Systematic assessment of plasma biomarkers in spinocerebellar ataxia.

BACKGROUND AND OBJECTIVES: Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated-tau (p-tau), and ß-amyloid (Aß) have emerged as promising markers in several neurodegenerative disorders, but whether they can be used as biomarkers in spinocerebellar ataxias (SCA) is yet to be determined. This study aimed to identify sensitive plasma markers for SCA and investigate their effectiveness in tracking ataxia severity, cognition, non-motor symptoms, and brain atrophy. METHODS: This observational study recruited consecutive participants from Huashan Hospital and the CABLE study from November 2019. Patients with SCA were genetically diagnosed, grouped according to the ataxia severity, and compared with healthy older individuals and patients with multiple system atrophy type C (MSA-C). Plasma NfL, GFAP, p-tau, and Aß levels were measured by Simoa in all participants. Analysis of covariance, Spearman correlation, and multivariable regression were used to explore candidate markers in SCA. RESULTS: A total of 190 participants (60 SCA, 56 MSA-C, and 74 healthy controls) were enrolled. Plasma NfL level increased early in the pre-ataxic stage of SCA (32.23 ± 3.07 vs. 11.41 ± 6.62 pg/mL in controls), was positively associated with the ataxia severity (r = 0.45, P = 0.005) and CAG repeat length (r = 0.51, P = 0.001), varied among the different SCA subtypes (39.57 ± 13.50 pg/mL in SCA3, which was higher than 28.17 ± 8.02 pg/mL in SCA2, 17.08 ± 6.78 pg/mL in SCA8, and 24.44 ± 18.97 pg/mL in rare SCAs; P < 0.05), and was associated with brainstem atrophy. NfL alone (area under the curve [AUC] 0.867) or combined with p-tau181 and Aß (AUC 0.929), showed excellent performance in discriminating SCA patients from controls. Plasma GFAP distinguished SCA from MSA-C with moderate accuracy (AUC > 0.700) and correlated with cognitive performance and cortical atrophy. Changes in levels of p-tau181 and Aß were observed in SCA patients compared to controls. They were both correlated with cognition, while Aß was also associated with non-motor symptoms, such as anxiety and depression. DISCUSSION: Plasma NfL may serve as a sensitive biomarker for SCA, and its level is elevated in the pre-ataxic stage. The different performance of NfL and GFAP indicates differences in the underlying neuropathology of SCA and MSA-C. Moreover, amyloid markers may be useful for detecting memory dysfunction and other non-motor symptoms in SCA.

Omics-based biomarkers discovery for Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorders presenting with the pathological hallmarks of amyloid plaques and tau tangles. Over the past few years, great efforts have been made to explore reliable biomarkers of AD. High-throughput omics are a technology driven by multiple levels of unbiased data to detect the complex etiology of AD, and it provides us with new opportunities to better understand the pathophysiology of AD and thereby identify potential biomarkers. Through revealing the interaction networks between different molecular levels, the ultimate goal of multi-omics is to improve the diagnosis and treatment of AD. In this review, based on the current AD pathology and the current status of AD diagnostic biomarkers, we summarize how genomics, transcriptomics, proteomics and metabolomics are all conducing to the discovery of reliable AD biomarkers that could be developed and used in clinical AD management.

Development and shelf life stability of new products for Pacific saury (Cololabis saira).

Pacific saury is a primarily wild-caught fish in Taiwan and contains high amounts of polyunsaturated fatty acids (PUFAs). Therefore, its consumption is encouraged by Taiwanese government due to its high nutrition values and affordable price. In this study, four products, Minced saury with pork, Minced saury with XO sauce, Crispy dried saury, and Saury roll with roe, were developed. Optimization of the processing and ingredients were determined by a group of expert panelists, then by a large group of regular consumers. Total bacterial count, coliform, Escherichia coli, volatile base nitrogen, water content, and water activity were analyzed for shelf-life stability. In addition, the indexes of oil oxidation such as acid values, peroxide, and thiobarbituric acid were determined for the oil quality of products. Compositions of fatty acids and fragrant compounds were also analyzed. All microbial, physicochemical, and oil oxidation indexes of the products complied with the official regulations and industrial standards of Taiwan. Composition of fragrant compounds closely related with sensory characteristics and PUFAs composition were not degraded by the processing and storage. A new brand name, Hsiung-Chou, and the logo were established and the products were contracted to manufacturers for commercial production. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05432-1.

