Potential adverse effects of face mask use on cardiopulmonary function and thermoregulation in robotic stroke rehabilitation during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease (COVID-19) pandemic led to the implementation of wearing face masks and social distancing in stroke rehabilitation to prevent airborne transmission and contain the virus. The use of masks causes hypoxia and dyspnea in patients with stroke, predisposing them to other harmful medical conditions. Despite the clinical importance of the potential risk of wearing masks during robotic stroke rehabilitation, no clinical evidence is available in the literature. OBJECTIVE: To examine the effects of stroke robotic rehabilitation with and without using a face mask on cardiopulmonary fatigue, muscle fatigue, O2 saturation, pulse, blood pressure (BP), and temperature in healthy adults and patients with hemiparetic stroke. METHOD: A total of 30 participants, comprising 20 males and 10 females, were enrolled in a case-control study and a cross-sectional randomized controlled trial conducted at the Center for Rehabilitation Hospital. The study population included 15 individuals with hemiparetic stroke (mean age: 57.26±8.69) and 15 healthy adult controls (mean age: 30.20±9.86). All participants underwent a 30-minute familiarization session, followed by experimental masked and unmasked robotic interactive gait training (RIGT) for at least 30 minutes. Clinical tests included the Borg Rating of Perceived Exertion, muscle fatigue via surface electromyography, O2 saturation, pulse, BP, and temperature. RESULTS: An analysis of covariance showed that compared to RIGT without a mask, RIGT with a mask showed adverse effects on BRPE, O2 saturation, and right rectus femoris muscle fatigue (P < 0.05) in the control and experimental groups. CONCLUSION: The clinical study revealed that compared to RIGT without a mask, RIGT with a mask affected cardiopulmonary fatigue, muscle fatigue, O2 saturation, pulse, and BP in healthy adults and participants with hemiparetic stroke.

Immediate effects of multimodal cognitive therapy in mild cognitive impairment.

BACKGROUND: Current therapeutic evidence suggests limited efficacy of the cognitive and exercise training in mild cognitive impairment (MCI) on depression, anxiety, memory retention, comprehension, calculation, concentration, orientation, dual-task performance, and sleep disorders. Nevertheless, the immediate effects of multimodal cognitive therapy (MCT) have recently developed and its individual effects remains unknown in MCI. OBJECTIVE: This study aimed to compare the immediate effects of MCT on cognitive and psychological measures between young healthy and older adults with MCI. METHODS: Forty young healthy and older adults with MCI underwent immediate MCT (5 minutes each), including transcranial direct current stimulation (tDCS), light therapy, computerized cognitive therapy (CCT), robotic-assisted gait training (RAGT), core breathing exercises (CBE), and music therapy. Outcome measures included memory retention, comprehension, calculation, attention, orientation, dual-task performance, awareness, depression, anxiety, and sleep disorders. The Mann-Whitney U test and Friedman's test were used at P < 0.05. RESULTS: Significant differences in depression, anxiety, memory retention, comprehension, calculation, attention, orientation, dual-task performance, and awareness were observed between the tDCS, CCT, and music therapy groups (P < 0.05). CONCLUSION: MCT was beneficial for mitigating depression, anxiety, memory retention, comprehension, calculation, attention, orientation, dual-task performance, and awareness.

The Effectiveness of a Multimodal Brain Empowerment Program in Mild Cognitive Impairment: A Single-Blind, Quasi-Randomized Experimental Study.

The present study aimed to determine a multimodal brain empowerment (MBE) program to mitigate the modifiable risk factors in mild cognitive impairment (MCI), and its therapeutic effects are unknown. MBE encompassing (1) tDCS, light therapy, computerized cognitive therapy (TLC) and (2) robot-assisted gait training, music therapy, and core exercise (REM) interventions were randomly assigned to 20 healthy young adults and 20 older adults with MCI. The electroencephalography (EEG) power spectrum and topographic event-related synchronization (ERS) analysis were used to assess intervention-related changes in neural activity during the MBE program. Outcome: The EEG results demonstrated that both multimodal TLC and REM decreased delta waves and increased theta, alpha, and beta waves (p < 0.001). ERS showed increased neural activation in the frontal, temporal, and parietal lobes during TLC and REM. Such enhanced neural activity in the region of interest supports potential clinical benefits in empowering cognitive function in both young adults and older adults with MCI.

