Prevalence of Thromboembolic Events, Including Venous Thromboembolism and Arterial Thrombosis, in Patients with COVID-19: A Systematic Review with Meta-Analysis.

Background: Many studies have evaluated thromboembolic events in COVID-19 patients, and most of them have reported a high estimation of the prevalence of such events. The present study sought to evaluate the prevalence of thromboembolic events in patients with COVID-19. Methods: This study is a systematic review with meta-analysis that investigated thromboembolic events in patients with COVID-19 from the start of the pandemic to August 31, 2021. The 4 main databases for collecting articles were Medline, Scopus, Google Scholar, and Web of Science. Deep vein thrombosis, pulmonary embolism, arterial thrombosis, and the overall rate of thromboembolic events were considered primary outcomes. Results: In a total of 63 studies (104 920 patients with COVID-19), the overall thrombosis rate was 21% (95% CI, 18% to 25%), the rate of deep vein thrombosis was 20% (95% Cl, 16% to 25%), the rate of pulmonary embolism was 8% (95% Cl, 6% to 10%), and the rate of arterial thrombosis was 5% (95% Cl, 3% to 7%). The prevalence of all primary outcomes in critically ill patients admitted to the intensive care unit (ICU) was significantly higher (P<0.05). In older patients, the prevalence of overall thrombosis, pulmonary embolism, or deep vein thrombosis was significantly higher (P<0.05). Conclusion: This study showed that COVID-19 increases the risk of thromboembolic events, especially in elderly and critically ill patients admitted to the ICU. Therefore, more strategies are needed to prevent thromboembolic events in patients with COVID-19, especially in ICU-admitted and elderly patients.

Hibernation of the Conduction System and Atrioventricular Block Reversibility Following Revascularization in Patients without Acute Coronary Syndrome.

Although myocardial infarction (MI) is a reversible cause of atrioventricular (AV) block, the association of ischemia other than MI with AV block is unclear. The purpose of this study is to investigate this relationship. Among patients nominated for pacemaker implantation due to AV block in two centers from 2017-2020, 120 patients with significant coronary artery disease (CAD) in angiography were included in the study. Patients were divided into two equal groups based on their CAD treatment approach: drug therapy and revascularization. Coronary lesions were divided into three types based on location: left anterior descending artery (type 1), dominant coronary with AV node branch (type 2), and a combination of both (type 3). After coronary disease treatment, all patients were followed up with for 14 months, and AV block reversibility was assessed. There were 7 cases of block reversibility in the revascularization group (11.7%) and 1 case in the medical group (1.7%), which differed significantly (P = .02). A history of acute coronary syndrome, smoking, opium use, chronic kidney disease, hypertension, age, sex, and chronic obstructive pulmonary disease were not significantly associated with reversible block. Also, the type of coronary obstruction had no significant relationship with block reversibility (P = .3, .5, and .8 for type 1, type 2, and type 3, respectively). Hibernation due to ischemia can be a reversible cause of an AV blockage. Therefore, it is recommended that significant coronary artery lesions be revascularized before pacemaker implantation.

Acute fibrinous constrictive pericarditis and large pericardial effusion as the first manifestation of systemic lupus erythematsous disease in an adult male patient.

Systemic lupus erythematosus (SLE) can have various manifestations. Although cardiac involvement is very common in SLE patients, a severe acute pericarditis as the first manifestation of SLE in a male patient is relatively rare. A 36-year-old male was admitted to our hospital with acute pericarditis, large circumferential fibrinous pericarditis, and major criteria of a high-risk case of acute pericarditis. After a complete investigation, the underlying disease was revealed to be SLE. All of his symptoms were completely resolved after 6 weeks of treatment with non-steroidal anti-inflammatory drugs and corticosteroids with no need for a pericardiocentesis. Patients with acute fibrinous pericarditis should be considered and precisely investigated for multiorgan autoimmune process such as SLE, to avoid unnecessary intervention, and minimize the risk of recurrence and chronicity of the condition.

