An Exergame-Integrated IoT-Based Ergometer System Delivers Personalized Training Programs for Older Adults and Enhances Physical Fitness: A Pilot Randomized Controlled Trial.

INTRODUCTION: Regular physical exercise is believed to counteract the adverse physiological consequences of aging. However, smart fitness equipment specifically designed for older adults is quite rare. Here we designed an exergame-integrated internet of things (IoT)-based ergometer system (EIoT-ergo) that delivers personalized exercise prescriptions for older adults. First, physical fitness was evaluated using the Senior Fitness Test (SFT) application. Then, radio frequency identification (RFID) triggered the EIoT-ergo to deliver the corresponding exercise session based on the individual level of physical fitness. The exercise intensity during each workout was measured to generate the next exercise session. Further, EIoT-ergo provides an exergame to help users control and maintain their optimal cadence while engaging in exercise. METHODS: This was a randomized controlled trial with 1:1 randomization. Participants were older adults, 50+ years of age (N = 35), who are active in their community. Participants in the EIoT-ergo group received a 12-week personalized exercise program delivered by EIoT-ergo for 30 min per session, with 2 sessions per week. Participants in the control group continued with their usual activities. A senior's fitness test and a health questionnaire were assessed at baseline and at a 13-week reassessment. The Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) was used to evaluate the satisfaction of EIoT-ergo. RESULTS: Compared with the control group, the EIoT-ergo group showed significant improvements in muscle strength (time-by-group interaction, sit-to-stand: ß = 5.013, p < 0.001), flexibility (back stretch: ß = 4.008, p = 0.005; and sit-and-reach: ß = 4.730, p = 0.04), and aerobic endurance (2-min step: ß = 9.262, p = 0.03). The body composition was also improved in the EIoT-ergo group (body mass index: ß = -0.737, p < 0.001; and skeletal muscle index: ß = 0.268, p = 0.03). Satisfaction with EIoT-ergo was shown in QUEST, with an average score of 4.4 ± 0.32 (5 for very satisfied). The percentage maximum heart rate in each session also indicated that EIoT-ergo can gradually build up the exercise intensity of users. CONCLUSIONS: EIoT-ergo was developed to provide personal identification, exergames, intelligent exercise prescriptions, and remote monitoring, as well as to significantly enhance the physical fitness of the elderly individuals under study.

Rose Bengal-Mediated Photodynamic Therapy to Inhibit Candida albicans.

Invasive Candida albicans infection is a significant opportunistic fungal infection in humans because it is one of the most common colonizers of the gut, mouth, vagina, and skin. Despite the availability of antifungal medication, the mortality rate of invasive candidiasis remains ~50%. Unfortunately, the incidence of drug-resistant C. albicans is increasing globally. Antimicrobial photodynamic therapy (aPDT) may offer an alternative or adjuvant treatment to inhibit C. albicans biofilm formation and overcome drug resistance. Rose bengal (RB)-mediated aPDT has shown effective cell killing of bacteria and C. albicans. In this study, the efficacy of RB-aPDT on multidrug-resistant C. albicans is described. A homemade green light-emitting diode (LED) light source is designed to align with the center of a well of a 96-well plate. The yeasts were incubated in the wells with different concentrations of RB and illuminated with varying fluences of green light. The killing effects were analyzed by the plate dilution method. With an optimal combination of light and RB, 3-log growth inhibition was achieved. It was concluded that RB-aPDT might potentially inhibit drug-resistant C. albicans.

Visual Effect on Brain Connectome That Scales Feedforward and Feedback Processes of Aged Postural System During Unstable Stance.

