Six-month follow-up of functional status in discharged patients with coronavirus disease 2019.

BACKGROUND: The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors. METHODS: We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge. RESULTS: We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33-12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06-10.81, p = 0.039). CONCLUSIONS: A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required.

Cognitive Function and White Matter Lesions in Medication-Overuse Headache.

PURPOSE: This study was designed to investigate the cognitive function and the white matter lesions (WMLs) and the relationship between them in medication-overuse headache (MOH) patients. METHODS: Subjects were enrolled and performed Montreal Cognitive Assessment (MoCA, Chinese-Beijing Version), Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD-24), and Pittsburgh Sleep Quality Index (PSQI) to evaluate the general cognitive function, anxiety, depression and sleep quality, and they were divided into three groups according to the MoCA scores: healthy controls, MOH with normal cognition group and MOH with cognitive impairment group. All the participants underwent MRI scans and images were obtained for WML evaluation with Fazekas scale. RESULTS: One hundred thirty-four participants were enrolled into this study, 46 of them for healthy controls, and 88 for MOH patients, 40 of the MOH patients for MOH with cognitive impairment group, and 48 for MOH with normal cognition group. MOH patients had significantly lower MoCA scores, including the scores of visuospatial and executive function, attention, and orientation, while they had significantly greater HAMA scores, HAMD-24 scores, PSQI scores, and deep white matter hyperintensity scores compared to healthy controls. And in MOH patients, the age, disease duration, monthly headache days, and periventricular white matter hyperintensity scores in patients with cognitive impairment were greater than those in patients with normal cognition. Moreover, the MoCA scores were negatively related to age, disease duration, monthly headache days, and Fazekas scale scores, and disease duration and monthly headache days were significant predictors of cognitive impairment in MOH patients. CONCLUSION: MOH patients showed cognitive impairment and increased WML burden. And in MOH patients, cognitive function was negatively related to WML burden, and disease duration and monthly headache days were potential predictors of cognitive impairment. Prompt and effective treatment to stop the progression of the disease may alleviate cognitive impairment in MOH patients.

Flexible Quasi-Solid-State Composite Electrolyte of Poly (Propylene Glycol)-co-Pentaerythritol Triacry-Late/Li1.5Al0.5Ge1.5(PO4)3 for High-Performance Lithium-Sulfur Battery.

With a higher theoretical specific capacity (1675 mAh g-1) and energy density (2600 Wh kg-1), the lithium-sulfur (Li-S) battery is considered as a promising candidate for a next-generation energy storage device. However, the shuttle effect of polysulfides as well as the large interfacial impedance between brittle solid electrolyte and electrodes lead to the capacity of the Li-S battery decaying rapidly, which limits the practical commercial applications of the Li-S battery. Herein, we reported a facile in situ ultraviolet (UV) curing method to prepare a flexible quasi-solid-state composite electrolyte (QSSCE) of poly(propylene glycol)-co-pentaerythritol triacrylate/Li1.5Al0.5Ge1.5(PO4)3 (PPG-co-PETA/LAGP). By combining the high Li-ion conductivity and mechanical strength of inorganic NASICON-structure LAGP and good flexibility of the crosslinked PPG-co-PETA with nanopore structure, the flexible QSSCE with 66.85 wt% LAGP exhibited high Li-ion conductivity of 5.95 × 10-3 S cm-1 at 25 °C, Li-ion transference number of 0.83 and wide electrochemical window of ~5.0 V (vs. Li/Li+). In addition, the application of QSSCE in the Li-S battery could suppress the shuttle effect of polysulfides effectively, thus the Li-S battery possessed the excellent electrochemical cyclic performance, showing the first-cycle discharge-specific capacity of 1508.1 mAh g-1, the capacity retention of 73.6% after 200 cycles with 0.25 C at 25 °C and good rate performance.

Involvement of 5-Hydroxytryptamine Receptor 2A in the Pathophysiology of Medication-Overuse Headache.

