Some researchers and clinics have reported that non-drug treatments for Alzheimer disease (AD) such as electrical stimulation, light stimulation, music stimulation, laser stimulation, and transcranial magnetic stimulation may have beneficial treatment effects. Following these findings, in this study, we performed multimodel physical stimulation on APP/PS1 mice using visible light, music with a γ rhythm, and an infrared laser. And the effects of physical stimulation on APP/PS1 mice were evaluated by behavioral analysis, the content of amyloid (Aβ40 and Aβ42), and NISSL staining of hippocampal tissue slices. The results of subsequent behavioral and tissue analyses showed that the multi-model physical stimulations could relieve APP/PS1 mice's dementia symptoms, such as the behavior ability, the content of Aβ40 and Aβ42 in the hippocampal tissue suspension, and Nissl staining for hippocampal tissue analyses.

Imagery plays an important role in our life. Motor imagery is the mental simulation of a motor act without overt motor output. Previous studies have documented the effect of motor imagery practice. However, its translational potential for patients as well as for athletes, musicians and other groups, depends largely on the transfer from mental practice to overt physical performance. We used bilateral transcranial direct current stimulation (tDCS) over sensorimotor areas to modulate neural lateralization patterns induced by unilateral mental motor imagery and the performance of a physical motor task. Twenty-six healthy older adults participated (mean age = 67.1 years) in a double-blind cross-over sham-controlled study. We found stimulation-related changes at the neural and behavioural level, which were polarity-dependent. Specifically, for the hand contralateral to the anode, electroencephalographic activity induced by motor imagery was more lateralized and motor performance improved. In contrast, for the hand contralateral to the cathode, hemispheric lateralization was reduced. The stimulation-related increase and decrease in neural lateralization were negatively related. Further, the degree of stimulation-related change in neural lateralization correlated with the stimulation-related change on behavioural level. These convergent neurophysiological and behavioural effects underline the potential of tDCS to improve mental and physical motor performance.

In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test their response to cold plasma in vitro. Intriguingly, short term plasma treatment stimulated cell growth. Longer exposure only modestly compromised cell viability but apparently supported the growth of cells that were enlarged in size and that showed enhanced metabolic activity. A significantly increased mitochondrial content in plasma treated cells supported this notion. On THP-1 cell proteome level, we identified an increase of protein translation with key regulatory proteins being involved in redox regulation (hypoxia inducible factor 2α), differentiation (retinoic acid signaling and interferon inducible factors), and cell growth (Yin Yang 1). Regulation of inflammation is a key element in many chronic diseases, and we found a significantly increased expression of the anti-inflammatory heme oxygenase 1 (HMOX1) and of the neutrophil attractant chemokine interleukin-8 (IL-8). Together, these results foster the view that cold physical plasma modulates the redox balance and inflammatory processes in wound related cells.

The decline in circulatory function with aging may be alleviated by a combination of gingival massage (physical stimulation) and mechanical cleaning. Several studies have reported the systemic effect of physical stimulation on various parts of the body, including its therapeutic effect on pain in the neck and shoulders that becomes evident with age, and improvement in blood circulation. In contrast, few studies have reported on the changes in gingival microcirculation induced by gingival massage, while no previous study has evaluated the effect of gingival microcirculation on age-related changes in the hemodynamics of the oral cavity. This study aimed to investigate how gingival massage affects age-related changes in gingival microcirculation. Male Wistar rats (7-week, 6-month and 1-year old) were prepared for a gingival massage group and a control group. Mechanical stimulation was applied on the maxillary molar gingiva for 5 seconds twice a week for 4 weeks. Subsequently, gingival reactive hyperemia was measured using a laser Doppler flowmeter. In addition, morphological analyses were also performed by hematoxylin and eosin and Indian ink staining and a vascular resin cast model. Base Flow, maximum response (Peak), and time required for the maximum response to halve (T1/2) were reduced in 1-year-old rats compared with the other age groups. In the mechanical stimulated group, T1/2 was increased in 7-week, 6-month, and 1-year-old rats, and total blood flow (Mass) was increased in 6-month and 1-year-old rats. In addition, clear blood vessel networks and loop-like revascularization were only observed in the mechanical stimulated group. Changes in age-related decline in gingival microcirculatory function and vascular construction were reported in this study, and the results suggested that gingival massage activates both the functional and morphological aspects of gingival microcirculation and may be effective for maintaining oral health.

