Inflammatory biomarkers predict higher risk of hyperglycemic crises but not outcomes in diabetic patients with COVID-19.

Background: Inflammation is a predictor of severe complications in patients with COVID-19 infection under a variety of clinical settings. A few studies suggested that COVID-19 infection was a trigger of hyperglycemic crises including diabetic ketoacidosis (DKA) and/or hyperglycemic hyperosmolar state (HHS). However, the association between inflammation and hyperglycemic crises in diabetic patients with COVID-19 infection is unclear. Methods: One hundred and twenty-four patients with type 2 diabetes mellitus (T2DM) and COVID-19 infection from January 2023 to March 2023 were retrospectively analyzed. Demographic, clinical, and laboratory data, especially inflammatory markers including white blood cell (WBC), neutrophils, neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP) and procalcitonin (PCT) were collected and compared between patients with or without DKA and/or HHS. Multivariable logistic regression analysis was conducted to explore the association between inflammatory biomarkers and the prevalence of hyperglycemic crises. Patients were followed up 6 months for outcomes. Results: Among 124 diabetic patients with COVID-19, 9 were diagnosed with DKA or HHS. Comparing COVID-19 without acute diabetic complications (ADC), patients with DKA or HHS showed elevated levels of c-reactive protein (CRP, P=0.0312) and procalcitonin (PCT, P=0.0270). The power of CRP and PCT to discriminate DKA or HHS with the area under the receiver operating characteristics curve (AUROC) were 0.723 and 0.794, respectively. Multivariate logistic regression indicated 1.95-fold and 1.97-fold increased risk of DKA or HHS with 1-unit increment of CRP and PCT, respectively. However, neither CRP nor PCT could predict poor outcomes in diabetic patients with COVID-19. Conclusion: In this small sample size study, we firstly found that elevated serum CRP and PCT levels increased the risk of hyperglycemic crises in T2DM patients with COVID-19 infection. More study is needed to confirm our findings.

[Effects of allicin on insulin resistance and free fatty acid levels in obese rats with periodontitis].

PURPOSE: To explore the effects of allicin on insulin resistance and free fatty acids (FFAs) levels in obese rats with periodontitis. METHODS: Forty rats were randomly divided into healthy group, periodontitis group, and low, medium and high dose groups, with 8 rats in each group. The healthy group was healthy rats, and the other groups were induced by sodium glutamate(MSG). After successfully establishing an obesity model, the maxillary molars were ligated and smeared to establish a periodontitis model. Both the periodontitis group and the healthy group were given normal saline, and the allicin low, medium and high dose groups were given allicin 20，40 and 60 mg·kg-1·d-1, mixed with feed for oral administration. After 21 days of treatment, the fasting blood glucose(FPG), fasting insulin (FINS), insulin resistance index (HOMA-IR) scores and FFAs levels of the homeostatic model in rats were detected. The protein expression of TLR4/MyD88 signaling pathway were compared. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: Compared with the healthy group, FPG, FINS levels, HOMA-IR, IL-6 and TNF-α levels of the periodontitis group were significantly increased, and the expression of TLR4 and MyD88 proteins was significantly increased(P＜0.05). Compared with the periodontitis group, FPG, FINS levels, HOMA-IR, IL-6 and TNF-α levels of low, medium and high-doses groups were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (P＜0.05). Compared with the low-dose group, the levels of FPG and FINS, HOMA-IR, IL-6 and TNF-α levels of the middle and high-dose groups were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (P＜0.05). Compared with the middle-dose group, the levels of FPG and FINS, HOMA-IR, IL-6 and TNF-α levels of the high-dose group were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (P＜0.05). After treatment, FFAs of the low, medium and high-dose groups were significantly lower than those before treatment(P＜0.05). Compared with the healthy group, FFAs levels of the periodontitis group, low-dose and medium-dose groups were significantly increased. Compared with the periodontitis group, FFAs levels of the low, medium and high-dose groups were significantly increased. Compared with the low-dose group, FFAs levels of the high-dose group were significantly increased. Compared with the middle-dose group, FFAs levels of the high-dose group were significantly increased (P＜0.05). CONCLUSIONS: Allicin can improve insulin resistance and obesity in obese rats with periodontitis, and its mechanism of action is related to the TLR4/MyD88 signaling pathway.

