Adverse clinical events after percutaneous coronary intervention in very elderly patients with acute coronary syndrome.

The number of very elderly patients with acute coronary syndrome (ACS) is increasing. Therefore, owing to the need for evidence-based treatment decisions in this population, this study aimed to examine the clinical outcomes during 1 year after percutaneous coronary intervention (PCI) in very elderly patients with ACS. This prospective multicenter observational study comprised 1337 patients with ACS treated with PCI, classified into the following four groups according to age: under 60, <60 years; sexagenarian, ≥60 and <69 years; septuagenarian, ≥70 and <80 years; and very elderly, ≥80 years. The primary endpoint was a composite of the first occurrence of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and bleeding within 1 year after PCI. We used the sexagenarian group as a reference and compared outcomes with those of the other groups. The incidence of the primary endpoint was significantly higher in the very elderly group than in the sexagenarian group (36 [12.7%] vs. 24 [6.9%], respectively; hazard ratio, 1.94; 95% confidence interval: 1.16-3.26; p = 0.012). The higher incidence of the primary endpoint was primarily driven by a higher incidence of all-cause death. When the multivariable analysis was used to adjust for patient characteristics and comorbidities, no difference was observed in the primary endpoint between the very elderly and sexagenarian groups (p = 0.96). The incidence of adverse events after PCI, particularly all-cause death, in very elderly patients with ACS was high. However, if several confounders are adjusted, comparable outcomes may be expected within 1 year after PCI among this population.

Characteristics of successful termination of atrial fibrillation by atrial antitachycardia pacing in patients with cardiac implantable electronic devices.

Asymptomatic paroxysmal atrial fibrillation (AF) is often found in patients implanted with cardiac implantable electronic devices (CIEDs). Second-generation atrial antitachycardia pacing (A-ATP) is effective in managing AF in patients implanted with CIEDs. The purpose of this study was to evaluate the efficacy and safety of A-ATP in patients implanted with CIEDs. This was a single-center retrospective study involving 91 patients (male 46 patients, mean age 74 ± 9 years) implanted with Reactive A-ATP equipped devices (84 patients with pacemakers, 6 with ICDs, and 1 with a CRT-D). The AF burden, rate of AF termination, and details of the activation of the A-ATP were analyzed in each patient. During a mean follow-up period of 21 ± 13 months, A-ATP was activated in 45 of 91 patients (49.5%). No patients had adverse events. Although the efficacy of the A-ATP varied among the patients, the median rate of AF termination was 44%. In comparison to the A-ATP start time, "0 min" had a higher AF termination rate by the A-ATP (39.4% vs. 24.4%, P = 0.011). The rate of termination by the A-ATP was high for AF with a long cycle length and a relatively regular rhythm. A-ATP successfully terminated AF episodes in some patients implanted with CIEDs. The optimal settings of the A-ATP will be determined in future studies.

The control of the arm's equilibrium position.

To generate a force, the brain activates muscles that act like springs to pull the arm toward a new equilibrium position. The equilibrium position (EP) is central to our understanding of the biological control of viscoelastic muscles. Although there is evidence of the EP during the control of limb posture, EPs have not been directly identified when the limb exerts a force against the environment. Here, we asked participants to apply a constant force in one of eight directions against a point-like constraint. This constraint was released abruptly to observe the final position to which the arm converged. Importantly, the same force magnitude was maintained while changing the arm's stiffness by modulating the strength of the hand's power grasp. The final position moved further away from the constraint as the arm became less stiff and was inversely proportional to the arm's stiffness, thereby confirming that the final position was the arm's EP. These results demonstrate how the EP changes with the arm's stiffness to produce a desired force in different directions.NEW & NOTEWORTHY According to numerous theories, the brain controls posture and movement by activating muscles that attract the limb toward a so-called equilibrium position, but the universality of this mechanism has not been shown for different motor behaviors. Here, we show that even when pushing or pulling against the environment, the brain achieves the desired force through an equilibrium position that lies beyond the physical constraint.

Clinical Findings, Response to Steroid Treatment, and Recurrence Rate in Alopecia Areata Patients with or without a Nonsynonymous Variant of Coiled-Coil Alpha-Helical Rod Protein 1.

