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Purpose: The triglyceride-glucose index (TyG) is an important parameter that reflects insulin resistance and its use has increased recently. Its relationship with cardiovascular diseases has been shown in previous studies. Our aim was to investigate the association of residual SYNTAX score (rSS) with TyG index in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Materials and Methods: A total of 663 STEMI patients who underwent primary percutaneous coronary intervention were included in the study. The patients were divided into 2 groups according to the TyG index level as high and low. The cut-off value for the TyG index was determined as 9.61 by ROC analysis. Coronary artery disease severity was calculated for both groups besides baseline clinical and demographic variables. Results: A total of 281 patients were evaluated in the high TyG index group and 386 patients in the low TyG index group. A rSS above 8 was considered high. The proportion of patients with high rSS in the increased TyG index group was found to be significantly higher than in the other group [114 (40.6) vs. 54 (14.0)]. In addition, higher TyG index is determined to be the independent predictor of higher rSS in logistic regression analysis. Conclusion: High TyG index had a strong association with rSS and higher TyG index was an independent predictor of increased rSS in patients with STEMI

We have discovered new anthracene derivatives with strong fluorescence properties in the visible region. They exhibit high binding affinities to microtubule proteins with the potential to be used as fluorescent probes for imaging applications.

Introduction: In this study, we aimed to investigate the relationship between the preprocedural logistic clinical SYNTAX score (Log CSS) and major cardiovascular events (MACE) in patients with true bifurcation lesions who underwent revascularization with the double stent strategy. Patients and Methods: A total of 233 non-ST elevation myocardial infarction (NSTEMI) patients who underwent revascularization with a double stent strategy were retrospectively included in the study. Anatomical SYNTAX score (SS) and log CSS were calculated. The patients were divided into two groups according to the cut-off value determined by ROC analysis. The prediction of two-year MACE with Log CSS was evaluated. Results: MACE developed in 33.9% of patients with high Log CSS and 8.5% of patients with low Log CSS (p< 0.001). In the Kaplan-Meier survival analysis, the long-term survival of the high Log CSS patients was significantly lower than the low Log CSS group (Log-rank p< 0.001). In multivariate COX analyses, high Log CCS (HR= 3.781; 95% CI= 1.706-8.377; p= 0.001) was the strongest independent predictor of MACE. Conclusion: Log CSS can be a simple and useful tool to predict the development of MACE in patients with true bifurcation lesions revascularized by percutaneous coronary intervention.

Introduction: Aortic angulation (AA), defined as the angle between the aortic annulus plane and the horizontal plane, may result in failed prosthesis positioning. The effect of AA on the procedural and short-term outcomes with the portico valves for transcatheter aortic valve implantation (TAVI) has not been fully investigated. The present study aimed to evaluate the impact of AA on device success and early outcomes of TAVI using a selfexpanding portico valve. Patients and Methods: Preoperative computed tomography scans of 121 consecutive patients treated with the portico valve were analyzed. TAVI device success and outcomes were determined according to VARC-3 definitions. Patients were divided into two groups based on mean AA. Results: The mean AA was 48.7 ± 8.9°. There were no differences in technical success (92.2 vs 89.5%, p= 0.604), device success (81.2% vs 77.2%, p= 0.582), and early safety endpoints (68.8% vs 61.4%, p= 0.397) between the AA≤ 48° and AA>48° groups. The frequency and severity of paravalvular aortic regurgitation (PAR) was statistically higher in patients with AA> 48° (p= 0.028). Moreover, an increased AA was also associated with valve malposition (12.3% vs. 1.6%, p= 0.018), prolonged procedure time (85 ± 26 vs. 75 ± 20 minutes, p= 0.028), and greater Δimplantation depth (2.2 ± 0.5 vs. 0.8 ± 0.1 mm; p Conclusion: Despite comparable device success and early outcomes rates, increased AA is associated with higher rates of PAR and valve malposition, with the self-expanding portico valve.