Exoskeleton-Assisted Sit-to-Stand Training Improves Lower-Limb Function Through Modifications of Muscle Synergies in Subacute Stroke Survivors.

Abnormal muscle synergies during sit-to-stand (STS) transitions have been observed post-stroke, which are associated with deteriorated lower-limb function and mobility. Although exoskeletons have been used in restoring lower-limb function, their effects on muscle synergies and lower-limb motor recovery remain unclear. Here, we characterized normal muscle synergy patterns during STS activity in ten healthy adults as a reference, comparing with pathological muscle synergy patterns in ten participants with subacute stroke. Moreover, we assessed the effects of a 3-week exoskeleton-assisted STS training intervention on muscle synergies and clinical scores in seven stroke survivors. We also investigated correlations between neuromuscular complexity of muscle synergies and clinical scores. Our results showed that the STS task involved three motor modules representing distinct biomechanical functions among healthy subjects. In contrast, stroke participants showed 3 abnormal modules for the paretic leg and 2 modules for the non-paretic leg. After the intervention, muscle synergies partially shifted towards the normal pattern observed in healthy subjects on the paretic side. On the non-paretic side, the synergy modules increased to three and neuromuscular coordination improved. Furthermore, the significant intervention-induced increases in Fugl-Meyer Assessment of Lower Extremity and Berg Balance Scale scores were associated with improved muscle synergies on the non-paretic side. These results indicate that the paretic side demonstrates abnormal changes in muscle synergies post-stroke, while the non-paretic side can synergistically adapt to post-stroke biomechanical deviations. Our data show that exoskeleton-based training improved lower-limb function post-stroke by inducing modifications in muscle synergies.

Exoskeleton-Assisted Anthropomorphic Movement Training for the Upper Limb After Stroke: The EAMT Randomized Trial.

BACKGROUND: Robot-assisted arm training is generally delivered in the robot-like manner of planar or mechanical 3-dimensional movements. It remains unclear whether integrating upper extremity (UE) natural coordinated patterns into a robotic exoskeleton can improve outcomes. The study aimed to compare conventional therapist-mediated training to the practice of human-like gross movements derived from 5 typical UE functional activities managed with exoskeletal assistance as needed for patients after stroke. METHODS: In this randomized, single-blind, noninferiority trial, patients with moderate-to-severe UE motor impairment due to subacute stroke were randomly assigned (1:1) to receive 20 sessions of 45-minute exoskeleton-assisted anthropomorphic movement training or conventional therapy. Treatment allocation was masked from independent assessors, but not from patients or investigators. The primary outcome was the change in the Fugl-Meyer Assessment for Upper Extremity from baseline to 4 weeks against a prespecified noninferiority margin of 4 points. Superiority would be tested if noninferiority was demonstrated. Post hoc subgroup analyses of baseline characteristics were performed for the primary outcome. RESULTS: Between June 2020 and August 2021, totally 80 inpatients (67 [83.8%] males; age, 51.9±9.9 years; days since stroke onset, 54.6±38.0) were enrolled, randomly assigned to the intervention, and included in the intention-to-treat analysis. The mean Fugl-Meyer Assessment for Upper Extremity change in exoskeleton-assisted anthropomorphic movement training (14.73 points; [95% CI, 11.43-18.02]) was higher than that of conventional therapy (9.90 points; [95% CI, 8.15-11.65]) at 4 weeks (adjusted difference, 4.51 points [95% CI, 1.13-7.90]). Moreover, post hoc analysis favored the patient subgroup (Fugl-Meyer Assessment for Upper Extremity score, 23-38 points) with moderately severe motor impairment. CONCLUSIONS: Exoskeleton-assisted anthropomorphic movement training appears to be effective for patients with subacute stroke through repetitive practice of human-like movements. Although the results indicate a positive sign for exoskeleton-assisted anthropomorphic movement training, further investigations into the long-term effects and paradigm optimization are warranted. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100044078.

Effects of repetitive peripheral magnetic stimulation for the upper limb after stroke: Meta-analysis of randomized controlled trials.