Impact of maintenance dose of eptifibatide in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is usually caused by a rupture in the atherosclerotic plaque, followed by platelet aggregation which ultimately leads to acute coronary artery occlusion. So far, few studies have investigated the effect of maintenance dose of Eptifibatide (glycoprotein IIb/IIIa inhibitor) in STEMI patients who underwent primary percutaneous coronary intervention (PPCI). Therefore, in this study, we investigated the effect of maintenance dose of Eptifibatide in patients with STEMI who underwent PPCI. 264 patients who had acute chest pain suggestive of STEMI were entered in the study. All patients received the same dose of bolus dose of Eptifibatide in the cardiac catheterization laboratory. Then the patients were randomly divided into two groups, one group (n = 147) received a maintenance dose of intravenous Eptifibatide (infusion of 2 µg/kg/min) and the other group (n = 117) did not receive this treatment. Standard medical treatment of STEMI after PPCI was performed based on guidelines and the same in both groups. All patients were evaluated 1, 2, and 3 months after the start of treatment in terms of predicted outcomes. RESULTS: The occurrence of 3-month major adverse cardiovascular events (MACE) between the case and control groups did not have a statistically significant difference (28.6% versus 35.0%; P value: 0.286). Also, investigations showed that the rate of re-infarction (P value: 0.024) and target lesion revascularization (P value: 0.003) was significantly lower in the group that received Eptifibatide infusion. CONCLUSIONS: Eptifibatide maintenance dose infusion in patients who undergo PPCI in the context of STEMI, does not significantly reduce MACE, although it does significantly reduce re-infarction and target lesion revascularization. It also does not increase the risk of bleeding and cerebrovascular events.

Carbon-based nanostructures for cancer therapy and drug delivery applications.

Synthesis, design, characterization, and application of carbon-based nanostructures (CBNSs) as drug carriers have attracted a great deal of interest over the past half of the century because of their promising chemical, thermal, physical, optical, mechanical, and electrical properties and their structural diversity. CBNSs are well-known in drug delivery applications due to their unique features such as easy cellular uptake, high drug loading ability, and thermal ablation. CBNSs, including carbon nanotubes, fullerenes, nanodiamond, graphene, and carbon quantum dots have been quite broadly examined for drug delivery systems. This review not only summarizes the most recent studies on developing carbon-based nanostructures for drug delivery (e.g. delivery carrier, cancer therapy and bioimaging), but also tries to deal with the challenges and opportunities resulting from the expansion in use of these materials in the realm of drug delivery. This class of nanomaterials requires advanced techniques for synthesis and surface modifications, yet a lot of critical questions such as their toxicity, biodistribution, pharmacokinetics, and fate of CBNSs in biological systems must be answered.

Engineered Nanoparticles inside a Microparticle Oral System for Enhanced Mucosal and Systemic Immunity.

Antigen delivery through an oral route requires overcoming multiple challenges, including gastrointestinal enzymes, mucus, and epithelial tight junctions. Although each barrier has a crucial role in determining the final efficiency of the oral vaccination, transcytosis of antigens through follicle-associated epithelium (FAE) represents a major challenge. Most of the research is focused on delivering an antigen to the M-cell for FAE transcytosis because M-cells can easily transport the antigen from the luminal site. However, the fact is that the M-cell population is less than 1% of the total gastrointestinal cells, and most of the oral vaccines have failed to show any effect in clinical trials. To challenge the current dogma of M-cell targeting, in this study, we designed a novel tandem peptide with a FAE-targeting peptide at the front position and a cell-penetrating peptide at the back position. The tandem peptide was attached to a smart delivery system, which overcomes the enzymatic barrier and the mucosal barrier. The result showed that the engineered system could target the FAE (enterocytes and M-cells) and successfully penetrate the enterocytes to reach the dendritic cells located at the subepithelium dome. There was successful maturation and activation of dendritic cells in vitro confirmed by a significant increase in maturation markers such as CD40, CD86, presentation marker MHC I, and proinflammatory cytokines (TNF-α, IL-6, and IL-10). The in vivo results showed a high production of CD4+ T-lymphocytes (helper T-cell) and a significantly higher production of CD8+ T-lymphocytes (killer T-cell). Finally, the production of mucosal immunity (IgA) in the trachea, intestine, and fecal extracts and systemic immunity (IgG, IgG1, and IgG2a) was successfully confirmed. To the best of our knowledge, this is the first study that designed a novel tandem peptide to target the FAE, which includes M-cells and enterocytes rather than M-cell targeting and showed that a significant induction of both the mucosal and systemic immune response was achieved compared to M-cell targeting.