Chitosan-miRNA functionalized microporous titanium oxide surfaces via a layer-by-layer approach with a sustained release profile for enhanced osteogenic activity.

BACKGROUND: The biofunctionalization of titanium implants for high osteogenic ability is a promising approach for the development of advanced implants to promote osseointegration, especially in compromised bone conditions. In this study, polyelectrolyte multilayers (PEMs) were fabricated using the layer-by-layer approach with a chitosan-miRNA (CS-miRNA) complex and sodium hyaluronate (HA) as the positively and negatively charged polyelectrolytes on microarc-oxidized (MAO) Ti surfaces via silane-glutaraldehyde coupling. METHODS: Dynamic contact angle and scanning electron microscopy measurements were conducted to monitor the layer accumulation. RiboGreen was used to quantify the miRNA loading and release profile in phosphate-buffered saline. The in vitro transfection efficiency and the cytotoxicity were investigated after seeding mesenchymal stem cells (MSCs) on the CS-antimiR-138/HA PEM-functionalized microporous Ti surface. The in vitro osteogenic differentiation of the MSCs and the in vivo osseointegration were also evaluated. RESULTS: The surface wettability alternately changed during the formation of PEMs. The CS-miRNA nanoparticles were distributed evenly across the MAO surface. The miRNA loading increased with increasing bilayer number. More importantly, a sustained miRNA release was obtained over a timeframe of approximately 2 weeks. In vitro transfection revealed that the CS-antimiR-138 nanoparticles were taken up efficiently by the cells and caused significant knockdown of miR-138 without showing significant cytotoxicity. The CS-antimiR-138/HA PEM surface enhanced the osteogenic differentiation of MSCs in terms of enhanced alkaline phosphatase, collagen production and extracellular matrix mineralization. Substantially enhanced in vivo osseointegration was observed in the rat model. CONCLUSIONS: The findings demonstrated that the novel CS-antimiR-138/HA PEM-functionalized microporous Ti implant exhibited sustained release of CS-antimiR-138, and notably enhanced the in vitro osteogenic differentiation of MSCs and in vivo osseointegration. This novel miRNA-functionalized Ti implant may be used in the clinical setting to allow for more effective and robust osseointegration.

Lin28B regulates the fate of grafted mesenchymal stem cells and enhances their protective effects against Alzheimer's disease by upregulating IGF-2.

Mesenchymal stem cells (MSCs) transplantation has emerged as a potential therapeutic approach for Alzheimer's disease (AD). However, the poor proliferation capacity and low survival rate of engrafted MSCs in the hostile microenvironment of AD limit their therapeutic efficiency. Lin28B is a conserved RNA-binding protein associated with cell self-renewal and survival. The purpose of the present study was to explore whether lin28B might influence the functions of implanted MSCs and strengthen their neuroprotective potential in AD. A gain-of-function assay was used to upregulate lin28B expression in MSCs by lentiviral transfection. Our in vitro results indicated that lin28B promoted MSCs proliferation and migration, and protected MSCs against Aß1-42-induced cell death by upregulating insulin-like growth factor-2 (IGF-2). Blockage of IGF-2 partially abrogated the above effects of lin28B. After intracerebroventricular injection into amyloid precursor protein/presenilin 1 mice, implanted MSCs were monitored using bioluminescence imaging. We observed that administration of MSCs transfected with lin28B significantly stimulated their proliferation and prolonged cell retention after delivery. Moreover, administration of the transfected MSCs markedly mitigated cognitive deficits, promoted amyloid plaque clearance, decreased the activation of microglia, and reduced neuronal cell death. The data above confirmed our hypothesis that lin28B is a crucial modulator determining the fate of transplanted MSCs by regulating IGF-2-associated pathways and thereby enhancing their protective effects against AD.

Free thyroxine level is associated with both relapse rate and poor neurofunction in first-attack Neuromyelitis Optica Spectrum Disorder (NMOSD) patients.