Older adults with degenerative declines in sensory systems depend strongly on visual input for postural control. By connecting advanced neural imaging and a postural control model, this study investigated the visual effect on the brain functional network that regulates feedback and feedforward processes of the postural system in older adults under somatosensory perturbations. Thirty-six older adults conducted bilateral stance on a foam surface in the eyes-open (EO) and eyes-closed (EC) conditions while their center of pressure (COP) and scalp EEG were recorded. The stochastic COP trajectory was modeled with non-linear stabilogram diffusion analysis (SDA) to characterize shifts in postural control in a continuum of feedback and feedforward processes. The EEG network was analyzed with the phase-lag index (PLI) and minimum spanning tree (MST). The results indicated that visual input rebalanced feedforward and feedback processes for postural sway, resulting in a greater critical point of displacement (CD), short-term effective diffusion coefficients (Ds) and short-term exponent (Hs), but the smaller critical point of time (CT) and long-term exponent (Hl) for the EC state. The EC network demonstrated stronger frontoparietal-occipital connectivity but weaker fronto-tempo-motor connectivity of the theta (4-7 Hz), alpha (8-12 Hz), and beta (13-35 Hz) bands than did the EO network. MST analysis revealed generally greater leaf fraction and maximal betweenness centrality (BCmax) and kappa of the EC network, as compared with those of the EO network. In contrast, the EC network exhibited a smaller diameter and average eccentricity than those of the EO network. The modulation of long-term negative feedback gain of the aged postural system with visual occlusion was positively correlated with leaf fraction, BCmax, and kappa, but negatively correlated with the diameter and average eccentricity for all EEG sub-bands. In conclusion, the aged brain functional network in older adults is tuned to visual information for modulating long-term negative feedback of the postural system under somatosensory perturbations.

Acute physiological responses to combined blood flow restriction and low-level laser.

PURPOSE: Blood flow restriction (BFR) is an innovation in fitness to train muscles with low loads at low oxygen levels. Low-level laser therapy (LLLT) is a bio-energetic approach to alleviate muscle fatigue during resistance training. This study investigated the immediate effect of LLLT pre-conditioning on BFR that accelerates muscle fatigue due to ischemia. METHODS: Fifteen young adults participated in this study of a crossover randomized design. They completed a low-load contraction with various pre-conditioning (blood flow restriction with low-level laser therapy (LLLT + BFR), blood flow restriction with sham low-level laser therapy (BFR), and control). Force fluctuation dynamics, muscle oxygen saturation of hemoglobin and myoglobin (SmO2), and discharge patterns of motor units (MU) were compared. RESULTS: Normalized SmO2 during low-load contractions significantly varied with the pre-contraction protocols (Control (83.6 ± 3.0%) > LLLT + BFR (70.3 ± 2.8%) > BFR (55.4 ± 2.4%). Also, force fluctuations and MU discharge varied with the pre-contraction protocols. Multi-scale entropy and mean frequency of force fluctuations were greater in the LLLT + BFR condition (31.95 ± 0.67) than in the BFR condition (29.47 ± 0.73). The mean inter-spike interval of MUs was greater in the LLLT + BFR condition (53.32 ± 2.70 ms) than in the BFR condition (45.04 ± 1.08 ms). In particular, MUs with higher recruitment thresholds exhibited greater LLLT-related discharge complexity (LLLT + BFR (0.201 ± 0.012) > BFR (0.154 ± 0.006)). CONCLUSIONS: LLLT pre-conditioning can minimize the BFR-related decline in muscle oxygen saturation, leading to force gradation and MU discharge in a cost-effective and complex manner.

Fatigue-related modulation of low-frequency common drive to motor units.

PURPOSE: This study investigated fatigue-related modulation of common neural inputs to motor units (MUs) under 5 Hz, which determines force precision control. METHODS: Twenty-seven adults performed a sequence of fatiguing contractions. The participants were assessed with a static isometric index abduction at 20% maximal voluntary contraction in the pre-test and post-test. Discharge characteristics of MUs of the first dorsal interosseous muscle were analyzed with decomposed EMG signals. RESULTS: Along with increases in the mean (58.40 ± 11.76 ms → 62.55 ± 10.83 ms, P = 0.029) and coefficient of variation (0.204 ± .014 → 0.215 ± 0.017, P = 0.002) in inter-spike intervals, the fatiguing contraction caused reductions in the mean frequency (16.84 ± 3.31 Hz → 15.59 ± 3.21 Hz, P = 0.027) and spectral dispersions (67.54 ± 4.49 → 62.64 ± 6.76 Hz, P = 0.007) of common neural drive, as estimated with smoothed cumulative motor unit spike trains (SCMUSTs). Stabilogram diffusion analysis of SCMUSTs revealed significant fatigue-related reductions in the long-term effective diffusion coefficient (1.91 ± 0.77 Hz2/s → 1.61 ± 0.61 Hz2/s, P = 0.020) and long-term scaling exponent (0.480 ± 0.013 Hz2/s → 0.471 ± 0.017 Hz2/s, P = 0.014). After fatiguing contraction, mutual information of force fluctuations and SCMUSTs was augmented roughly by 12.95% (P = 0.041). CONCLUSIONS: Muscular fatigue could compress and shift the low-frequency common drive to MUs toward lower spectral bands, thereby enhancing transmission of twitch forces through the muscle-tendon complex with a low-pass filter property. The fatigue-induced changes involve increased closed-loop control of the common modulation of MU discharge rates.

