Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus.

Image 1.

Structural changes in spinal cord following optic neuritis: Insights from quantitative spinal MRI.

OBJECTIVES: Previous studies have demonstrated that optic neuritis (ON) affects brain plasticity. However, whether ON affects the spinal cord remains unclear. We aimed to investigate the spinal cord changes in ON and their associations with disability. METHODS: A total of 101 ON patients, and 41 healthy controls (HC) were retrospectively recruited. High-resolution imaging was conducted using a Magnetization Prepared Rapid Acquisition Gradient-Echo (MP-RAGE) sequence for T1-weighted images and an echo planar imaging (EPI) sequence for Diffusion Tensor Imaging (DTI) data collection. Additionally, patients' disability and cognitive impairment were evaluated using the Expanded Disability Status Scale (EDSS) and the Paced Auditory Serial Addition Test (PASAT), respectively. The quantitative spinal MRI was employed to examine the cross-sectional area (CSA) and diffusion indicators, with a specific focus on calculating the average values across the C2-C7 cervical spinal cord segments. CSA, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between groups. Correlation analyses were performed between CSA, diffusion indicators, and clinical variables. RESULTS: No significant differences were found in CSA between ON patients and HCs. MD (p = 0.007) and RD (p = 0.018) were increased in ON patients compared with HCs, and AD was decreased in ON (p = 0.013). The AD values of the ON patients were significantly positively correlated with PASAT scores (r = 0.37, p < 0.001). CONCLUSIONS: This study provided imaging evidence for DTI abnormalities in patients with ON. Spinal cord DTI can improve our knowledge of the path physiology of ON, and clinical progression.

Safety of teriflunomide in Chinese adult patients with relapsing multiple sclerosis: A phase IV, 24-week multicenter study.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant (n = 42) and wild type groups (n = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] µg/mL; wild type, 49.1 [32.0] µg/mL) and area under plasma concentration-time curve over a dosing interval (AUCtau) (variant, 1731.3 [769.0] µg∙h/mL; wild type, 1564.5 [1053.0] µg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION: NCT04410965, https://clinicaltrials.gov.

Clinical features of MOGAD with brainstem involvement in the initial attack versus NMOSD and MS.

OBJECTIVE: To assess the characteristics of Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) with brainstem involvement in the first event (BSIFE) and make comparisons with aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and multiple sclerosis (MS). METHODS: From 2017 to 2022, this study identified MOG-IgG-positive patients with brainstem or both brainstem and cerebellum lesions in the first episode. As a comparison group, AQP4-IgG-NMOSD (n = 30) and MS (n = 30) patients with BSIFE were enroled. RESULTS: Thirty-five patients (35/146, 24.0%) were the BSIFE of MOGAD. Isolated brainstem episodes occurred in 9 of the 35 (25.7%) MOGAD patients, which was similar to MS (7/30, 23.3%) but was lower than AQP4-IgG-NMOSD (17/30, 56.7%, P = 0.011). Pons (21/35, 60.0%), medulla oblongata (20/35, 57.1%) and middle cerebellar peduncle (MCP, 19/35, 54.3%) were the most frequently affected areas. Intractable nausea (n = 7), vomiting (n = 8) and hiccups (n = 2) happened in MOGAD patients, but EDSS of MOGAD was lower than AQP4-IgG-NMOSD (P = 0.001) at the last follow-up. MOGAD patients with or without BSIFE did not significantly differ in terms of the ARR (P = 0.102), mRS (P = 0.823), or EDSS (P = 0.598) at the most recent follow-up. Specific oligoclonal bands appeared in MOGAD (13/33, 39.4%) and AQP4-IgG-NMOSD (7/24, 29.2%) in addition to MS (20/30, 66.7%). Fourteen MOGAD patients (40.0%) experienced relapse in this study. When the brainstem was involved in the first attack, there was an increased likelihood of a second attack occurring at the same location (OR=12.22, 95%CI 2.79 to 53.59, P = 0.001). If the first and second events were both in the brainstem, the third event was likely to occur at the same location (OR=66.00, 95%CI 3.47 to 1254.57, P = 0.005). Four patients experienced relapses after the MOG-IgG turned negative. CONCLUSION: BSIFE occurred in 24.0% of MOGAD. Pons, medulla oblongata and MCP were the most frequently involved regions. Intractable nausea, vomiting and hiccups occurred in MOGAD and AQP4-IgG-NMOSD, but not MS. The prognosis of MOGAD was better than AQP4-IgG-NMOSD. In contrast to MS, BSIFE may not indicate a worse prognosis for MOGAD. When patients with BSIFE, MOGAD tent to reoccur in the brainstem. Four of the 14 recurring MOGAD patients relapsed after the MOG-IgG test turned negative.

