who were certified by the public long-term care insurance system in Japan and registered at one of 77 care managing offices in Shinjuku city. METHODS: Special needs regarding food intake and risks associated with receiving emergency foods were assessed by government-certified care managers. RESULTS: Data were acquired from 1,271 care recipients. Notably, 23.1% of the sampled population had special needs regarding food intake at all times (e.g. non-oral intake or need for texture-modified foods). An additional 11.5% were estimated to experience difficulty when ingesting common emergency foods, despite the ability to consume regular foods. CONCLUSION: A relatively large portion of community-dwelling elderly people will be at risk of aspiration due to the intake of commonly distributed emergency foods following a disaster. Appropriate preparation based on an assessment of special needs regarding food intake is therefore required when planning for future disasters.

Determinants of Incomplete Asthma Control in Patients with Allergic Rhinitis and Asthma.

BACKGROUND: Characterizing associations between the upper and lower airways is important for asthma management. OBJECTIVES: This study aimed to assess the determinants of incomplete asthma control in patients with allergic rhinitis (AR) and asthma. METHODS: Multiple factors including age, sex, atopy, smoking history, medication use, Asthma Control Questionnaire (ACQ) score, FEV1, fraction of exhaled nitric oxide (Feno), and rhinitis questionnaire score were examined. AR was defined by rhinitis symptoms and the sensitization to inhaled allergens. ACQ was used to dichotomize the subjects into the incompletely controlled group (ACQ score ≥0.75) and the well-controlled group. The factors that contribute to incomplete asthma control were assessed by a multivariate analysis. RESULTS: A total of 260 patients with AR and asthma were enrolled and 108 patients (42%) were classified as incomplete asthma control. The incompletely controlled group was older (P < .05), and had more airflow limitation, more airway inflammation, and more severe rhinitis symptoms (all P < .001). In contrast, the well-controlled group was more likely to be taking nasal corticosteroids (NCSs) (P < .01). In a multivariate model adjusted by age, asthma treatment, airflow limitation, and Feno, persistence and severity of rhinitis (odds ratio [OR], 2.57; 95% CI, 1.41-4.70, and OR, 2.00; 95% CI, 1.10-3.65) and nonuse of NCSs (OR, 3.83; 95% CI, 1.50-9.81) were independently associated with incomplete asthma control. CONCLUSIONS: The persistence and severity of AR and the use of NCSs were associated with the level of asthma control in patients with AR and asthma. Further studies are required to determine whether appropriate treatment of rhinitis would improve asthma control.

Persistently high exhaled nitric oxide and loss of lung function in controlled asthma.

BACKGROUNDS: It remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function. METHODS: This was a 3-year prospective study. We examined the changes in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1) and FeNO in 140 patients with controlled asthma. We initially determined the FeNO cut-off point for identifying patients with a rapid decline in FEV1 (>40 mL/yr). Next, a total of 122 patients who maintained high or non-high FeNO were selected, and the associations between the FeNO trend and changes in FEV1 and bronchodilator response (BDR) were investigated. RESULTS: A FeNO level >40.3 ppb yielded 43% sensitivity and 86% specificity for identifying patients with a rapid decline in FEV1. Patients with persistently high FeNO had higher rates of decline in FEV1 (42.7 ± 37.5 mL/yr) than patients with non-high FeNO (16.7 ± 31.5 mL/yr) (p < 0.0005). The changes in BDR from baseline to the end of the study, in patients who had high or non-high levels of FeNO were -0.8% and 0.1%, respectively (p < 0.01). In a multivariate analysis adjusted by age, body mass index, asthma control, blood eosinophil numbers, and FEV1% of predicted, a FeNO level of ≥40 ppb was independently associated with an accelerated decline in FEV1 (p < 0.05). CONCLUSIONS: This study suggests that FeNO is potentially valuable tool for identifying individuals who are at risk of a progressive loss of lung function among patients with controlled asthma.

Progression of Irreversible Airflow Limitation in Asthma: Correlation with Severe Exacerbations.

BACKGROUND: Severe exacerbations of asthma are periods of excess functional and pathological changes in the airways that have been proposed to induce airway remodeling. OBJECTIVE: The objective of this study was to explore whether severe exacerbations are correlated with the decline in post-bronchodilator forced expiratory volume in 1 second (FEV1) and loss of bronchodilator reversibility (BDR). METHODS: We examined the changes in FEV1 and BDR in 140 nonsmoking patients with well-controlled asthma at baseline and correlated these changes with the frequency of severe asthma exacerbations. RESULTS: A 3-year follow-up assessment was completed in 128 patients. A total of 28 (21.9%) patients experienced at least 1 severe exacerbation with a mean rate of 0.16 year(-1). The exacerbation rate was significantly correlated with an annual rate of decline in FEV1 (ρ = 0.49, P < .0001). Both patients with 1 exacerbation and those with 2 or more exacerbations had greater declines in FEV1 than patients with no exacerbations (no exacerbation, 13.6 mL/year; 1 exacerbation, 41.3 mL/year; 2 or more exacerbations, 58.3 mL/year; P < .01 and P < .0001, respectively). The changes in BDR from baseline to the end of the study in patients who did or did not experience an exacerbation were -1.2% and 0.1%, respectively (P < .0005). The changes in BDR were significantly correlated with the annual rates of change in FEV1 (r = 0.40, P < .0001). CONCLUSION: The occurrence of severe exacerbations of asthma is correlated with the progression of irreversible airflow limitation over time. This suggests that asthma exacerbations could have the long-term adverse consequences of structural and functional changes in the airways.