Contrasting Age Effects on Complexity of Tracking Force and Force Fluctuations During Monorhythmic Contraction.

This study contrasted the stochastic force component between young and older adults, who performed pursuit tracking/compensatory tracking by exerting in-phase/antiphase forces to match a sinusoidal target. Tracking force was decomposed into the force component containing the target frequency and the nontarget force fluctuations (stochastic component). Older adults with inferior task performance had higher complexity (entropy across time; p = .005) in total force. For older adults, task errors were negatively correlated with force fluctuation complexity (pursuit tracking: r = -.527 to -.551; compensatory tracking: r = -.626 to -.750). Notwithstanding an age-related increase in total force complexity (p = .004), older adults exhibited lower complexity of the stochastic force component than young adults did (low frequency: p = .017; high frequency: p = .035). Those older adults with a higher complexity of stochastic force had better task performance due to the underlying use of a richer gradation strategy to compensate for impaired oscillatory control.

Naphthoquinone derivative PPE8 induces endoplasmic reticulum stress in p53 null H1299 cells.

Endoplasmic reticulum (ER) plays a key role in synthesizing secretory proteins and sensing signal function in eukaryotic cells. Responding to calcium disturbance, oxidation state change, or pharmacological agents, ER transmembrane protein, inositol-regulating enzyme 1 (IRE1), senses the stress and triggers downstream signals. Glucose-regulated protein 78 (GRP78) dissociates from IRE1 to assist protein folding and guard against cell death. In prolonged ER stress, IRE1 recruits and activates apoptosis signal-regulating kinase 1 (ASK1) as well as downstream JNK for cell death. Naphthoquinones are widespread natural phenolic compounds. Vitamin K3, a derivative of naphthoquinone, inhibits variant tumor cell growth via oxygen uptake and oxygen stress. We synthesized a novel naphthoquinone derivative PPE8 and evaluated capacity to induce ER stress in p53 null H1299 and p53 wild-type A549 cells. In H1299 cells, PPE8 induced ER enlargement, GRP78 expression, and transient IER1 activation. Activated IRE1 recruited ASK1 for downstream JNK phosphorylation. IRE1 knockdown by siRNA attenuated PPE8-induced JNK phosphorylation and cytotoxicity. Prolonged JNK phosphorylation may be involved in PPE8-induced cytotoxicity. Such results did not arise in A549 cells, but p53 knockdown by siRNA restored PPE8-induced GRP78 expression and JNK phosphorylation. We offer a novel compound to induce ER stress and cytotoxicity in p53-deficient cancer cells, presenting an opportunity for treatment.

Design of a novel flexible capacitive sensing mattress for monitoring sleeping respiratory.

In this paper, an algorithm to extract respiration signals using a flexible projected capacitive sensing mattress (FPCSM) designed for personal health assessment is proposed. Unlike the interfaces of conventional measurement systems for poly-somnography (PSG) and other alternative contemporary systems, the proposed FPCSM uses projected capacitive sensing capability that is not worn or attached to the body. The FPCSM is composed of a multi-electrode sensor array that can not only observe gestures and motion behaviors, but also enables the FPCSM to function as a respiration monitor during sleep using the proposed approach. To improve long-term monitoring when body movement is possible, the FPCSM enables the selection of data from the sensing array, and the FPCSM methodology selects the electrodes with the optimal signals after the application of a channel reduction algorithm that counts the reversals in the capacitive sensing signals as a quality indicator. The simple algorithm is implemented in the time domain. The FPCSM system is used in experimental tests and is simultaneously compared with a commercial PSG system for verification. Multiple synchronous measurements are performed from different locations of body contact, and parallel data sets are collected. The experimental comparison yields a correlation coefficient of 0.88 between FPCSM and PSG, demonstrating the feasibility of the system design.