Background: Mental fatigue is a psychobiological state caused by extended periods of cognitive effort, and evidence suggests that mentally fatigued athletes present impaired physical performance. Different ergogenic aids have been proposed to counteract the deleterious effects of mental fatigue, but whether brain stimulation can counteract mental fatigue is still unknown. This scenario is even more obscure considering the effects of these interventions (mental fatigue induction and brain stimulation) in a very experienced population consisting of master athletes. Method: Ten master swimmers (30 ± 6 years old and 14 ± 8 years of experience) participated in the study. They underwent four experimental conditions before an 800-m freestyle test: mental fatigue with brain stimulation; mental fatigue without brain stimulation; absence of mental fatigue with brain stimulation; and absence of mental fatigue and no brain stimulation. Mental fatigue was induced by a cognitively demanding Stroop Color Test, whereas stimulation was applied on the temporal cortex. After that, the athletes swan 800 m as fast as possible and provided their ratings of perceived exertion (RPE) every 200 m. Results: Mental fatigue was effectively induced, as evidenced by a greater fatigue perception and more errors in the last blocks of the cognitive task. Mental fatigue induction did not influence performance (time to complete the swimming trial) and RPE. Similarly, brain stimulation failed to change these two parameters, regardless of mental fatigue induction. Conclusion: The prolonged physical performance of experienced master athletes is not influenced, under the present conditions, by mental fatigue induction, cerebral stimulation, and their association.

We have been developing a non-thermal, drug-free tumor therapy called Nano-Pulse Stimulation (NPS) that delivers ultrashort electric pulses to tumor cells which eliminates the tumor and inhibits secondary tumor growth. We hypothesized that the mechanism for inhibiting secondary tumor growth involves stimulating an adaptive immune response via an immunogenic form of apoptosis, commonly known as immunogenic cell death (ICD). ICD is characterized by the emission of danger-associated molecular patterns (DAMPs) that serve to recruit immune cells to the site of the tumor. Here we present evidence that NPS stimulates both caspase 3/7 activation indicative of apoptosis, as well as the emission of three critical DAMPs: ecto-calreticulin (CRT), ATP and HMGB1.

It is currently known that pluripotent stem cells can be committed in vitro to the cardiac lineage by the modulation of specific signaling pathways, but it is also well known that, despite the significant increase in cardiomyocyte yield provided by the currently available conditioned media, the resulting cardiogenic commitment remains a highly variable process. Previous studies provided evidence that radio electric fields asymmetrically conveyed through the Radio Electric Asymmetric Conveyer (REAC) technology are able to commit R1 embryonic stem cells and human adipose derived stem cells toward a cardiac phenotype. The present study aimed at investigating whether the effect of physical stimulation by REAC in combination with specific chemical inductors enhance the cardiogenic potential in human induced pluripotent stem cells (iPSCs). The appearance of a cardiac-like phenotype in iPSCs cultured in the presence of a cardiogenic medium, based upon BMP4 and a WNT-inhibitor, was consistently increased by REAC treatment used only during the early fate differentiation for the first 72 hours. REAC-exposed iPSCs exhibited an upregulation in the expression of specific cardiogenic transcripts and morphologically in the number of beating clusters, as compared to cells cultured in the cardiogenic medium alone. Our results indicate that physical modulation of cellular dynamics provided by the REAC offers an affordable strategy to mimic iPSC cardiac-like fates in the presence of a cardiogenic milieu.

