Development of Wearable Devices for Collecting Digital Rehabilitation/Fitness Data from Lower Limbs.

Lower extremity exercises are considered a standard and necessary treatment for rehabilitation and a well-rounded fitness routine, which builds strength, flexibility, and balance. The efficacy of rehabilitation programs hinges on meticulous monitoring of both adherence to home exercise routines and the quality of performance. However, in a home environment, patients often tend to inaccurately report the number of exercises performed and overlook the correctness of their rehabilitation motions, lacking quantifiable and systematic standards, thus impeding the recovery process. To address these challenges, there is a crucial need for a lightweight, unbiased, cost-effective, and objective wearable motion capture (Mocap) system designed for monitoring and evaluating home-based rehabilitation/fitness programs. This paper focuses on the development of such a system to gather exercise data into usable metrics. Five radio frequency (RF) inertial measurement unit (IMU) devices (RF-IMUs) were developed and strategically placed on calves, thighs, and abdomens. A two-layer long short-term memory (LSTM) model was used for fitness activity recognition (FAR) with an average accuracy of 97.4%. An intelligent smartphone algorithm was developed to track motion, recognize activity, and calculate key exercise variables in real time for squat, high knees, and lunge exercises. Additionally, a 3D avatar on the smartphone App allows users to observe and track their progress in real time or by replaying their exercise motions. A dynamic time warping (DTW) algorithm was also integrated into the system for scoring the similarity in two motions. The system's adaptability shows promise for applications in medical rehabilitation and sports.

Bluetooth-Based Healthcare Information and Medical Resource Management System.

This paper presents a healthcare information and medical resource management platform utilizing wearable devices, physiological sensors, and an indoor positioning system (IPS). This platform provides medical healthcare information management based on the physiological information collected by wearable devices and Bluetooth data collectors. The Internet of Things (IoT) is constructed for this medical care purpose. The collected data are classified and used to monitor the status of patients in real time with a Secure MQTT mechanism. The measured physiological signals are also used for developing an IPS. When the patient is out of the safety zone, the IPS will send an alert message instantly by pushing the server to remind the caretaker, easing the caretaker's burden and offering extra protection for the patient. The presented system also provides medical resource management with the help of IPS. The medical equipment and devices can be tracked by IPS to tackle some equipment rental problems, such as lost and found. A platform for the medical staff work coordination information exchange and transmission is also developed to expedite the maintenance of medical equipment, providing the shared medical information to healthcare and management staff in a timely and transparent manner. The presented system in this paper will finally reduce the loading of medical staff during the COVID-19 pandemic period.

Identification of discriminative neuroimaging markers for patients on hemodialysis with insomnia: a fractional amplitude of low frequency fluctuation-based machine learning analysis.

BACKGROUND AND OBJECTIVE: Insomnia is one of the common problems encountered in the hemodialysis (HD) population, but the mechanisms remain unclear. we aimed to (1) detect the spontaneous brain activity pattern in HD patients with insomnia (HDWI) by using fractional fractional amplitude of low frequency fluctuation (fALFF) method and (2) further identify brain regions showing altered fALFF as neural markers to discriminate HDWI patients from those on hemodialysis but without insomnia (HDWoI) and healthy controls (HCs). METHOD: We compared fALFF differences among HDWI subjects (28), HDWoI subjects (28) and HCs (28), and extracted altered fALFF features for the subsequent discriminative analysis. Then, we constructed a support vector machine (SVM) classifier to identify distinct neuroimaging markers for HDWI. RESULTS: Compared with HCs, both HDWI and HDWoI patients exhibited significantly decreased fALFF in the bilateral calcarine (CAL), right middle occipital gyrus (MOG), left precentral gyrus (PreCG), bilateral postcentral gyrus (PoCG) and bilateral temporal middle gyrus (TMG), whereas increased fALFF in the bilateral cerebellum and right insula. Conversely, increased fALFF in the bilateral CAL/right MOG and decreased fALFF in the right cerebellum was observed in HDWI patients when compared with HDWoI patients. Moreover, the SVM classification achieved a good performance [accuracy = 82.14%, area under the curve (AUC) = 0.8202], and the consensus brain regions with the highest contributions to classification were located in the right MOG and right cerebellum. CONCLUSION: Our result highlights that HDWI patients had abnormal neural activities in the right MOG and right cerebellum, which might be potential neural markers for distinguishing HDWI patients from non-insomniacs, providing further support for the pathological mechanism of HDWI.