Through diffusion tensor magnetic resonance imaging to evaluate the original properties of neural pathways of patients with partial seizures and secondary generalization by individual anatomic reference atlas.

To investigate white matter (WM) abnormalities in neocortical epilepsy, we extract supratentorial WM parameters from raw tensor magnetic resonance images (MRI) with automated region-of-interest (ROI) registrations. Sixteen patients having neocortical seizures with secondarily generalised convulsions and 16 age-matched normal subjects were imaged with high-resolution and diffusion tensor MRIs. Automated demarcation of supratentorial fibers was accomplished with personalized fiber-labeled atlases. From the individual atlases, we observed significant elevation of mean diffusivity (MD) in fornix (cres)/stria terminalis (FX/ST) and sagittal stratum (SS) and a significant difference in fractional anisotropy (FA) among FX/ST, SS, posterior limb of the internal capsule (PLIC), and posterior thalamic radiation (PTR). For patients with early-onset epilepsy, the diffusivities of the SS and the retrolenticular part of the internal capsule were significantly elevated, and the anisotropies of the FX/ST and SS were significantly decreased. In the drug-resistant subgroup, the MDs of SS and PTR and the FAs of SS and PLIC were significantly different. Onset age was positively correlated with increases in FAs of the genu of the corpus callosum. Patients with neocortical seizures and secondary generalisation had microstructural anomalies in WM. The changes in WM are relevant to early onset, progression, and severity of epilepsy.

Investigation of Subcortical Gray Matter in Patients with Non-lesional Neocortical Focal Epilepsy.

PURPOSE: To investigate whether there is any change in the subcortical gray matter of patients with neocortical focal epilepsy without visible magnetic resonance imaging (MRI) abnormalities. METHODS: MRI morphometric parameter data from 24 patients and 29 neurologically normal controls were analyzed. All of the MRI scans were reported to have no any anomaly. Differences were evaluated by vertex-wise shape analysis. RESULTS: A shape analysis showed significant surface reductions at the anterior-ventral and the posteriordorsal aspects of the bilateral thalami, the global left caudate nucleus, part of the bilateral dorsal putamen and the left hippocampus. CONCLUSION: Patients with focal seizures and secondary generalization had smaller volumes and microstructural anomalies in subcortical gray matter regions.

Painless skin electroporation as a novel way for insulin delivery.

BACKGROUND: Rigorous research efforts have been undertaken worldwide to develop a needle-free insulin delivery for many decades with limited success. This translational study aims to deliver insulin through skin with painless electroporation. METHODS: A recently designed microelectrode array was used to deliver insulin in mice with diabetes under electroporation conditions that are painless and harmless on human skin. RESULTS: Under such condition, a therapeutic amount of insulin was delivered successfully through mouse skin. Electroporation alone increased insulin transport around 100-fold compared with passive diffusion. Increased skin temperature to 40°C for 20 min augmented insulin transport to 237-fold more than the control value. Repeated electroporation showed no harm on human skin. CONCLUSION: The results indicate the potential of painless delivery of insulin through human skin in future clinical practice.

Methylene blue-mediated photodynamic inactivation as a novel disinfectant of enterovirus 71.

OBJECTIVES: We tested whether methylene blue, an inexpensive and safe photosensitizer, is feasible for photodynamic inactivation of enterovirus 71 (EV71) in the environment. METHODS: By escalating light doses and photosensitizer concentrations, photoinactivation of EV71 and other enteroviruses was examined in vitro. Viral transmission in the environment was simulated with a neonatal mouse model in vivo. Possible mechanisms were analysed with alterations of viral DNA and proteins after treatments. RESULTS: Photodynamic inactivation of EV71 in suspensions occurred in a dose-dependent manner. The optimal condition for photoinactivating EV71 required a light dose of 200 J/cm(2) in the presence of methylene blue. This photodynamic condition was also able to inactivate other enteroviruses, including poliovirus 1 and coxsackieviruses A2, A3, A16 and B3. In an imitation environment, EV71 spread on a solid surface was inactivated by methylene blue-mediated photodynamic inactivation and prevented EV71 transmission to mice. Western blot and RT-PCR analysis indicated that both the viral proteins and the genome were disrupted after photodynamic inactivation. CONCLUSIONS: Methylene blue-mediated photodynamic inactivation may provide a novel way to eliminate environmentally contaminated sources of EV71 to prevent infection.