Introduction: Repetitive peripheral magnetic stimulation (rPMS) can stimulate profound neuromuscular tissues painlessly to evoke action potentials in motor axons and induce muscle contraction for treating neurological conditions. It has been increasingly used in stroke rehabilitation as an easy-to-administer approach for therapeutic neuromodulation. Objective: We performed this meta-analysis of randomized controlled trials to systematically evaluate the effects of rPMS for the upper limb in patients with stroke, including motor impairment, muscle spasticity, muscle strength, and activity limitation outcomes. Methods: The meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, EMBASE, Web of Science, Cochrane Library, and Physiotherapy Evidence Database (PEDro) were searched for articles published before June 2022. Forest plots were employed to estimate the pooled results of the included studies, and the I2 statistical analysis was used to identify the source of heterogeneity. Publication bias was examined by Egger's regression tests or visual inspection of the funnel plots. Results: The database searches yielded 1052 potential eligible literature; of them, five randomized controlled trials met the eligible criteria, involving a total of 188 participants. Patients in the rPMS group showed better improvement in motor impairment as measured by the FM-UE (MD: 5.39 [95% CI, 4.26 to 6.52]; P < 0.001; I2 = 0%) compared with the control group. Among the secondary outcomes, no difference was found in the improvement of muscle spasticity (SMD: 0.36 [95% CI, -0.05 to 0.77]; P = 0.08; I2 = 41%). There was a significant difference in the proximal (SMD: 0.58 [95% CI, 0.10 to 1.06]; P = 0.02; I2 = 0%) but not the distal muscle strength (SMD: 1.18 [95% CI, -1.00 to 3.36]; P = 0.29; I2 = 93%). Moreover, the activity limitation outcomes were significantly improved with rPMS intervention (SMD: 0.59 [95% CI, 0.08 to 1.10]; P = 0.02; I2 = 0%). Conclusion: This meta-analysis showed that rPMS might improve upper limb motor impairment, proximal muscle strength, and activity limitation outcomes but not muscle spasticity and distal strength in patients after stroke. Due to the limited number of studies, further randomized clinical trials are still warranted for more accurate interpretation and clinical recommendation.

Imaging and pathological diagnosis of primary intracranial malignant melanoma: A case report and literature review.

RATIONALE: Primary intracranial malignant melanoma (PIMM) is a rare malignant tumor that lacks specific clinical manifestations. Preoperative diagnosis is difficult to differentiate from meningiomas on computed tomography (CT) scans. Magnetic resonance imaging (MRI) usually shows typical characteristics with high signal intensity on T1WI and low signal intensity on T2WI. PIMM is highly invasive, insensitive to chemoradiotherapy, and has a poor prognosis. PATIENT CONCERNS: A 27-year-old woman was admitted to the hospital with a headache for 10 days. She did not experience nausea, vomiting, dizziness, or any other discomfort. A computerized tomography (CT) scan demonstrated a high-density mass in the left cerebellum with patchy calcification at the posterior edge, and heterogeneous enhancement was observed on a contrast-enhanced scan. MRI revealed typical characteristics of high signal intensity on T1WI and low signal intensity on T2WI. The signal characteristics of FLAIR were similar to those of T2WI, and diffusion-weighted imaging (DWI) sequence showed limited diffusion of the tumor. Magnetic resonance spectroscopy revealed increased choline (Cho) and decreased creatine (Cr) and N-acetyl aspartate (Naa) in the tumor. INTERVENTIONS: The patient underwent tumor resection and postoperative chemoradiotherapy and immunotherapy. PATHOLOGICAL DIAGNOSIS: Histological and Immunohistochemistry (IHC) tests confirmed the diagnosis of PIMM. In addition, genetic testing revealed GNAQ gene variation. OUTCOMES: No recurrence or complications were observed during the follow-up for 6 months. LESSONS: PIMM is rare, and its pathological diagnosis should be closely combined with clinical and medical history. GNAQ is a common variant of PIMM and is expected to be a therapeutic target.

Nerve growth factor causes epinephrine release dysfunction by regulating phenotype alterations and the function of adrenal medullary chromaffin cells in mice with allergic rhinitis.