Development of an Electronic Stethoscope and a Classification Algorithm for Cardiopulmonary Sounds.

With conventional stethoscopes, the auscultation results may vary from one doctor to another due to a decline in his/her hearing ability with age or his/her different professional training, and the problematic cardiopulmonary sound cannot be recorded for analysis. In this paper, to resolve the above-mentioned issues, an electronic stethoscope was developed consisting of a traditional stethoscope with a condenser microphone embedded in the head to collect cardiopulmonary sounds and an AI-based classifier for cardiopulmonary sounds was proposed. Different deployments of the microphone in the stethoscope head with amplification and filter circuits were explored and analyzed using fast Fourier transform (FFT) to evaluate the effects of noise reduction. After testing, the microphone placed in the stethoscope head surrounded by cork is found to have better noise reduction. For classifying normal (healthy) and abnormal (pathological) cardiopulmonary sounds, each sample of cardiopulmonary sound is first segmented into several small frames and then a principal component analysis is performed on each small frame. The difference signal is obtained by subtracting PCA from the original signal. MFCC (Mel-frequency cepstral coefficients) and statistics are used for feature extraction based on the difference signal, and ensemble learning is used as the classifier. The final results are determined by voting based on the classification results of each small frame. After the testing, two distinct classifiers, one for heart sounds and one for lung sounds, are proposed. The best voting for heart sounds falls at 5-45% and the best voting for lung sounds falls at 5-65%. The best accuracy of 86.9%, sensitivity of 81.9%, specificity of 91.8%, and F1 score of 86.1% are obtained for heart sounds using 2 s frame segmentation with a 20% overlap, whereas the best accuracy of 73.3%, sensitivity of 66.7%, specificity of 80%, and F1 score of 71.5% are yielded for lung sounds using 5 s frame segmentation with a 50% overlap.

Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19.

The COVID-19 pandemic is a worldwide health emergency which calls for an unprecedented race for vaccines and treatment. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein, S-2P. To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of neutralizing antibodies in sera of immunized mice against pseudotyped lentivirus reporter or live wild-type SARS-CoV-2. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018 and alum as a candidate vaccine to prevent COVID-19 disease.

MiR-291a-3p regulates the BMSCs differentiation via targeting DKK1 in dexamethasone-induced osteoporosis.

Osteoporosis is a skeleton disease affecting 55% of people over age 60, and the number is still increasing due to an ageing population. One method to prevent osteoporosis is to increase the formation of new bone while preventing the resorption of older bone. Thus, osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) is of great importance in improving the treatment of osteoporosis. On the other hand, glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders, but long-term exposure to GCs can induce osteoporosis. In present study, we treated BMSCs with dexamethasone (DEX) to simulate GC-induced osteoporosis. MTT assay, ALP activity, and Alizarin Red were used to evaluate the role miRNA-291a-3p in the DEX-induced osteogenic differentiation suppression. Further, we used qPCR and western blot to investigate the mechanisms of miRNA-291a-3p affecting BMSCs differentiation. The results showed that miRNA-291a-3p could improve the cell viability, osteogenic differentiation, and ALP activity, which are suppressed by DEX in BMSCs. Furthermore, we found that the osteogenesis genes Runx2, DMP1, and ALP were upregulated whereas the lipogenic genes C/EBPα and PPARγ were downregulated when miRNA-291a-3p mimics were transfected. Additionally, we demonstrated that miRNA-291a-3p promoted BMSCs' osteogenic differentiation by directly suppressing DKK1 mRNA and protein expression and subsequently activating Wnt/ß-catenin signaling pathway. Our study suggests that miR-291a-3p plays an important role in preventing osteoporosis and may serve as a potential miRNA osteoporosis biomarker.