Crystalline polysaccharides: A review.

The biodegradability and mechanical properties of polysaccharides are dependent on their architecture (linear or branched) as well as their crystallinity (size of crystals and crystallinity percent). The amount of crystalline zones in the polysaccharide significantly governs their ultimate properties and applications (from packaging to biomedicine). Although synthesis, characterization, and properties of polysaccharides have been the subject of several review papers, the effects of crystallization kinetics and crystalline domains on the properties and application have not been comprehensively addressed. This review places focus on different aspects of crystallization of polysaccharides as well as applications of crystalline polysaccharides. Crystallization of cellulose, chitin, chitosan, and starch, as the main members of this family, were discussed. Then, application of the aforementioned crystalline polysaccharides and nano-polysaccharides as well as their physical and chemical interactions were overviewed. This review attempts to provide a complete picture of crystallization-property relationship in polysaccharides.

Pulmonary valve sarcoma in patient with coronavirus disease of 2019 (COVID-19), mimicking pulmonary thromboembolism, a very rare case.

Pulmonary artery and pulmonary valve sarcoma are malignant and very rare vascular tumors with aggressive clinical course and very poor outcomes. Patients affected by coronavirus disease of 2019 (COVID-19) are at a higher risk for thromboembolism complication. We describe a young woman with a history of coronavirus pneumonia and progressive dyspnea, hemodynamic disturbance, edema with initial evaluation, and clinical diagnosis of pulmonary thromboembolism. But further imaging study and pathology demonstrated giant sarcoma of pulmonary valve, obstructing pulmonary valve and extending to right ventricular outflow tract and main of pulmonary artery.

Encapsulation of an anticancer drug Isatin inside a host nano-vehicle SWCNT: a molecular dynamics simulation.

The use of carbon nanotubes as anticancer drug delivery cargo systems is a promising modality as they are able to perforate cellular membranes and transport the carried therapeutic molecules into the cellular components. Our work describes the encapsulation process of a common anticancer drug, Isatin (1H-indole-2,3-dione) as a guest molecule, in a capped single-walled carbon nanotube (SWCNT) host with chirality of (10,10). The encapsulation process was modelled, considering an aqueous solution, by a molecular dynamics (MD) simulation under a canonical NVT ensemble. The interactions between the atoms of Isatin were obtained from the DREIDING force filed. The storage capacity of the capped SWCNT host was evaluated to quantify its capacity to host multiple Isatin molecules. Our results show that the Isatin can be readily trapped inside the volume cavity of the capped SWCNT and it remained stable, as featured by a reduction in the van der Waals forces between Isatin guest and the SWCNT host (at approximately - 30 kcal mol-1) at the end of the MD simulation (15 ns). Moreover, the free energy of encapsulation was found to be - 34 kcal mol-1 suggesting that the Isatin insertion procedure into the SWCNT occurred spontaneously. As calculated, a capped SWCNT (10,10) with a length of 30 Å, was able to host eleven (11) molecules of Isatin, that all remained steadily encapsulated inside the SWCNT volume cavity, showing a potential for the use of carbon nanotubes as drug delivery cargo systems.

α-Helical Antimicrobial Peptide Encapsulation and Release from Boron Nitride Nanotubes: A Computational Study.

INTRODUCTION: Antimicrobial peptides are potential therapeutics as anti-bacteria, anti-viruses, anti-fungi, or anticancers. However, they suffer from a short half-life and drug resistance which limit their long-term clinical usage. METHODS: Herein, we captured the encapsulation of antimicrobial peptide HA-FD-13 into boron nitride nanotube (BNNT) (20,20) and its release due to subsequent insertion of BNNT (14,14) with molecular dynamics simulation. RESULTS: The peptide-BNNT (20,20) van der Waals (vdW) interaction energy decreased to -270 kcal·mol-1 at the end of the simulation (15 ns). However, during the period of 0.2-1.8 ns, when half of the peptide was inside the nanotube, the encapsulation was paused due to an energy barrier in the vicinity of BNNT and subsequently the external intervention, such that the self-adjustment of the peptide allowed full insertion. The free energy of the encapsulation process was -200.12 kcal·mol-1, suggesting that the insertion procedure occurred spontaneously. DISCUSSION: Once the BNNT (14,14) entered into the BNNT (20,20), the peptide was completely released after 83.8 ps. This revealed that the vdW interaction between the BNNT (14,14) and BNNT (20,20) was stronger than between BNNT (20,20) and the peptide; therefore, the BNNT (14,14) could act as a piston pushing the peptide outside the BNNT (20,20). Moreover, the sudden drop in the vdW energy between nanotubes to the value of the -1300 Kcal·mol-1 confirmed the self-insertion of the BNNT (14,14) into the BNNT (20,20) and correspondingly the release of the peptide.