The presence of allergic rhinitis (AR) is an increased risk factor for the occurrence of bronchial asthma (BA). Nerve growth factor (NGF), in addition to its key role in the development and differentiation of neurons, may also be an important inflammatory factor in AR and BA. However, the pathogenesis of the progression of AR to BA remains to be elucidated. The present study aimed to investigate the ability of NGF to mediate nasobronchial interactions and explore possible underlying molecular mechanisms. In the present study, an AR mouse model was established and histology of nasal mucosa tissue injury was determined. The level of phenylethanolamine N­methyl transferase in adrenal medulla was determined by immunofluorescence. Primary adrenal medullary chromaffin cells (AMCCs) were isolated and cultured from the adrenal medulla of mice. The expression levels of synaptophysin (SYP), STAT1, JAK1, p38 and ERK in NGF­treated and untreated AMCCs were detected by reverse­transcription­quantitative PCR and western blotting. The epinephrine (EPI) and norepinephrine (NE) concentrations were measured by ELISA. It was found that the expression of SYP in AMCCs was enhanced in the presence of NGF, whereas, the concentration of EPI decreased significantly under the same conditions. Furthermore, NGF mediated the phenotypic and functional changes of AMCCs, resulting in decreased EPI secretion via JAK1/STAT1, p38 and ERK signaling. In conclusion, these findings could provide novel evidence for the role of NGF in regulating neuroendocrine mechanisms.

Epidemiology of autism spectrum disorders: Global burden of disease 2019 and bibliometric analysis of risk factors.

Background: To explore the geographical pattern and temporal trend of autism spectrum disorders (ASD) epidemiology from 1990 to 2019, and perform a bibliometric analysis of risk factors for ASD. Methods: In this study, ASD epidemiology was estimated with prevalence, incidence, and disability-adjusted life-years (DALYs) of 204 countries and territories by sex, location, and sociodemographic index (SDI). Age-standardized rate (ASR) and estimated annual percentage change (EAPC) were used to quantify ASD temporal trends. Besides, the study performed a bibliometric analysis of ASD risk factors since 1990. Publications published were downloaded from the Web of Science Core Collection database, and were analyzed using CiteSpace. Results: Globally, there were estimated 28.3 million ASD prevalent cases (ASR, 369.4 per 100,000 populations), 603,790 incident cases (ASR, 9.3 per 100,000 populations) and 4.3 million DALYs (ASR, 56.3 per 100,000 populations) in 2019. Increases of autism spectrum disorders were noted in prevalent cases (39.3%), incidence (0.1%), and DALYs (38.7%) from 1990 to 2019. Age-standardized rates and EAPC showed stable trend worldwide over time. A total of 3,991 articles were retrieved from Web of Science, of which 3,590 were obtained for analysis after removing duplicate literatures. "Rehabilitation", "Genetics & Heredity", "Nanoscience & Nanotechnology", "Biochemistry & Molecular biology", "Psychology", "Neurosciences", and "Environmental Sciences" were the hotspots and frontier disciplines of ASD risk factors. Conclusions: Disease burden and risk factors of autism spectrum disorders remain global public health challenge since 1990 according to the GBD epidemiological estimates and bibliometric analysis. The findings help policy makers formulate public health policies concerning prevention targeted for risk factors, early diagnosis and life-long healthcare service of ASD. Increasing knowledge concerning the public awareness of risk factors is also warranted to address global ASD problem.

Classification for Memory Activities: Experiments and EEG Analysis Based on Networks Constructed via Phase-Locking Value.

Electroencephalogram (EEG) plays a crucial role in the study of working memory, which involves the complex coordination of brain regions. In this research, we designed and conducted series of experiments of memory with various memory loads or target forms and collected behavioral data as well as 32-lead EEG simultaneously. Combined with behavioral data analysis, we segmented EEG into slices; then, we calculated phase-locking value (PLV) of Gamma rhythms between every two leads, conducted binarization, constructed brain function network, and extracted three network characteristics of node degree, local clustering coefficient, and betweenness centrality. Finally, we inputted these network characteristics of all leads into support vector machines (SVM) for classification and obtained decent performances; i.e., all classification accuracies are greater than 0.78 on an independent test set. Particularly, PLV application was restricted to the narrow-band signals, and rare successful application to EEG Gamma rhythm, defined as wide as 30-100 Hz, had been reported. In order to address this limitation, we adopted simulation on band-pass filtered noise with the same frequency band as Gamma to help determine the PLV binarizing threshold. It turns out that network characteristics based on binarized PLV have the ability to distinguish the presence or absence of memory, as well as the intensity of the mental workload at the moment of memory. This work sheds a light upon phase-locking investigation between relatively wide-band signals, as well as memory research via EEG.