Mechanisms Linking Ethical Leadership to Ethical Sales Behavior.

This study investigated the relationship between ethical leadership and ethical sales behavior. A total of 248 matched surveys with participant responses from insurance agents and their customers were collected. The insurance agents were asked to rate the ethical leadership of their leaders, the ethical climate in their organization, and their individual moral identity. Customers were asked to rate the perceived ethical sales behavior of the insurance agents. This empirical study utilized moderated mediation techniques to analyze the data. Results indicated that ethical climate mediated the relationship between ethical leadership and ethical sales behavior when moral identity was high, however, did not when moral identity was low. The research framework including contextual effects (i.e., ethical climate) and individual differences in moral judgment (i.e., moral identity) can provide a comprehensive picture of how ethical leadership influences ethical sales behavior. Theoretical and practical implications of these findings are also discussed.

Interleukin-1ß secreted from betanodavirus-infected microglia caused the death of neurons in giant grouper brains.

High interleukin (IL)-1ß gene expression was observed in dead giant grouper brains after nervous necrosis virus (NNV) infection. To investigate the neuronal death caused by NNV infection, primary tissue culture of giant grouper brains (pGB) was performed. In NNV-infected pGB cells, the viral capsid protein was detected in both neurons and microglia; furthermore, microglial proliferation and neuronal death were observed. The culture supernatant (CS) of NNV-infected pGB cells contained IL-1ß and tumor necrosis factor-α, which were mainly released from the microglia. A new batch of pGB cells was treated with CS, resulting in neuronal death, which could be prevented by blocking the IL-1ß in the CS by using anti-IL-1ß polyclonal antibodies. Moreover, pGB cells treated with recombinant IL-1ß showed microglial proliferation and neuronal death. Thus, NNV infection may activate microglial proliferation and stimulate microglial secretion of IL-1ß, which is a critical cytokine responsible for neuronal death in NNV-infected grouper brains.

Humoral and cytokine responses in giant groupers after vaccination and challenge with betanodavirus.

Giant groupers were immunized with two dosages (Vhigh and Vlow) of inactivated nervous necrosis virus (NNV) and subsequently challenged with NNV at 4 weeks post vaccination (wpv). Several indicators were used to analyze the protective effects of the NNV vaccine. The neutralizing antibody titer of fish serum mostly corresponded to the survival rate of immunized fish in the NNV challenge test. Extravascular IgM+ cells were detected in the brains of both NNV-infected and noninfected groupers. After NNV infection, CD8α and IgM gene expression increased in the brains, indicating CD8α+ and IgM+ lymphocyte infiltration. Moreover, the NNV load was not the highest in dead grouper brains, suggesting that this load in the brain was not the key factor for the death of groupers. However, the brains of dead fish showed the highest expression of the interleukin (IL)-1ß gene, a neurotoxic factor in the brain. Therefore, IL-1ß overexpression is likely to be associated with the death of NNV-infected groupers.

Decreasing salinity of seawater moderates immune response and increases survival rate of giant groupers post betanodavirus infection.

Giant groupers (Epinephelus lanceolatus), an important aquaculture fish in Asia, are attacked by nervous necrosis virus (NNV), belonging to betanodavirus. Environmental salinity can affect fish immunity and physiology. We examined whether decreasing salinity from 30 to 15 ppt during acclimation of groupers could affect survival with NNV infection and the associated factors. Although NNV infection decreased muscle moisture, up-regulated the gene expression of Na(+)-K(+)-2Cl(-) cotransporter isoform 2, and elevated plasma cortisol level in groupers, these factors were not related to the higher mortality of groupers reared at 30-ppt salinity (S30-groupers), compared to 15-ppt reared groupers (S15-groupers). Infected S30-groupers exhibited high leukocyte count and innate immune gene expression level. Moreover, NNV-infected dead S30-groupers showed high IL-1ß gene expression level but low NNV load in the brain. The high or excess IL-1ß gene expression levels in the brain of NNV-infected S30-groupers may be the factor in high mortality.