BACKGROUND: To investigate whether the serum free thyroxine (FT4) level is a prognostic factor for the first-attack neuromyelitis optica spectrum disorders (NMOSD). METHODS: This retrospective study enrolled 109 patients with first-attack NMOSD. The Expanded Disability Status Scale (EDSS) and the relapse rate were used to evaluate the outcomes. The logistic regression model was used to analyze the independent effects of FT4 on relapse and final EDSS. Kaplan-Meier analysis, scatter plot smoothing method, and two-phase piecewise linear regression model were used to investigate the relationship between the FT4 level and the relapse rate. RESULTS: Multivariate analysis revealed that serum FT4 level might be a risk factor for both final EDSS (ß = 0.17; 95% confidence interval: 0.03-0.32) and the relapse rate (HR = 1.18; 95% confidence interval: 1.05-1.32). Furthermore, 1400 days after the onset, nearly 100% of patients in the high-FT4 group relapsed, while only 40% of the patients in the low-FT4 group relapsed. Finally, we found that the relationship between the FT4 level and the NMOSD relapse rate was nonlinear. The risk of NMOSD relapse increased with the FT4 level up to the inflection point of 12.01 pmol/L (HR = 1.45; 95% confidence interval: 1.06-1.98). When the FT4 level was > 12.01 pmol/L, there was no correlation between the FT4 level and the risk of NMOSD relapse (HR = 1.05; 95% confidence interval: 0.78-1.41). CONCLUSION: Serum FT4 level may be a prognostic indicator for the first-attack in patients with NMOSD. High FT4 levels are associated with poor neurofunctions and a high relapse rate in patients with the first-attack in patients with NMOSD.

Numerical and theoretical analysis on the absorption properties of metasurface-based terahertz absorbers with different thicknesses.

In this paper, we numerically and theoretically discuss the novel absorption properties of a conventional metasurface-based terahertz (THz) electromagnetic (EM) absorber with different dielectric thicknesses. Two absorption modes are presented in the considered frequency band due to the increased dielectric thickness, and both modes can achieve near-unity absorptions when the dielectric layers reach additional nλ(d)/2 (n=1, 2) thicknesses, where λ(d) is the operating wavelength at the peak absorption in the dielectric slabs. The surface currents between the metasurface resonators and ground plane are not associated any longer, different from the conventional thin absorbers. Moreover, the EM wave energies are completely absorbed by the metasurface resonators and dielectric layer, and the main function of ground plane is to reflect the incident EM waves back to the resonators. The discussed novel absorption properties are analyzed and explained by classical EM theory and interference theory after numerical demonstrations. These findings can broaden the potential applications of the metasurface-based absorbers in the THz frequency range for different requirements.

Association of grip strength and walking pace with the risk of incident Parkinson's disease: a prospective cohort study of 422,531 participants.

BACKGROUND: Muscle weakness is a prominent feature of Parkinson's disease, but whether the occurrence of this deficit in healthy adults is associated with subsequent PD diagnosis remains unclear. OBJECTIVE: This study sought to examine the relationship between muscle strength, represented by grip strength and walking pace, and the risk of incident PD. METHODS: A total of 422,531 participants from the UK biobank were included in this study. Longitudinal associations of grip strength and walking pace with the risk of incident PD were investigated by Cox proportional hazard models adjusting for several well-established risk factors. Subgroup and sensitivity analyses were also conducted for further validation. RESULTS: After a median follow-up of 9.23 years, 2,118 (0.5%) individuals developed incident PD. For per 5 kg increment of absolute grip strength, there was a significant 10.2% reduction in the risk of incident PD (HR = 0.898, 95% CI [0.872-0.924], P < 0.001). Similarly, per 0.05 kg/kg increment of relative grip strength was related to a 9.2% reduced risk of incident PD (HR = 0.908, 95% CI [0.887-0.929], P < 0.001). Notably, the associations remained consistent when grip strength was calculated as quintiles. Moreover, participants with a slower walking pace demonstrated an elevated risk of incident PD (HR = 1.231, 95%CI [1.075-1.409], P = 0.003). Subgroup and sensitivity analyses further validated the robustness of the observed associations. CONCLUSION: Our findings showed a negative association of grip strength and walking pace with the risk of incident PD independent of important confounding factors. These results hold potential implications for the early screening of people at high-risk of PD.

Case Report: A balloon-based technique to remove a pearl-like embolus out of the coronary artery.

Coronary embolism is considered a rare non-atherosclerotic etiology of acute myocardial infarction, whereas atrial fibrillation is the main etiology of coronary embolism. We report a rare case of a patient with coronary embolism with a specific pearl-like embolus attributed to atrial fibrillation. For this patient, we used a balloon-based technique to successfully remove the embolus from the coronary artery.

Slc7a11 stimulates glutathione synthesis to preserve fatty acid metabolism in primary hepatocytes.