Self-perception and anticipated efficacy of the anti-dementia multimodal program in 100 older adults with mild cognitive impairment.

BACKGROUND: Effective and sustainable interventions are clearly needed for mild cognitive impairment (MCI) patients. Despite the clinical importance of the multimodal intervention approach, only one study using a multimodal approach demonstrated promising improvements in memory, attention, and executive functions, which also correlated with functional magnetic resonance imaging (MRI) blood oxygenation level dependent (BOLD) changes in cerebral activation in 50 MCI patients. OBJECTIVE: To investigate the self-perception and anticipated efficacy of each element of the BRAIN-FIT multimodal intervention program (robotic-assisted gait training (RAGT), computerized cognitive therapy, music, light, transcranial direct current stimulation (tDCS), and diaphragmatic breathing exercises) and the correlation between memory, concentration, depression, and sleep in older adults with MCI. METHODS: One hundred participants (mean±standard deviation: 8.63±78.4 years; 47 women) with MCI were recruited from a major university medical center and community dementia relief center. The survey questionnaire comprised four domains with 21 questions, including four pertaining to general demographic characteristics, eight related to exercise and activity, three related to sleep, and nine related to the BRAIN-FIT program. Chi-squared test was used to analyze the Likert scale data. The descriptive frequencies were calculated. Additionally, Spearman's rho statistics measure the rank-order association. The statistical significance was at P < 0.05. RESULTS: A strong correlation was observed between memory and concentration (r = 0.850, P = 0.000), memory and depression (r = 0.540, P = 0.000), memory and sleep (r = 0.502, P = 0.000), concentration and depression (r = 0.602, P = 0.000), concentration and sleep (r = 0.529, P = 0.000) and sleep and depression (r = 0.497, P = 0.000). The correlation between medical services and sleep (r = 0.249, P = 0.012) was moderate. The chi-square test revealed a significant difference in memory and low-intensity duration of exercise (χ2[3,N = 100] = 11.69, P = 0.01), concentration and high-intensity exercise duration (χ2[3,N = 100] = 10.08, P = 0.02), concentration with low-intensity exercise duration (χ2[3,N = 100] = 21.11, P = 0.00), depression with high-intensity (χ2[3,N = 100] = 10.36, P = 0.02), high-intensity duration of exercise (χ2[3,N = 100] = 10.48, P = 0.02); low-intensity (χ2[3,N = 100] = 7.90, P = 0.48), and low-intensity duration of exercise (χ2[3,N = 100] = 9.69, P = 0.02). Additionally, significant differences were observed between sleep and high-intensity (χ2[3, N = 100] = 10.36, P = 0.02), low-intensity (χ2[3, N = 100] = 18.14, P = 0.00), and low-intensity duration of exercise (χ2[3, N = 100] = 18.30, P = 0.00). Among the participants 5% answered RAGT, and 20% responded that they had experienced computerized cognitive therapy. Music therapy (20 %), diaphragmatic breathing exercises (45 %), and light therapy (10 %) were used. No patient had experienced tDCS. Conversely, 11% of the participants answered RAGT for programs they wanted to experience and 21% responded to computerized cognitive therapy. 25% of music therapy, 22% of diaphragmatic breathing exercises, 5% of light therapy, and 16% of tDCS participants said they wanted to experience it. Finally, 63% of the participants wanted to participate in the BRAIN-FIT program. CONCLUSION: The present study's results provide clinical evidence-based insights into the utilization of BRAIN-FIT in MCI to maximize cognitive score improvement of memory, concentration, depression, and sleep. Therefore, when designing the BRAIN-FIT, six intervention items were set in proportion to the preference based on the survey, to reduce participants' feeling of repulsion. The program was configured according to exercise intensity.

