White Matter Hyperintensities on Post-Stroke Balance and Gait Recovery: A Prospective Cohort Study Protocol.

INTRODUCTION: White matter hyperintensities (WMH) are commonly associated with balance and gait disturbances. Little is known whether WMH may affect post-stroke balance and gait recovery. We aim to investigate the association of post-stroke balance and gait recovery with imaging marker of WMH on magnetic resonance imaging (MRI). METHODS: This prospective cohort study will enroll consecutive patients with first-ever ischemic hemisphere stroke, between September 2023 and December 2024. Clinical data will be collected on day 30±3 and at 3-month after stroke onset. WMH on FLAIR are graded according to the modified Fazekas scale. Resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) will be acquired to evaluate functional and structural connectivity. The primary endpoint is balance recovery, defined as a Postural Assessment Scale for Stroke score of 32 or higher at 3-month. The secondary endpoint is gait recovery, assessed using the modified Fugl-Meyer Gait Assessment at 3-month. We will investigate the association of post-stroke balance and gait recovery with WMH severity as well as WMH-related functional and structural connectivity. CONCLUSION: The study may contribute to clarify the effect of WMH on post-stroke balance and gait disorder recovery.

The Effect of Cerebellar Repetitive Transcranial Magnetic Stimulation on Dysphagia due to Posterior Circulation Stroke, a Randomized Controlled Trial Protocol.

INTRODUCTION: Cerebellum might be active during the task of swallowing. Little is known whether cerebellar repetitive transcranial magnetic stimulation (rTMS) could improve post-stroke dysphagia (PSD) due to occlusion in the posterior circulation. This paper describes the rationale and design of a randomized controlled trial that aims to determine the effect of cerebellar rTMS on dysphagia due to posterior circulation stroke. METHODS AND ANALYSIS: Thirty patients with PSD due to occlusion in the posterior circulation will be randomly divided to receive real (n = 20) or sham (n = 10) cerebellar rTMS. Patients in the real rTMS group will receive 250 pulses rTMS at a low intensity with 10 Hz frequency for 10 days (five consecutive days per week). The severity of dysphagia will be assessed with videofluoroscopic swallowing study (VFSS) using the Rosenbek penetration aspiration scale (PAS), the pharyngeal constriction ratio (PCR), and the dysphagia outcome and severity scale (DOSS) before and immediately after the last session and then again after 1 and 3 months. The functional magnetic resonance imaging (fMRI) will be assessed before and after the last session and then again after 1 month and 3 months. The primary outcome is the improvement of swallowing function determined by PAS, PCR, and DOSS. The secondary outcomes include changes in brain connectivity network detected using fMRI. DISCUSSION: This study will determine whether cerebellar rTMS improves dysphagia due to posterior circulation stroke in Chinese patients. Our findings will contribute to a new approach for swallowing function recovery after posterior circulation stroke.

Determinants for a low dose of alteplase and its relationship to a lower intracerebral bleeding risk in acute ischemic stroke.

Background: Factors for the utilization of intravenous thrombolysis with a low-dose of alteplase (0.6mg/kg) and whether the low-dose of alteplase could reduce the risk of intracerebral bleeding in acute ischemic stroke (AIS) remains uncertain. Aims: We aimed to investigate determinants for the utilization of intravenous thrombolysis with a low-dose of alteplase. We further assessed the association between the low-dose of alteplase and the intracerebral bleeding risk in AIS patients. Method: We included AIS patients who received intravenous thrombolysis using alteplase in this multicenter retrospective observational study. We investigated the association between baseline characteristics and the utilization of a low-dose of alteplase to identify determinants. We assessed the association of the low-dose of alteplase with the risk of symptomatic intracranial hemorrhage (sICH) using a multivariable logistic regression model. We further compared the rate of sICH and any ICH in patients in the low-dose group to those in the standard-dose group, using propensity score-matching data. Results: A total of 506 AIS patients were included in this study. The mean age was 67 (interquartile range [IQR] 59-75), and 178 (35.2%) were women. A total of 96 patients were treated with the low-dose. Age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00 -1.04, p = 0.042), having a previous ischemic stroke (adjusted OR 2.01, 95%CI 1.11 - 3.64 p = 0.021) and increasing baseline systolic blood pressure (adjusted OR 1.12, 95%CI 1.00 - 1.26, p = 0.049) were determinants for the utilization of the low-dose. Multivariable logistic regression analysis showed that the low-dose was significantly associated with a reduced risk of sICH (adjusted OR 0.13, 95%CI 0.03 - 0.62, p = 0.01). Propensity score analysis showed that the rate of sICH was significantly lower in the low-dose group compared to standard-dose group (2 [2.3%] vs 10 [11.4%], p = 0.032). There was no significant difference in the rate of any ICH between two groups (14 [15.9%] vs 18 [20.5%], p = 0.434). Conclusions: Patients with increasing age, a higher baseline systolic blood pressure, and previous ischemic stroke were at a higher odd of receiving a low-dose of alteplase. The low-dose was associated with a lower risk of developing symptomatic intracranial hemorrhage.

