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Pulmonary hypertension (PH) is a life-threatening disease characterized by a progressive narrowing of pulmonary arterioles. Although VEGF is highly expressed in lung of patients with PH and in animal PH models, the involvement of angiogenesis remains elusive. To clarify the pathophysiological function of angiogenesis in PH, we compared the angiogenic response in hypoxia (Hx) and SU5416 (a VEGFR2 inhibitor) plus Hx (SuHx) mouse PH models using 3D imaging. The 3D imaging analysis revealed an angiogenic response in the lung of the Hx-PH, but not of the severer SuHx-PH model. Selective VEGFR2 inhibition with cabozantinib plus Hx in mice also suppressed angiogenic response and exacerbated Hx-PH to the same extent as SuHx. Expression of endothelial proliferator-activated receptor γ coactivator 1α (PGC-1α) increased along with angiogenesis in lung of Hx-PH but not SuHx mice. In pulmonary endothelial cell–specific Ppargc1a-KO mice, the Hx-induced angiogenesis was suppressed, and PH was exacerbated along with increased oxidative stress, cellular senescence, and DNA damage. By contrast, treatment with baicalin, a flavonoid enhancing PGC-1α activity in endothelial cells, ameliorated Hx-PH with increased Vegfa expression and angiogenesis. Pulmonary endothelial PGC-1α–mediated angiogenesis is essential for adaptive responses to Hx and might represent a potential therapeutic target for PH.

Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, the authors show that vascular injury induces the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response as a protective mechanism.

Most blood vessels are surrounded by adipose tissues known as perivascular adipose tissue (PVAT). Emerging experimental data have implicated the potential involvement of PVAT in the pathogenesis of cardiovascular disease: PVAT might be a source of inflammatory mediators under pathological conditions such as metabolic disorders, chronic inflammation, and aging, leading to vascular pathologies, while having vasculo-protective roles in a healthy state. PVAT has been also gaining attention in human disease conditions. Recent integrative omics approaches have greatly enhanced our understanding of the molecular mechanisms underlying the diverse functions of PVAT. This review summarizes recent progress in PVAT research and discusses the potential of PVAT as a target for the treatment of atherosclerosis.

Sexual dimorphism exists in the epidemiology of cardiovascular disease (CVD), which indicates the involvement of sexual hormones in the pathophysiology of CVD. In particular, ample evidence has demonstrated estrogen's protective effect on the cardiovascular system. While estrogen receptors, bound to estrogen, act as a transcription factor which regulates gene expressions by binding to the specific DNA sequence, a subpopulation of estrogen receptors localized at the plasma membrane induces activation of intracellular signaling, called “non-nuclear signaling” or “membrane-initiated steroid signaling of estrogen”. Although the precise molecular mechanism of non-nuclear signaling as well as its physiological impact was unclear for a long time, recent development of genetically modified animal models and pathway-selective estrogen receptor stimulant bring new insights into this pathway. We review the published experimental studies on non-nuclear signaling of estrogen, and summarize its role in cardiovascular system, especially focusing on: (1) the molecular mechanism of non-nuclear signaling; (2) the design of genetically modified animals and pathway-selective stimulant of estrogen receptor.

Glycogen storage disease type III (GSD-III) is an autosomal recessive metabolic disorder caused by mutations in the AGL gene, and may develop various types of pulmonary hypertension (PH). Here, we report a case of 24-year-old man with GSD-IIIb with two novel null variants in AGL (c.2308 + 2T>C and c.3045_3048dupTACC). He developed multi-drug-resistant pulmonary veno-occlusive disease (PVOD) and was registered as a candidate for lung transplantation. No pathogenic variants were detected in previously known causative genes for pulmonary hypertension and the underlying mechanism of coincidence of two rare diseases was unknown. We discuss the association of the loss of glycogen-debranching enzyme with incident PVOD.