Neuroblastoma is the most common solid tumor in children. New treatment approaches are needed because of the harmful side effects and costs of the methods used in the treatment of neuroblastoma. Medicinal and aromatic plants are important for new treatment approaches due to their minimal side effects and economic advantages. Therefore, the present study was carried out to examine the cytotoxic effect of Chaerophyllum macropodum extract on human neuroblastoma (SH-SY5Y) and fibroblast (HDFa) cell lines. 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase release (LDH) assays were used to determine the cytotoxic effect of C. macropodum. The extracts were analyzed for their phenolic content by HPLC-PDA. Major components were determined as 63.600% o-coumaric acid, 15.606% catechine hydrate, 8.713% rosmarinic acid, 4.376% clorogenic acid, and 3.972% salicylic acid. The obtained results from cytotoxicity testing revealed that C. macropodum exerted a significant cytotoxic effect on human neuroblastoma cells at all tested concentrations (p 0.05). But it did not lead to any cytotoxic potential on human fibroblasts. As a result, the obtained data clearly revealed C. macropodum exerted a selective cytotoxic action on neuroblastoma cells for the first time.

Background Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients. Results We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

Background: Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are associated with metabolic abnormalities. Integrative analysis of human clinical data and animal studies have contributed to a better understanding of the molecular and cellular pathways involved in the progression of NDDs. Previously, we have reported that the combined metabolic activators (CMA), which include the precursors of nicotinamide adenine dinucleotide and glutathione can be utilized to alleviate metabolic disorders by activating mitochondrial metabolism. Methods: We first analysed the brain transcriptomics data from AD patients and controls using a brain-specific genome-scale metabolic model (GEM). Then, we investigated the effect of CMA administration in animal models of AD and PD. We evaluated pathological and immunohistochemical findings of brain and liver tissues. Moreover, PD rats were tested for locomotor activity and apomorphine-induced rotation. Findings: Analysis of transcriptomics data with GEM revealed that mitochondrial dysfunction is involved in the underlying molecular pathways of AD. In animal models of AD and PD, we showed significant damage in the high-fat diet groups' brain and liver tissues compared to the chow diet. The histological analyses revealed that hyperemia, degeneration and necrosis in neurons were improved by CMA administration in both AD and PD animal models. These findings were supported by immunohistochemical evidence of decreased immunoreactivity in neurons. In parallel to the improvement in the brain, we also observed dramatic metabolic improvement in the liver tissue. CMA administration also showed a beneficial effect on behavioural functions in PD rats. Interpretation: Overall, we showed that CMA administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the AD and PD animal models and is a promising treatment for improving the metabolic parameters and brain functions in NDDs. PoLiMeR Innovative Training Network ; SNIC ; ScandiBio Therapeutics ; ScandiBio Therapeutics and Knut ; Knut och Alice Wallenbergs Stiftelse

Complications of chronic non-healing wounds led to the emergence of nanotechnology-based therapies to enhance healing, facilitate tissue repair, and prevent wound-related complications like infections. Here, we design alpha lipoic acid (ALA) conjugated hexagonal boron nitride (hBN) and boron carbide (B4C) nanoparticles (NPs) to enhance wound healing in human dermal fibroblast (HDFa) cell culture and characterize its antimicrobial properties against Staphylococcus aureus (S. aureus, gram positive) and Escherichia coli (E. coli, gram negative) bacterial strains. ALA molecules are integrated onto hBN and C4B NPs through esterification procedure, and molecular characterizations are performed by using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and UV-vis spectroscopy. Wound healing and antimicrobial properties are investigated via the use of cell viability assays, scratch test, oxidative stress, and antimicrobial activity assays. Based on our analysis, we observe that ALA-conjugated hBN NPs have the highest wound-healing feature and antimicrobial activity compared to ALA-B4C. On the other hand, hBN, ALA-B4C, and ALA compounds showed promising regenerative and antimicrobial properties. Also, we find that ALA conjugation enhances wound healing and antimicrobial potency of hBN and B4C NPs. We conclude that the ALA-hBN conjugate is a potential candidate to stimulate regeneration process for injuries.