Immune gene expressions in grouper larvae (Epinephelus coioides) induced by bath and oral vaccinations with inactivated betanodavirus.

Nervous necrosis virus (NNV) has caused mass mortality in many mariculture fish species. Bath vaccination of inactivated NNV and oral immunization of recombinant NNV coat protein are reported to protect grouper larvae against NNV infection. However, the information of immune gene expression in grouper larvae (Epinephelus coioides) after bath and oral immunizations is still limited. In this study, grouper larvae were respectively bath- and orally immunized with binary ethylenimine (BEI)-inactivated NNV, and the expression levels of immune genes were analyzed. Significant gene expressions of IL-1ß, Mx, MHC-I, MHC-II, CD8α, IgM and IgT were observed in bath- and orally immunized fish 1-4 weeks post immunization (wpi). Particularly, the up-regulation of IL-1ß and Mx gene expression lasted for 4 weeks. The IgT gene expression in gill was only induced by bath immunization, while that in gut was only stimulated by oral immunization. Both immunizations elicited MHC-I and CD8α gene expression relative to cellular immunity. Furthermore, NNV RNA genome, which was detected in inactivated NNV, could induce Mx gene expression in grouper brain (GB) cells, indicating that NNV RNA genome could be recognized by pathogen-recognition receptors (PRRs). In summary, bath and oral vaccinations with BEI-inactivated NNV triggered the gene expression of not only humoral immunity but also cellular immunity.

Dietary supplementation of Pediococcus pentosaceus enhances innate immunity, physiological health and resistance to Vibrio anguillarum in orange-spotted grouper (Epinephelus coioides).

Groupers (Epinephelus spp.) are economically important fish species in Southeast Asian aquaculture. Vibriosis caused by Vibro spp. is one of the severe bacterial diseases that devastate the grouper aquaculture industry. Probiotics have been reported to show the potential to enhance fish immunity and to antagonize pathogens. In our previous study, a lactic acid bacterium Pediococcus pentosaceus strain 4012 (LAB4012), isolated from cobia intestine, protects cobia from photobacteriosis after a 2-week feeding. In this study, we examined the potential of LAB4012 to be a probiotic for the orange-spotted grouper through feeding, thus to guard against vibriosis. In vitro, LAB4012 culture supernatant with low pH suppressed the growth of Vibrio anguillarum, and lactic acid in the metabolite of LAB4012 appeared to be the major factor to the growth inhibition of V. anguillarum. In vivo, the challenge test showed that the cumulative mortality of the LAB4012-fed groupers was significantly lower than that of the control fish after V. anguillarum infection. Supplementation of LAB4012 in commercial diet not only enhanced the growth rate and erythrocyte numbers of the groupers, but also regulated the gene expression of the pro-/anti-inflammatory cytokines. One day post-infection of V. anguillarum, the leukocyte numbers in the peripheral blood and the phagocytic activity of the head-kidney phagocytes in the LAB4012-fed groupers were found significantly increased, when compared with those without LAB4012-feeding. These results suggested that LAB4012 can be a dietary probiotic for groupers in modulating the immunity and protecting the groupers from V. anguillarum infection.

Diet supplementation of Pediococcus pentosaceus in cobia (Rachycentron canadum) enhances growth rate, respiratory burst and resistance against photobacteriosis.

Cobia (Rachycentron canadum) is an economically important fish species for aquaculture in tropical and sub-tropical areas. Cobia aquaculture industry has severely damaged due to photobacteriosis caused by Photobacterium damselae subsp. piscicida (Pdp), especially in Taiwan. Antibiotics and vaccines have been applied to control Pdp infection, but the efficacy has been inconsistent. One species of lactic acid bacteria, Pediococcus pentosaceus strain 4012 (LAB 4012), was isolated from the intestine of adult cobia, and its culture supernatant can effectively inhibit Pdp growth in vitro. The acidic pH derived from metabolic acids in LAB culture supernatant was demonstrated to be an important factor for the suppression. After a 2-week feeding of LAB 4012, the growth rate of the fed cobia was 12% higher than that of the non-fed group, and the relative percentage of survival (RPS) of the fed cobia was found to be 74.4 in Pdp immersion challenge. In addition, the respiratory burst (RB) of peripheral blood leukocytes (PBL) in the LAB 4012-fed group was significantly higher than that of the non-fed group. Although feeding LAB 4012 did not improve specific antibody response in cobia after immunization with Pdp vaccine, it still significantly raised the survival rate by 22% over that of the non-fed group after Pdp immersion challenge. Judging by the quick induction of high protection against Pdp infection and promotion of growth in larvae, LAB 4012 was considered to be a viable probiotic for cobia aquaculture.