Noncompetitive immunoassay detection system for haptens on the basis of antimetatype antibodies.

BACKGROUND: Small molecules classified as haptens are generally measured by competitive immunoassay, which is theoretically inferior to noncompetitive sandwich immunoassay in terms of sensitivity and specificity. We created a method for developing sandwich immunoassays to measure haptens on the basis of antimetatype antibodies. METHODS: We generated antimetatype monoclonal antibodies against a hapten-antibody immunocomplex using an ex vivo antibody development system, the Autonomously Diversifying Library (ADLib) system. We selected 2 haptens, estradiol (E2) and 25-hydroxyvitamin D [25(OH)D], as analytes. Sandwich immunoassays for these 2 haptens were developed by use of a 96-well microtiter plate and a fully automated chemiluminescence analyzer, and the performances of these immunoassays were investigated. RESULTS: The developed assays exhibited sensitivity high enough to detect target haptens in serum samples. The limit of detection of the ELISA for E2 was 3.13 pg/mL, and that of the fully automated chemiluminescent enzyme immunoassay (CLEIA) system was 2.1 ng/mL for 25(OH)D. The cross-reactivity with immunoreactive derivatives was effectively improved compared with the competitive assay. The CVs for the sandwich ELISA for E2 were 4.2%-12.6% (intraassay) and 6.2%-21.8% (total imprecision). The CVs for the sandwich CLEIA for 25(OH)D were 1.0%-2.3% (intraassay) and 1.9%-3.5% (total imprecision). In particular, the sandwich CLEIA for 25(OH)D showed correlations of r = 0.99 with both LC-MS/MS and a commercially available (125)I RIA. CONCLUSIONS: Our method represents a potentially simple and practical approach for routine assays of haptens, including vitamins, hormones, drugs, and toxins.

Changes in forced expiratory volume in 1 second over time in patients with controlled asthma at baseline.

BACKGROUND: A predominant feature of asthma is an accelerated rate of decline in forced expiratory volume in 1 s (FEV1), but data on the variability and factors associated with this change in patients with controlled asthma are largely unknown. METHODS: 140 patients with controlled asthma were enrolled based on the Global Initiative for Asthma guidelines. We examined the data of a prospective analysis of the association between asthma control and change in FEV1 over time. RESULTS: A 3-year follow-up assessment was completed in 128 patients. The mean rate of change in FEV1 was a decline of 22.2 mL yr(-1), with significant variation in the levels of change. The between patient standard deviation for the rate of decline was 34.1 mL yr(-1). We next classified the subjects of less than the 25th percentile as rapid decliners, and greater than the 25th percentile as non-rapid decliners. The decrease in the Asthma Control Test score over a 3-year period was higher for rapid decliners than that for non-rapid decliners (p < 0.001). The rapid decliner was more likely to be older, to have higher levels of FeNO, and to have had severe exacerbations during the study. Patients with severe exacerbations had a greater annual decline in FEV1 compared to patients with no exacerbations (-13.6 vs. -53.2 mL yr(-1), p < 0.0001). CONCLUSIONS: Among patients with controlled asthma at baseline, the rate of change in FEV1 is highly variable. Severe exacerbations are strongly associated with a rapid loss of lung function.

TLR3 activation augments matrix metalloproteinase production through reactive nitrogen species generation in human lung fibroblasts.

