Motor flexibility to stabilize the toe position during obstacle crossing in older adults: an investigation using an uncontrolled manifold analysis.

Introduction: An age-related decrease in the ability to exploit the abundant degrees of freedom of the body, referred to as motor flexibility, leads to a heightened fall risk. The present study investigated motor flexibility to stabilize the toe position during obstacle crossing in older adults and its correlation with the magnitude of foot elevation. Methods: Twenty-six older adults (70.9 ± 7.4 years old) and 21 younger adults (25.4 ± 5.0 years old) walked and crossed an obstacle, during which the dominant limb was always the leading limb. An uncontrolled manifold (UCM) analysis was used to quantify the flexibility during obstacle crossing as the synergy index, with the vertical toe position being regarded as the performance variable and the segment angles of the lower limbs as the elemental variables. Results and discussion: The results showed that older participants had a significantly lower synergy index for the trailing limb before the moment of obstacle crossing than younger participants, suggesting reduced flexibility in part. The results also showed that, regardless of age, foot elevation was negatively correlated with the synergy index, suggesting that a so-called "conservative strategy" (i.e., a tendency to show extraordinarily high foot elevation to ensure collision avoidance) may be related to their reduced motor flexibility.

Effect of the Visual Illusion on Stepping-Over Action and Its Association with Gaze Behavior.

An adequate foot clearance height while stepping over an obstacle is important for safety in daily life. In the present study, we examined whether visual illusions affect foot clearance during a stepping-over action, and whether this is further influenced by gaze behavior. Twelve participants stepped over an obstacle placed four meters away under conditions of three different obstacle characteristics: white, horizontal, or vertical lines. We measured the participants' foot clearances during the step-over action and their gaze behavior during the approaching phase. Participants stepped significantly higher over the obstacles in the vertical lines (illusion) condition. The duration of gaze fixation on the obstacle positively correlated with increased foot clearance in the vertical condition, suggesting that the effect of the visual illusion on foot clearance was enhanced by prolonged gaze fixation. Conversely, prolonged fixation negatively correlated with foot clearance in the white (control) condition, implying that a cautious perception of an obstacle may contribute to efficient stepping-over action.

Approaching Process in Walking through an Aperture for Individuals with Stroke.

Muroi et al. show that individuals with stroke have improved collision avoidance behavior when passing through an aperture while entering from the paretic-side of the body. However, the underlying mechanism remains unknown. We reanalyzed Muroi et al.'s data to reveal how individuals with stroke walk through an aperture by examining changes in walking velocity and behavioral complexity (i.e., sample entropy, an index of (ir)regularity of time series, regarded lower entropy as more regular and less complex) by focusing on the approaching process. The results showed that individuals with stroke reduced their walking velocity and behavioral complexity before passing through the narrow aperture when approaching from the paretic side. We interpreted that the improved obstacle avoidance when penetrating from the paretic side may be due to careful body rotation and adjusting the walking velocity in advance.

Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases.

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4+ cTfh cells were significantly decreased and the percentage of IFN-γ+ cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR.

Effect of auditory deprivation on adaptive locomotion: Interaction with lower visual field occlusion.

Auditory stimuli have been suggested to play a role in adequately controlling movement; however, their influence is not fully understood, particularly regarding dynamic behaviors, such as adaptive locomotion. This study aimed to investigate whether auditory deprivation affects adaptive locomotion. In particular, we aimed to elucidate the role of the auditory sense in obstacle avoidance by manipulating the visual field, which provides crucial sensory information for movement control. Sixteen participants approached a 15-cm obstacle located 6 m away and stepped over it under four different conditions that combined two factors: the hearing condition controlled by wearing earmuffs with and without holes, and the lower visual field condition controlled by carrying opaque white and transparent boards. Spatiotemporal variables during the approach to the obstacle were measured using an electronic walkway, whereas foot clearance over the obstacle was assessed using a motion-capture system. Participants who experienced auditory deprivation and lower visual field occlusion demonstrated greater variability in step length when approaching the obstacle compared with the other conditions. The leading and trailing foot clearances were higher under lower visual field occlusion conditions. Furthermore, when participants were under conditions of auditory deprivation, greater variability was observed in the clearance of the leading foot. These results suggest that auditory information contributes to movement stabilization during adaptive locomotion. Our findings provide evidence that auditory and visual senses complement each other during motor actions, indicating that adaptive locomotion can be influenced by the integration of multiple sensory inputs.