Comparative Effectiveness of Artificial Intelligence-Based Interactive Home Exercise Applications in Adolescents with Obesity.

The rate of obesity in adolescents has increased due to social distancing measures and school closures caused by the COVID-19 pandemic. These issues have caused adolescents to change their lifestyles and eating habits. Furthermore, the growth in inactive behavior and computer screen or watching TV time, as well as the reduction in physical activity, could similarly be related with obesity. To overcome this problem, we recently developed an artificial intelligence (AI)-based gesture recognition game application called Super Kids Adventure (SUKIA, Funrehab, Daejeon, Korea), which provides inexpensive and motivational game applications. This research is designed to assess the effects of SUKIA and Nintendo Switch (NINS) on calorie consumption, VO2 max, 6-minute walking test (6MWT) as well as body mass index (BMI), and the Borg rating of perceived exertion scale (RPE) in adolescents with obesity. A convenience sample of 24 adolescents with obesity were randomized into either the NINS or SUKIA groups 5 days/week for 3 weeks. Analysis of variance (ANOVA) and independent t-tests were presented with significant level at p < 0.05, and the analysis indicated that SUKIA showed superior effects on calorie consumption, VO2 max, and RPE compared to NINS. Our results provide evidence that SUKIA can more effectively improve cardiopulmonary function and calorie consumption than NINS in adolescents with obesity during COVID-19.

Stage 2: Who Are the Best Candidates for Robotic Gait Training Rehabilitation in Hemiparetic Stroke?

We aimed to compare the effects of robotic-assisted gait training (RAGT) in patients with FAC < 2 (low initial functional ambulation category [LFAC]) and FAC ≥ 2 (high initial functional ambulation category [HFAC]) on sensorimotor and spasticity, balance and trunk stability, the number of steps and walking distance in subacute hemiparetic stroke. Fifty-seven patients with subacute hemiparetic stroke (mean age, 63.86 ± 12.72 years; 23 women) were assigned to two groups. All patients received a 30-min Walkbot-assisted gait training session, 3 times/week, for 6 weeks. Clinical outcomes included scores obtained on the Fugl-Meyer Assessment (FMA) scale, Modified Ashworth Scale (MAS), Berg Balance Scale (BBS), trunk impairment scale (TIS), and the number of walking steps and walking distance. Analysis of covariance and analysis of variance were conducted at p < 0.05. Significant main effects of time in both groups on number of walking steps and distance (p < 0.05) were observed, but not in MAS (p> 0.05). Significant changes in FMA, BBS, and TIS scores between groups (p < 0.05) were observed. Significant main effects of time on BBS and TIS were demonstrated (p < 0.05). Our study shows that RAGT can maximize improvement in the functional score of FMA, BBS, TIS, steps, and distance during neurorehabilitation of subacute stroke patients regardless of their FAC level.

Efficacy and local irritation evaluation of Eriobotrya japonica leaf ethanol extract.

BACKGROUND: Although Eriobotrya japonica leaves have been studied as a raw material for various cosmetic products, little is known about the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of Eriobotrya japonica leaf ethanol extract (EJEE). METHODS: This study was conducted to evaluate the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of EJEE using different in vitro models. In addition, we investigated the potential irritation of EJEE to skin and eye using animal alternative tests. RESULTS: The total content of polyphenols, one of the active constituents of EJEE, was analyzed by high-performance liquid chromatography and found to contain 88.68 mg tannic acid equivalent/g. EJEE showed a concentration-dependent 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging activity, and a superoxide dismutase-like activity. The anti-inflammatory effect of 0.5% (w/v) EJEE was demonstrated by a reduction in lipopolysaccharide-induced nitric oxide and tumor necrosis factor-alpha levels in RAW 264.7 cells. EJEE also significantly inhibited melanogenesis in melanocyte stimulating hormone-induced B16F1 cells. EJEE did not show any irritation in skin and eye in animal alternative test. CONCLUSIONS: These results indicate that the EJEE possesses anti-oxidant, anti-inflammatory, and anti-melanogenic activities, while it did not induce toxicity or irritation in neither skin nor eye. Therefore, EJEE can be used as a cosmetic ingredient for skin improvement.