Traditional in vitro bioengineering approaches whereby only individual biophysical cues are manipulated at any one time are highly inefficient, falling short when recapitulating the complexity of the cardiac environment. Multiple biophysical cues are present in the native myocardial niche and are essential during development, as well as in maintenance of adult cardiomyocyte (CM) phenotype in both health and disease. This study establishes a novel biofabrication workflow to study and manipulate hiPSC-CMs and to understand how these cells respond to a multiplexed biophysical environment, namely 3D shape and substrate stiffness, at a single cell level. Silicon masters were fabricated and developed to generate inverse patterns of the desired 3D shapes in bas relief, which then were used to mold the designed microwell arrays into a hydrogel. Polyacrylamide (PAAm) was modified with the incorporation of acrylic acid to provide a carboxylic group conjugation site for adhesion motifs, without compromising capacity to modulate stiffness. In this manner, two individual parameters can be finely tuned independently within the hydrogel: the shape of the 3D microwell and its stiffness. The design allows the platform to isolate single hiPSC-CMs to study solely biophysical cues in the absence of cell-cell physical interaction. Under physiologic-like physical conditions (3D shape resembling that of adult CM and 9.83 kPa substrate stiffness that mimics muscle stiffness), isolated single hiPSC-CMs exhibit increased Cx-43 density, cell membrane stiffness and calcium transient amplitude; co-expression of the subpopulation-related MYL2-MYL7 proteins; and higher anisotropism than cells in pathologic-like conditions (flat surface and 112 kPa substrate stiffness). This demonstrates that supplying a physiologic or pathologic microenvironment to an isolated single hiPSC-CM in the absence of any physical cell-to-cell communication in this biofabricated platform leads to a significantly different set of cellular features, thus presenting a differential phenotype. Importantly, this demonstrates the high plasticity of hiPSC-CMs even in isolation. The ability of multiple biophysical cues to significantly influence isolated single hiPSC-CM phenotype and functionality highlights the importance of fine-tuning such cues for specific applications. This has the potential to produce more fit-for-purpose hiPSC-CMs. Further understanding of human cardiac development is enabled by the robust, versatile and reproducible biofabrication techniques applied here. We envision that this system could be easily applied to other tissues and cell types where the influence of cellular shape and stiffness of the surrounding environment is hypothesized to play an important role in physiology.

Mechanical vibrations seem to affect the behaviour of different cell types and the functions of different organs. Pressure waves, including acoustic waves (sounds), could affect cytoskeletal molecules via coherent changes in their spatial organization and mechano-transduction signalling. We analyzed the sounds spectra and their fractal features. Cardiac muscle HL1 cells were exposed to different sounds, were stained for cytoskeletal markers (phalloidin, beta-actin, alpha-tubulin, alpha-actinin-1), and studied with multifractal analysis (using FracLac for ImageJ). A single cell was live-imaged and its dynamic contractility changes in response to each different sound were analysed (using Musclemotion for ImageJ). Different sound stimuli seem to influence the contractility and the spatial organization of HL1 cells, resulting in a different localization and fluorescence emission of cytoskeletal proteins. Since the cellular behaviour seems to correlate with the fractal structure of the sound used, we speculate that it can influence the cells by virtue of the different sound waves' geometric properties that we have photographed and filmed. A theoretical physical model is proposed to explain our results, based on the coherent molecular dynamics. We stress the role of the systemic view in the understanding of the biological activity.

Subthalamic nucleus deep brain stimulation (STN-DBS) reduces tremor, muscle stiffness, and bradykinesia in people with Parkinson's Disease (PD). Walking speed, known to be reduced in PD, typically improves after surgery; however, other important aspects of gait may not improve. Furthermore, balance may worsen and falls may increase after STN-DBS. Thus, interventions to improve balance and gait could reduce morbidity and improve quality of life following STN-DBS. Physical therapy (PT) effectively improves balance and gait in people with PD, but studies on the effects of PT have not been extended to those treated with STN-DBS. As such, the efficacy, safety, and feasibility of PT in this population remain to be determined. The purpose of this pilot study is to address these unmet needs. We hypothesize that PT designed to target balance and gait impairment will be effective, safe, and feasible in this population.

Purpose: This systematic review aims to examine the efficacy of transcranial direct current stimulation (tDCS) combined with physical training on the excitability of the motor cortex, physical performance, and motor learning. Methods: A systematic search was performed on PubMed, Web of Science, and EBSCO databases for relevant research published from inception to August 2020. Eligible studies included those that used a randomized controlled design and reported the effects of tDCS combined with physical training to improve motor-evoked potential (MEP), dynamic posture stability index (DPSI), reaction time, and error rate on participants without nervous system diseases. The risk of bias was assessed by the Cochrane risk of bias assessment tool. Results: Twenty-four of an initial yield of 768 studies met the eligibility criteria. The risk of bias was considered low. Results showed that anodal tDCS combined with physical training can significantly increase MEP amplitude, decrease DPSI, increase muscle strength, and decrease reaction time and error rate in motor learning tasks. Moreover, the gain effect is significantly greater than sham tDCS combined with physical training. Conclusion: tDCS combined with physical training can effectively improve the excitability of the motor cortex, physical performance, and motor learning. The reported results encourage further research to understand further the synergistic effects of tDCS combined with physical training.