Altered amide proton transfer weighted and diffusion signals in patients with multiple sclerosis: correlation with neurofilament light chain and disease duration.

Objectives: To compare the signal alterations of amide proton transfer (APT), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) in white matter (WM) lesions in multiple sclerosis (MS), compared with healthy controls (HCs), and to investigate the relationships between these changes and clinical measurements such as serum neurofilament light chain (sNfL). Materials and methods: Twenty-nine patients with relapsing-remitting MS (21 females and 8 males) and 30 HCs (23 females and 7 males) were recruited. APT-weighted (APTw) and diffusion tensor imaging (DTI) data were acquired using a 3.0-T magnetic resonance system. APTw and DTI images were registered to FLAIR-SPIR images and assessed by two neuroradiologists. MTRasym (3.5 ppm), ADC, FA values for MS and HC are calculated using mean values from all regions of interest (ROI). The ROI criteria were: (1) for MS patients, ROI were defined as MS lesions, and each lesion was identified. (2) The WM around each HC's lateral ventricle (frontal lobe, parietal lobe, and centrum semiovale) was assessed bilaterally. The diagnostic efficacy of MTRasym (3.5 ppm), ADC, and FA in the lesions of MS patients was compared using receiver operating characteristic (ROC) curve analysis. The associations between MTRasym (3.5 ppm), ADC, and FA values and the clinical measurements were investigated further. Results: The MTRasym (3.5 ppm) and ADC values of brain lesions were increased, while FA values were decreased in patients with MS. The diagnostic area under curve (AUC) of MTRasym (3.5 ppm), ADC, and FA value was 0.891 (95% CI: 0.813, 0.970), 0.761 (95% CI: 0.647, 0.875) and 0.970 (95% CI: 0.924, 1.0), respectively. sNfL was considerably positively correlated with MTRasym (3.5 ppm) (P = 0.043, R = 0.38) and disease durations were significantly negatively correlated with FA (P = 0.046, R = -0.37). Conclusion: Amide proton transfer-weighted (APTw) and DTI are potential imaging methods for assessing brain lesions in patients with MS at the molecular and microscopic levels, respectively. The association between APTw, DTI parameters and clinical factors implies that they may play a role in disease damage monitoring.

TRPV4 is not the molecular sensor for bacterial lipopolysaccharides-induced calcium signaling.

Lipopolysaccharides (LPS) is one of the most potent pathogen-associated signals for the immune system of vertebrates. In addition to the canonical pathway of LPS detection mediated by toll-like receptor 4 (TLR4) signaling pathway, TRP channel-mediated pathways endow sensory neurons and epithelial cells with the ability to detect and react to bacterial endotoxins. Previous work revealed that LPS triggers TRPV4-dependent calcium influx in urothelial cells (UCs) and mouse tracheobronchial epithelial cells (mTEC). In marked contrast, here we show that most subtypes of LPS could not directly activate TRPV4 channel. Although LPS from Salmonella enterica serotype Minnesota evoked a [Ca2+]i response in freshly isolated human bronchial epithelial cells (ECs), freshly isolated mouse ear skin single-cell suspensions, or HEK293T cells transiently transfected with mTRPV4, this activation occurred in a TRPV4-independent manner. Additionally, LPS from either E. coli strains or Salmonella enterica serotype Minnesota did not evoke significant difference in inflammation and pain hyperalgesia between wild type and TRPV4 deficient mice. In summary, our results demonstrate that in vitro and in vivo effects induced by LPS are independent of TRPV4, thus providing a clarity to the questioned role of LPS in TRPV4 activation.