A glasses-type wearable device for monitoring the patterns of food intake and facial activity.

Here we present a new method for automatic and objective monitoring of ingestive behaviors in comparison with other facial activities through load cells embedded in a pair of glasses, named GlasSense. Typically, activated by subtle contraction and relaxation of a temporalis muscle, there is a cyclic movement of the temporomandibular joint during mastication. However, such muscular signals are, in general, too weak to sense without amplification or an electromyographic analysis. To detect these oscillatory facial signals without any use of obtrusive device, we incorporated a load cell into each hinge which was used as a lever mechanism on both sides of the glasses. Thus, the signal measured at the load cells can detect the force amplified mechanically by the hinge. We demonstrated a proof-of-concept validation of the amplification by differentiating the force signals between the hinge and the temple. A pattern recognition was applied to extract statistical features and classify featured behavioral patterns, such as natural head movement, chewing, talking, and wink. The overall results showed that the average F1 score of the classification was about 94.0% and the accuracy above 89%. We believe this approach will be helpful for designing a non-intrusive and un-obtrusive eyewear-based ingestive behavior monitoring system.

Inhibition of lipopolysaccharide-induced proinflammatory responses by Buddleja officinalis extract in BV-2 microglial cells via negative regulation of NF-kB and ERK1/2 signaling.

Buddleja officinalis has been traditionally used in the supportive treatment of inflammatory and neuronal diseases in Korea and China. Although several reports have shown the anti-inflammatory effects of Buddleja officinalis, the anti-neuroinflammatory effect has remained unclear. In this study, we aimed to investigate the inhibitory effects of flower buds of B. officinalis Maximowicz water extract (BOWE) on LPS-induced inflammatory processes in BV-2 microglial cells. BOWE dose-dependently inhibited the production of nitric oxide as well as iNOS mRNA expression. Moreover, BOWE prevented IL-1ß and IL-6 mRNA expression. However, BOWE had no effect on LPS-induced COX-2 or TNF-a mRNA expression. The extract also had no effect on LPS-stimulated p38 MAPK, JNK, and c-Jun phosphorylation, whereas ERK1/2 phosphorylation was strongly inhibited by BOWE. BOWE also inhibited the LPS-induced degradation of IkB-α, and LPS-induced phosphorylation of p65 NF-kB protein. These data indicate that BOWE inhibited the nitric oxide production and pro-inflammatory gene expression in BV-2 microglial cells, possibly through a negative regulation of the NF-kB and ERK1/2 pathways. Further identification of the direct target molecule(s) of BOWE is required to support its use as an anti-neuroinflammatory agent against the neurodegenerative disorders.

Antiplatelet activity of Phellinus baummii methanol extract is mediated by cyclic AMP elevation and inhibition of collagen-activated integrin-α(IIb) ß3 and MAP kinase.