BACKGROUND: Recent studies indicated that analgesic overuse upregulated 5-hydroxytryptamine receptor 2A (5-HT2AR) and subsequently activated nitric oxide synthase (NOS) and thus induced latent sensitization, which provided a mechanistic basis for medication-overuse headache (MOH). Moreover, glycogen synthase kinase-3ß (GSK-3ß) was regulated by serotonin receptors and the phosphorylation of GSK-3ß affected NOS activity, indicating that GSK-3ß could be involved in the regulation of NOS activity by 5-HT2AR in MOH pathophysiology. Herein, we performed this study to investigate the role of 5-HT2AR in MOH pathophysiology and the role of GSK-3ß in the regulation of NOS activity by 5-HT2AR. MATERIALS AND METHODS: Wistar rats were daily administered with paracetamol (200 mg/kg) for 30 days to set animal models for pre-clinical MOH research. After the rat MOH models were successfully established, the expression of 5-HT2AR and NOS, GSK-3ß activity in trigeminal nucleus caudalis (TNC) were assayed. Then, 5-HT2AR antagonist ketanserin and agonist DOI were applied to investigate the effect of 5-HT2AR on NOS activity in TNC of MOH rats, and GSK-3ß antagonist LiCl and agonist perifosine were applied to explore the role of GSK-3ß in the activation of NOS by 5-HT2AR. RESULTS: We found that the expression of 5-HT2AR and NOS, GSK-3ß activity were enhanced in TNC of MOH rats. 5-HT2AR modulator regulated the activity of NOS and GSK-3ß in TNC of MOH rats, and drugs acting on GSK-3ß affected NOS activity. CONCLUSION: These data suggest that GSK-3ß may mediate the activation of NOS by 5-HT2AR and underline the role of 5-HT2AR in MOH pathophysiology.

The effect of vascular risk factor burden on the severity of COVID-19 illness, a retrospective cohort study.

BACKGROUND: Patients with cardiovascular comorbidities are at high risk of poor outcome from COVID-19. However, how the burden (number) of vascular risk factors influences the risk of severe COVID-19 disease remains unresolved. Our aim was to investigate the association of severe COVID-19 illness with vascular risk factor burden. METHODS: We included 164 (61.8 ± 13.6 years) patients with COVID-19 in this retrospective study. We compared the difference in clinical characteristics, laboratory findings and chest computed tomography (CT) findings between patients with severe and non-severe COVID-19 illness. We evaluated the association between the number of vascular risk factors and the development of severe COVID-19 disease, using a Cox regression model. RESULTS: Sixteen (9.8%) patients had no vascular risk factors; 38 (23.2%) had 1; 58 (35.4%) had 2; 34 (20.7%) had 3; and 18 (10.9%) had ≥4 risk factors. Twenty-nine patients (17.7%) experienced severe COVID-19 disease with a median (14 [7-27] days) duration between onset to developing severe COVID-19 disease, an event rate of 4.47 per 1000-patient days (95%CI 3.10-6.43). Kaplan-Meier curves showed a gradual increase in the risk of severe COVID-19 illness (log-rank P < 0.001) stratified by the number of vascular risk factors. After adjustment for age, sex, and comorbidities as potential confounders, vascular risk factor burden remained associated with an increasing risk of severe COVID-19 illness. CONCLUSIONS: Patients with increasing vascular risk factor burden have an increasing risk of severe COVID-19 disease, and this population might benefit from specific COVID-19 prevention (e.g., self-isolation) and early hospital treatment measures.

Separate double-layer repair versus en masse repair for delaminated rotator cuff tears: a systematic review and meta-analysis.

OBJECTIVE: Delaminated rotator cuff tears are a common shoulder disorder in elderly individuals. Either arthroscopic separate double-layer repair (DR) or en masse repair (ER) is used to treat a delaminated rotator cuff tear. We conducted this systematic review and meta-analysis to compare the clinical outcomes of arthroscopic ER versus DR intervention. METHODS: Five studies were acquired from PubMed, Medline, Embase, CNKI, Google, and the Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed with RevMan 5.3. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. The Cochrane Collaboration's risk of bias tool and Newcastle-Ottawa Scale were used to assess the risk of bias. RESULTS: Five studies, including two randomized controlled trials (RCTs) and three observational studies, were assessed. The methodological quality of the trials ranged from low to high. The pooled results for the Shoulder Rating Scale of the University of California at Los Angeles (UCLA) score, visual analog scale (VAS) score, Constant score, and range of motion (ROM) showed that the outcomes were not statistically significant between the two interventions. The difference in retear rate was not statistically significant (OR = 0.69, 95% CI = 0.36-1.33, P = 0.27). The sensitivity analysis proved the stability of the pooled results, and publication bias was not apparent. CONCLUSIONS: Both arthroscopic ER and DR interventions had benefits in delaminated rotator cuff tear treatment. ER and DR treatments were equally effective and had the same retear rate. The arthroscopic DR technique could not be recommended as the optical choice for delaminated rotator cuff tears based on current evidence.