Persistently betanodavirus-infected barramundi (Lates calcarifer) exhibit resistances to red sea bream iridovirus infection.

Nervous necrosis virus (NNV) and red sea bream iridovirus (RSIV) are two important pathogens that have caused acute, highly contagious, and widespread diseases among wild and cultured fish, especially at larval and juvenile stages. We discovered that the pathogenicity of NNV to the 80 days post-hatch (dph) barramundi is lower than that to the 14 dph barramundi. Following NNV challenge, no mortality occurred in the 80 dph barramundi, but NNV RNA2 and barramundi Mx (BMx) gene expression was detected in the brain and liver. The 80 dph barramundi pre-challenged with NNV became more resistant to the following RSIV challenge (mortality: 62%) compared to the NNV-free barramundi challenged with RSIV (mortality: 100%). A similar phenomenon was revealed in the cell culture system that RSIV proliferated less progeny in the barramundi brain (BB) cell line which exhibit persistent NNV infection than in NNV-free cured BB (cBB) cell line. The potential factors involved in the resistance of the persistently NNV-infected barramundi and BB cells to the secondary RSIV infection were examined in this study. We prove that barramundi anti-NNV polyclonal antibodies do not cross-neutralize RSIV, and NNV infection does not interfere with RSIV replication. However, the interferon (IFN) response and BMx gene expression in cBB cells suppresses the RSIV proliferation. Our study suggests that the NNV-induced IFN response and BMx expression are responsible for the resistance of barramundi to RSIV infection.

Colon may provide new therapeutic targets for treatment of chronic kidney disease with Chinese medicine.

Chronic kidney disease (CKD) has become a worldwide health and social problem. Retarding its progression to end-stage renal disease is beneficial both to the patients and the healthcare system. Plenty of clinical trials have indicated that enema with Chinese medicine could effectively prevent chronic renal failure, and was widely used in the clinical practice. However, studies on mechanism were still nearly blank, which may prevent further improvement of therapeutic efficacy. Recent studies had discovered that colon was an important organ where uremic toxins were generated. The uremic toxins involved could not only promote CKD progression, but also was closely correlated with CKD mortality. Reducing production and promoting excretion of toxins were confirmed to reduce renal tubule interstitial fibrosis and delay renal progression. On the basis of the theory of gut-kidney axis above, we had conducted pilot clinical researches to evaluate the effect of enema with Chinese medicine on the intestinal flora, gut barrier, enterogenous uremic toxins and renal protection. The preliminary results revealed that rheum enema through colon could accelerate intestinal dynamics, improve intestinal barrier function, regulate intestinal flora and reduce production and absorption of intestine-derived uremic toxins such as indoxyl sulfate, which may reduce renal fibrosis and delay renal progression. Further studies could provide more evidence for colon as a new therapeutic target for the treatment of CKD with Chinese medicine.

Multidimensional relationships between paternalistic leadership and perceptions of organizational ethical climates.

This study investigated how paternalistic leadership is linked to ethical climates based on a multidimensional construct perspective. This experimental study utilized the partial least squares (PLS) techniques to analyze the data. Participants were 258 civil servants working in various public sectors in Taiwan, who were asked to rate their leaders' paternalistic leadership behaviors and their perception of the ethical climates in their organizations using the Paternalistic Leadership Scale and the Ethical Climate Questionnaire. Using the unidimensional constructs of paternalistic leadership and ethical climates, prior research showed vidence of a positive relationship; however, in the current study, multidimensional relations among these constructs may be positive or negative. The findings of this study suggested that leaders may implement specific types of paternalistic leadership to enhance the intended ethical climate in their organizations.