BACKGROUND: Alopecia areata (AA) is considered complex genetic and tissue-specific autoimmune disease. We recently discovered a nonsynonymous variant in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene within the AA risk haplotype. And a water avoidance stress test on CCHCR1 knockout mice induced AA-like lesions. OBJECTIVE: To investigate the difference clinical findings of AA in patients with the CCHCR1 variant and without. METHODS: We conducted a retrospective analysis of the data from 142 AA patients. Among these patients, 20 (14.1%) had a variant of CCHCR1. We evaluated the sex distribution of the patients, age at onset, distribution of the clinical types, prevalence of a positive family history of AA, prevalence of association of AA with atopic dermatitis, response to steroid therapy, and recurrence rate. We used multivariate logistic regression analysis and Fisher's exact test for statistical analysis. We also investigate electron microscopic observations of hair samples with the CCHCR1 variant and without. RESULTS: The results showed a significant correlation between the CCHCR1 variant and the recurrence rate compared with the variant-negative group (p=0.0072). Electron microscopy revealed abnormalities in the hair shaft structure and hair cuticle in patients with the CCHCR1 variant (p=0.00174). CONCLUSION: Our results suggest that AA with CCHCR1 variant is clinically characterized by a high recurrence rate and hair morphological abnormality.

Competition Increases the Effort Put Into a Physical Interaction Task.

Physical interaction can enhance motor learning, but it remains unclear what type of interaction is best suited to increasing the active effort put into a task, which should support learning. Here, we used the same interactive tracking task with different instructions to induce three training conditions: competition, collaboration, and self-improvement, where partners improve their own performance while interacting haptically with each other. The effort was gauged by measuring the total normalized muscle activity. Feedback of task performance and the haptic dynamics were identical in all three training conditions, so the effort needed to complete the task was the same. Only the instructions to 'compete with the partner', 'improve your and your partner's accuracy' and 'improve your accuracy' were different among the competition, collaboration, and self-improvement conditions, respectively. Despite having the same goal of maximizing self-performance during competition and self-improvement, participants exerted significantly more effort during competition, and their tracking accuracy was highest during competitive practice. Least effort was put into collaboration but tracking accuracy during collaboration was comparable to self-improvement. Our results suggest that interactive haptic competition can induce higher active drive or effort than either collaborative training or self-focused practice.

Physically interacting humans regulate muscle coactivation to improve visuo-haptic perception.

When moving a piano or dancing tango with a partner, how should I control my arm muscles to sense their movements and follow or guide them smoothly? Here we observe how physically connected pairs tracking a moving target with the arm modify muscle coactivation with their visual acuity and the partner's performance. They coactivate muscles to stiffen the arm when the partner's performance is worse and relax with blurry visual feedback. Computational modeling shows that this adaptive sensing property cannot be explained by the minimization of movement error hypothesis that has previously explained adaptation in dynamic environments. Instead, individuals skillfully control the stiffness to guide the arm toward the planned motion while minimizing effort and extracting useful information from the partner's movement. The central nervous system regulates muscle activation to guide motion with accurate task information from vision and haptics while minimizing the metabolic cost. As a consequence, the partner with the most accurate target information leads the movement.NEW & NOTEWORTHY Our results reveal that interacting humans inconspicuously modulate muscle activation to extract accurate information about the common target while considering their own and the partner's sensorimotor noise. A novel computational model was developed to decipher the underlying mechanism: muscle coactivation is adapted to combine haptic information from the interaction with the partner and own visual information in a stochastically optimal manner. This improves the prediction of the target position with minimal metabolic cost in each partner, resulting in the lead of the partner with the most accurate visual information.

Lateralization of Impedance Control in Dynamic Versus Static Bimanual Tasks.

In activities of daily living that require bimanual coordination, humans often assign a role to each hand. How do task requirements affect this role assignment? To address this question, we investigated how healthy right-handed participants bimanually manipulated a static or dynamic virtual object using wrist flexion/extension while receiving haptic feedback through the interacting object's torque. On selected trials, the object shook strongly to destabilize the bimanual grip. Our results show that participants reacted to the shaking by increasing their wrist co-contraction. Unlike in previous work, handedness was not the determining factor in choosing which wrist to co-contract to stabilize the object. However, each participant preferred to co-contract one hand over the other, a choice that was consistent for both the static and dynamic objects. While role allocation did not seem to be affected by task requirements, it may have resulted in different motor behaviours as indicated by the changes in the object torque. Further investigation is needed to elucidate the factors that determine the preference in stabilizing with either the dominant or non-dominant hand.