Abstract Introduction Essential oil inhalation has various effects on the human body. However, its effects on cognitive function and the neural basis remain unclear. We aimed to investigate the effects of inhaling lemon, sandalwood, and kusunoki essential oils on human brain activity and memory function using multichannel electroencephalography and brain source activity estimation. Methods Participants performed a letter 2‐back working memory task during electroencephalography measurements before and after essential oil inhalation. Brain activation, task difficulty, concentration degree, and task performance were compared among the essential oils and a fragrance‐free control. Results Task performance significantly improved after lemon essential oil inhalation. Lemon essential oil inhalation resulted in delta and theta band activation in the prefrontal cortex, including the anterior cingulate gyrus and orbitofrontal cortex, superior temporal gyrus, parahippocampal gyrus, and insula. During inhalation, persistent alpha band activation was observed in the prefrontal cortex, including the anterior cingulate gyrus. Sandalwood essential oil inhalation led to beta and gamma band activation in the prefrontal cortex, including the anterior cingulate gyrus. Conclusion Our findings demonstrate that different essential oils have specific effects on brain activity related to emotion and memory processing.

Neurofeedback (NF) shows promise in enhancing memory, but its application to the medial temporal lobe (MTL) still needs to be studied. Therefore, we aimed to develop an NF system for the memory function of the MTL and examine neural activity changes and memory task score changes through NF training. We created a memory NF system using intracranial electrodes to acquire and visualise the neural activity of the MTL during memory encoding. Twenty trials of a tug-of-war game per session were employed for NF and designed to control neural activity bidirectionally (Up/Down condition). NF training was conducted with three patients with drug-resistant epilepsy, and we observed an increasing difference in NF signal between conditions (Up–Down) as NF training progressed. Similarities and negative correlation tendencies between the transition of neural activity and the transition of memory function were also observed. Our findings demonstrate NF’s potential to modulate MTL activity and memory encoding. Future research needs further improvements to the NF system to validate its effects on memory functions. Nonetheless, this study represents a crucial step in understanding NF’s application to memory and provides valuable insights into developing more efficient memory enhancement strategies.

Abstract Percutaneous coronary intervention (PCI) is sometimes considered as an alternative therapeutic strategy to surgical revascularization in patients with coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF). However, the types or conditions of patients that receive the clinical benefit of left ventricular reverse remodelling (LVRR) remain unknown. The purpose of this study was to investigate the determinants of LVRR following PCI in CAD patients with reduced LVEF. From 4394 consecutive patients who underwent PCI, a total of 286 patients with reduced LV systolic function (LVEF

Abstract Some clinical trials showed that omega-3 fatty acid (FA) reduced cardiovascular events, but it remains unknown whether omega-3 FA supplementation changes the composition of FAs and their metabolites in the heart and how the changes, if any, exert beneficial effects on cardiac structure and function. To clarify these issues, we supplied omega-3 FA to mice exposed to pressure overload, and examined cardiac structure and function by echocardiography and a proportion of FAs and their metabolites by gas chromatography and liquid chromatography-tandem mass spectrometry, respectively. Pressure overload induced cardiac hypertrophy and dysfunction, and reduced concentration of all FAs’ components and increased free form arachidonic acid and its metabolites, precursors of pro-inflammatory mediators in the heart. Omega-3 FA supplementation increased both total and free form of eicosapentaenoic acid, a precursor of pro-resolution mediators and reduced free form arachidonic acid in the heart. Omega-3 FA supplementation suppressed expressions of pro-inflammatory cytokines and the infiltration of inflammatory cells into the heart and ameliorated cardiac dysfunction and fibrosis. These results suggest that omega-3 FA-induced changes of FAs composition in the heart have beneficial effects on cardiac function via regulating inflammation.

Great progress has been made in the understanding of the pathophysiology of cardiovascular diseases (CVDs), and this has improved the prevention and prognosis of CVDs. However, while sex differences in CVDs have been well documented and studied for decades, their full extent remains unclear. Results of the latest clinical studies provide strong evidence of sex differences in the efficacy of drug treatment for heart failure, thereby possibly providing new mechanistic insights into sex differences in CVDs. In this review, we discuss the significance of sex differences, as rediscovered by recent studies, in the pathogenesis of CVDs. First, we provide an overview of the results of clinical trials to date regarding sex differences and hormone replacement therapy. Then, we discuss the role of sex differences in the maintenance and disruption of cardiovascular tissue homeostasis.