The effect of CBT and its modifications for relapse prevention in major depressive disorder: a systematic review and meta-analysis.

BACKGROUND: The risk of relapse in major depressive disorder (MDD) is associated with high worldwide disease burden. Cognitive behavioral therapy (CBT) and its modifications might be effective in relapse prevention. The aim of this review was to evaluate the efficacy of these treatments for reducing relapse of MDD. METHODS: The retrieval was performed in the databases of MEDLINE via Pubmed, EMBASE and PsycINFO via OVID, The Cochrane Library and four Chinese databases. Clinical trials registry platforms and references of relevant articles were retrieved as well. Hazard ratio (HR) and corresponding 95% confidence interval (CI) were used to pool evidences. RESULTS: A total of 16 eligible trials involving 1945 participants were included. In the first 12 months, CBT was more efficacious than control in reducing the risk of developing a new episode of depression for MDD patients in remission (HR:0.50, 95%CI:0.35-0.72, I2 = 11%). Mindfulness-based cognitive therapy (MBCT) was more efficacious than control only among patients with 3 or more previous depressive episodes (HR:0.46, 95%CI:0.31-0.70, I2 = 38%). Besides, compared with maintenance antidepressant medication (m-ADM), MBCT was a more effective intervention (HR:0.76, 95%CI:0.58-0.98, I2 = 0%). These positive effects might be only maintained at two and nearly 6 years follow up for CBT. CONCLUSION: The use of CBT for MDD patients in remission might reduce risk of relapse. Besides, the effect of MBCT was moderated by number of prior episodes and MBCT might only be effective for MDD patients with 3 or more previous episodes. Further exploration for the influence of previous psychological intervention is required.

[Imaging and biomechanics researches of reconstructing lumbosacral stability after L 5 vertebrectomy via anterolateral approach].

Objective: To investigate the feasibility of anterolateral approach for L 5 vertebral resection, bone grafting, and screw rod fixation by imaging and biomechanics researches. Methods: Twenty formalized adult cadavers (12 males and 8 females) were randomly divided into 2 groups; L 5 vertebral resection, bone graft, and screw rod fixation was performed on 10 specimens by using anterolateral approach (experimental group), and on the other 10 specimens by combined anterior and posterior approach. CT scanning and three-dimensional reconstruction were performed in the experimental group; preoperative maximal safe entry angle and depth of screws and intraoperative actual entry angle and depth of screws were measured; the sacral screw position was observed after operation. The biomechanical test was done in 2 groups. Results: Twenty specimens smoothly underwent L 5 excision and reconstruction. CT scan showed that there was no significant difference in maximal safe entry angle and depth of screws between males and females in experimental group before operation ( P>0.05); the maximal safe entry angle and depth were 51.93° and 47.88 mm for anterior screw, and were 37.04° and 46.28 mm for posterior screw. After operation, depth of the sacral anterior and posterior screws were appropriate, which did not pierce into the spinal canal. The biomechanical test results indicated that the flexion, extension, and lateral flexion displacements, and vertical compression stiffness showed no significant difference between 2 groups ( P>0.05). Conclusion: For L 5 lesions not invading posterior column, to use L 5 vertebral resection, bone graft, and screw rod fixation by anterolateral approach is a safe and feasible method to reconstruct lumbosacral stability, with the advantages of no changing posture, less operation time and incision, and prevention of bone graft shift, but effectiveness need further be identified.

Chronic Obstructive Pulmonary Disease as a Risk Factor for Cognitive Dysfunction: A Meta-Analysis of Current Studies.