Effects of micronization on the physico-chemical properties of peels of three root and tuber crops.

BACKGROUND: The aim of this study was to investigate the effect of micronization on the physicochemical properties of the peels of root and tuber crops, including yam (Dioscorea alata L.), taro (Colocasia esculenta L.) and sweet potato (Ipomea batatas L.). Two continuous milling sections, including hammer milling and ball milling, were applied to three samples to obtain micro-sized particles of root and tuber peels. The micronization by ball-milling treatment for 10 h was carried out to investigate the distribution of particle sizes and the changes in physiochemical properties. RESULTS: The results indicate that the peels of three crops appeared to be significantly decreased in particle size after 10 h of ball-milling treatment. Moreover, the ball-milling treatments resulted in the redistribution of fiber components from insoluble fiber to soluble fiber. The micronization treatments decreased the bulk density but increased the solubility and water-holding capacities of the micronized peels. CONCLUSION: Our findings suggested that micronization treatments can improve functional properties of the fiber components of micronized peels, which provide a good source of dietary fiber in food applications.

A novel application of the S-transform in removing powerline interference from biomedical signals.

Powerline interference always disturbs recordings of biomedical signals. Numerous methods have been developed to reduce powerline interference. However, most of these techniques not only reduce the interference but also attenuate the 60 Hz power of the biomedical signals themselves. In the present study, we applied the S-transform, which provides an absolute phase of each frequency in a multi-resolution time-frequency analysis, to reduce 60 Hz interference. According to results from an electrocardiogram (ECG) to which a simulated 60 Hz noise was added, the S-transform de-noising process restored a power spectrum identical to that of the original ECG coincident with a significant reduction in the 60 Hz interference. Moreover, the S-transform de-noised the signal in an intensity-independent manner when reducing the 60 Hz interference. In both a real ECG signal from the MIT database and natural brain activity contaminated with 60 Hz interference, the S-transform also displayed superior merit to a notch filter in the aspect of reducing noise and preserving the signal. Based on these data, a novel application of the S-transform for removing powerline interference is established.

Postural tremor and control of the upper limb in air pistol shooters.

A postural tremor appears whenever someone attempts to maintain a steady position against gravity. We examined the postural tremor that occurred while air pistol shooters were taking aim so as to compare the coordinative control of the shooters and to identify the features critical to successful shooting. Ten elite and ten pre-elite athletes participated in pistol shooting at 10 m, and the postural tremors in the pistol and upper limb were recorded with lightweight accelerometers. Exploratory analysis showed that the elite shooters had smaller tremor amplitudes than the pre-elite shooters in the pistol and distal arm segments. Compared with the pre-elite shooters, the elite shooters had a smaller tremor amplitude in the lateral direction relative to that in the vertical direction, together with weaker tremor coupling in the lateral direction and stronger vertical coupling of the pistol-hand complex. The resulting shot performance was inversely related to the amplitude of the tremor and to the 8-12 Hz spectral peak of the lateral tremor in the pistol-hand complex. We conclude that the postural tremors of air pistol shooters are associated with the skill of the shooters, and that the elite shooters could optimize the control of the pistol-hand complex, which strongly determined success in shooting.

Age effect on fatigue-induced limb acceleration as a consequence of high-level sustained submaximal contraction.

In reference to electromyographic measurement, the study was conducted to reassess differences in the behavior of fatigue-related neuromuscular function between young and elderly humans with limb acceleration (LA). Fourteen young and fourteen elderly subjects performed sustained index abduction at 75% of their maximal voluntary contractions (MVC) until task failure. Measures of neuromuscular function, including temporal/spectral features of muscle activity of the first dorsal interosseous (FDI) and LA of the index and hand, were monitored. The results showed a manifest fatigue-induced increase in LA of the index in the elderly group, but not in the young group. In contrast, only the young group developed a significant increase in amplitude of the electromyography (EMG) until task failure. Spectral analyses of LA in the index reflected marked age-dependent reorganization following muscle fatigue, with a greater reduction of relative spectral amplitude of LA in the range of 20-40 Hz, but a lesser reduction in coherence between EMG and LA in the elderly group. In line with fatigue-associated restructuring of LA, the mechanical coupling of the metacarpophalangeal joint was more severely undermined in the elderly group than in the young group. The present study manifested an age-related difference in the relative contributions of neural versus mechanical factors to muscle fatigue. Subsequent to a high-level sustained submaximal isometric contraction, a predominant mechanical failure of the musculotendon complex in the elderly was featured with LA, whereas EMG measurement characterized prevailing impairment of neuromuscular propagation in the young.