Bone marrow-derived mesenchymal stem cells improve post-ischemia neurological function in rats via the PI3K/AKT/GSK-3ß/CRMP-2 pathway.

BACKGROUND: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is a potential therapy for cerebral ischemia. However, the underlying protective mechanism remains undetermined. Here, we tested the hypothesis that transplantation of BMSCs via intravenous injection can alleviate neurological functional deficits through activating PI3K/AKT signaling pathway after cerebral ischemia in rats. METHODS: A cerebral ischemic rat model was established by the 2 h middle cerebral artery occlusion (MCAO). Twenty-four hours later, BMSCs (1 × 106 in 1 ml PBS) from SD rats were injected into the tail vein. Neurological function was evaluated by modified neurological severity score (mNSS) and modified adhesive removal test before and on d1, d3, d7, d10 and d14 after MCAO. Protein expressions of AKT, GSK-3ß, CRMP-2 and GAP-43 were detected by Western-bolt. NF-200 was detected by immunofluorescence. RESULTS: BMSCs transplantation did not only significantly improve the mNSS score and the adhesive-removal somatosensory test after MCAO, but also increase the density of NF-200 and the expression of p-AKT, pGSK-3ß and GAP-43, while decrease the expression of pCRMP-2. Meanwhile, these effects can be suppressed by LY294002, a specific inhibitor of PI3K/AKT. CONCLUSION: These data suggest that transplantation of BMSCs could promote axon growth and neurological deficit recovery after MCAO, which was associated with activation of PI3K/AKT /GSK-3ß/CRMP-2 signaling pathway.

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.

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.

Serum elabela and apelin levels during different stages of chronic kidney disease.

PURPOSE: The association of serum elabela (ELA) and apelin with the progression of chronic kidney disease (CKD) is unknown. We determined if serum ELA and apelin levels were associated with CKD stage. METHODS: This observational study involved 60 CKD patients and 20 healthy, age-, race-, and gender-matched controls. The participants were grouped according to renal function as follows: normal control group, CKD1 group (stage-1 CKD, 20 patients), CKD3 group (stage-3 CKD, 20 patients), and CKD5 group (stage-5 CKD, 20 patients) in accordance with the Kidney Disease Outcomes - Quality Initiative criteria. We recorded the demographic, clinical, and biochemical data of all participants. Serum ELA and apelin levels were measured using commercially available enzyme-linked immunosorbent assays. RESULTS: Serum ELA levels gradually and significantly declined with decreases in the estimated glomerular filtration rate (eGFR). Serum ELA showed significant negative correlations with serum creatinine (r = -0.529, p < .001), blood urea nitrogen (r = -0.575, p < .001), systolic blood pressure (r = -0.455, p < .001), and diastolic blood pressure (r = -0.450, p < .001), and significant positive correlations with hemoglobin (r = 0.523, p < .001) and eGFR (r = 0.728, p < .001). Multiple regression analysis showed that eGFR independently influenced serum ELA levels. No significant association was found between serum apelin levels and CKD progression. CONCLUSION: In CKD patients, serum ELA levels decreased with decreasing eGFR. This finding may provide a new target for the prediction, diagnosis, and staging of CKD.