Coronavirus Disease 2019 Vaccine-Induced Flare-Up of Severe Bronchial Asthma Previously Controlled With Dupilumab: A Case Report.

The widespread after-effects of the coronavirus disease 2019 (COVID-19) are still a grave threat worldwide. Among them are adverse reactions to vaccines, including those most observed following Pfizer-BioNTech (BNT162b2) vaccine administration, namely, local reactions at the injection site, fatigue, headache, myalgia, chills, arthralgia, and fever. Patients with asthma particularly present with unique adverse reactions to the BNT162b2 vaccine, notably, an exacerbation in their asthma symptoms as highlighted through the current case report. In this case, a 50-year-old woman had been undergoing treatment for bronchial asthma in the form of inhalation steroids and dupilumab, as well as systemic steroid prednisolone as maintenance therapy. She had mild injection site reactions after her first three COVID-19 vaccinations. She also experienced acute exacerbation requiring hospitalization after the fourth and fifth doses. Her symptoms resolved following steroid therapy. The close association between the timing of vaccinations and the onset of clinical symptoms suggests that the exacerbation episodes were triggered by the vaccine. Therefore, although the BNT162b2 vaccine is safe to administer in patients with bronchial asthma, cases reporting patients sensitized to the BNT162b2 vaccine developing bronchial asthma or experiencing asthma exacerbations should not be neglected. Clinicians should be aware of the possibility of flare-ups induced by repeated COVID-19 vaccinations in such patients.

Pneumocystis Pneumonia Infection Following the Initiation of Pembrolizumab Therapy for Lung Adenocarcinoma.

Pneumocystis pneumonia (PCP) is an opportunistic infection that presents a ground-glass appearance in the lungs on chest radiography. Interstitial lung disease is a commonly reported adverse effect of immune checkpoint inhibitor (ICI) treatment; however, there are few reports of ICI treatment-associated PCP infection. A 77-year-old man with lung adenocarcinoma was administered pembrolizumab and hospitalized for dyspnea 2 weeks after treatment. Chest computed tomography showed bilateral ground-glass opacities in all lung lobes. PCP was therefore diagnosed, and steroids and sulfamethoxazole-trimethoprim were initiated. Following treatment, the patient's condition improved promptly. This report suggests that ICI treatment can cause PCP infection.

Relationship between adaptability during turning and the complexity of walking before turning in older adults.

In this study, the relationship between behavioral complexity (sample entropy, SEn) during steady walking and the quickness of subsequent turning performance in older adults. Herein, healthy older and younger adults (n = 12 each) were instructed to walk straight and then turn into an intersection surrounded by four pylons. This walking task was performed under two turning conditions: reactive and pre-planned turning, where the direction of turning was unknown until immediately before turning or was informed beforehand, respectively. For older adults, behavioral complexity was comparable under both conditions, but was higher under reactive than pre-planned turning condition for younger adults. This suggests that older adults cannot adapt their walking patterns in response to turning conditions. Correlation analysis showed that older adults with lower SEn had more difficulty in turning rapidly under reactive turning condition, indicating a relationship between the two variables. Thus, deterioration of the reactive turning performance in older adults is related to stereotyped movements during steady walking.

Programmed Death-Ligand 1-Positive Squamous Cell Carcinoma Spontaneously Regressed after Percutaneous Needle Biopsy.

Spontaneous lung cancer regression is a very rare course of disease. A 60-year-old male patient was admitted to our hospital with pneumonia and a 19 mm-sized nodule shadow in the S4 of the left lung on chest computed tomography (CT). A percutaneous needle biopsy was performed, and a diagnosis of programmed death-ligand 1-positive squamous cell lung carcinoma was made based on pathological findings. The patient was followed up with imaging because the lesion has reduced in size on chest CT. We report the possibility that cellular immune mechanisms triggered by needle biopsy contributed to spontaneous regression.

Fractal Dynamics in a Whole-Body Dynamic Balance Sport, Slacklining: A Comparison of Novices and Experts.