Chitosan-based blends for biomedical applications.

Polysaccharides are the most abundant naturally available carbohydrate polymers; composed of monosaccharide units covalently connected together. Chitosan is the most widely used polysaccharides because of its exceptional biocompatibility, mucoadhesion, and chemical versatility. However, it suffers from a few drawbacks, e.g. poor mechanical properties and antibacterial activity for biomedical applications. Blending chitosan with natural or synthetic polymers may not merely improve its physicochemical and mechanical properties, but may also improve its bioactivity-induced properties. This review paper summarizes progress in chitosan blends with biodegradable polymers and polysaccharides and their biomedical applications. Blends of chitosan with alginate, starch, cellulose, pectin and dextran and their applications were particularly addressed. The critical and challenging aspects as well as the future ahead of the use of chitosan-based blends were eventually enlightened.

Fracture fingerprint of polycrystalline C3N nanosheets: Theoretical basis.

Polycrystalline carbon nanosheets are composed of several randomly rotated monocrystalline regions facing each other in grain boundaries-the cause of stress concentration-that affects the mechanics of 2D carbon nanostructures. They have been widely used in different fields, particularly in electronic devices. Herein, heterogeneous graphitic carbon nitride (C3N) was considered as typical of polycrystalline carbon nanosheets for modelling its fracture behavior. The number of grains with random configuration, temperature, and crack length were systematically changed to track the mode and the intensity of failure of model nanosheets. Molecular dynamics simulations predictions unraveled the interatomic interaction in the C-C and C-N bonds. An increase in the number of grain boundaries from 3 to 25 as well as the length of crack led to more than 70% fall in the Young's modulus of polycrystalline carbon platelets. Stress intensity factor decreased against temperature, but increased by crack length enlargement demonstrating higher fracture toughness of small cracks. This theoretical approach can be generalized to capture the unique fracture fingerprint of polycrystalline carbon structures of different types.

Boron Nitride Nanotube as an Antimicrobial Peptide Carrier: A Theoretical Insight.

INTRODUCTION: Nanotube-based drug delivery systems have received considerable attention because of their large internal volume to encapsulate the drug and the ability to penetrate tissues, cells, and bacteria. In this regard, understanding the interaction between the drug and the nanotube to evaluate the encapsulation behavior of the drug in the nanotube is of crucial importance. METHODS: In this work, the encapsulation process of the cationic antimicrobial peptide named cRW3 in the biocompatible boron nitride nanotube (BNNT) was investigated under the Canonical ensemble (NVT) by molecular dynamics (MD) simulation. RESULTS: The peptide was absorbed into the BNNT by van der Waals (vdW) interaction between cRW3 and the BNNT, in which the vdW interaction decreased during the simulation process and reached the value of -142.7 kcal·mol-1 at 4 ns. DISCUSSION: The increase in the potential mean force profile of the encapsulated peptide during the pulling process of cRW3 out of the nanotube showed that its insertion into the BNNT occurred spontaneously and that the inserted peptide had the desired stability. The energy barrier at the entrance of the BNNT caused a pause of 0.45 ns when half of the peptide was inside the BNNT during the encapsulation process. Therefore, during this period, the peptide experienced the weakest movement and the smallest conformational changes.

Nanotechnology-assisted microfluidic systems: from bench to bedside.