Exertion dependent alternations in force fluctuation and limb acceleration during sustained fatiguing contraction.

The study was conducted to contrast exertion-dependent changes in electromyography (EMG), force fluctuation (FF), and limb acceleration (LA) during isometric contraction to attain a versatile picture of muscle fatigue. Fifteen volunteers performed sustained index abduction at 25 and 75% maximal voluntary contractions (MVC) until failure at the tasks; meanwhile, changes in temporal/spectral features of force, muscle activity of the first dorsal interosseous (FDI), and acceleration of the index and hand were monitored. The results showed a manifest increase in all recorded signals for the 25% MVC paradigm, especially for LA, which demonstrated the largest increment in amplitude. In addition to progressive enhancement of the mechanical coupling of the metacarpophalangeal (MCP) joint, the 25% MVC paradigm added to EMG-FF and EMG-LA coherences (CohEMG-FF and CohEMG-LA) at 8-12 Hz and the shift of the spectral peak of the LA to higher frequencies. In contrast, the 75% MVC paradigm did not modulate significantly the spectral peak of LA. Also, CohEMG-FF, CohEMG-LA at 8-12 Hz, and the mechanical coupling of the MCP joint, were conversely undermined consequent to the high exertion paradigm. The present study suggests that LA was most susceptible to muscle fatigue following sustained contraction at a lower exertion level, and diverging alternations among various physiological signals ascribed to exertion-dependent contributions of central and peripheral origins to muscle fatigue.

Postural fluctuations during pointing from a unilateral or bilateral stance.

An experiment was conducted to compare the effects of bilateral and unilateral stance on postural fluctuations and intralimb coordination during active balance control. Fifteen participants stood bilaterally and unilaterally while conducting a pointing task with an outstretched arm. Excursion of center of foot pressure (CoP) and limb movements were recorded with a force plate and eight dual-axis accelerometers, respectively. Compared to bilateral stance, unilateral stance resulted in wider CoP trajectories and greater postural fluctuations, especially in the lower limbs. The limb-dependent postural fluctuations during unilateral stance were associated with an increased coupling between the upper limb segments and a decreased coupling between the segments of the stance leg. Unilateral stance further resulted in greater regularity and spectral changes in postural fluctuations of the trunk and lower limb due to increased central oscillations (8-15 Hz). The observed structural differences in postural fluctuations between unilateral and bilateral stance strongly suggested that the postural control system modulates joint stiffness in a stance-dependent manner. Probably, in unilateral stance, attentive control was shifted to the stance leg at the expense of increasing arm stiffness to reduce movement redundancy.

Painless electroporation with a new needle-free microelectrode array to enhance transdermal drug delivery.

A microelectrode array was designed to minimize the pain sensation of electroporation for enhancing transdermal drug delivery. The influence of the size of the electrode-skin contact area and of the distance between electrodes on the pain sensation was tested on human volunteers. The pain level decreased with the dimension of electrode-skin contact area and with inter-electrode distance. When both reached about 0.5 mm, the pain level was not perceptible even at the threshold of transdermal electroporation level of sixty electric pulses at 150 V, 1 ms at 1-10 Hz. An array of 11 x 11 alternately connected electrodes with 0.6 x 0.6 mm dimension was fabricated. The electric thresholds for effective drug delivery, using toluidine blue O as a marker on mouse skin, was found to be the same for microelectrode arrays as for larger electrodes and wider inter-electrode distances. In vivo transdermal electroporation using microelectrode array with 180 pulses of 150 V, 0.2 ms at 1 Hz, followed by 30 min methotrexate (MTX) occlusion increased more than 4 fold the systemic MTX level in mice. The results demonstrated the potential of painless delivery of significant amounts of chemotherapeutic agents through skin with the new electrode arrays in a clinical setting.