Balance strategy in hoverboard control.

This study examines how people learn to perform lower limb control in a novel task with a hoverboard requiring to maintain dynamic balance. We designed an experiment to investigate the learning of hoverboard balance and two control strategies: A hip strategy, which mainly uses hip movements to change the angle of the foot, and an ankle strategy relying more on ankle motion to control the orientation of hoverboard plates controlling the motion. Motor learning was indicated by a significant [Formula: see text]% decrease in the trial completion time (p < 0.001) and a significant 24 ± 11% decrease in total muscle activation (p < 0.001). Furthermore, the participants, who had no prior experience riding a hoverboard, learned an ankle strategy to maintain their balance and control the hoverboard. This is supported by significantly stronger cross-correlation, phase synchrony, lower dynamic time warping distance between the hoverboard plate orientation controlling hoverboard motion, and the ankle angle when compared to the hip angle. The adopted ankle strategy was found to be robust to the foot orientation despite salient changes in muscle group activation patterns. Comparison with results of an experienced hoverboard rider confirmed that the first-time riders adopted an ankle strategy.

Prognostic impact of right ventricular function affected by pulmonary hypertension in hospitalized heart failure patients.

BACKGROUND: Pulmonary hypertension (PH) may affect right ventricular (RV) function; however, the prognostic implications of RV function in patients with heart failure and PH remain unclear. We aimed to investigate the impact of RV function on the prognosis of hospitalized heart failure patients with and without PH. METHODS: This observational study initially included 1,349 consecutive hospitalized heart failure patients. After excluding patients who died in hospital, whose left ventricular (LV) function was preserved, and whose echocardiography data were incomplete, 573 patients with heart failure and reduced LV ejection fractions (HFrEF) were analyzed. The patients were grouped according to RV dysfunction that was defined as an RV-tissue Doppler imaging systolic velocity (RV-TDI s') of ≤9.5 cm/s. The primary endpoint was a composite of cardiovascular death and rehospitalization as a consequence of heart failure. RESULTS: Overall, the patients with reduced RV function had significantly higher event rates than those with preserved RV function (log-rank test p = 0.01). This prognostic impact was observed in the patients with PH (p = 0.001) and was not evident among the patients without PH (p = 0.39). In the patients with PH, reduced RV function independently predicted the prognosis after adjusting for the covariates (adjusted hazard ratio: 3.12; 95% confidence interval: 1.44 to 6.73). CONCLUSION: RV dysfunction that was estimated during hospitalization using the RV-TDI s', which is a simply determined index, may predict clinical outcomes in hospitalized patients with HFrEF and PH after discharge, but not in those without PH.

Adapting the visuo-haptic perception through muscle coactivation.

While the nervous system can coordinate muscles' activation to shape the mechanical interaction with the environment, it is unclear if and how the arm's coactivation influences visuo-haptic perception and motion planning. Here we show that the nervous system can voluntarily coactivate muscles to improve the quality of the haptic percept. Subjects tracked a randomly moving visual target they were physically coupled to through a virtual elastic band, where the stiffness of the coupling increased with wrist coactivation. Subjects initially relied on vision alone to track the target, but with practice they learned to combine the visual and haptic percepts in a Bayesian manner to improve their tracking performance. This improvement cannot be explained by the stronger mechanical guidance from the elastic band. These results suggest that with practice the nervous system can learn to integrate a novel haptic percept with vision in an optimal fashion.

The Alopecia Areata Phenotype Is Induced by the Water Avoidance Stress Test In cchcr1-Deficient Mice.

We recently discovered a nonsynonymous variant in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene within the alopecia areata (AA) risk haplotype. We also reported that the engineered mice with this risk allele exhibited. To investigate more about the involvement of the CCHCR1 gene in AA pathogenesis, we developed an AA model using C57BL/6N cchcr1 gene knockout mice. In this study, mice (6-8 weeks) were divided into two groups: cchcr1-/- mice and wild-type (WT) littermates. Both groups were subjected to a water avoidance stress (WAS) test. Eight weeks after the WAS test, 25% of cchcr1-/- mice exhibited non-inflammatory foci of alopecia on the dorsal skin. On the other hand, none of wild-type littermates cause hair loss. The foci resembled human AA in terms of gross morphology, trichoscopic findings and histological findings. Additionally, gene expression microarray analysis of cchcr1-/- mice revealed abnormalities of hair related genes compared to the control. Our results strongly suggest that CCHCR1 is associated with AA pathogenesis and that cchcr1-/- mice are a good model for investigating AA.