Primary hepatocytes are widely used as a tool for studying metabolic function and regulation in the liver. However, the metabolic properties of primary hepatocytes are gradually lost after isolation. Here, we illustrated that fatty acid metabolism is the major compromised metabolic process in isolated primary hepatocytes, along with drastically decreased GSH and ROS content, while lipid peroxidation is increased. Gain- and loss-of-function studies revealed that Slc7a11 expression is critical in maintaining fatty acid metabolism and facilitating hormone-induced fatty acid metabolic events, which is synergistic with dexamethasone treatment. Intriguingly, Slc7a11 expression and dexamethasone treatment cooperatively upregulated AKT and AMPK signaling and mitochondrial complex expression in primary hepatocytes. Furthermore, direct treatment with reduced GSH or inhibition of ferroptosis is sufficient to drive protective effects on fatty acid metabolism in primary hepatocytes. Our results demonstrate that Slc7a11 expression in isolated primary hepatocytes induces GSH production, which protects against ferroptosis, to increase fatty acid metabolic gene expression, AKT and AMPK signaling and mitochondrial function in synergy with dexamethasone treatment, thereby efficiently preserving primary hepatocyte metabolic signatures, thus providing a promising approach to better reserve primary hepatocyte metabolic activities after isolation to potentially improve the understanding of liver biological functions from studies using primary hepatocytes.

Transcatheter aortic valve implantation for patients with heyde syndrome: A literature review of case reports.

Objective: A systematic review of international case reports of patients with Heyde syndrome (HS) treated by transcatheter aortic valve implantation (TAVI) was conducted to explore the clinical characteristics of this group of patients and sirgical success. Methods: Electronic databases, including PubMed, Embase and CNKI, were searched with combinations of the search terms, Heyde syndrome, gastrointestinal bleeding, aortic stenosis, angiodysplasia and transcatheter aortic valve replacement. All case reports were screened according to inclusion criteria, and HS patient data was summarized. Results: A total of 31 case reports concerned patients with a history of aortic stenosis and repeated gastrointestinal bleeding. Ultrasonic cardiograms (UCG) were recorded for 27 cases, including those with critical aortic stenosis (n = 26). Gastrointestinal sequelae were reported in 22 cases with duodenal and jejunal being the most common (n = 9). High-molecular-weight multimers of von Willebrand Factor (vWF-HMWM) were measured in 17 cases with the majority being lower (n = 15) and the minority normal (n = 2). All patients experienced recurrent bleeding after medication and endoscopic therapy and symptoms improved after TAVI (31/31). vWF was at normal levels in 11/12 cases post-TAVI. Twenty-five patients were followed up and 22 had no recurrence of symptoms giving an efficacy rate of 88% for TAVI in HS patients. Conclusions: HS is characterized by angiodysplasia, aortic stenosis and von Willebrand disease with frequent recurrence of bleeding after drug and endoscopic treatment. TAVI is an effective therapy with an 88% resolution rate.

Recent Progress in Single-Nucleotide Polymorphism Biosensors.

Single-nucleotide polymorphisms (SNPs), the most common form of genetic variation in the human genome, are the main cause of individual differences. Furthermore, such attractive genetic markers are emerging as important hallmarks in clinical diagnosis and treatment. A variety of destructive abnormalities, such as malignancy, cardiovascular disease, inherited metabolic disease, and autoimmune disease, are associated with single-nucleotide variants. Therefore, identification of SNPs is necessary for better understanding of the gene function and health of an individual. SNP detection with simple preparation and operational procedures, high affinity and specificity, and cost-effectiveness have been the key challenge for years. Although biosensing methods offer high specificity and sensitivity, as well, they suffer drawbacks, such as complicated designs, complicated optimization procedures, and the use of complicated chemistry designs and expensive reagents, as well as toxic chemical compounds, for signal detection and amplifications. This review aims to provide an overview on improvements for SNP biosensing based on fluorescent and electrochemical methods. Very recently, novel designs in each category have been presented in detail. Furthermore, detection limitations, advantages and disadvantages, and challenges have also been presented for each type.

Acute myocardial infarction after inactivated COVID-19 vaccination: a case report and literature review.

A number of vaccines have been developed and deployed globally to restrain the spreading of the coronavirus disease 2019 (COVID-19). The adverse effect following vaccination is an important consideration. Acute myocardial infarction (AMI) is a kind of rare adverse event after COVID-19 vaccination. Herein, we present a case of an 83-year-old male who suffered cold sweat ten minutes after the first inactivated COVID-19 vaccination and AMI one day later. The emergency coronary angiography showed coronary thrombosis and underlying stenosis in his coronary artery. Type II Kounis syndrome might be a potential mechanism, which is manifested as coronary thrombosis secondary to allergic reactions in patients with underlying asymptomatic coronary heart disease. We also summarize the reported AMI cases post COVID-19 vaccination, as well as overview and discuss the proposed mechanisms of AMI after COVID-19 vaccination, thus providing insights for clinicians to be aware of the possibility of AMI following COVID-19 vaccination and potential underlying mechanisms.