The present study investigated whether fractal dynamics can be observed during single-leg standing on a slackline. We also examined whether the temporal structure differs with skill level. To address these questions, we compared single-leg standing performance between novices (N=5) and experts (N=5) in terms of fractal dynamics in both ankles (i.e., stance and swing legs), center of mass, and head acceleration time series using detrended fluctuation analysis. Participants were required to perform single-leg standing on a slackline. To collect motion data while slacklining, we used a three-dimensional motion capture system and obtained time-series data on the position. We conducted detrended fluctuation analysis on the original acceleration time series and random shuffled time series to examine the fractal dynamics in each body part's fluctuation. Results suggest that experts showed persistent temporal structure in the swinging leg, center of mass, and head fluctuations in the horizontal direction, while that of novices did not differ from random fluctuations. These findings revealed that experts performing a single-leg standing task on a slackline show fractal dynamics. This might reflect their flexible or adaptive exploratory behavior in the performer-environment system and contribute to the dynamic stability of whole-body dynamic balancing.

Impact of Joint Fixation on Postural Dynamics during Single-Leg Stance.

We investigated the relationship between the mechanical degrees of freedom (DoF) and its postural dynamics. The joint DoF was fixed to constrain the mechanical DoF. Nine participants were required to perform a single-leg stance task. The center of pressure trajectory data was analyzed. Ankle fixation induced a larger amount of variability in the anteroposterior direction, and less dimensionality and complexity in the mediolateral direction. These results suggest that the ankle joint fixation caused limited postural sway in the mediolateral direction; therefore, functional DoF and complexity decreased. In contrast, it increased the amount of postural sway variability in the anteroposterior direction. Our findings imply a direct relationship between the mechanical DoF of the human movement system and its postural dynamics.

The influence of a vibrotactile biofeedback system on postural dynamics during single-leg standing in healthy older adults.

The effectiveness of sensory substitution technology, such as haptic-based vibrotactile biofeedback (VBF), has been verified for balance training and rehabilitation. However, whether VBF training changes postural dynamics in older people remains unknown. This study investigated the influence of VBF training on postural dynamics during single-leg standing in older adults, using detrended fluctuation analysis (DFA). Twenty older adults participated in this study. Measurement of postural sway comprised three phases: first measurement session as a baseline test, postural training (day 1), and second measurement session (day 2). The BF group received BF training during the balance training session, while the control group practiced single-leg stance without BF. The center of pressure (CoP) trajectory was recorded in the first measurement session (pre) and second measurement session (post) at 50 Hz. DFA revealed the presence of two linear scaling regions in the CoP, indicating the presence of fast- and slow-scale fluctuations. For the BF group, slow-scale postural dynamics revealed more anti-persistent behavior after training in the anterior-posterior direction. However, the control group showed a change toward more random dynamics after training. These different influences suggest that the BF system might improve error correction strategies during single-leg standing for older adults, while single-leg standing training without the BF system might cause the loss of controllability in single-leg standing. Further, the results of the DFA are discussed in the context of balance training using VBF.

Adaptive locomotion during subtle environmental changes in younger and older adults.

For older adults especially, to perform everyday activities safely, adaptive locomotion that adjusts basic locomotion pattern according to the environmental features is critical. It is unknown, however, whether their locomotor patterns can be modified when there are subtle environmental changes. We examined adaptive limb movements, focusing on obstacle avoidance and age-related changes during such situations. Younger (102, with a mean age of 27.5 years) and older (101, with a mean age of 78.3 years) participants walked across one obstacle (150 mm height) four different times. The obstacles were then covertly raised or lowered by 10% of the baseline obstacle height (i.e., 165 mm for ascending and 135 mm for descending conditions), and participants were asked to repeat the activity. We measured leading and trailing foot clearances, the vertical distances between toe tips and the upper edge of the obstacle. In the ascending condition, both groups adjusted and raised their limb clearance according to the obstacle height change. Alternatively, foot clearance of the leading limb for the lowered obstacle did not change among the older adults, whereas it changed in the young adults (lowered their clearance). No changes were observed in the trailing foot clearance for the descending conditions in either age group. Our results suggest that when facing environmental changes that compromise safe mobility, individuals can adapt leading limb movement based on subtle environmental changes, irrespective of age. In case of other changes (i.e., in low-risk situations), however, the ability of adaptive locomotion may be affected by aging.

Incidence and risk factors for hyperkalaemia in patients treated for COVID-19 with nafamostat mesylate.