Viral infection often triggers asthma exacerbation and contributes to airway remodeling. Cell signaling in viral infection is mainly mediated through TLR3. Many mediators are involved in airway remodeling, but matrix metalloproteinases (MMPs) are key players in this process in asthma. However, the role of TLR3 activation in production of MMPs is unknown. In this study, we examined the effects of polyinosinic-polycytidylic acid [poly(I:C)], a ligand for TLR3, on production of MMPs in human lung fibroblasts, with a focus on nitrosative stress in TLR3 modulation of MMP production. After lung fibroblasts were treated with poly(I:C), production of MMP-1, -2, and -9 and inducible NO synthase (iNOS) was assessed. The roles of NF-κB and IFN regulatory factor-3 (IRF-3) in the poly(I:C)-mediated production of MMPs and the responsiveness to poly(I:C) of normal lung fibroblasts and asthmatic lung fibroblasts were also investigated. Poly(I:C) augmented production of MMPs and iNOS in fibroblasts, and an iNOS inhibitor diminished this production of MMPs. Poly(I:C) stimulated translocation of NF-κB and IRF-3 into the nucleus in fibroblasts and inhibition of NF-κB or IRF-3 abrogated the poly(I:C)-induced increase in both iNOS expression and release of MMPs. Poly(I:C)-induced production of iNOS and MMPs was greater in asthmatic fibroblasts than in normal fibroblasts. We conclude that viral infection may induce nitrosative stress and subsequent MMP production via NF-κB- and IRF-3-dependent pathways, thus potentiating viral-induced airway remodeling in asthmatic airways.

Ongoing allergic rhinitis impairs asthma control by enhancing the lower airway inflammation.

BACKGROUND: The relationship between allergic rhinitis and asthma is well accepted; however, little is known about the mechanism that underlies the interactions between the upper and lower airways. OBJECTIVE: To investigate the symptomatic and inflammatory linkages between allergic rhinitis and asthma in patients with atopy. METHODS: We enrolled 520 patients with asthma who were taking inhaled corticosteroids, and examined them by using the Asthma Control Questionnaire, spirometry, exhaled nitric oxide fraction (FENO), visual analog scale for nasal symptoms, allergic rhinitis questionnaire, and serum specific IgE (study 1). The symptomatic and inflammatory marker responses to nasal corticosteroids in patients with incompletely controlled asthma (Asthma Control Questionnaire > 0.75) and moderate-to-severe persistent allergic rhinitis were also observed (study 2). RESULTS: A total of 348 patients (66.9%) had atopy and allergic rhinitis. There was a striking difference in the proportion of patients with incomplete asthma control, depending on the presence as well as the activity of rhinitis (no rhinitis, 11.0%; mild intermittent, 20.4%; moderate-to-severe intermittent, 44.6%; mild persistent, 53.1%; moderate-to-severe persistent, 65.7%). The FENO levels were increased with the activity of rhinitis, and the nasal visual analog scale was positively correlated with the FENO levels (r = 0.31; P < .0001). The additive treatment with nasal corticosteroids improved the nasal visual analog scale, Asthma Control Questionnaire, and FENO levels, and the changes in these variables were correlated with each other in all parameters (all P < .001). CONCLUSION: This observational study of patients with atopy indicates that the ongoing allergic rhinitis is related to worsening of asthma by enhancing the lower airway inflammation.

Development of a sphingosylphosphorylcholine detection system using RNA aptamers.

Sphingosylphosphorylcholine (SPC) is a lysosphingolipid that exerts multiple functions, including acting as a spasmogen, as a mitogenic factor for various types of cells, and sometimes as an inflammatory mediator. Currently, liquid chromatography/tandem mass spectrometry (LC/MS/MS) is used for the quantitation of SPC. However, because of the complicated procedures required it may not be cost effective, hampering its regular usage in a routine practical SPC monitoring. In this report, we have generated RNA aptamers that bind to SPC with high affinity using an in vitro selection procedure and developed an enzyme-linked aptamer assay system using the minimized SPC aptamer that can successfully distinguish SPC from the structurally related sphingosine 1-phosphate (S1P). This is the first case of the Systematic Evolution of Ligands by EXponential enrichment (SELEX) process being performed with a lysosphingolipid. The SPC aptamers would be valuable tools for the development of aptamer-based medical diagnosis and for elucidating the biological role of SPC.

The actin-related protein hArp8 accumulates on the mitotic chromosomes and functions in chromosome alignment.

The actin family consists of conventional actin and various actin-related proteins (Arps). Some of these Arps are localized in the nucleus, and a fraction of each of these nuclear Arps is functionally involved in chromatin remodeling and histone acetyltransferase complexes. On the other hand, in mitotic cells, the localization and function of the nuclear Arps are largely unknown. Human Arp8 (hArp8), an ortholog of yeast nuclear Arp8, was recently found to be associated with the hINO80-chromatin remodeling complex along with hArp5. Here we report that hArp8, but not hArp5, accumulates on mitotic chromosomes. This is the first example where a member of the actin family is found to be associated with mitotic chromosomes. Expression of truncated hArp8 proteins and depletion of endogenous hArp8 by RNA interference caused misalignment of mitotic chromosomes, suggesting that chromosome-associated hArp8 has a role in chromosome behavior. In contrast, depletion of hIno80 and hArp5 did not cause misalignment of chromosomes, suggesting that the role of hArp8 at mitotic chromosomes is independent of the activity of hINO80 complexes. These findings provide the first insight into a novel function of actin family members in mitosis.