Zoledronic acid inhibits osteoclastogenesis and bone resorptive function by suppressing RANKL­mediated NF­κB and JNK and their downstream signalling pathways.

Targeting excessive osteoclast differentiation and activity is considered a valid therapeutic approach for osteoporosis. Zoledronic acid (ZOL) plays a pivotal role in regulating bone mineral density. However, the exact molecular mechanisms responsible for the inhibitory effects of ZOL on receptor activator of nuclear factor (NF)­κB ligand (RANKL)­induced osteoclast formation are not entirely clear. The present study aimed to investigate the role of ZOL in osteoclast differentiation and function, and to determine whether NF­κB and mitogen­activated protein kinase, and their downstream signalling pathways, are involved in this process. RAW264.7 cells were cultured with RANKL for differentiation into osteoclasts, in either the presence or absence of ZOL. Osteoclast formation was observed by tartrate­resistant acid phosphatase staining and bone resorption pit assays using dentine slices. The expression of osteoclast­specific molecules was analysed using reverse transcription­quantitative polymerase chain reaction and western blotting assays to deduce the molecular mechanisms underlying the role of ZOL in osteoclastogenesis. The results showed that ZOL significantly attenuated osteoclastogenesis and bone resorptive capacity in vitro. ZOL also suppressed the activation of NF­κB and the phosphorylation of c­Jun N­terminal kinase. Furthermore, it inhibited the expression of the downstream factors c­Jun, c­Fos and nuclear factor of activated T cells c1, thereby decreasing the expression of dendritic cell­specific transmembrane protein and other osteoclast­specific markers. In conclusion, ZOL may have therapeutic potential for osteoporosis.

A systematic review and meta-analysis on the prevalence of stigma in infectious diseases, including COVID-19: a call to action.

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.

Kinematic Evaluation via Inertial Measurement Unit Associated with Upper Extremity Motor Function in Subacute Stroke: A Cross-Sectional Study.

Kinematic evaluation via portable sensor system has been increasingly applied in neurological sciences and clinical practice. However, conventional kinematic evaluation rarely extends the context beyond the motor impairment level. In addition, kinematic tasks with numerous items could be complex and time consuming that pose a burden to test applications and data processing. The study aimed to explore the correlation of finger-to-nose task (FNT) kinematics via Inertial Measurement Unit with upper limb motor function in subacute stroke. In this study, six FNT kinematic variables were used to measure movement time, smoothness, and velocity in 37 participants with subacute stroke. Upper limb motor function was evaluated with the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), and modified Barthel Index (MBI). As a result, mean velocity, peak velocity, and the number of movement units were associated with the clinical assessments. The multivariable linear regression models could estimate 55%, 51%, and 32% of variance in FMA-UE, ARAT, and MBI, respectively. In addition, age, gender, type of stroke, and paretic side had no significant effects on these associations. Results show that FNT kinematic variables measured via Inertial Measurement Unit are associated with upper extremity motor function in individuals with subacute stroke. The objective kinematic evaluation may be suitable for predicting clinical measures of motor impairment and capacity to understand upper extremity motor recovery and clinical decision making after stroke. This trial is registered with ChiCTR1900026656.

Serum­derived exosomes from house dust mite­sensitized guinea pigs contribute to inflammation in BEAS­2B cells via the TLR4­NF­κB pathway.