Clinical Characteristics and Outcomes of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder With Brainstem Lesions as Heralding Prodrome.

Objective: The present study sought to differentiate multiple sclerosis and neuromyelitis optica spectrum disorder patients at their first attack by describing and distinguishing their clinical features, radiographic characteristics, and immunologic characteristics of serum and cerebrospinal fluid. Methods: We retrospectively studied 58 patients with multiple sclerosis (MS) and 52 patients with neuromyelitis optica spectrum disorder (NMOSD) by referencing brainstem lesions as the prodromal events. Their demographics and presentation at the time of the first attack was evaluated including their gender, age, clinical features of the first attack, the expanded disability status scale (EDSS), brainstem lesion(s) by head MRI, and immunological indices of serum and cerebrospinal fluid. Results: The NMOSD group had more female patients (4.8 vs. 1.9, p < 0.05), and was older than the MS group (37.81 ± 16.60 vs. 27.57 ± 11.17, p <0.001). NMOSD patients also had a significantly higher association with autoimmune diseases or positive autoimmune antibodies (p < 0.01). There was no significant difference in the EDSS scores between the two groups (p = 0.420). Central hiccups, vomiting, and pyramidal tract signs were more common in the NMOSD group than the MS group (p < 0.001, p < 0.001, p < 0.01), while eye movement abnormalities were more common with MS (p < 0.01). There were no significant differences in other clinical manifestations such as vertigo, diplopia, limb weakness, numbness, and eating difficulty. MS patients were more likely to have midbrain and pons imaging lesions (p < 0.001, p < 0.001), while NMOSD patients had more lesions in the medulla oblongata (p < 0.001). The lesions in the MS group were mostly located in the periphery, while those in the NMOSD group were centrally located (p < 0.001, p < 0.001). Patchy lesions were more common in MS patients (p < 0.001), while large lesions were more common in the NMOSD group (p < 0.001). Finally, serum AQP4 Ab was found only in the NMOSD group (p < 0.001). Conclusion: Patients with MS and NMOSD have differentiating clinical manifestations at the time of their first brainstem lesions which include central hiccups, vomiting, pyramidal tract signs, and abnormal eye movements. Additionally, distinct imaging manifestations such as lesion location(s) and morphology may also aid in the development of pathognomonic criteria leading to timely initial diagnosis of MS and NMOSD.

Transcranial alternating current stimulation for treating depression: a randomized controlled trial.

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

Coupling of brain activity and structural network in multiple sclerosis: A graph frequency analysis study.

The brain activities and the underlying wiring diagrams are vulnerable in multiple sclerosis (MS). Also, it remains unknown whether the complex coupling between these functional and structural brain properties would be affected. To address this issue, we adopted graph frequency analysis to quantify the high-order structural-functional interactions based on a combination of brain diffusion and functional MRI data. The structural-functional decoupling index was proposed to measure how much brain regional functional activity with different graph frequency was organized atop the underlying wiring diagram in MS. The identified patterns in MS included (1) disruption of inherent structural-functional coupling in the somatomotor network (ß = 0.05, p = 0.03), and (2) excessive decrease of decoupling in the subcortical (ß = -0.10, p = 0.02), visual (ß = -0.04, p = 0.01), and dorsal attention networks (ß = -0.12, p = 0.03). Besides, this structural-functional coupling signature in the somatomotor network was associated with cognitive worsening of MS patients (ß = -24.31, p = 0.006). Overall, our study unveiled a unique signature of brain structural-functional reorganization in MS.

COVID-19 pandemic: study on simple, easy, and practical relaxation techniques while wearing medical protective equipment.