[Effects of Chinese herbal enema therapy combined basic treatment on BUN, SCr, UA, and IS in chronic renal failure patients].

OBJECTIVE: To assess the clearance role and safety of Chinese herbal enema therapy (CHET) in clearing enterogenic uremic toxins in chronic renal failure (CRF) patients, thus providing evidence for further optimizing the comprehensive treatment. METHODS: Using nonrandomized concurrent control trial, 96 CRF inpatients of Department of Nephropathy, Guangdong Provincial Hospital of Traditional Chinese Medicine, from March 2010 to December 2010 were assigned to the treatment group and the control group according to their willingness. All patients were treated with basic treatment referring to clinical plans in the non-dialysis phase, while those in the treatment group were additionally treated with CHET, once daily, 2 weeks as one therapeutic course. The symptoms, serum enterogenic uremic toxin levels [including indoxyl sulfate (IS), blood urea nitrogen (BUN), and uric acid (UA)], and serum creatinine (SCr) were observed in the two groups between and after treatment. The adverse reactions were also monitored during the treatment period. The clinical efficacy and safety were also assessed. RESULTS: Totally 84 patients completed this clinical observation, 48 in the treatment group and 36 in the control group. The levels of SCr, BUN, and IS were obviously lower in the treatment group after treatment, showing statistical difference when compared with before treatment (P<0.01). There was no statistical difference in each index in the control group between before and after treatment (P>0.05). The post-treatment the IS level was lower in the treatment group than in the control group with statistical difference (P<0.05). Symptoms like fatigue, soreness of waist and knees, constipation and edema were partially relieved in both groups (P<0.05, P<0.01). The ratios of anorexia and nausea in patients of the treatment group was lowered after treatment (P<0.05). Besides, patients in the treatment group could defecate for more than once daily during the enema treatment period, dominated as rotten and soft feces. No severe adverse event occurred during the treatment period. CONCLUSION: CHET combined basic treatment could lower the serum levels of enterogenic uremic toxins (IS and BUN) of CRF patients in a short period.

Motivational orientations and task autonomy fit: effects on organizational attraction.

The main purpose of this study was to investigate whether there is congruence between applicant needs (i.e., motivational orientations) and what is available (i.e., task autonomy) from an organizational perspective based on the fit between needs and supply. The fit between work motivation and task autonomy was examined to see whether it was associated with organizational attraction. This experimental study included two phases. Phase 1 participants consisted of 446 undergraduate students, of whom 228 were recruited to participate in Phase 2. The fit relations between task autonomy and intrinsic motivation and between task control and extrinsic motivation were characterized. Findings indicated that the fit between work motivation and task autonomy was positively associated with organizational attraction. Based on these results, it may be inferred that employers should emphasize job characteristics such as autonomy or control orientations to attract individuals, and focus on the most suitable work motivations for their organizations.

Computational pharmaceutical analysis of anti-Alzheimer's Chinese medicine Coptidis Rhizoma alkaloids.

Alzheimer's disease (AD) is an age-related neurodegenerative disease, affecting over 20 million people worldwide. Until recently, two major hypotheses were proposed regarding the molecular mechanism of pathogenesis: the cholinergic hypothesis and the amyloid cascade hypothesis. At present, acetylcholinesterase inhibitors are the most effective therapy for AD. Most pharmacological research has focused on the ability of acetylcholinesterase to alleviate cholinergic deficit and improve neurotransmission. Coptidis rhizoma and its isolated alkaloids are reported to possess a variety of activities, including neuroprotective and antioxidant effects. However, as yet no theoretical analysis exists to support this hypothesis. To examine this theory, we applied a computational pharmaceutical analysis to reveal that Chinese medicine Coptidis rhizoma alkaloids have much higher activities than Donepezil (commercial name is Aricept) by docking and scoring.