A user operating a mechanical devise receives sensory information (e.g., sounds and vibrations) generated by the mechanical operation in response to the operation input. With the digitization of products, the mechanical operation response is removed as is the associated sensory information, thus there is no confirmation of the completed operation. Adding a digital sound or vibration could solve this problem. The challenge, however, is designing an operation response without inducing any sense of discrepancy. The purpose of this study was to create a quantitative, objective method to evaluate the sense of discrepancy to the operation response and the habituation to the response. We investigated the possibility of using an event-related potential component (P300), believed to reflect attention to stimuli, as a quantitative evaluation method of the sense of discrepancy. Experiment 1: We studied the sense of discrepancy between the type of operation response (sound, vibration, none), and the shutter operation of a mirrorless single-lens camera, using subjective evaluation and the P300. We confirmed that the P300 amplitude corresponded to the degree of the sense of discrepancy. Experiment 2: With the mouse click being the operation sound, the attenuation of the P300 amplitude by the repeated operation was consistent with the subjective habituation to the response. We conclude, based on these results, that the P300 amplitude could help determine the sense of discrepancy to the operation response and the habituation to the response.

One becomes accustomed to repeated exposures, even for a novel event. In the present study, we investigated how predictability affects habituation to novelty by applying a mathematical model of arousal that we previously developed, and through the use of psychophysiological experiments to test the model's prediction. We formalized habituation to novelty as a decrement in Kullback-Leibler divergence from Bayesian prior to posterior (i.e., information gain) representing arousal evoked from a novel event through Bayesian update. The model predicted an interaction effect between initial uncertainty and initial prediction error (i.e., predictability) on habituation to novelty: the greater the initial uncertainty, the faster the decrease in information gain (i.e., the sooner habituation occurs). This prediction was supported by experimental results using subjective reports of surprise and event-related potential (P300) evoked by visual-auditory incongruity. Our findings suggest that in highly uncertain situations, repeated exposure to stimuli can enhance habituation to novel stimuli.

Human creative thinking is unique and capable of generating novel and valuable ideas. Recent research has clarified the contribution of different brain networks (default mode network, DN; executive control network; salience network) to creative thinking. However, the effects of brain stimulation on brain networks during creative thinking and on creative performance have not been clarified. The present study was designed to examine the changes in functional connectivity (FC) and effective connectivity (EC) of the large-scale brain network, and the ensuing changes in creative performance, induced by transcranial direct current stimulation (tDCS). Fourteen healthy male students underwent two tDCS sessions, one with actual stimulation and one with sham stimulation, on two separate days. Participants underwent tDCS (anode over the left dorsolateral prefrontal cortex, DLPFC; cathode over the right inferior parietal lobule, IPL) for 20 min. Before and after the tDCS session, electroencephalography signals were acquired from 32 electrodes over the whole head during the creative thinking task. On FC analysis, the delta band FC between the posterior cingulate cortex and IPL significantly increased only after real stimulation. We also found that the change of flexibility score was significantly correlated with the change in: (i) delta band FC between mPFC and left lateral temporal cortex (LTC) and (ii) alpha band FC between IPL and right LTC. On EC analysis, decreased flow within the DN (from left LTC to right IPL) was observed. Our results reveal that tDCS could affect brain networks, particularly the DN, during creative thinking and modulate key FC in the generation of flexible creative ideas.

Abstract Background Fulminant myocarditis is a life-threatening disease, and myocardial damage expands the right ventricle as well as the left ventricle in some cases. There is a mortality rate of over 40% in patients with fulminant myocarditis who need mechanical circulatory support by peripheral venoarterial extracorporeal membrane oxygenation. Case presentation We report a case of a 27-year-old Japanese woman who was successfully bridged to recovery by using a biventricular assist device. She was diagnosed with fulminant myocarditis, and peripheral venoarterial extracorporeal membrane oxygenation was established on the same day. Her left ventricular ejection fraction rapidly decreased from 40% to 5% in 3 days and weaning from venoarterial extracorporeal membrane oxygenation was deemed difficult. Therefore, we performed a ventricular assist device implantation on day 4. A left ventricular assist device was implanted first. However, adequate blood flow did not circulate to the left side of her heart because of right-sided heart failure. Thus, an additional implant of a right ventricular assist device was performed during the operation. Her left ventricular ejection fraction recovered to 50% on day 10. The biventricular assist device was successfully removed on day 14. She has not experienced worsening of biventricular function during her follow-ups for 4 years. Conclusions Ventricular assist device therapy should be considered if there is no improvement in cardiac function in patients with fulminant myocarditis regardless of several days of support by venoarterial extracorporeal membrane oxygenation. A right ventricular assist device should always be implemented when necessary because biventricular involvement is not uncommon in fulminant myocarditis.