BACKGROUND: No studies have reported on how to relieve distress or relax in medical health workers while wearing medical protective equipment in coronavirus disease 2019 (COVID-19) pandemic. The study aimed to establish which relaxation technique, among six, is the most feasible in first-line medical health workers wearing medical protective equipment. METHODS: This was a two-step study collecting data with online surveys. Step 1: 15 first-line medical health workers were trained to use six different relaxation techniques and reported the two most feasible techniques while wearing medical protective equipment. Step 2: the most two feasible relaxation techniques revealed by step 1 were quantitatively tested in a sample of 65 medical health workers in terms of efficacy, no space limitation, no time limitation, no body position requirement, no environment limitation to be done, easiness to learn, simplicity, convenience, practicality, and acceptance. RESULTS: Kegel exercise and autogenic relaxation were the most feasible techniques according to step 1. In step 2, Kegel exercise outperformed autogenic relaxation on all the 10 dimensions among the 65 participants while wearing medical protective equipment (efficacy: 24 v. 15, no space limitation: 30 v. 4, no time limitation: 31 v. 4, no body position requirement: 26 v. 4, no environment limitation: 30 v. 11, easiness to learn: 28 v. 5, simplicity: 29 v. 7, convenience: 29 v. 4, practicality: 30 v. 14, acceptance: 32 v. 6). CONCLUSION: Kegel exercise seems a promising self-relaxation technique for first-line medical health workers while wearing medical protective equipment among COVID-19 pandemic.

Clinical and Imaging Features of Patients With Encephalitic Symptoms and Myelin Oligodendrocyte Glycoprotein Antibodies.

Background: Myelin oligodendrocyte glycoprotein-antibody (MOG-ab)-associated disease (MOGAD) has highly heterogenous clinical and imaging presentations, in which encephalitis is an important phenotype. In recent years, some atypical presentations in MOG-ab-associated encephalitis (MOG-E) have been increasingly reported but have not yet been described well. The aim of the study was to describe the clinical and imaging features of patients with MOG-E in our center. Atypical phenotypes would be reported, which is expected to expand the spectrum of MOGAD. Methods: We reviewed medical records of 59 patients with MOGAD diagnosed in our center and identified cases who had ever experienced encephalitic symptoms. Three hundred ten patients with autoimmune encephalitis (AE) were also reviewed, and cases with positive MOG-ab were identified. Besides, patients with chronically progressive encephalitis were identified from 13 MOG-E and 310 AE patients. We collected demographic, clinical, laboratory, radiological, and outcome data to explore clinical and imaging characteristics in MOG-E, especially in the atypical phenotype of chronically progressive encephalitis. Results: We identified 13 patients (7 males, 6 females) with MOG-E. The median age at onset was 33 years (range 13~62 years). Most (9/13, 69.2%) of patients showed acute or subacute onset of encephalitic symptoms. Brain MRI abnormalities were observed in all patients. The most common lesion locations on MRI were cortical/subcortical (11/13, 84.6%), deep/periventricular white matter (10/13, 76.9%) and corpus callosum (4/13, 30.8%). Brain MRI patterns were categorized into four phenotypes. The most common pattern was cortical encephalitis with leptomeningeal enhancement/brain atrophy (10/13, 76.9%). Eight (8/13, 61.5%) patients had a good response to immunotherapy. Four (4/13, 30.8%) patients with chronically progressive course were identified from MOG-E cohort. They showed leukodystrophy-like pattern, multifocal hazy lesions, or cortical encephalitis on MRI. With immunotherapy, they only showed mild or no improvement. We also identified four (4/310, 1.3%) patients with chronically progressive course from AE cohort. They had better outcomes than counterparts in MOG-E. Conclusions: This study demonstrates that encephalitic presentations in MOGAD had complex clinical patterns. Chronically progressive encephalitis may be a new phenotype of MOGAD. We recommend to test MOG-ab in subacute and chronic progressive dementia with leukodystrophy-like MRI lesions.

Multi-parametric MRI phenotype with trustworthy machine learning for differentiating CNS demyelinating diseases.