Nanobiotechnology influences many different areas, including the medical, food, energy, clothing, and cosmetics industries. Considering the wide usage of nanomaterials, it is necessary to investigate the toxicity potentials of specific nanosized molecules. Boron-containing nanoparticles (NPs) are attracting much interest from scientists due to their unique physicochemical properties. However, there is limited information concerning the toxicity of boron-containing NPs, including cobalt boride (Co2B) NPs. Therefore, in this study, Co2B NPs were characterized using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. Then, we performed 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, and neutral red (NR) assays for assessing cell viability against Co2B NP exposure on cultured human pulmonary alveolar epithelial cells (HPAEpiC). In addition, whole-genome microarray analysis was carried out to reveal the global gene expression differentiation of HPAEpiC cells after Co2B NP application. The cell viability tests unveiled an IC50 value for Co2B NPs of 310.353 mg/L. The results of our microarray analysis displayed 719 gene expression differentiations (FC ≥ 2) among the analyzed 40,000 genes. The performed visualization and integrated discovery (DAVID) analysis revealed that there were interactions between various gene pathways and administration of the NPs. Based on gene ontology biological processes analysis, we found that the P53 signaling pathway, cell cycle, and cancer-affecting genes were mostly affected by the Co2B NPs. In conclusion, we suggested that Co2B NPs would be a safe and effective nanomolecule for industrial applications, particularly for medical purposes.

Background Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administrated Combined Metabolic Activators (CMA) to the AD rat model and observed that administration of CMA activated the mitochondrial functions and eventually improved the AD-associated histological parameters in the animals. CMA consists of NAD + and glutathione precursors and includes L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate. Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II trial and studied the effect of CMA administration on the global metabolism of AD patients. The primary endpoint was on the difference in cognitive and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. We also performed a comprehensive human plasma metabolome and proteome analysis. Results Based on our analysis, we showed a significant decrease of ADAS-Cog scores on Day 84 vs Day 0 (p = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant enhancement (p = 0.0073) in ADAS-Cog scores between CMA and placebo groups in patients with higher ADAS-Cog scores. Improved cognitive functions were endorsed with relevant hippocampal volumes and cortical thickness alterations. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism are significantly improved after treatment. Conclusion In conclusion, our results show that treating AD patients with CMA leads to enhanced cognitive functions associated with the improved metabolome, proteome and structural neuroimaging parameters, suggesting a role for such a therapeutic regimen in treating patients, especially with severe AD. Trial registration: ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

Background: Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administrated Combined Metabolic Activators (CMA) to the AD rat model and observed that administration of CMA activated the mitochondrial functions and eventually improved the AD-associated histological parameters in the animals. CMA consists of NAD+ and glutathione precursors and includes L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate. Methods: Here, we designed a randomised, double-blinded, placebo-controlled phase-II trial and studied the effect of CMA administration on the global metabolism of AD patients. The primary endpoint was on the difference in cognitive and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. We also performed a comprehensive human plasma metabolome and proteome analysis. Results: Based on our analysis, we showed a significant decrease of ADAS-Cog scores on Day 84 vs Day 0 (p=0.00001, 29% improvement) in the CMA group. Moreover, there was a significant enhancement (p=0.0073) in ADAS-Cog scores between CMA and placebo groups in patients with higher ADAS-Cog scores. Improved cognitive functions were endorsed with relevant hippocampal volumes and cortical thickness alterations. Moreover, the plasma levels of proteins and metabolites associated with NAD+ and glutathione metabolism are significantly improved after treatment. Conclusion: In conclusion, our results show that treating AD patients with CMA leads to enhanced cognitive functions associated with the improved metabolome, proteome and structural neuroimaging parameters, suggesting a role for such a therapeutic regimen in treating patients, especially with severe AD.Trial registration: ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