Testosterone (T) reduces male fat mass, but the underlying mechanisms remain elusive, limiting its clinical relevance in hypogonadism-associated obesity. Here, we subjected chemically castrated high-fat diet-induced adult obese male mice to supplementation with T or the nonaromatizable androgen dihydrotestosterone (DHT) for 20 weeks. Both hormones increased lean mass, thereby indirectly increasing oxygen consumption and energy expenditure. In addition, T but not DHT decreased fat mass and increased ambulatory activity, indicating a role for aromatization into estrogens. Investigation of the pattern of aromatase expression in various murine tissues revealed the absence of Cyp19a1 expression in adipose tissue while high levels were observed in brain and gonads. In obese hypogonadal male mice with extrahypothalamic neuronal estrogen receptor alpha deletion (N-ERαKO), T still increased lean mass but was unable to decrease fat mass. The stimulatory effect of T on ambulatory activity was also abolished in N-ERαKO males. In conclusion, our work demonstrates that the fat-burning action of T is dependent on aromatization into estrogens and is at least partially mediated by the stimulation of physical activity via extrahypothalamic ERα signaling. In contrast, the increase in lean mass upon T supplementation is mediated through the androgen receptor and indirectly leads to an increase in energy expenditure, which might also contribute to the fat-burning effects of T.

Cancer-related cognitive impairment (CRCI) occurs frequently in patients living with cancer, with consequences on quality of life. Recently, research on the management of these difficulties has focused on computerized cognitive stimulation and computerized physical activity programs. This systematic review presents the state of knowledge about interventions based on computerized-cognitive stimulation and/or physical activity to reduce CRCI. The review followed the PRISMA guidelines. A search was conducted in PUBMED and Web of Science databases. Risk of bias analysis was conducted using the Rob2 tool and the quality of evidence was conducted following the GRADE approach. A total of 3776 articles were initially identified and 20 of them met the inclusion criteria. Among them, sixteen investigated computerized-cognitive stimulation and four computerized-physical activity. Most of the studies were randomized controlled trials and assessed the efficacy of a home-based intervention on objective cognition in adults with cancer. Overall, cognitive improvement was found in 11/16 computerized-cognitive stimulation studies and 2/4 computerized-physical activity studies. Cognitive stimulation or physical activity improved especially cognitive complaints, memory, and attention. These results suggest the efficacy of both computerized-cognitive stimulation and physical activity. However, we report a high risk of bias for the majority of studies and a low level of quality of evidence. Therefore, further investigations are needed to confirm the efficacy of these interventions and to investigate the possible added benefit on cognition of a combined computerized-cognitive/physical intervention.

Evidence has shown that brain and abdominal (T abd) temperatures are regulated by distinct physiological mechanisms. Thus, the present study examined whether central cholinergic stimulation would change the dynamics of exercise-induced increases in T abd and thalamic temperature (T thal), an index of brain temperature. Adult male Wistar rats were used in all of the experiments. Two guide cannulae were implanted in the rats, one in the thalamus and the other in the right lateral cerebral ventricle, to measure T thal and to centrally inject a cholinergic agonist, respectively. Then, a temperature sensor was implanted in the abdominal cavity. On the day of the experiments, the rats received an intracerebroventricular injection of 2 μL of 10(-2)M physostigmine (Phy) or a vehicle solution (Veh) and were subjected to treadmill running until volitional fatigue occurred. T thal was measured using a thermistor connected to a multimeter, and T abd was recorded by telemetry. Phy injection delayed the exercise-induced increases in T thal (37.6 ± 0.2°C Phy vs 38.7 ± 0.1°C Veh at the 10th min of exercise) and in T abd. Despite the delayed hyperthermia, Phy did not change the rats' physical performance. In addition, the more rapid exercise-induced increase in T thal relative to Tabd in the rats treated with Veh was abolished by Phy. Collectively, our data indicate that central cholinergic stimulation affects the dynamics of exercise-induced increases in T thal and T abd. These results also provide evidence of the involvement of cholinoceptors in the modulation of brain heat loss during physical exercise.