BACKGROUND: Misdiagnosis of multiple sclerosis (MS) and neuromyelitis optica (NMO) may delay the treatment, resulting in poor prognosis. However, the precise identification of these two diseases is still challenging in clinical practice. We aimed to evaluate the value of quantitative radiomic features extracted from the brain white matter lesions for differential diagnosis of MS and NMO. METHODS: We recruited 116 CNS demyelinating patients including 78 MS, and 38 NMO. Three neuroradiologists performed visual differential diagnosis based on brain MRI for comparison purpose. A multi-level scheme was designed to harness the selection of discriminative and stable radiomics features extracted from brain while mater lesions in T1-MPRAGE, T2 sequences and clinical factors. Based on the imaging phenotype composed of the selected radiomic and clinical features, Multi-parametric Multivariate Random Forest (MM-RF) model was constructed and verified with both 10-fold cross-validation and independent testing. Result interpretation was provided to build trust in diagnostic decisions. RESULTS: Eighty-six patients were randomly selected to form the training set while the rest 30 patients for independent testing. On the training set, our MM-RF model achieved accuracy 0.849 and AUC 0.826 in 10-fold cross-validation, which were significantly higher than clinical visual analysis (0.709 and 0.683, p < 0.05). In the independent testing, the MM-RF model achieved AUC 0.902, accuracy 0.871, sensitivity 0.873, specificity 0.869, respectively. Furthermore, age, sex and EDSS were found mildly correlated with the radiomic features (p of all < 0.05). CONCLUSIONS: Multi-parametric radiomic features have potential as practical quantitative imaging biomarkers for differentiating MS from NMO.

Status of Immunotherapy Acceptance in Chinese Patients With Multiple Sclerosis: Analysis of Multiple Sclerosis Patient Survival Report 2018.

Objective: The prevalence of multiple sclerosis (MS) in China is low, although it has been increasing recently. Owing to the paucity of data on immunotherapy acceptance in the Chinese population, we conducted this study to analyze factors affecting the acceptance of immunotherapy and selection of disease-modifying therapies (DMTs) based on personal and clinical data of patients with MS. Methods: In this study, data were obtained from the Multiple Sclerosis Patient Survival Report 2018, which was the first national survey of patients with MS in China. There were 1,212 patients with MS from 31 provinces who were treated at 49 Chinese hospitals over a 4-month period from May 2018 to August 2018, and the patients were asked to complete online questionnaires to assess their understanding of the disease. Results: In general, highly educated patients with frequent relapses were more willing to receive treatment regardless of DMTs or other immunotherapy, and patients with more understanding of the disease opted to be treated. Younger patient population, patients with severe disease course, and those with more symptoms were likely to choose the treatment. Moreover, a higher proportion of women chose to be treated with DMTs than with other immunotherapies. Conclusions: Education status and patient awareness of the disease impact the treatment acceptance in Chinese patients with MS. Therefore, we call for improving the awareness of MS disease and social security to help patients to improve their quality of life.

Anti-contactin-associated protein-like 2 antibody-associated cerebellar ataxia: A case report and literature review.

The spectrum of anti-contactin-associated protein-like 2 (CASPR2) antibody-associated disease is expanding and the involvement of cerebellum was reported in the past few years. We report a 45-year-old male with chronically progressive cerebellar ataxia. CASPR2 antibodies were detected in his serum and cerebellar atrophy was observed on MRI. His symptoms improved prominently with steroids and intravenous immunoglobulins. 23 cases with CASPR2 antibodies and cerebellar ataxia were identified from previous publications. Most of patients showed acute or subacute onset with other typical presentations of anti-CASPR2 antibody-associated disease, such as limbic encephalitis. Immunotherapy was effective in the majority of patients.

Syphilitic meningomyelitis misdiagnosed as spinal cord tumor: Case and review.