Premenopausal females have a lower incidence of death from cardiovascular disease (CVD) than male counterparts, supporting the notion that estrogen is protective against the development and progression of CVD. Although large-scale randomized trials of postmenopausal hormone replacement therapy failed to show cardiovascular benefits, recent ELITE study demonstrated anti-atherosclerotic benefits of exogenous estrogen depending on the initiation timing of the therapy. These results have urged us to better understand the mechanisms for actions of estrogens on CVD. Here, we review experimental and human studies, highlighting the emerging role of estrogen's non-nuclear actions linking to NO-cGMP signaling pathways.

We have been studying a sightseeing support application using Bluetooth Low Energy (BLE) beacons and mobile phones since 2014 to support sightseeing in Nikko, one of Japan’s World Heritage sites. Travelers can receive information relating to their position by using this application. We tried to use some psychological effects to increase travelers’ satisfaction when they receive such information. Moreover, we tried to emphasize travel memories of the place (scenery, culture, food, etc.) to encourage them to revisit or inspire their friends to visit it. Our tests prove the usefulness of our sightseeing support application for enhancing the travel experience. However, we had not yet developed a function to provide information that met the travelers’ intentions or needs. Moreover, it is hazardous to use a smartphone during walking, especially in an unfamiliar place. If a traveler uses a smartphone during walking, they might miss the beautiful scenery, historic buildings, and exotic atmosphere. We tried to adapt our sightseeing support application for use with a wearable device (smartwatch) to avoid using a smartphone during walking and introduced a prospect theory to evaluate information according to personal interest and behavior. Our experiments proved that our application provided the most appropriate sightseeing information to travelers and prevented danger during walking.

Acceptance of novelty depends on the receiver's emotional state. This paper proposes a novel mathematical model for predicting emotions elicited by the novelty of an event under different conditions. It models two emotion dimensions, arousal and valence, and considers different uncertainty levels. A state transition from before experiencing an event to afterwards is assumed, and a Bayesian model estimates a posterior distribution as being proportional to the product of a prior distribution and a likelihood function. Our model uses Kullback-Leibler divergence of the posterior from the prior, which we termed information gain, to represent arousal levels because it corresponds to surprise, a high-arousal emotion, upon experiencing a novel event. Based on Berlyne's hedonic function, we formalized valence as a summation of reward and aversion systems that are modeled as sigmoid functions of information gain. We derived information gain as a function of prediction errors (i.e., differences between the mean of the posterior and the peak likelihood), uncertainty (i.e., variance of the prior that is proportional to prior entropy), and noise (i.e., variance of the likelihood function). This functional model predicted an interaction effect of prediction errors and uncertainty on information gain, which we termed the arousal crossover effect. This effect means that the greater the uncertainty, the greater the information gain for a small prediction error. However, for large prediction errors, greater uncertainty means a smaller information gain. To verify this effect, we conducted an experiment with participants who watched short videos in which different percussion instruments were played. We varied uncertainty levels by using familiar and unfamiliar instruments, and we varied prediction error magnitudes by including congruent or incongruent percussive sounds in the videos. Event-related potential P300 amplitudes and subjective reports of surprise in response to the percussive sounds were used as measures of arousal levels, and the findings supported the hypothesized arousal crossover effect. The concordance between our model's predictions and our experimental results suggests that Bayesian information gain can be decomposed into uncertainty and prediction errors and is a valid measure of emotional arousal. Our model's predictions of arousal may help identify positively accepted novelty.