Phellinus baumii is a mushroom that has been used as folk medicine against various diseases and is reported to have antidiabetic, anticancer, antioxidant, antiinflammatory and antihypertensive activities. However, information on the effects of P. baumii extract in platelet function is limited. Therefore, the aim of this study was to examine the impact of a P. baumii methanol extract (PBME) on platelet activation and to investigate the mechanism behind its antiplatelet activity. PBME effects on agonist-induced platelet aggregation, granule secretion, [Ca²âº](i) mobilization, α(IIb) ß3 activation, cyclic AMP release and mitogen-activated protein kinase (MAPK) phosphorylations were studied using rat platelets. PBME dose-dependently inhibited collagen, thrombin and ADP-induced platelet aggregation with an IC50 of 51.0 ± 2.4, 54.0 ± 2.1 and 53.0 ± 4.3 µg/mL, respectively. Likewise, thrombin-induced [Ca²âº](i) and collagen-activated ATP secretions were suppressed in PBME treated platelets. Aggregation and ATP secretion were also markedly attenuated by PBME alone or in combination with PP2 (Src inhibitor) and U-73122 (PLC inhibitor) in collagen-stimulated platelets. Besides, PBME treatment elevated basal cyclic AMP levels and inhibited collagen-induced integrin-α(IIb) ß3 activation. Moreover, PBME attenuated extracellular-signal-regulated protein kinase 2 (ERK2) and c-Jun N-terminal kinase 1 (JNK1) phosphorylations. Further PD98059 (ERK inhibitor) and SP60025 (JNK inhibitor) reduced collagen-induced platelet aggregation and ATP secretion. In conclusion, the observed PBME antiplatelet activity may be mediated by activation of cyclic AMP and inhibition of ERK2 and JNK1 phosphorylations. Finally, these data suggest that PBME may have therapeutic potential for the treatment of cardiovascular diseases that involve aberrant platelet function.

12 Arylstibonic acids that inhibit the DNA binding of five B-ZIP dimers.

Previously, we identified an arylstibonic acid, NSC13778 that specifically binds to the basic region of the C/EBPalpha B-ZIP domain and disrupts DNA binding. We now examine a panel of 14 additional arylstibonic acid derivatives of NSC13778 for their ability to inhibit the DNA binding of five B-ZIP dimers (c-Fos|JunD, VBP, C/EBPalpha, C/EBPbeta, and CREB). They show various specificities at inhibiting the DNA binding of five B-ZIP domains. NSC13746 inhibits the DNA binding of C/EBPbeta and CREB at 100nM and promiscuously inhibiting the DNA binding of all five proteins in the 1muM range. Dialysis experiments indicate that NSC 13746 binding to the B-ZIP domain is reversible. Thermal denaturation studies indicate that NSC13746 binds the B-ZIP domain. Some compounds specifically inhibit DNA binding, with VBP and c-Fos|JunD being most easily disrupted. These compounds inhibit, with similar specificities to the pure B-ZIP domains, the DNA binding of nuclear extract to the AP1 DNA sequence but no inhibition is observed to SP1 containing oligonucleotide. Transient transfection assays indicate that NSC13746 can inhibit the TPA induced activation of two B-ZIP dependent reporters. These experiments suggest that arylstibonic acids are promising leads for inhibiting the DNA binding of a group of B-ZIP proteins in cells.

Histological and proteomic analysis of reversible H-RasV12G expression in transgenic mouse skin.

We have used a two-transgene tetracycline system to reversibly express oncogenic H-Ras(V12G) in mouse skin and primary keratinocytes culture using the bovine keratin 5 promoter. Induction of H-Ras(V12G) expression in skin at 30 days after birth causes epidermal basal cell hyperplasia, an eruption of keratinous cysts and loss of hair follicles by 3 weeks. Subsequent H-Ras(V12G) de-induction for 3 days results in massive apoptosis in the non-H-Ras(V12G)-expressing stroma as well as in the suprabasal cells of the epidermis. Several procaspases such as CASP3, 1alpha, 5 and 12 disappeared, whereas the pro-apoptotic proteins AIF, Bax and Fas ligand were induced in H-Ras(V12G) de-induction skin. This process is followed by a wave of cell division at 14 days as hair follicles regrew, returning to near normal histology and skin appearance by 30 days. Using Kinetworkstrade mark multi-immunoblotting screens, the phosphorylation status of 37 proteins and expression levels of 75 protein kinases in the skin were determined in three samples: (i) wild-type skin, (ii) hyperplastic H-Ras(V12G)-expressing skin and (iii) skin where H-Ras(V12G) expression was suppressed for 7 days. Following H-Ras(V12G) induction, 16 kinases were increased over 2-fold, and 2 kinases were reduced over 50%. This included increased phosphorylation of both known downstream H-Ras(V12G) targets and unknown H-Ras(V12G) targets. After H-Ras(V12G) suppression, many but not all protein changes were reversed. These results from skin and primary keratinocytes are organized to reflect the molecular events that cause the histological changes observed. These proteomic changes identify markers that may mediate the oncogenic addiction paradigm.