Context: Syphilitic meningomyelitis is a rare manifestation of neurosyphilis, not well described in the literature.Methods: We reported a rare case of a 29-year-old female with syphilitic meningomyelitis. Her clinical manifestations and imaging findings were discussed with the related literatures reviewed.Results: The patient presented with progressive bilateral lower extremities numbness and weakness for months. Laboratory tests revealed positive serum Treponema pallidum Hemagglutinin Test (TPHA) and rapid plasma reagin test (RPR). The cerebral spinal fluid (CSF) was positive with TPHA but negative for RPR with lymphocytic pleocytosis and elevated protein. Spinal MRI showed swelling and high-signal intensity of thoracic spinal cord except T6-7 level with associated gadolinium enhancement ("flip-flop sign") and peripheral strip-like enhancement on T1WI ("candle guttering appearance"). She was initially diagnosed as spinal cord tumor due to the chronic clinical onset and cord swelling with central enhancement found on thoracic MRI. After dramatic clinical and radiographic improvement with dexamethosone and serological tests of syphilis, she was diagnosed as probable syphilitic meningomyelitis. Till now, there are 12 cases of syphilitic myelitis reported with spinal cord MR images. Thoracic cord is the predominant involved segment (10/12), "candle guttering appearance" is the most common enhancing characteristics of the lesion (7/12), "flip-flop sign" may be seen in the stage with significant inflammation (3/12).Conclusion: Syphilitic meningomyelitis can occur at early or late stage of syphilis, the onset may be acute, subacute or chronic. The imaging findings suggested focal inflammation of the spinal cord. Prognosis is relatively good after proper treatment.

Two Cases of Female Chinese Adult-Onset Krabbe Disease with One Novel Mutation and a Review of Literature.

This study presented two Chinese adult female patients who were diagnosed with adult-onset Krabbe disease (KD) and reviewed this disease in Chinese patients. Two young female adults in their 20s were enrolled in this study. Clinical data, including symptoms, magnetic resonance imaging (MRI) scanning, and laboratory studies were collected. Sequence alignment and structural modeling were carried out to analyze the pathogenesis of the disease. Both patients were adult-onset and both had a mild clinical course, presented with spastic weakness. The MRI study showed demyelination confined to the corticospinal tracts and parieto-occipital white matter. The ß-galactocerebrosidase (GALC) activity was obviously decreased in both patients. Gene test of GALC showed that both patients were compound heterozygotes; proband I was a carrier of p.L634S (c.1901 T > C) and p.I250T (c.749 T > C), while proband II was a carrier of p.L634S (c.1901 T > C) and a new variant of c.283_284del. Molecular analysis revealed the variants may influence the function of GALC. We provided two Chinese adult-onset KD, and the clinical and genetic characteristics of proband II was especially rare due to asymmetric symptoms, spinal cord involvement, and the identification of a new point mutation c.283_284del in the GALC gene. Variant c.749 T > C can present mild syndromes except for severe cases. c.283_284del is a new variant that may occur in adult-onset type.

Post-COVID-19 Epidemic: Allostatic Load among Medical and Nonmedical Workers in China.

BACKGROUND: As the fight against the COVID-19 epidemic continues, medical workers may have allostatic load. OBJECTIVE: During the reopening of society, medical and nonmedical workers were compared in terms of allostatic load. METHODS: An online study was performed; 3,590 Chinese subjects were analyzed. Socio-demographic variables, allostatic load, stress, abnormal illness behavior, global well-being, mental status, and social support were assessed. RESULTS: There was no difference in allostatic load in medical workers compared to nonmedical workers (15.8 vs. 17.8%; p = 0.22). Multivariate conditional logistic regression revealed that anxiety (OR = 1.24; 95% CI 1.18-1.31; p < 0.01), depression (OR = 1.23; 95% CI 1.17-1.29; p < 0.01), somatization (OR = 1.20; 95% CI 1.14-1.25; p < 0.01), hostility (OR = 1.24; 95% CI 1.18-1.30; p < 0.01), and abnormal illness behavior (OR = 1.49; 95% CI 1.34-1.66; p < 0.01) were positively associated with allostatic load, while objective support (OR = 0.84; 95% CI 0.78-0.89; p < 0.01), subjective support (OR = 0.84; 95% CI 0.80-0.88; p < 0.01), utilization of support (OR = 0.80; 95% CI 0.72-0.88; p < 0.01), social support (OR = 0.90; 95% CI 0.87-0.93; p < 0.01), and global well-being (OR = 0.30; 95% CI 0.22-0.41; p < 0.01) were negatively associated. CONCLUSIONS: In the post-COVID-19 epidemic time, medical and nonmedical workers had similar allostatic load. Psychological distress and abnormal illness behavior were risk factors for it, while social support could relieve it.