Airway epithelial cells, which are the first physical defense barrier against allergens, play a pivotal role in immunity, airway inflammation and airway remodeling. The damage and dysfunction of these cells trigger the development of airway inflammatory diseases. Exosomes, which exist in various bodily fluids, mediate cell­cell communication and participate in the immune response process. The present study aimed to investigate whether serum exosomes play a pro­inflammatory role in bronchial epithelial cells (BEAS­2B cells) and, if so, explore the underlying molecular mechanisms. A guinea pig model of House dust mite (HDM)­induced asthma was established by sensitizing the rodents with HDM and PBS, and serum­derived exosomes were harvested. It was found that serum­derived exosomes from HDM­sensitized guinea pigs displayed higher levels of exosomal markers than those from controls. Additionally, western blot analysis and reverse transcription­quantitative PCR indicated that serum­derived exosomes from HDM­sensitized guinea pigs carried heat shock protein 70 and triggered an inflammatory response in BEAS­2B cells via the toll­like receptor 4 (TLR4)­NF­κB pathway. However, TAK­242, an inhibitor of the expression of TLR4, blocked the activation of the TLR4­NF­κB pathway. These findings provided a novel mechanism for exosome­mediated inflammatory responses and a new perspective for the intervention of inflammatory airway disorders.

Preliminary Assessment of a Postural Synergy-Based Exoskeleton for Post-Stroke Upper Limb Rehabilitation.

Upper limb exoskeletons have drawn significant attention in neurorehabilitation because of the anthropomorphic mechanical structure analogous to human anatomy. Whereas, the training movements are typically unorganized because most exoskeletons ignore the natural movement characteristic of human upper limbs, particularly inter-joint postural synergy. This paper introduces a newly developed exoskeleton (Armule) for upper limb rehabilitation with a postural synergy design concept, which can reproduce activities of daily living (ADL) motion with the characteristics of human natural movements. The semitransparent active control strategy with the interactive force guidance and visual feedback ensured the active participation of users. Eight participants with hemiplegia due to a first-ever, unilateral stroke were recruited and included. They participated in exoskeleton therapy sessions for 4 weeks, with passive/active training under trajectories and postures with the characteristics of human natural movements. The primary outcome was the Fugl-Meyer Assessment for Upper Extremities (FMA-UE). The secondary outcomes were the Action Research Arm Test(ARAT), modified Barthel Index (mBI), and metric measured with the exoskeleton After the 4-weeks intervention, all subjects showed significant improvements in the following clinical measures: the FMA-UE (difference, 11.50 points, p = 0.002), the ARAT (difference, 7.75 points ), and the mBI (difference, 17.50 points, p = 0.003 ) score. Besides, all subjects showed significant improvements in kinematic and interaction force metrics measured with the exoskeleton. These preliminary results demonstrate that the Armule exoskeleton could improve individuals' motor control and ADL function after stroke, which might be associated with kinematic and interaction force optimization and postural synergy modification during functional tasks.

Long-Term Impact of COVID-19 on Mental Health among the General Public: A Nationwide Longitudinal Study in China.

COVID-19 might have long-term mental health impacts. We aim to investigate the longitudinal changes in mental problems from initial COVID-19 peak to its aftermath among general public in China. Depression, anxiety and insomnia were assessed among a large-sample nationwide cohort of 10,492 adults during the initial COVID-19 peak (28 February 2020 to 11 March 2020) and its aftermath (8 July 2020 to 8 August 2020) using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Insomnia Severity Index. We used generalized estimating equations and linear mixed models to explore factors associated with long-term mental health symptoms during COVID-19. During the five months, mental health symptoms remained consistently elevated (baseline 46.4%; follow-up 45.1%). Long-term depression, anxiety and insomnia were associated with several personal and work-related factors including quarantine (adjusted OR for any mental health symptoms 1.31, 95%CI 1.22-1.41, p < 0.001), increases in work burden after resuming work (1.77, 1.65-1.90, p < 0.001), occupational exposure risk to COVID-19 (1.26, 1.14-1.40, p < 0.001) and living in places severely affected by initial COVID-19 peak (1.21, 1.04-1.41, p = 0.01) or by a COVID-19 resurgence (1.38, 1.26-1.50, p < 0.001). Compliance with self-protection measures, such as wearing face masks (0.74, 0.61-0.90, p = 0.003), was associated with lower long-term risk of mental problems. The findings reveal a pronounced and prolonged mental health burden from the initial COVID-19 peak through to its aftermath in China. We should regularly monitor the mental health status of vulnerable populations throughout COVID-19.

Robot-Assisted Arm Training in Stroke Individuals With Unilateral Spatial Neglect: A Pilot Study.