The tripeptide H-Gly-Pro-Glu-OH (GPE) and its analogs began to take much interest from scientists for developing effective novel molecules in the treatment of several disorders including Alzheimer's disease, Parkinson's disease, and stroke. The peptidomimetics of GPEs exerted significant biological properties involving anti-inflammatory, antiapoptotic, and anticancer properties. The assessments of their hematological toxicity potentials are critically required for their possible usage in further preclinical and clinical trials against a wide range of pathological conditions. However, there is so limited information on the safety profiling of GPE and its analogs on human blood tissue from cytotoxic, oxidative, and genotoxic perspectives. And, their embryotoxicity potentials were not investigated yet. Therefore, in this study, measurements of mitochondrial viability (using MTT assay) and lactate dehydrogenase (LDH) release as well as total antioxidant capacity (TAC) assays were performed on cultured human whole blood cells after treatment with GPE and its three novel peptidomimetics for 72 h. Sister chromatid exchange (SCE), micronucleus (MN), and 8-oxo-2-deoxyguanosine (8-OH-dG) assays were performed for determining the genotoxic damage potentials. In addition, the nuclear division index (NDI) was figured out for revealing their cytostatic potentials. Embryotoxicity assessments were performed on cultured human pluripotent NT2 embryonal carcinoma cells by MTT and LDH assays. The present results from cytotoxicity, oxidative, genotoxicity, and embryotoxicity testing clearly propounded that GPEs had good biosafety profiles and were trouble-free from the toxicological point of view. Noncytotoxic, antioxidative, nongenotoxic, noncytostatic, and nonembryotoxic features of GPE analogs are worthwhile exploring further and may exert high potentials for improving the development of novel disease-modifying agents.

Monoamine oxidase B (MAO-B) is an enzyme that metabolizes several chemicals, including dopamine. MAO-B inhibitors are used in the treatment of Parkinson’s Disease (PD), and the inhibition of this enzyme reduces dopamine turnover and oxidative stress. The absence of dopamine results in PD pathogenesis originating from decreased Acetylcholinesterase (AChE) activity and elevated oxidative stress. Here, we performed a molecular docking analysis for the potential use of costunolide and parthenolide terpenoids as potential MAO-B inhibitors in the treatment of PD. Neuroprotective properties of plant-originated costunolide and parthenolide terpenoids were investigated in a cellular PD model that was developed by using MPP+ toxicity. We investigated neuroprotection mechanisms through the analysis of oxidative stress parameters, acetylcholinesterase activity and apoptotic cell death ratios. Our results showed that 100 µg/mL and 50 µg/mL of costunolide, and 50 µg/mL of parthenolide applied to the cellular disease model ameliorated the cytotoxicity caused by MPP+ exposure. We found that acetylcholinesterase activity assays exhibited that terpenoids could ameliorate and restore the enzyme activity as in negative control levels. The oxidative stress parameter analyses revealed that terpenoid application could enhance antioxidant levels and decrease oxidative stress in the cultures. In conclusion, we reported that these two terpenoid molecules could be used in the development of efficient treatment strategies for PD patients.

Tetralogy of Fallot is the most common cyanotic congenital heart defect and accounts for about 5% of all congenital cardiopathies. The definitive treatment modality for tetralogy of Fallot is reparative surgery, which is recommended to be performed by the time of diagnosis. Without surgical repair, most patients would die during their childhood. In the past, survival data indicated that 66% of persons with tetralogy of Fallot not surgically treated lived until the age of 1, 49% lived until the age of 3, and 24% lived until the age of 10. We present a patient with uncorrected tetralogy of Fallot who lived up to 72 years of age. The patient with a history of 4 live births presented to the emergency department with dyspnea, and in our echocardiography, we found that the patient with uncorrected tetralogy of Fallot had pericardial tamponade. When we review the current literature, she is the oldest uncorrected patient with tetralogy of Fallot in our country and the female patient with the highest number of live births among patients with uncorrected Tetralogy of Fallot in the world.