In Chinese medicine acupuncture points are treated by physical stimuli to counteract various diseases. These stimuli include mechanical stress as applied during the needle manipulation or tuina, high temperatures as applied during moxibustion, and red laser light applied during laser acupuncture. This study aimed to investigate cellular responses to stimuli that might occur in the tissue of acupuncture points. Since they have a characteristically high density of mast cells that degranulate in response to acupuncture, we asked whether these processes lead to ATP release. We tested in in vitro experiments on mast cells of the human mast-cell line HMC-1 the effects of the physical stimuli; mechanical stress was applied by superfusion of the cells with hypotonic solution, heat was applied by incubation of the cells at 52°C, and red laser light of 657 nm was used for irradiation. We demonstrate that all the stimuli induce ATP release from model human mast HMC-1 cells, and this release is associated with an intracellular free Ca(2+) rise. We hypothesize that ATP released from mast cells supplements the already known release of ATP from keratinocytes and, by acting on P2X receptors, it may serve as initial mediator of acupuncture-induced analgesia.

Epidemiological studies suggest that physical exercise or cognitive stimulation might contribute to lower the risk of developing dementia disorders such as Alzheimer's disease (AD). Here, we used the well-established enrichment environment (EE) paradigm to study the impact of prolonged physical activity and cognitive stimulation in a mouse model of AD overexpressing only Aβ4-42 peptides. These mice display age-dependent memory and motor deficits, in the absence of human amyloid precursor protein (APP) overexpression. We demonstrate that housing under EE conditions leads to an entire preservation of recognition and spatial memory, as well as a rescue of motor deficits in this mouse model. Moreover, we find that Tg4-42hom mice present a typical floating phenotype in the Morris water maze task that could be completely ameliorated upon long-term EE housing. Our findings are in line with epidemiological studies suggesting that physical activity and cognitive stimulation might represent efficient strategies to prevent age-related neurodegenerative disorders such as AD.

People with intellectual and multiple disabilities tend to engage in very low levels of physical activity.

Pharmacologic therapy is the primary treatment used to manage Parkinson's disease (PD) symptoms. However, it becomes less effective with time and some symptoms do not respond to medication. Complementary interventions are therefore required for PD. Recent studies have implemented transcranial direct current stimulation (tDCS) in combination with other modalities of interventions, such as physical and cognitive training. Although the combination of tDCS with physical and cognitive training seems promising, the existing studies present mixed results. Therefore, a systematic review of the literature is necessary.

This article shows our work for developing an elder care platform for social interaction and physical and cognitive stimulation using the Pepper robot and Android OS as clients, based on the knowledge acquired on our long-term social robotics research experience. The first results of the user's acceptance of the solution are presented in this article. The platform is able to provide different services to the user, such as information, news, games, exercises or music. The games, which have a bi-modal way of interacting (speech and a touch screen interface), have been designed for cognitive stimulation based on the items of the mini-mental state examination. The results of the user's performance are stored in a cloud database and can be reviewed by therapists through a web interface that also allows them to establish customized therapy plans for each user. The platform has been tested and validated, first using adult people and then deployed to an elder care facility where the robot has been interacting with users for a long period of time. The results and feedback received have shown that the robot can help to keep the users physically and mentally active as well as establish an emotional link between the user and the robot.

In the course of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a dysregulated adult hippocampal neurogenesis has been suggested as a potential mechanism for early cognitive decline. Previous work has shown that mice overexpressing wild type Notch3 and mice overexpressing Notch3 with a CADASIL mutation display impaired cell proliferation and survival of newly born hippocampal neurons prior to vascular abnormalities. Here, we aimed to elucidate how the long-term survival of these newly generated neurons is regulated by Notch3. Knowing that adult neurogenesis can be robustly stimulated by physical exercise and environmental enrichment, we also investigated the influence of such stimuli as potential therapeutic instruments for a dysregulated hippocampal neurogenesis in the CADASIL mouse model. Therefore, young-adult female mice were housed in standard (STD), environmentally enriched (ENR) or running wheel cages (RUN) for either 28 days or 6 months. Mice overexpressing mutated Notch3 and developing CADASIL (TgN3R169C), and mice overexpressing wild type Notch3 (TgN3WT) were used. We found that neurogenic stimulation by RUN and ENR is apparently impaired in both transgenic lines. The finding suggests that a disturbed neurogenic process due to Notch3-dependent micromilieu changes might be one vascular-independent mechanism contributing to cognitive decline observed in CADASIL.