The present study aimed to examine the effect of transpulmonary administration of caffeine on working memory and related brain functions by electroencephalography measurement. The participants performed working memory tasks before and after vaporizer-assisted aspiration with inhalation of caffeinated- and non-caffeinated liquids in the caffeine and sham conditions, respectively. Transpulmonary administration of caffeine tended to increase the rate of correct answers. Moreover, our findings suggest that transpulmonary administration of caffeine increases the theta-band activity in the right prefrontal, central, and temporal areas during the task assigned post-aspiration. Our results may indicate an efficient and fast means of eliciting the stimulatory effects of transpulmonary administration of caffeine.

Thermal factors not only affect the thermal comfort sensation of occupants, but also affect their arousal level, productivity, and health. Therefore, it is necessary to control thermal factors appropriately. In this study, we aim to design a thermal environment that improves both the arousal level and thermal comfort of the occupants. To this end, we investigated the relationships between the physiological indices, subjective evaluation values, and task performance under several conditions of changes in the indoor ambient temperature. In particular, we asked subjects to perform a mathematical task and subjective evaluation related to their thermal comfort sensation and drowsiness levels. Simultaneously, we measured their physiological parameters, such as skin temperature, respiration rate, electroencephalography, and electrocardiography, continuously. We investigated the relationship between the comfort sensation and drowsiness level of occupants, and the physiological indices. From the results, it was confirmed that changes in the indoor ambient temperature can improve both the thermal comfort and the arousal levels of occupants. Moreover, we proposed the evaluation indices of the thermal comfort and the drowsiness level of occupants using physiological indices.

Recently, variety of products and services has become diverse, and it is getting more difficult to produce innovative product which matches user needs. For the reason, idea generation which is expected to produce methods of generating creative idea is getting more necessary. In idea generation, numeral methods of generating idea are proposed, some of which are brainstorming, KJ method, user observation and design ethnography. However, most of the processes are dependent on designers themselves, and this is because most part of idea generation process is still remained to be unexplained. We propose idea generation model from the cognitive psychological point of view. With the model, we propose that by activating nonverbal memory which is abundant information resource compared to verbal memory, creative idea is expected to be generated. On the other hand, there is attention: the system which controls the visual information processing is suppressing nonverbal memory activation. In this paper, we propose that dispersing attention makes nonverbal memory system more activated. We created attention dispersion system using eye tracker, and attempted an experiment to access effect on idea processing. From the experiment, participants gave more terms when their attention was dispersed, compared to trail without support on attention dispersion.

Indoor thermal quality affects the conditions of the occupant who is doing tasks in an indoor environment, and also task performance. Therefore, appropriate control of thermal factors is important to improve the conditions of occupant, such as thermal comfort sensation and the arousal level which is related to task performance. In order to determine guidelines how to control the thermal factors for improving the comfort sensation and arousal level, it is necessary to evaluate the condition of occupant by using quantitative and continuously measurable indices such as physiological indices. In this study, we aimed to clarify the relationship between the condition of occupant and physiological indices which is affected by changes in thermal factor and task level. We measured subjective evaluation and physiological indices such as electroencephalogram (EEG), electrocardiogram (ECG), respiration, and skin temperature of 10 participants in 4 experimental conditions consisted of different temperature and arithmetic task level. From the result of time-series analysis and correlation analysis among the experimental conditions, the subjective evaluation value, and physiological indices, it is showed that difference of task level can affect to the correlation between the conditions of occupant and physiological indices. These result suggests that the effect of task level on physiological indices should be considered in order to evaluate the conditions of occupant by using physiological indices.