Analysis of clinical characteristics and imagological features of the aortic dissection patients with negative D-dimer results.

Background: D-dimer (DD) is a vital biomarker to rule out the diagnosis of aortic dissection (AD). However, the DD level in some patients with AD is not high in clinical practice, which often leads to missed diagnosis; therefore, understanding the characteristics of patients with AD and negative DD is of great clinical value. Methods: From May 2015 to October 2020, 286 patients with AD who visited the first medical contact (FMC) within 24 h of symptom onset and were hospitalized in the Xiamen Cardiovascular Hospital of Xiamen University were enrolled in this study. Clinical characteristics and outcomes of patients were assessed. Results: Among them, 13 cases (approximately 4.5%) had negative DD results. Compared to patients with positive DD results, patients with negative DD results had significantly higher platelet counts and lower aortic dissection detection risk scores (ADD-RS). The imagological analysis showed that patients with AD and negative DD had lower extension scores and milder damage to the mesenteric artery and three branches of the aortic arch. Furthermore, the results of the multivariable analysis showed that white blood cell count (WBC) [odds ratio (OR): 1.379, P = 0.028], FMC (OR: 0.904, P = 0.028), and extension score (OR: 1.623, P = 0.046) were associated with negative DD result. Conclusions: Patients with AD and negative DD results had longer FMC and lower WBC. Imaging showed a smaller tear extension range and less damage to the mesenteric artery and three branches of the aortic arch. A negative DD result could not completely rule out AD even if the ADD-RS was zero.

Tauopathies: new perspectives and challenges.

BACKGROUND: Tauopathies are a class of neurodegenerative disorders characterized by neuronal and/or glial tau-positive inclusions. MAIN BODY: Clinically, tauopathies can present with a range of phenotypes that include cognitive/behavioral-disorders, movement disorders, language disorders and non-specific amnestic symptoms in advanced age. Pathologically, tauopathies can be classified based on the predominant tau isoforms that are present in the inclusion bodies (i.e., 3R, 4R or equal 3R:4R ratio). Imaging, cerebrospinal fluid (CSF) and blood-based tau biomarkers have the potential to be used as a routine diagnostic strategy and in the evaluation of patients with tauopathies. As tauopathies are strongly linked neuropathologically and genetically to tau protein abnormalities, there is a growing interest in pursuing of tau-directed therapeutics for the disorders. Here we synthesize emerging lessons on tauopathies from clinical, pathological, genetic, and experimental studies toward a unified concept of these disorders that may accelerate the therapeutics. CONCLUSIONS: Since tauopathies are still untreatable diseases, efforts have been made to depict clinical and pathological characteristics, identify biomarkers, elucidate underlying pathogenesis to achieve early diagnosis and develop disease-modifying therapies.

Recent progress of microfluidic chips in immunoassay.

Microfluidic chip technology is a technology platform that integrates basic operation units such as processing, separation, reaction and detection into microchannel chip to realize low consumption, fast and efficient analysis of samples. It has the characteristics of small volume need of samples and reagents, fast analysis, low cost, automation, portability, high throughout, and good compatibility with other techniques. In this review, the concept, preparation materials and fabrication technology of microfluidic chip are described. The applications of microfluidic chip in immunoassay, including fluorescent, chemiluminescent, surface-enhanced Raman spectroscopy (SERS), and electrochemical immunoassay are reviewed. Look into the future, the development of microfluidic chips lies in point-of-care testing and high throughput equipment, and there are still some challenges in the design and the integration of microfluidic chips, as well as the analysis of actual sample by microfluidic chips.

Association of Kidney Function with Risk of Incident Dementia: A Prospective Cohort Study of 275,167 UK Biobank Participants.