Cognitive dysfunction has been shown to be associated with many risk factors, such as smoking, diabetes, and body mass index. Chronic obstructive pulmonary disease (COPD), a common disease within the elderly population, has also been found to be related to cognitive decline. However, whether COPD is a risk factor of cognitive dysfunction is not well established. The purpose of this meta-analysis is to investigate the role COPD plays in cognitive dysfunction. PubMed, Cochrane library and Web of Science databases were searched. Three cohort studies and eleven cross-sectional studies were found to be eligible. According to our results, COPD patients had a higher risk of cognitive dysfunction than controls (OR [odds ratio]: 1.72; 95% CI, 1.12-2.65; p = 0.01). The exacerbation of COPD was strongly correlated with cognitive decline. COPD patients performed worse than controls on the Mini- Mental State Examination test, but the results were not statistically significant (OR: -0.79; 95% CI, [-1.78, 0.19]; p = 0.11). Thus, more attention should be given to the occurrence of cognitive decline in COPD patients. The prevention and control of COPD exacerbation are critical.

Curcumin inhibits Aß-induced microglial inflammatory responses in vitro: Involvement of ERK1/2 and p38 signaling pathways.

Amyloid ß (Aß) plays an important role in Alzheimer's disease (AD) by inducing microglia activation. Once activated, microglial cells promote the release of reactive species and cytokines that are known to enhance immune responses in AD brain. Thus, negative regulators of microglia activation are considered as potential therapeutic candidates for AD. Curcumin, the major yellow pigment in turmeric (Curcuma longa), is proposed for its anti-inflammatory properties. Several studies have indicated the suppressive effects of curcumin on LPS-induced microglia activation and MAPK activities. However, the effects of curcumin on Aß-treated microglia and the possible mechanisms are still not fully understood. In the present study, we found that curcumin improved microglial viability against Aß42 in a time- and dose-dependent manner and remarkably suppressed Aß42-induced CD68 expression. Moreover, curcumin concentration-dependently abolished Aß42-induced interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production in mRNA and protein levels in microglia. Besides, curcumin exerted an inhibitory effect on phosphorylation of ERK1/2 and p38 in Aß42-activated microglia. Further experiments indicated that blockage of ERK1/2 and p38 pathways reduced inflammatory cytokines production from microglia. These results show that curcumin suppresses ERK1/2 and p38 signaling, thus, attenuating inflammatory responses of brain microglia.

Inhibition of glycogen synthase kinase-3ß attenuates glucocorticoid-induced suppression of myogenic differentiation in vitro.

Glucocorticoids are the only therapy that has been demonstrated to alter the progress of Duchenne muscular dystrophy (DMD), the most common muscular dystrophy in children. However, glucocorticoids disturb skeletal muscle metabolism and hamper myogenesis and muscle regeneration. The mechanisms involved in the glucocorticoid-mediated suppression of myogenic differentiation are not fully understood. Glycogen synthase kinase-3ß (GSK-3ß) is considered to play a central role as a negative regulator in myogenic differentiation. Here, we showed that glucocorticoid treatment during the first 48 h in differentiation medium decreased the level of phosphorylated Ser9-GSK-3ß, an inactive form of GSK-3ß, suggesting that glucocorticoids affect GSK-3ß activity. We then investigated whether GSK-3ß inhibition could regulate glucocorticoid-mediated suppression of myogenic differentiation in vitro. Two methods were employed to inhibit GSK-3ß: pharmacological inhibition with LiCl and GSK-3ß gene knockdown. We found that both methods resulted in enhanced myotube formation and increased levels of muscle regulatory factors and muscle-specific protein expression. Importantly, GSK-3ß inhibition attenuated glucocorticoid-induced suppression of myogenic differentiation. Collectively, these data suggest the involvement of GSK-3ß in the glucocorticoid-mediated impairment of myogenic differentiation. Therefore, the inhibition of GSK-3ß may be a strategy for preventing glucocorticoid-induced muscle degeneration.

Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in Aß1-42 insult in vitro.

This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aß1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aß1-42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aß1-42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1.

Efficacy of intravenous propacetamol hydrochloride in the treatment of an acute attack of migraine.