The Roles of Dominance of the Nitric Oxide Fractions Nitrate and Nitrite in the Epilepsy-Prone EL Mouse Brain.

BACKGROUND: Oxidative stress is thought to be closely related to epileptogenesis. We have previously reported that nitric oxide (NO) levels are higher in epilepsy-prone EL mice between the ages of 3 and 8 weeks than in control mice. However, NO is divided into two fractions, nitrite (NO2) and nitrate (NO3), which appear to play different roles in epileptogenesis. METHODS: NO2 and NO3 levels were measured, in EL mice and the control mice, in the parietal cortex, which is thought to be the primary epileptogenetic center in EL mice, and measured in the hippocampus, which is thought to be the secondary center. RESULTS: NO3 levels in the hippocampus and parietal cortex of the immature EL mice (3 to 8 weeks of age) were significantly higher than those in the control mice; NO2 levels were significantly higher in the EL mice throughout the study period. The NO3 levels were significantly higher than the NO2 levels in the immature EL mice, but after the onset of ictogenesis at 10 weeks of age, the relative levels of the two fractions reversed. CONCLUSION: The reversal of the NO fraction distribution at the onset of seizures that we observed may be related to the developmental process of seizure susceptibility in the neural network of EL mice.

The Effect of Continuous Intake of Lactobacillus gasseri OLL2716 on Mild to Moderate Delayed Gastric Emptying: A Randomized Controlled Study.

Probiotics have been suggested to be effective for functional dyspepsia, but their effect on gastric motility is not clear. We evaluated the effect of Lactobacillus gasseri OLL2716 (LG21 strain) on mild to moderate delayed gastric emptying by a double-blind, parallel-group, placebo-controlled, randomized trial. Participants (n = 28) were randomly assigned to ingest LG21 strain-containing yogurt (LG21 strain group) or LG21 strain-free yogurt (placebo group) for 12 weeks. The 13C gastric emptying breath test was performed to measure the gastric emptying rate over time following ingestion of a liquid meal, and the time to reach the peak (Tmax) was used as an indicator of gastric emptying. We also measured the salivary amylase concentration, an indicator of autonomic dysfunction under stress. The per-protocol population (n = 27, male n = 4, female n = 23) was evaluated for efficacy. When a ≥30% reduction in the difference between participant's Tmax and the Japanese mean Tmax was defined as an improvement, the odds ratio of improvement in delayed gastric emptying compared to placebo after 12 weeks was 4.1 (95% confidence interval, 0.8 to 20.2). Moreover, salivary amylase concentrations were significantly lower than in the placebo group, indicating an improvement in autonomic function. The present data were not enough to support the beneficial effects of the LG21 strain on delayed gastric emptying. However, if we define the odds ratio in further study investigated with a larger number of participants, LG21 strain might be expected to have some impact on delayed gastric emptying.

Computational reproductions of external force field adaption without assuming desired trajectories.

Optimal feedback control is an established framework that is used to characterize human movement. However, it is not fully understood how the brain computes optimal gains through interactions with the environment. In the past study, we proposed a model of motor learning that identifies a set of feedback and feedforward controllers and a state predictor of the arm musculoskeletal system to control free reaching movements. In this study, we applied the model to force field adaptation tasks where normal reaching movements are disturbed by an external force imposed on the hand. Without a priori knowledge about the arm and environment, the model was able to adapt to the force field by generating counteracting forces to overcome it in a manner similar to what is reported in the behavioral literature. The kinematics of the movements generated by our model share characteristic features of human movements observed before and after force field adaptation. In addition, we demonstrate that the structure and learning algorithm introduced in our model induced a shift in the end-point's equilibrium position and a static force modulation, accompanied by a fast and a slow learning process. Importantly, our model does not require desired trajectories, yields movements without specifying movement duration, and predicts force generation patterns by exploring the environment. Our model demonstrates a possible mechanism through which the central nervous system may control and adapt a point-to-point reaching movement without specifying a desired trajectory by continuously updating the body's musculoskeletal model.