Background: Robot-assisted arm training (RAT) is an innovative exercise-based therapy that provides highly intensive, adaptive, and task-specific training, yet its effects for stroke individuals with unilateral spatial neglect remain to be explored. The study was aimed to investigate the effects of RAT on unilateral spatial neglect, arm motor function, activities of daily living, and social participation after stroke. Methods: In a pilot randomized controlled trial, individuals with unilateral spatial neglect after right hemisphere stroke were equally allocated to intervention group and control group, 45-min training daily, 5 days/week, for 4 weeks. Outcome measures included the Behavioral Inattention Test-conventional section (BIT-C), Catherine Bergego Scale (CBS), Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Modified Barthel Index (MBI), and World Health Organization Disability Assessment Schedule Version 2.0 (WHODAS 2.0). Results: From November 2018 to February 2021, 20 stroke patients (mean age 47.40 ± 8.47) were enrolled in the study. Robot-assisted arm training was feasible and safe for individuals with unilateral spatial neglect. Both groups had significant improvements in all outcome measures. Participants assigned to RAT therapy had significantly greater improvements in BIT-C (difference, 7.70; 95% CI, 0.55-14.85, P = 0.04), FMA-UE (difference, 5.10; 95% CI, 1.52-8.68, P = 0.01), and WHODAS 2.0 (difference, -7.30; 95% CI, -12.50 to -2.10, P = 0.01). However, the change scores on CBS and MBI demonstrated no significance between the groups. Conclusion: Our findings provide preliminary support for introducing robot-assisted arm training to remediate unilateral spatial neglect after stroke. The training program focusing on neglect of contralateral space and affected upper extremity may be effective in neglect symptoms, motor function recovery, and social participation, while not generalizing into improvements in activities of daily living. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/) on 17 October 2019, identifier: ChiCTR1900026656.

Mental Health Status of Late-Middle-Aged Adults in China During the Coronavirus Disease 2019 Pandemic.

Background: The novel coronavirus 2019 (COVID-19) pandemic and related compulsory measures have triggered a wide range of psychological issues. However, the effect of COVID-19 on mental health in late-middle-aged adults remains unclear. Methods: This cross-sectional, web-based survey recruited 3,730 participants (≥ 50 years old) between February 28 and March 11 of 2020. The Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, and Acute Stress Disorder Scale were used to evaluate depression, anxiety, insomnia, and acute stress symptoms. Multivariate logistic regression analysis was fitted to explore risk factors that were associated with the selected outcomes. Results: The mean age of the participants was 54.44 ± 5.99 years, and 2,026 (54.3%) of the participants were female. The prevalence of depression, anxiety, insomnia, and acute stress symptoms among late-middle-aged adults in China during the COVID-19 pandemic was 20.4, 27.1, 27.5, and 21.2%, respectively. Multivariable logistic regression analyses showed that participants who were quarantined had increased odds ratios for the four mental health symptoms, and those with a good understanding of the COVID-19 pandemic displayed a decreased risk for all mental health symptoms among late-middle-aged adults. In addition, participants with a low income and with a risk of COVID-19 exposure at work had a remarkably high risk of depression, anxiety, and acute stress symptoms. Conclusions: Mental health symptoms in late-middle-aged adults in China during the COVID-19 pandemic are prevalent. Population-specific mental health interventions should be developed to improve mental health outcomes in late-middle-aged adults during this public health emergency.

Exoskeleton-Assisted Anthropomorphic Movement Training (EAMT) for Poststroke Upper Limb Rehabilitation: A Pilot Randomized Controlled Trial.