WHAT IS KNOWN AND OBJECTIVE: Nafamostat mesylate (NM) is used clinically in combination with antiviral drugs to treat coronavirus disease (COVID-19). One of the adverse events of NM is hyperkalaemia due to inhibition of the amiloride-sensitive sodium channels (ENaC). The incidence and risk factors for hyperkalaemia due to NM have been studied in patients with pancreatitis but not in COVID-19. COVID-19 can be associated with hypokalaemia or hyperkalaemia, and SARS-CoV-2 is thought to inhibit ENaC. Therefore, frequency and risk factors for hyperkalaemia due to NM may differ between COVID-19 and pancreatitis. Hyperkalaemia may worsen the respiratory condition of patients. The objective of this study was to determine the incidence and risk factors for hyperkalaemia in COVID-19 patients treated with favipiravir, dexamethasone and NM. METHODS: This retrospective study reviewed the records of hospitalized COVID-19 patients treated with favipiravir and dexamethasone, with or without NM, between March 2020 and January 2021. Multivariable logistic regression analysis was performed to identify the risk factors for hyperkalaemia. RESULTS AND DISCUSSION: Of 45 patients who received favipiravir and dexamethasone with NM for the treatment of COVID-19, 21 (47%) experienced hyperkalaemia. The duration of NM administration was a significant predictor of hyperkalaemia (odds ratio: 1.55, 95% confidence interval: 1.04-2.31, p = 0.031). The receiver-operating characteristic curve analysis determined that the cut-off value for predicting the number of days until the onset of hyperkalaemia was 6 days and the area under the curve was 0.707. WHAT IS NEW AND CONCLUSION: This study revealed that the incidence of hyperkalaemia is high in patients treated for COVID-19 with NM, and that the duration of NM administration is a key risk factor. When NM is administered for the treatment of COVID-19, it should be discontinued within 6 days to minimize the risk of hyperkalaemia.

Association of age-related cognitive and obstacle avoidance performances.

An association between cognitive impairment and tripping over obstacles during locomotion in older adults has been suggested. However, owing to its memory-guided movement, whether this is more pronounced in the trailing limb is poorly known. We examined age-related changes in stepping over, focusing on trailing limb movements, and their association with cognitive performance. Age-related changes in obstacle avoidance were examined by comparing the foot kinematics of 105 older and 103 younger adults when stepping over an obstacle. The difference in the clearance between the leading and trailing limbs (Δ clearance) was calculated to determine the degree of decrement in the clearance of the trailing limb. A cognitive test battery was used to evaluate cognitive function among older adults to assess their association with Δ clearance. Older adults showed a significantly lower clearance of the trailing limb than young adults, resulting in greater Δ clearance. Significant correlations were observed between greater Δ clearance and scores on the Montreal Cognitive Assessment and immediate recall of the Wechsler Memory Scale-Revised Logical Memory test. Therefore, memory functions may contribute to the control of trailing limb movements, which can secure a safety margin to avoid stumbling over an obstacle during obstacle avoidance locomotion.

An Approach to Aligning Categorical and Continuous Time Series for Studying the Dynamics of Complex Human Behavior.

An emerging perspective on human cognition and performance sees it as a kind of self-organizing phenomenon involving dynamic coordination across the body, brain and environment. Measuring this coordination faces a major challenge. Time series obtained from such cognitive, behavioral, and physiological coordination are often complicated in terms of non-stationarity and non-linearity, and in terms of continuous vs. categorical scales. Researchers have proposed several analytical tools and frameworks. One method designed to overcome these complexities is recurrence quantification analysis, developed in the study of non-linear dynamics. It has been applied in various domains, including linguistic (categorical) data or motion (continuous) data. However, most previous studies have applied recurrence methods individually to categorical or continuous data. To understand how complex coordination works, an integration of these types of behavior is needed. We aimed to integrate these methods to investigate the relationship between language (categorical) and motion (continuous) directly. To do so, we added temporal information (a time stamp) to categorical data (i.e., language), and applied joint recurrence analysis methods to visualize and quantify speech-motion coordination coupling during a rap performance. We illustrate how new dynamic methods may capture this coordination in a small case-study design on this expert rap performance. We describe a case study suggesting this kind of dynamic analysis holds promise, and end by discussing the theoretical implications of studying complex performances of this kind as a dynamic, coordinated phenomenon.

Bimanual Coordination in a Whole-Body Dynamic Balance Sport, Slacklining: A Comparison of Novice and Expert.

As previous studies have suggested that bimanual coordination is important for slacklining, the authors questioned whether this important skill plays a role in the performance of a fundamental task of slacklining. To address this question, the authors compared single-leg standing on the slackline between novices and experts in terms of bimanual coordination dynamics within a dynamical systems framework using relative phase and recurrence quantification analysis measures. Five novices and five experts participated in the experiment. Participants were required to perform single-leg standing on a slackline. To collect motion data while slacklining, the authors used a 3D motion capture system and obtained time series data on the wrist position of both hands. The authors compared bimanual coordination dynamics between novices and experts. Although this preliminary study was limited in its sample size, the results suggest that experts tend to show a more antiphase coordination pattern than novices do and that they can more sustainably coordinate their hands compared with novices in terms of temporal structure in diagonal-related recurrence measures (i.e., maxline, mean line, and percentage determinism).