Targeting of mTORC1/2 by dihydroevocarpine induces cytotoxicity in acute myeloid leukemia.

Interactions between the tumor cells and bone marrow (BM) microenvironment promote survival, growth, and chemoresistance of acute myeloid leukemia (AML). The mTOR pathway plays a key role in mediating the AML-BM microenvironment interactions. Here, we report the anti-AML activity of a natural monomer extracted from the Chinese medicinal herb Evodia rutaecarpa, dihydroevocarpine. Our results showed that dihydroevocarpine-induced cytotoxicity, apoptosis, and G0/G1 arrest in AML cells, and inhibited the tumor growth in an AML xenograft model. Importantly, our study revealed that the dihydroevocarpine treatment inhibited the mTOR pathway via suppressing the mTORC1/2 activity, and thus overcame the protective effect of the BM microenvironment on AML cells. Taken together, our findings suggest that dihydroevocarpine could be used as a potential anti-AML agent alone or a therapeutic adjunct in AML therapy, particularly in the presence of the BM microenvironment.

ROS-Responsive Nanoparticles for Suppressing the Cytotoxicity and Immunogenicity Caused by PM2.5 Particulates.

Although the negative impacts of particulate matter (PM2.5) on human health have been well recognized, very few efforts have been paid to find new strategies to suppress the toxicity of PM2.5 both in vitro and in vivo. In this study, reactive oxygen species (ROS)-responsive nanoparticles made of poly(1,4-phenleneacetonedimethylene thioketal) (PPADT) were used to load immunosuppressant drug tacrolimus (FK506) with a drug loading efficiency of around 44%. The PPADT particles showed very good ROS-responsiveness and were degraded in an oxidation environment. By exhausting intracellular ROS, they could effectively suppress the toxicity of A549 lung epithelial cells and RAW264.7 macrophages induced by the PM2.5 particulates collected from three different regions in China. Moreover, the inflammatory response of PM2.5 could also be significantly suppressed, showing much better performance than the free FK506 drugs both in vitro and in vivo. This concept-proving research demonstrates the promising application for the ROS-sensitive drug release particles in dispelling the toxicity and suppressing the inflammation of PM2.5 pollutes, shedding a new light in the design and applications of stimuli-responsive systems in the bionanotechnology and healthcare fields.

Nanodiamonds of Different Surface Chemistry Influence the Toxicity and Differentiation of Rat Bone Mesenchymal Stem Cells In Vitro.

The nanodiamonds (NDs) have attracted much attention in biomedical applications due to their excellent magnetic and optical properties. However, comprehensive study of different surfacemodified NDs on toxicity and differentiation of mesenchymal stem cells are very deficient. In this study, three types of NDs, i.e., ND-COOH, ND-NH+3 and ND-PEG were co-cultured with rat bone mesenchymal stem cells (MSCs) to assess their biosafety and effects on differentiation. In a dry state, they had a similar diameter of about 6-7 nm, and aggregated into ˜100 nm (hydrodynamic size) in cell culture medium. Co-culture with MSCs showed that the ND-COOH and ND-PEG had lower cytotoxicity than ND-NH+3. Alkaline comet assay showed slight genotoxicity for all the NDs regardless of their surface coatings. The reactive oxygen species (ROS) test showed that the cytotoxicity and genotoxicity of NDs may be attributed to the NDs-mediated intracellular oxidative stress. All the NDs did not show significant impact on the osteogenic differentiation of MSCs, whereas the ND-COOH and ND-PEG slightly impaired the adipogenic differentiation. Taken together, these findings provide some momentous implications for the design of surface chemical structures of NDs for their applications in biological field.

Complete response of Ctnnb1-mutated tumours to ß-catenin suppression by locked nucleic acid antisense in a mouse hepatocarcinogenesis model.