OBJECTIVE: To investigate the feasibility of exoskeleton-assisted anthropomorphic movement training (EAMT) and its effects on upper extremity motor impairment, function, and kinematics after stroke. DESIGN: A single-blind pilot randomized controlled trial. SETTING: Stroke rehabilitation inpatient unit. PARTICIPANTS: Participants with a hemiplegia (N=20) due to a first-ever, unilateral, subacute stroke who had a score of 8-47 on the Fugl-Meyer Assessment for Upper Extremity (FMA-UE). INTERVENTIONS: The exoskeleton group received EAMT therapy that provided task-specific training under anthropomorphic trajectories and postures. The control group received conventional upper limb therapy. For both groups, therapy was delivered at the same intensity, frequency, and duration: 45 minutes daily, 5 days per week, for 4 weeks. MAIN OUTCOME MEASURES: Primary outcome: feasibility analysis. SECONDARY OUTCOMES: FMA-UE, Action Research Arm Test (ARAT), modified Barthel Index (MBI), and kinematic metrics during exoskeleton therapy. RESULTS: Twenty participants with subacute stroke were recruited and completed all therapy sessions. EAMT therapy was feasible and acceptable for the participants. The recruitment rate, retention rate, and number of therapists required for EAMT therapy were acceptable compared with other robotic trials. EAMT was determined to be safe, as no adverse event occurred except tolerable muscle fatigue in 2 participants. There were significant between-group differences in the change scores of FMA-UE (difference, 4.30 points; P=.04) and MBI (difference, 8.70 points; P=.03) in favor of EAMT therapy. No significant between-group difference was demonstrated for the change scores of ARAT (P=.18). Participants receiving EAMT showed significant improvements in kinematic metrics after treatment (P<.01). CONCLUSIONS: Our results indicate that EAMT is a feasible approach and may improve upper extremity motor impairment, activities of daily living, and kinematics after stroke. However, fully powered randomized controlled trials are warranted to confirm the results of this pilot study and explore the underlying mechanisms by which EAMT therapy might work.

Association Between Finger-to-Nose Kinematics and Upper Extremity Motor Function in Subacute Stroke: A Principal Component Analysis.

BACKGROUND: Kinematic analysis facilitates interpreting the extent and mechanisms of motor restoration after stroke. This study was aimed to explore the kinematic components of finger-to-nose test obtained from principal component analysis (PCA) and the associations with upper extremity (UE) motor function in subacute stroke survivors. METHODS: Thirty-seven individuals with subacute stroke and twenty healthy adults participated in the study. Six kinematic metrics during finger-to-nose task (FNT) were utilized to perform PCA. Clinical assessments for stroke participants included the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), and Modified Barthel Index (MBI). RESULTS: Three principal components (PC) accounting for 91.3% variance were included in multivariable regression models. PC1 (48.8%) was dominated by mean velocity, peak velocity, number of movement units (NMU) and normalized integrated jerk (NIJ). PC2 (31.1%) described percentage of time to peak velocity and movement time. PC3 (11.4%) profiled percentage of time to peak velocity. The variance explained by principal component regression in FMA-UE (R 2 = 0.71) were higher than ARAT (R 2 = 0.59) and MBI (R 2 = 0.29) for stroke individuals. CONCLUSION: Kinematic components during finger-to-nose test identified by PCA are associated with UE motor function in subacute stroke. PCA reveals the intrinsic association among kinematic metrics, which may add value to UE assessment and future intervention targeted for kinematic components for stroke individuals. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn/) on 17 October 2019, identifier: ChiCTR1900026656.

Role of receptor tyrosine kinases mediated signal transduction pathways in tumor growth and angiogenesis-New insight and futuristic vision.

In the past two decades, significant progress has been made in the past two decades towards the understanding of the basic mechanisms underlying cancer growth and angiogenesis. In this context, receptor tyrosine kinases (RTKs) play a pivotal role in cell proliferation, differentiation, growth, motility, invasion, and angiogenesis, all of which contribute to tumor growth and progression. Mutations in RTKs lead to abnormal signal transductions in several pathways such as Ras-Raf, MEK-MAPK, PI3K-AKT and mTOR pathways, affecting a wide range of biological functions including cell proliferation, survival, migration and vascular permeability. Increasing evidence demonstrates that multiple kinases are involved in angiogenesis including RTKs such as vascular endothelial growth factor, platelet derived growth factor, epidermal growth factor, insulin-like growth factor-1, macrophage colony-stimulating factor, nerve growth factor, fibroblast growth factor, Hepatocyte Growth factor, Tie 1 & 2, Tek, Flt-3, Flt-4 and Eph receptors. Overactivation of RTKs and its downstream regulation is implicated in tumor initiation and angiogenesis, representing one of the hallmarks of cancer. This review discusses the role of RTKs, PI3K, and mTOR, their involvement, and their implication in pro-oncogenic cellular processes and angiogenesis with effective approaches and newly approved drugs to inhibit their unrestrained action.