Accelerated tumor formation in a fatless mouse with type 2 diabetes and inflammation.

Epidemiologic studies show a positive association between obesity and cancer risk. In addition to increased body adiposity and secretion of fat-derived hormones, obesity is also linked to insulin resistance, type 2 diabetes, and chronic inflammation. We used the fatless A-ZIP/F-1 transgenic mouse to dissociate the relative role of each of these underlying factors in the development of cancer. These mice are unique in that they do not have white fat but do develop type 2 diabetes. In two cancer models, the classic two-stage skin carcinogenesis protocol and the C3(1)/T-Ag transgenic mouse mammary tumor model, A-ZIP/F-1 mice displayed higher tumor incidence, tumor multiplicity, and decreased tumor latency than wild-type mice. We examined circulating levels of adipokines, growth factors, and cytokines. As expected, adipokines (i.e., leptin, adiponectin, and resistin) were undetectable or found at very low levels in the blood of fatless mice. However, insulin, insulin-like growth factor-I, growth hormone, vascular endothelial growth factor, and proinflammatory Th2 cytokines, such as interleukin (IL)-1beta, IL-4, and IL-6, were elevated in A-ZIP/F-1 mice. Additionally, we examined multiple phosphorylated proteins (i.e., protein kinase B/Akt and ErbB2/HER-2 kinase) associated with cancer development. Results show that many of these phosphorylated proteins were activated specifically in the A-ZIP/F-1 skin but not in the wild-type skin. These findings suggest that adipokines are not required for the promotion of tumor development and thus contradict the epidemiologic data linking obesity to carcinogenesis. We postulate that insulin resistance and inflammation are responsible for the positive correlation with cancer observed in A-ZIP/F-1 mice.

A new hepatocytic isoform of PLZF lacking the BTB domain interacts with ATP7B, the Wilson disease protein, and positively regulates ERK signal transduction.

The promyelocytic leukemia zinc finger (PLZF) protein has been described as a transcriptional repressor of the BTB-domain/zinc-finger family, and shown to regulate the expression of Hox genes during embryogenesis and the expression of cyclin A in the cell cycle progression. Here, a 45-kDa isoform of PLZF without a BTB domain was identified via yeast two-hybrid screening using the C-terminal region of ATP7B as bait in our determination of the biological roles of the Wilson disease protein outside of its copper-binding domain. Our immunoprecipitation experiments showed that the hepatocytic isoform of PLZF could specifically interact with the C-terminal region of ATP7B. The immunostaining of HepG2 cells revealed that the ATP7B and PLZF proteins were apparently colocalized into the trans-Golgi complexes. It was also determined that disruption of PLZF expression in the HepG2 cells affected an attenuation of ERK activity in a dose-dependent manner. The hepatocytic activities of ERK kinase were found to be enhanced as the result of PLZF or ATP7B expression, but this enhancement was abrogated by the deletion of the C-terminal region of ATP7B. Furthermore, a transgenic Drosophila strain that ectopically expressed the hepatocytic deltaBTB-PLZF exhibited phenotypic changes in eye and wing development, and these alterations were fully recovered as the result of ATP7B expression, indicating the obvious in vivo interaction between the two proteins. Those PLZF-induced abnormalities were attributed to the enhancement of ERK signaling, as was shown by phenotypic reversions with loss-of-function mutations in ERK signal transduction in Drosophila. These data suggest the existence of a mechanism that regulates ERK signaling via the C-terminus of ATP7B and the ATP7B-interacting hepatocytic PLZF.