Frailty is a characteristic of older patients with heart failure, who undergo functional decline during hospitalization. At present, continuous intravenous infusion of diuretics is widely used for the treatment of hospitalized patients with heart failure. In this prospective, randomized, open-label controlled trial, we tested whether an early switch from continuous intravenous infusion therapy to oral treatment with diuretics prevents functional decline in patients hospitalized for heart failure.A total of 59 patients hospitalized for heart failure were randomized to either continuous intravenous infusion (n = 30) or oral medication (n = 29) within 48 h of admission. The primary outcome was the Barthel index, a universally utilized scale to assess the functional status of patients in their activities of daily living, assessed at 10 days. Secondary outcomes included the number of daily steps counted using pedometers and average hospital costs.Barthel index scores were significantly higher in the oral medication group than in the intravenous group (78.1 ± 20.8 vs. 59.6 ± 34.2, P = 0.029). The number of daily steps was significantly higher in the oral treatment group relative to the intravenous group (P < 0.001), and the average hospital costs were similar between the randomized groups. Multivariate analysis revealed that oral medication was a significant independent predictor of Barthel index score at day 10, and the number of daily steps was significantly associated with the patient's functional outcome.This trial showed that, in patients hospitalized for heart failure, oral medication increased functional independence during hospitalization compared with sustained continuous intravenous infusion, most likely because the release from the infusion line enabled the patients to be more mobile. Notably, these beneficial effects were achieved without increasing hospital costs.

Estrogen promotes the proliferation and migration of vascular endothelial cells (ECs), which likely underlies its ability to accelerate re-endothelialization and reduce adverse remodeling after vascular injury. In previous studies, we have shown that the protective effects of E2 (the active endogenous form of estrogen) in vascular injury require the estrogen receptor alpha (ERα). ERα transduces the effects of estrogen via a classical DNA binding, "genomic" signaling pathway and via a more recently-described "rapid" signaling pathway that is mediated by a subset of ERα localized to the cell membrane. However, which of these pathways mediates the effects of estrogen on endothelial cells is poorly understood. Here we identify a triple point mutant version of ERα (KRR ERα) that is specifically defective in rapid signaling, but is competent to regulate transcription through the "genomic" pathway. We find that in ECs expressing wild type ERα, E2 regulates many genes involved in cell migration and proliferation, promotes EC migration and proliferation, and also blocks the adhesion of monocytes to ECs. ECs expressing KRR mutant ERα, however, lack all of these responses. These observations establish KRR ERα as a novel tool that could greatly facilitate future studies into the vascular and non-vascular functions of ERα rapid signaling. Further, they support that rapid signaling through ERα is essential for many of the transcriptional and physiological responses of ECs to E2, and that ERα rapid signaling in ECs, in vivo, may be critical for the vasculoprotective and anti-inflammatory effects of estrogen.

A consumer's emotional response to a product is influenced by cognitive processes, such as memories associated with use of the product and expectations of its performance. Here, we propose a cognitive neural model of Expectology, called PEAM (Prediction - Experience - Appraisal - Memory), as a novel tool that considers consumers' emotional responses in order to aid in product design. The PEAM model divides cognitive processes associated with product use into 4 phases: prediction, experience, appraisal, and memory. We examined the spatiotemporal changes in brain activity associated with product evaluation and memory during the prediction phase, by obtaining electroencephalograms (EEGs). EEGs of 10 healthy participants with normal or corrected-to-normal vision were recorded while they viewed images of products as well as when they provided a preference rating for each product. Our results revealed significantly increased neural activity in the gamma frequency in the temporal areas, the brain regions where declarative memory is stored, and in the prefrontal area for products that were rated as preferable. Our data suggest that memory is used for product evaluation in the prediction phase. These findings also suggest that activity in these specific brain areas are reliable predictors for product evaluation.

Using multiple linear regression analysis, we defined equations to describe basic psycho-acoustic quantities, such as sharpness, tonality, roughness and fluctuation strength, to estimate how people react to various types of auditory signals. The HEV/EV auditory signal is a very important audio-guidance for pedestrians. It must be recognizable in a city crowd, as well as within a comfortable hearing range. In common practice, sensory evaluation tests are used to estimate the human auditory experience, but these tests are expensive due to the large size of the required test pool. Through investigating the correlation between sensory evaluation test results and basic psycho-acoustic quantities for 22 signals, we developed equations that predict the results of sensory evaluation tests inexpensively. Our method has been confirmed through the agreement between results obtained from our equations and that of sensory evaluations. We showed that the tendency of actual sensory evaluation could be predicted by the prediction relation of sensory evaluation using the metrics of sharpness, tonality, roughness, and fluctuation strength. With the increase in the number of samples, the dispersion in the prediction range spread. Therefore, it seems that the related item which is not taken into the present consideration needs to be added for improvement in the further predictive accuracy.