Evidence-based clinical practice guidelines for peptic ulcer disease 2020.

The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an English version. The revised guidelines consist of nine items: epidemiology, hemorrhagic gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcers, non-H. pylori, and nonsteroidal anti-inflammatory drug (NSAID) ulcers, remnant gastric ulcers, surgical treatment, and conservative therapy for perforation and stenosis. Therapeutic algorithms for the treatment of peptic ulcers differ based on ulcer complications. In patients with NSAID-induced ulcers, NSAIDs are discontinued and anti-ulcer therapy is administered. If NSAIDs cannot be discontinued, the ulcer is treated with proton pump inhibitors (PPIs). Vonoprazan (VPZ) with antibiotics is recommended as the first-line treatment for H. pylori eradication, and PPIs or VPZ with antibiotics is recommended as a second-line therapy. Patients who do not use NSAIDs and are H. pylori negative are considered to have idiopathic peptic ulcers. Algorithms for the prevention of NSAID- and low-dose aspirin (LDA)-related ulcers are presented in this guideline. These algorithms differ based on the concomitant use of LDA or NSAIDs and ulcer history or hemorrhagic ulcer history. In patients with a history of ulcers receiving NSAID therapy, PPIs with or without celecoxib are recommended and the administration of VPZ is suggested for the prevention of ulcer recurrence. In patients with a history of ulcers receiving LDA therapy, PPIs or VPZ are recommended and the administration of a histamine 2-receptor antagonist is suggested for the prevention of ulcer recurrence.

Flexible Assimilation of Human's Target for Versatile Human-Robot Physical Interaction.

Recent studies on the physical interaction between humans have revealed their ability to read the partner's motion plan and use it to improve one's own control. Inspired by these results, we develop an intention assimilation controller (IAC) that enables a contact robot to estimate the human's virtual target from the interaction force, and combine it with its own target to plan motion. While the virtual target depends on the control gains assumed for the human, we show that this does not affect the stability of the human-robot system, and our novel scheme covers a continuum of interaction behaviours from cooperation to competition. Simulations and experiments illustrate how the IAC can assist the human or compete with them to prevent collisions. In this article, we demonstrate the IAC's advantages over related methods, such as faster convergence to a target, guidance with less force, safer obstacle avoidance and a wider range of interaction behaviours.

Analogous adaptations in speed, impulse and endpoint stiffness when learning a real and virtual insertion task with haptic feedback.

Humans have the ability to use a diverse range of handheld tools. Owing to its versatility, a virtual environment with haptic feedback of the force is ideally suited to investigating motor learning during tool use. However, few simulators exist to recreate the dynamic interactions during real tool use, and no study has compared the correlates of motor learning between a real and virtual tooling task. To this end, we compared two groups of participants who either learned to insert a real or virtual tool into a fixture. The trial duration, the movement speed, the force impulse after insertion and the endpoint stiffness magnitude decreased as a function of trials, but they changed at comparable rates in both environments. A ballistic insertion strategy observed in both environments suggests some interdependence when controlling motion and controlling interaction, contradicting a prominent theory of these two control modalities being independent of one another. Our results suggest that the brain learns real and virtual insertion in a comparable manner, thereby supporting the use of a virtual tooling task with haptic feedback to investigate motor learning during tool use.

Independent control of cocontraction and reciprocal activity during goal-directed reaching in muscle space.

The movement in a joint is facilitated by a pair of muscles that pull in opposite directions. The difference in the pair's muscle force or reciprocal activity results in joint torque, while the overlapping muscle force or the cocontraction is related to the joint's stiffness. Cocontraction knowingly adapts implicitly over a number of movements, but it is unclear whether the central nervous system can actively regulate cocontraction in a goal-directed manner in a short span of time. We developed a muscle interface where a cursor's horizontal position was determined by the reciprocal activity of the shoulder flexion-extension muscle pair, while the vertical position was controlled by its cocontraction. Participants made goal-directed movements to single and via-point targets in the two-dimensional muscle space, learning to move the cursor along the shortest path. Simulations using an optimal control framework suggest that the reciprocal activity and the cocontraction may be controlled independently by the CNS, albeit at a rate orders of magnitude slower than the muscle's maximal activation speed.