Neuroblastoma is the most common solid tumor in children. New treatment approaches are needed because of the harmful side effects and costs of the methods used in the treatment of neuroblastoma. Medicinal and aromatic plants are important for new treatment approaches due to their minimal side effects and economic advantages. Therefore, the present study was carried out to examine the cytotoxic effect of Chaerophyllum macropodum extract on human neuroblastoma (SH-SY5Y) and fibroblast (HDFa) cell lines. 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and Lactate dehydrogenase release (LDH) assays were used to determine the cytotoxic effect of Chaerophyllum macropodum. The results revealed that Chaerophyllum macropodum had a significant cytotoxic effect on neuroblast cells at all concentrations used (p Chaerophyllum macropodum exerts a selective effect on neuroblastoma cells for the first time.

Titanium diboride (TiB2) and zinc borate (Zn3BO6) have been utilized in wide spectrum industrial areas because of their favorable properties such as a high melting point, good wear resistance, high hardness and thermal conductivity. On the other hand, the biomedical potentials of TiB2 and Zn3BO6 are still unknown because there is no comprehensive analysis that uncovers their biocompatibility features. Thus, the toxicogenomic properties of TiB2 and Zn3BO6 nanoparticles (NPs) were investigated on human primary alveolar epithelial cell cultures (HPAEpiC) by using different cell viability assays and microarray analyses. Protein-Protein Interaction Networks Functional Enrichment Analysis (STRING) was used to associate differentially expressed gene probes. According to the results, up to 10 mg/L concentration of TiB2 and Zn3BO6 NPs application did not stimulate a cytotoxic effect on the HPAEpiC cell cultures. Microarray analysis revealed that TiB2 NPs exposure enhances cellular adhesion molecules, proteases and carrier protein expression. Furthermore, Zn3BO6 NPs caused differential gene expressions in the cell cycle, cell division and extracellular matrix regulators. Finally, STRING analyses put forth that inflammation, cell regeneration and tissue repair-related gene interactions were affected by TiB2 NPs application. Zn3BO6 NPs exposure significantly altered inflammation, lipid metabolism and infection response activator-related gene interactions. These investigations illustrated that TiB2 and Zn3BO6 NPs exposure may affect different aspects of cellular machineries such as immunogenic responses, tissue regeneration and cell survival. Thus, these types of cellular mechanisms should be taken into account before the use of the related NPs in further biomedical applications.

Integrative production of new nanocomposites has been used to enhance favorable features of biomaterials for unlocking ultimate potential of different molecules. In the present study, advantageous properties of diamond like carbons (DLC) and germanium (Ge) like greater biocompatibility and antibacterial attributes were aimed to combined into a thin film. For this purpose, 400 nm DLC-Ge nanocomposite was coated on the borosilicate glasses via the magnetron sputtering and surface characteristics was analyzed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and The Raman spectrum. Biocompatibility analysis were performed by 3-(4,5-Dimethylthiazol-2-yl) (MTT) cell viability assay and Hoechst 33258 fluorescent staining genotoxicity assessments on the human fibroblast cell line (HDFa). Finally, antibacterial properties of DLC-Ge nanocomposite coatings were investigated by Pseudomonas aeruginosa (ATCC 27853) and Staphylococcus aureus (ATCC 25923) bacterial attachment analysis. As a result of magnetron sputtering coating, nearly 400 nm thick DLC-Ge nanocomposite film showed a smooth, a non-porous, and a dense characteristic. Cell viability analysis showed that Ge-DLC coatings permits %95 cell surface growth of fibroblast cells. Also, there were no significant difference in aspect of nuclear abnormalities compared to the (-) control which showed nonmutagenic features of the thin film. Finally, antibacterial attachment analysis put forth that Ge-DLC coatings inhibits bacterial adhesion as %40 and %25 rates for P. aeruginosa and S. aureus bacterial strains, respectively. From these results, DLC-Ge nanocomposites could be proposed as a potential new biomaterial for various biomedical applications.