A case of tracheal pleomorphic adenoma misdiagnosed as asthma.

A 51-year-old woman had an incidental finding of a tracheal tumor during oesophagogastroduodenoscopy following the diagnosis of asthma for 2 months. A computed tomography scan revealed a 15-mm tumor in the subglottis. Endoscopic resection was performed safely, and pleomorphic adenoma was diagnosed histologically. The patient's condition was satisfactory 30 months after the procedure. Tracheal pleomorphic adenoma is rare and may be misdiagnosed as asthma. If the tumor is large, surgery may be required; however, endoscopic polypectomy may be effective if the tumor is small. Therefore, early diagnosis of tracheal pleomorphic adenoma is important. At the first visit, the flow-volume curve suggested upper airway obstruction, which should have raised the suspicion of an upper airway obstruction. In patients with suspected asthma, early pulmonary function testing is needed to substantiate asthma diagnosis and prevent an alternative diagnosis being missed.

Feasibility of rapid on-site cytological evaluation of lung cancer by a trained pulmonologist during bronchoscopy examination.

OBJECTIVE: Rapid on-site cytological evaluation (ROSE) in bronchoscopy is a useful ancillary technique. ROSE is usually performed by a cytopathologist or cytotechnologist. However, because of staff shortages and reduced availability, ROSE cannot be performed in every hospital. We aimed to evaluate the accuracy of ROSE when performed by a trained pulmonologist, comparing the diagnosis results with the final diagnosis of cytopathologists. METHODS: We performed a retrospective cohort study on 125 patients who underwent bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endobronchial ultrasonography with a guide sheath (EBUS-GS) for peripheral pulmonary lesions by conventional bronchoscopy at Sapporo Medical University Hospital between March 2012 and September 2018. ROSE was performed by a pulmonologist who was trained by a cytotechnologist for a total of 1 month. DiffQuik® staining for ROSE was used to prepare cytology slides. The results of ROSE were compared with the final diagnosis obtained using Papanicolaou staining by cytopathologists. RESULTS: In all procedures, the sensitivity, specificity and diagnostic accuracy of ROSE were 88.5%, 83.0% and 86.4%, respectively. There was no significant difference in the sensitivity, specificity, positive predictive value, negative predictive value or accuracy between EBUS-TBNA and EBUS-GS. CONCLUSIONS: ROSE of lung cancer by a trained pulmonologist can be highly accurate and deemed as feasible and useful for not only EBUS-TBNA but also EBUS-GS.

Balance Training With a Vibrotactile Biofeedback System Affects the Dynamical Structure of the Center of Pressure Trajectories in Chronic Stroke Patients.

Haptic-based vibrotactile biofeedback (BF) is a promising technique to improve rehabilitation of balance in stroke patients. However, the extent to which BF training changes temporal structure of the center of pressure (CoP) trajectories remains unknown. This study aimed to investigate the effect of vibrotactile BF training on the temporal structure of CoP during quiet stance in chronic stroke patients using detrended fluctuation analysis (DFA). Nine chronic stroke patients (age; 81.56 ± 44 months post-stroke) received a balance training regimen using a vibrotactile BF system twice a week over 4 weeks. A Wii Balance board was used to record five 30 s trials of quiet stance pre- and post-training at 50 Hz. DFA revealed presence of two linear scaling regions in CoP indicating presence of fast- and slow-scale fluctuations. Averaged across all trials, fast-scale fluctuations showed persistent dynamics (α = 1.05 ± 0.08 for ML and α = 0.99 ± 0.17 for AP) and slow-scale fluctuations were anti-persistent (α = 0.35 ± 0.05 for ML and α = 0.32 ± 0.05 for AP). The slow-scale dynamics of ML CoP in stroke patients decreased from pre-training to post-BF training (α = 0.40 ± 0.13 vs. 0.31 ± 0.09). These results suggest that the vibrotactile BF training affects postural control strategy used by chronic stroke patients in the ML direction. Results of the DFA are further discussed in the context of balance training using vibrotactile BF and interpreted from the perspective of intermittent control of upright stance.