Altered Functional Connectivity in White and Gray Matter in Patients With Multiple Sclerosis.

Background: Functional magnetic resonance imaging (fMRI) has been widely used to assess neural activity changes in gray matter (GM) in patients with multiple sclerosis (MS); however, brain function alterations in white matter (WM) relatively remain under-explored. Purpose: This work aims to identify the functional connectivity in both the WM and the GM of patients with MS using fMRI and the correlations between these functional changes and cumulative disability as well as the lesion ratio. Materials and Methods: For this retrospective study, 37 patients with clinically definite MS and 43 age-matched healthy controls were included between 2010 and 2014. Resting-state fMRI was performed. The WFU Pick and JHU Eve atlases were used to define 82 GM and 48 WM regions in common spaces, respectively. The time courses of blood oxygen level-dependent (BOLD) signals were averaged over each GM or WM region. The averaged time courses for each pair of GM and WM regions were correlated. All 82 × 48 correlations for each subject formed a functional correlation matrix. Results: Compared with the healthy controls, the MS patients had a decreased temporal correlation between the WM and the GM regions. Five WM bundles and four GM regions had significantly decreased mean correlation coefficients (CCs). More specifically, the WM functional alterations were negatively correlated with the lesion volume in the bilateral fornix, and the mean GM-averaged CCs of the WM bundles were inversely correlated with the lesion ratio (r = -0.36, P = 0.012). No significant correlation was found between WM functional alterations and the paced auditory serial addition test score, Expanded Disease Severity Scale score, and Multiple Sclerosis Severity Score (MSSS) in MS. Conclusions: These findings highlight current gaps in our knowledge of the WM functional alterations in patients with MS and may link WM function with pathological mechanisms.

An effective method for extracting anthocyanins from blueberry based on freeze-ultrasonic thawing technology.

The aim of this study was to develop an effective method for extracting anthocyanins from blueberry Vaccinium spp. (ABVS) using freeze-ultrasonic thawing technology (FUTE). Various parameters including freezing time, ultrasonic time, ultrasonic temperature and liquid-solid ratio were optimized by a single-factor design and multiple response surface methodology. The amounts of extracted anthocyanin and cyanidin-3-O-glucoside were measured by UV and HPLC respectively. The maximum yield of anthocyanins was achieved by freezing the samples for 5.43 min in liquid nitrogen at the liquid-solid ratio of 24.07:1 mL/g, followed by ultrasonic thawing at 41.64 °C for 23.56 min. The yield and antioxidant effects of ABVS extracted using FUTE, ultrasound-assisted extraction (UAE) and freeze-thawing extraction (FTE) were compared in order to determine the overall efficacy of FUTE. In addition to the higher content, FUTE extracted ABVS showed greater ability to scavenge DPPH·, ABTS+ and superoxide anions, and inhibit lipid peroxidation compared to the ABVS extracted by UAE or FTE. The reducing power of the FUTE-derived ABVS was intermediate between that of the UAE and FTE samples. Taken together, FUTE can rapidly and effectively extract ABVS and retain its antioxidant capacity.

Mental Health and Psychosocial Problems of Medical Health Workers during the COVID-19 Epidemic in China.

OBJECTIVE: We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak. METHODS: An online survey was run from February 19 to March 6, 2020; a total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2). RESULTS: Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05). CONCLUSIONS: During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.