The prevalent exposition of metallic nanoparticles (MNPs) to the aquatic medium and their negative influence on human life is one of the major concerns global. Stress mechanization, as a non-specific and pervasive response, involves all physiological systems, particularly the closely interconnected neuroendocrine and immune systems. In this study, which was designed to obtain more data on the biological effects of ulexit, which prevents oxidative DNA damage by protecting against toxicity damage and offers new antioxidant roles. The concomitant use of ulexite (UX, as 18.75 mg/l) as a natural therapeutic agent against exposure to magnetic nanoparticles (Fe3O4-MNPs/0.013 ml/l) on Oncorhynchus mykiss was investigated for 96 h. The brain tissues were taken at the 48th and 96th hours of the trial period, the effects on neurotoxic, pro-inflammatory cytokine genes, antioxidant immune system, DNA and apoptosis mechanisms were analyzed. In the present study, it was determined that AChE activity and BDNF level in the brain tissue decreased over time in the Fe3O4-MNPs group compared to the control, and UX tried to depress this inhibition. While inhibition was determined in antioxidant system biomarkers (SOD, CAT, GPx, and GSH values), an induction was observed in lipid peroxidation indicators (MDA and MPO values) in Fe3O4-MNPs applied group. The same group data showed that TNF-alpha, IL-6, 8-OHdG and caspase-3 levels were increased, but Nrf-2 levels were decreased. The alterations in all biomarkers were found to be significant at the p < 0.05 level. In general, it was determined that Fe3O4-MNPs caused stress in O. mykiss and UX exhibited a positive effect on this stress management.

Tricuspid stenosis occurs after the implantation of a ventricular pacemaker lead and is a rare complication. An inflammatory response is stimulated when the pacemaker leads are passing through the tricuspid valve which leads to fibrosis in the long-term. In our case report, we aim to present a patient with asymptomatic multiple pacemaker lead related tricuspid stenosis and with a history of severe COVID-19 pneumonia.

Abstract: Alzheimer's Disease (AD) is one of the most important neurodegenerative diseases and it covers 60% of whole dementia cases. AD is a constantly progressing neurodegenerative disease as a result of the production of β-amyloid (Aβ) protein and the accumulation of hyper-phosphorylated Tau protein; it causes breakages in the synaptic bonds and neuronal deaths to a large extent. Millions of people worldwide suffer from AD because there is no definitive drug for disease prevention, treatment or slowdown. Over the last decade, multiple target applications have been developed for AD treatments. These targets include Aβ accumulations, hyper-phosphorylated Tau proteins, mitochondrial dysfunction, and oxidative stress resulting in toxicity. Various natural or semisynthetic antioxidant formulations have been shown to protect brain cells from Aβ induced toxicity and provide promising potentials for AD treatment. Ferulic acid (FA), a high-capacity antioxidant molecule, is naturally synthesized from certain plants. FA has been shown to have different substantial biological properties, such as anticancer, antidiabetic, antimicrobial, anti-inflammatory, hepatoprotective, and cardioprotective actions, etc. Furthermore, FA exerted neuroprotection via preventing Aβ-fibril formation, acting as an anti-inflammatory agent, and inhibiting free radical generation and acetylcholinesterase (AChE) enzyme activity. In this review, we present key biological roles of FA and several FA derivatives in Aβ-induced neurotoxicity, protection against free radical attacks, and enzyme inhibitions and describe them as possible therapeutic agents for the treatment of AD.

The structural and electronic properties of BaNiSn3-type SrAuSi3 and ThCr2Si2-type SrAu2Si2 have been investigated by using the planewave pseudopotential method and the density functional theory. The electronic structures and phonon dispersion relations of these two materials have been analyzed with and without the inclusion of spin-orbit interaction, and similarities and differences highlighted. By integrating the Eliashberg spectral function alpha F-2(omega), the average electron-phonon coupling parameter is determined to be lambda=0.47 for SrAuSi3 and 0.42 for SrAu2Si2. The largest contribution to the electron-phonon coupling for SrAuSi3 comes from the Si p electrons near the Fermi energy and Si-related vibrations. Using a reasonable value of mu* = 0.12 for the effective Coulomb repulsion parameter, the superconducting critical temperature T-c for SrAuSi3 is found to be 1.47 K which compares very well with its experimental value of 1.54 K. (C) 2016 Published by Elsevier Ltd.