BACKGROUND: Previous studies have reported inconsistent associations between chronic kidney disease (CKD) and dementia. OBJECTIVE: To evaluate whether CKD is a risk factor for dementia and compare the performance of different measures of calculating estimated glomerular filtration rate (eGFR). METHODS: 275,167 participants from UK Biobank were included and eGFR at baseline was calculated using serum creatinine (eGFRcr), cystatin C (eGFRcys), and creatinine-cystatin C equations (eGFRcr-cys). Restricted cubic splines and Cox regression models were performed to assess the relationship of eGFR with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: We observed a U-shaped relationship between each eGFR and risk of all-cause dementia and VaD, with eGFRcys and eGFRcr-cys showing a closer linkage (peGFRcys <0.0001, peGFRcrhboxcys<0.0001 and peGFRcr = 0.0001). Lower and supranormal eGFR were related to increased risk of all-cause dementia. Compared to the reference category of 90-104 ml/min/1.73 m2, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause dementia for eGFRcr-cys 30-59, <30, and ≥105 ml/min/1.73 m2 were 1.26 (95% CI [1.05-1.50], p = 0.012), 2.62 (95% CI [1.54-4.47], p < 0.001), and 1.41 (95% CI [1.17-1.70], p < 0.001). No statistically significant association was observed between eGFR with risk of AD. CONCLUSION: This prospective study identified impaired kidney function as a critical risk factor for dementia and noted the application of cystatin C strengthened the relationship between CKD and dementia, underlining the significant value of preserving kidney function to reduce the risk of dementia and considering cystatin C measurement as part of clinical practice.

Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis.

Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 µL exosomes via the tail vein (200 µg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1ß release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.

The proGnostic role of caRdiac rehAbilitation in patients with left ventriCular anEurysm formation after anterior myocardial infarction (the GRACE study): Study rationale and design of a prospective randomized controlled trial.

Background: Cardiac rehabilitation (CR) is an essential intervention after acute myocardial infarction (MI). However, it is still unclear whether patients with left ventricular aneurysm (LVA) formation after anterior MI would benefit from CR programs. This clinical trial is designed to assess the role of CR in patients with LVA formation after anterior MI. Trial design: The GRACE study is a single-center, single-blind, prospective, randomized controlled clinical trial in China. 100 subjects aged 18-75 years with LVA formation after anterior MI will be recruited and randomized 1:1 to the CR or control group. Both groups will receive standard drug treatment and routine health education according to the guidelines. Participants in the CR group will additionally receive tailored CR programs delivered over a period of 36 sessions. These participants will then be followed up for 1-year. The primary outcome is peak oxygen uptake measured by cardiopulmonary exercise testing after CR programs. The secondary outcomes are cardiac function and EuroQol 5-Dimension-3 Level index scores after CR program and 1-year and major adverse cardiac cerebrovascular events, a composite of cardiovascular mortality, non-fatal MI, non-fatal stroke, malignant arrhythmia or hospitalization for heart failure during the follow-up period. Conclusions: This single-center, single-blind, prospective, randomized controlled clinical trial will determine whether CR improves physical capacity and clinical outcomes in patients with LVA formation after anterior MI. Trial registration: Chinese Clinical Trial Registry ChiCTR2200058852. Registered on 18 April 2022.

Modifiable risk factors for incident dementia and cognitive impairment: An umbrella review of evidence.

BACKGROUND: Dementia and cognitive impairment can be attributed to genetic and modifiable factors. Considerable evidence emerged in modifiable factors and urgently requires standardized evaluation. We conducted an umbrella review to evaluate the strength and validity of the existing evidence. METHODS: We searched PubMed, Embase, CINAHL and Cochrane Database of Systematic Reviews to identify relevant systematic reviews and meta-analyses of prospective studies regarding the associations of dementia and cognitive impairment with modifiable factors. For each association, we analyzed the summary effect size, 95 % confidence interval, 95 % prediction interval, heterogeneity, small study effect and excess significance bias. Mendelian randomization studies were descriptively reviewed further exploring the causality of the associations. RESULTS: In total, 12,015 articles were identified, of which 118 eligible studies yielded 243 unique associations. Convincing evidence was found for associations of dementia and cognitive impairment with early-life education, midlife to late-life plasma glucose, BMI, atrial fibrillation, benzodiazepine use, and gait speed. Suggestive to highly suggestive evidence was found for that of midlife to late-life blood pressure, homocysteine, cerebrovascular diseases, hearing impairment, respiratory illness, anemia, smoking, alcohol consumption, diet, sleep, physical activity and social engagement. Among convincing evidence, Mendelian randomization studies verified causal relationships of education and plasma glucose with Alzheimer's disease. LIMITATIONS: Low quality of the studies included. CONCLUSIONS: Modifiable risk factors identified in this study, especially those with high-level evidence, should be considered in dementia prevention. Our results support a valuable rationale for future experimental designs to establish further evidence for the associations in larger populations.