BACKGROUND & AIMS: Hepatocellular cancer (HCC) remains a disease of poor prognosis, highlighting the relevance of elucidating key molecular aberrations that may be targeted for novel therapies. Wnt signalling activation, chiefly due to mutations in CTNNB1, have been identified in a major subset of HCC patients. While several in vitro proof of concept studies show the relevance of suppressing Wnt/ß-catenin signalling in HCC cells or tumour xenograft models, no study has addressed the impact of ß-catenin inhibition in a relevant murine HCC model driven by Ctnnb1 mutations. METHODS: We studied the in vivo impact of ß-catenin suppression by locked nucleic acid (LNA) antisense treatment, after establishing Ctnnb1 mutation-driven HCC by diethylnitrosamine and phenobarbital (DEN/PB) administration. RESULTS: The efficacy of LNA directed against ß-catenin vs. scrambled on Wnt signalling was demonstrated in vitro in HCC cells and in vivo in normal mice. The DEN/PB model leads to HCC with Ctnnb1 mutations. A complete therapeutic response in the form of abrogation of HCC was observed after ten treatments of tumour-bearing mice with ß-catenin LNA every 48h as compared to the scrambled control. A decrease in ß-catenin activity, cell proliferation and increased cell death was evident after ß-catenin suppression. No effect of ß-catenin suppression was evident in non-Ctnnb1 mutated HCC, observed after DEN-only administration. CONCLUSIONS: Thus, we provide the in vivo proof of concept that ß-catenin suppression in HCC will be of significant therapeutic benefit, provided the tumours display Wnt activation via mechanisms like CTNNB1 mutations.

Treadmill exercise enhances therapeutic potency of transplanted bone mesenchymal stem cells in cerebral ischemic rats via anti-apoptotic effects.

BACKGROUND: The transplantation of bone marrow stromal cells (MSCs) has proved to ameliorate ischemic brain injury in animals, but most transplanted MSCs undergo apoptosis in the ischemic penumbra, greatly compromising the therapeutic value of this treatment. Meanwhile, cell apoptosis can be inhibited by post-ischemia exercise which has been demonstrated to improve the expression of related anti-apoptotic proteins. The present study investigated whether treadmill exercise enhances the neuroprotective effects of transplanted MSCs in a rat experimental stroke model. RESULT: Rats were subjected to 2-h middle cerebral artery occlusion (MCAO). Twenty-four hours after reperfusion, they were assigned randomly to receive no MSCs treatment and no exercise (control group), intravenous transplantation of MSCs and treadmill exercise (MSCs + Ex group), MSCs transplantation only (MSCs group) and treadmill exercise only (Ex group). Neurological assessment, TUNEL staining and western blot were performed. Compared with the MSCs group and Ex group, the MSCs + Ex group reported markedly improved neurological function, significantly decreased apoptotic cells, and increased expressions of survivin and bcl-2 (p < 0.05 or p < 0.01, respectively). Interestingly, the treadmill exercise significantly inhibited the apoptosis of transplanted MSCs. As a result, the number of engrafted MSCs in the MSCs + Ex group was significantly higher than that in the MSC group (p < 0.01). CONCLUSIONS: Treadmill exercise enhances the therapeutic potency of MSCs by improving neurological function and possibly inhibiting the apoptosis of neuron cells and transplanted MSCs. These effects may involve an increased expression of survivin and bcl-2.

Selection of dialysis methods for end-stage kidney disease patients with diabetes.

The increasing prevalence of diabetes has led to a growing population of end-stage kidney disease (ESKD) patients with diabetes. Currently, kidney transplantation is the best treatment option for ESKD patients; however, it is limited by the lack of donors. Therefore, dialysis has become the standard treatment for ESKD patients. However, the optimal dialysis method for diabetic ESKD patients remains controversial. ESKD patients with diabetes often present with complex conditions and numerous complications. Furthermore, these patients face a high risk of infection and technical failure, are more susceptible to malnutrition, have difficulty establishing vascular access, and experience more frequent blood sugar fluctuations than the general population. Therefore, this article reviews nine critical aspects: Survival rate, glucose metabolism disorder, infectious complications, cardiovascular events, residual renal function, quality of life, economic benefits, malnutrition, and volume load. This study aims to assist clinicians in selecting individualized treatment methods by comparing the advantages and disadvantages of hemodialysis and peritoneal dialysis, thereby improving patients' quality of life and survival rates.

Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling.

Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia. However, whether there is a synergistic effect between the two remains unclear. In this study, we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes (MSC-exos) via the tail vein and underwent 14 successive days of treadmill exercise. Neurological assessment, histopathology, and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume, evident synaptic formation and axonal regeneration, and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment. These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone. Mechanistically, further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling. These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment, which may be related to activation of the JNK1/c-Jun signaling pathway. This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.

A phylotranscriptomic dataset of angiosperm species under cold stress.

Angiosperms are one of the most diverse and abundant plant groups that are widely distributed on Earth, from tropical to temperate and polar zones. The wide distribution of angiosperms may be attributed to the evolution of sophisticated mechanisms of environmental adaptability, including cold tolerance. Since the development of high-throughput sequencing, transcriptome has been widely utilized to gain insights into the molecular mechanisms of plants in response to cold stress. However, previous studies generally focused on single or two species, and comparative transcriptome analyses for multispecies responding to cold stress were limited. In this study, we selected 11 representative angiosperm species, performed phylotranscriptome experiments at four time points before and after cold stress, and presented a profile of cold-induced transcriptome changes in angiosperms. Our multispecies cold-responsive RNA-seq datasets provide valuable references for exploring conserved and evolutionary mechanisms of angiosperms in adaptation to cold stress.

Orthogroup and phylotranscriptomic analyses identify transcription factors involved in the plant cold response: A case study of Arabidopsis BBX29.

C-repeat binding factors (CBFs) are well-known transcription factors (TFs) that regulate plant cold acclimation. RNA sequencing (RNA-seq) data from diverse plant species provide opportunities to identify other TFs involved in the cold response. However, this task is challenging because gene gain and loss has led to an intertwined community of co-orthologs and in-paralogs between and within species. Using orthogroup (closely related homologs) analysis, we identified 10,549 orthogroups in five representative eudicots. A phylotranscriptomic analysis of cold-treated seedlings from eudicots identified 35 high-confidence conserved cold-responsive transcription factor orthogroups (CoCoFos). These 35 CoCoFos included the well-known cold-responsive regulators CBFs, HSFC1, ZAT6/10, and CZF1 among others. We used Arabidopsis BBX29 for experimental validation. Expression and genetic analyses showed that cold-induction of BBX29 is CBF- and abscisic acid-independent, and BBX29 is a negative regulator of cold tolerance. Integrative RNA-seq and Cleavage Under Targets and Tagmentation followed by sequencing analyses revealed that BBX29 represses a set of cold-induced TFs (ZAT12, PRR9, RVE1, MYB96, etc.). Altogether, our analysis yielded a library of eudicot CoCoFos and demonstrated that BBX29 is a negative regulator of cold tolerance in Arabidopsis.

Elabela Attenuates the TGF-ß1-Induced Epithelial-Mesenchymal Transition of Peritoneal Mesothelial Cells in Patients Receiving Peritoneal Dialysis.