BACKGROUND: Triptans are a family of selective serotonin (5-HT1B/1D) receptor agonists that are widely used to treat acute migraine attacks. Their efficacy is limited by side effects and the gastrointestinal manifestations of migraine. AIM: To compare the efficacy of a single intravenous administration of propacetamol, a prodrug of paracetamol (acetaminophen) with a single dose of oral rizatriptan in treating acute migraine attacks. METHODS: Patients were selected from those who presented to the emergency room with a diagnosed migraine attack and who had not previously taken any analgesics. They were randomized into 2 groups: treatment with a single 1g IV dose of propacetamol or with a single oral dose of 5mg rizatriptan. Their Visual Analogue Scale (VAS) pain scores were assessed before and at 30, 60, and 120min after treatment. RESULTS: The patients who received the propacetamol had significantly improved VAS scores at 60min compared to the rizatriptan group. There were no significant differences in VAS scores at 30 or 120min post-treatment. CONCLUSION: Propacetamol is either equivalent or superior in efficacy to rizatriptan for treating acute migraine attacks, while having the advantage of parenteral administration in patients whose migraines are accompanied by nausea and vomiting.

White matter lesions in chronic migraine with medication overuse headache: a cross-sectional MRI study.

Analgesic overuse often happens to migraine patients, especially chronic migraineurs, and migraine has been demonstrated to be associated with white matter lesions (WMLs). The aim of this study was to investigate the relationship between medication overuse headache (MOH) and WMLs in chronic migraine (CM) patients. Subjects were enrolled and divided into three groups: healthy controls, CM without MOH (CMwoMOH), and CM with MOH (CM-MOH). Most of the CM patients used non-steroidal anti-inflammatory drugs (NSAIDs) as acute headache medications. All the participants underwent magnetic resonance imaging scans and images were obtained for WML evaluation with semiquantitative scales. One hundred and forty-one participants were included, 45 of them for controls, 38 for CMwoMOH, and 58 for CM-MOH. In women, CMwoMOH patients had a higher prevalence of high WML load compared with controls and CM-MOH patients. In men, however, all the study groups showed no differences in the prevalence of high WML load. CMwoMOH women had increased risks of high deep white matter lesion (DWML) load compared with controls, while they had no risks of high periventricular white matter lesion (PVWML) load. CM-MOH women had no risks of high DWML load, but they had reduced risks of high PVWML load. The association of CM-MOH with high WML load in women was not changed when compared with CMwoMOH. Age was independently associated with high WML load among women. These data suggest that MOH caused by NSAIDs is not a risk factor for WMLs. Rather, NSAID overuse probably protects MOH patients from WMLs through anti-inflammatory effects.

Effects of matrix metalloproteinase-1 on the myogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro.

Matrix metalloproteinase-1 (MMP-1) is a member of the family of zinc-dependent endopeptidases that are capable of degrading extracellular matrix (ECM) and certain non-matrix proteins. It has been shown that MMP-1 can enhance muscle regeneration by improving the differentiation and migration of myoblasts. However, it is still not known whether MMP-1 can promote the myogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). To address this question, we isolated BMSCs from C57BL/6J mice and investigated the effects of MMP-1 on their proliferation and myogenic differentiation. Our results showed that MMP-1 treatment, which had no cytotoxic effects on BMSCs, increased the mRNA and protein levels of MyoD and desmin in a dose-dependent manner, indicating that MMP-1 promoted myogenic differentiation of BMSCs in vitro. These results suggest that BMSCs may have a therapeutic potential for treating muscular disorders.

A comparative study of bone marrow mesenchymal stem cell functionality in C57BL and mdx mice.

Patients with DMD have low bone mass and a high incidence of fractures, but the cellular and molecular mechanisms underlying this pathological condition are unknown. Because bone marrow mesenchymal stem cells (BMSCs) are the progenitors of bone-forming osteoblasts, we hypothesized that DMD leads to dysfunction in the differentiation of BMSCs. We isolated BMSCs from C57BL control and mdx mutant mice, a well-established mouse model of DMD, and compared their abilities of proliferation, differentiation, and the expression of lineage-specific genes. Results showed that the proliferation and osteogenic and myogenic differentiation of BMSCs from mdx mice were significantly lower than those from C57BL mice. Because mutations in dystrophin gene cause DMD, our results demonstrate that dystrophin deficiency leads to dysfunction in the differentiation and proliferation of BMSCs.