Peritoneal fibrosis (PF), a common complication in patients receiving peritoneal dialysis (PD), is primarily caused by the epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs). PF is the main reason for patients on PD to withdraw from PD. Effective treatment is unavailable for this complication at present. Elabela (ELA) is a polypeptide hormone secreted by the vascular endothelium and kidney. Peptide hormones ELA and apelin (APLN) have various protective effects on the cardiovascular and urinary systems and have potential therapeutic effects on organ fibrosis. ELA and APLN are less studied in PD population. Here, we aimed to investigate the clinical significance of ELA in patients on PD and to evaluate the therapeutic effect of ELA on EMT of HPMCs. Compared with those in patients with stage 5 chronic kidney disease who are not on dialysis, serum ELA levels in patients on PD increased with the improvement of residual renal function at PD duration <36 months and decreased to pre-dialysis levels at PD duration ≥36 months, suggesting that dialysis duration is the main risk factor affecting serum ELA levels in patients on PD. In addition, serum APLN levels decreased in the early stage of PD and recovered to the pre-dialysis level with the prolongation of dialysis time. Notably, serum APLN levels were positively correlated with dialysis duration in patients undergoing PD. To establish the EMT model, we stimulated HPMCs using transforming growth factor-beta 1 (TGF-ß1) in cell experiments performed in vitro. ELA-32 treatment reversed the TGF-ß1-induced reduction in the expression of the epithelial cell marker and suppressed the expression of mesenchymal cell markers by inhibiting the phosphorylation of SMAD2/3, ERK1/2, and AKT. Therefore, our findings imply that ELA-32 can interfere with the EMT of HPMCs by inhibiting the activation of the TGF-ß/SMAD2/3, ERK1/2, and AKT pathways, providing novel insights on the potential therapeutic use of ELA for treating PD-related PF.

Psychological stress and coping strategies among frontline healthcare workers supporting patients with coronavirus disease 2019: a retrospective study and literature review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak might have a psychological impact on frontline healthcare workers. However, the effectiveness of coping strategies was less reported. OBJECTIVES: We aimed to investigate the sources of stress and coping strategies among frontline healthcare workers fighting against COVID-19. We also performed a literature review regarding the effects of coping methods on psychological health in this population. METHODS: We included frontline healthcare workers who completed an online survey using self-made psychological stress questionnaires in a cross-sectional study. We evaluated the association between potential factors and high-stressed status using a logistic regression model. We performed the principal component analysis with varimax rotation for factor analysis. We also performed a systematic review of published randomized controlled studies that reported the effects of coping methods on psychological health in COVID-19 healthcare workers. RESULTS: We included 107 [32 (29-36) years] respondents in the final analysis, with a response rate of 80.5%. A total of 41 (38.3%) respondents were high-stressed. Compared with the low-stressed respondents, those with high-stress were less likely to be male (46.3% versus 72.7%, p = 0.006), nurses (36.6% versus 80.3%, p < 0.001), and more likely to have higher professional titles (p = 0.008). The sources of high-stress in frontline healthcare workers were categorized into 'work factor', 'personal factor', and 'role factor'. A narrative synthesis of the randomized controlled studies revealed that most of the coping methods could improve the psychological stress in healthcare workers during the COVID-19 pandemic. CONCLUSION: Our findings suggest that some frontline healthcare workers experienced psychological stress during the early pandemic. Effective coping strategies are required to help relieve the stress in this population.

Association Between Previous Stroke and Severe COVID-19: A Retrospective Cohort Study and an Overall Review of Meta-Analysis.

Objective: The objective of this study was to investigate the association between previous stroke and the risk of severe coronavirus disease 2019 (COVID-19). Methods: We included 164 (61.8 ± 13.6 years) patients with COVID-19 in a retrospective study. We evaluated the unadjusted and adjusted associations between previous stroke and severe COVID-19, using a Cox regression model. We conducted an overall review of systematic review and meta-analysis to investigate the relationship of previous stroke with the unfavorable COVID-19 outcomes. Results: The rate of severe COVID-19 in patients with previous stroke was 28.37 per 1,000 patient days (95% confidence interval [CI]: 10.65-75.59), compared to 3.94 per 1,000 patient days (95% CI: 2.66-5.82) in those without previous stroke (p < 0.001). Previous stroke was significantly associated with severe COVID-19 using a Cox regression model (unadjusted [hazard ratio, HR]: 6.98, 95% CI: 2.42-20.16, p < 0.001; adjusted HR [per additional 10 years]: 4.62, 95% CI: 1.52-14.04, p = 0.007). An overall review of systematic review and meta-analysis showed that previous stroke was significantly associated with severe COVID-19, mortality, need for intensive care unit admission, use of mechanical ventilation, and an unfavorable composite outcome. Conclusion: Previous stroke seems to influence the course of COVID-19 infection; such patients are at high risk of severe COVID-19 and might benefit from early hospital treatment measures and preventive strategies.