With significant advancements in research technologies, and an increasing global population, microfluidic and nanofluidic systems (such as point-of-care, lab-on-a-chip, organ-on-a-chip, etc) have started to revolutionize medicine. Devices that combine micron and nanotechnologies have increased sensitivity, precision and versatility for numerous medical applications. However, while there has been extensive research on microfluidic and nanofluidic systems, very few have experienced wide-spread commercialization which is puzzling and deserves our collective attention. For the above reasons, in this article, we review research advances that combine micro and nanotechnologies to create the next generation of nanomaterial-based microfluidic systems, the latest in their commercialization success and failure and highlight the value of these devices both in industry and in the laboratory.

Self-assembled heptamethine cyanine dye dimer as a novel theranostic drug delivery carrier for effective image-guided chemo-photothermal cancer therapy.

Near-infrared (NIR)-induced dye-based theranostic drug delivery carriers are used for critical image-guided chemo-photothermal cancer therapy. However, most carriers fail to deliver sufficient heat and fluorescence efficiently due to direct π-π stacking of the aromatic rings of the NIR dye and drug. In the work reported herein, we examined a self-assembled heptamethine cyanine dye dimer (CyD) with improved heat and fluorescence delivery that was developed by manipulating the unique structural and optical properties of the dimer. The H-aggregation of CyD in an aqueous solution generated a great amount of heat by transforming the energy of the excited electrons into non-radiative energy. Moreover, the disulfide bond of CyD assisted nanoparticles with a drug by minimizing the interaction between the NIR dye and drug, and also by releasing the drug in a redox environment. As a result, DOX encapsulated within CyD (CyD/DOX) showed strong heat generation and fluorescence imaging in tumor-bearing mice, allowing detection of the tumor site and inhibition of tumor growth by chemo-photothermal therapy. The multiplicity of features supplied by the newly developed CyD demonstrated the potential of CyD/DOX as an NIR dye-based theranostic drug-delivery carrier for effective chemo-photothermal cancer therapy.

Insight into the Self-Insertion of a Protein Inside the Boron Nitride Nanotube.

Nanotubes have been considered as promising candidates for protein delivery purposes due to distinct features such as their large enough volume of cavity to encapsulate the protein, providing the sustain and target release. Moreover, possessing the properties of suitable cell viabilities, and biocompatibility on the wide range of cell lines as a result of structural stability, chemical inertness, and noncovalent wrapping ability, boron nitride nanotubes (BNNTs) have caught further attention as protein nanocarriers. However, to assess the encapsulation process of the protein into the BNNT, it is vital to comprehend the protein-BNNT interaction. In the present work, the self-insertion process of the protein SmtA, metallothionein, into the BNNT has been verified by means of the molecular dynamics (MD) simulation under NPT ensemble. It was revealed that the protein was self-inserted into the BNNT through the protein-BNNT van der Waals (vdW) interaction, which descended and reached the average value of -189.63 kcal·mol-1 at 15 ns of the simulation time. The potential mean force (PMF) profile of the encapsulated protein with increasing trend, which was obtained via the pulling process unraveled that the encapsulation of the protein into the BNNT cavity proceeded spontaneously and the self-inserted protein had reasonable stability. Moreover, due to the strong hydrogen interactions between the nitrogen atoms of BNNT and hydrogen atoms of SmtA, there was no evidence of an energy barrier in the vicinity of the BNNT entrance, which resulted in the rapid adsorption of this protein into the BNNT.

Tissue engineering with electrospun electro-responsive chitosan-aniline oligomer/polyvinyl alcohol.

Mimicking the native tissue is an ultimate goal in tissue engineering. In this study, conductive chitosan was synthesized by coupling with aniline oligomers, and then conductive nanofibers were fabricated using electrospinning technique to mimic the tissue structure and properties. The conductivity of the resulting biomaterial was adjusted to ca. 10-5 S/cm, which can recapitulate electrical properties of the tissue. The structure of nanofiber was evaluated using scanning electron microscopy noticing that the aniline oligomer addition to the system decreased the diameter of the nanofiber because of its hydrophobic nature. Conductive nanofiber exhibited on-demand drug release feature of the conductive webs, signaled by 40% rise in the drug release at 40 min after electrical stimulation in comparison with non-stimulated webs, characteristic of a promising drug release platform. Moreover, biocompatibility evaluation using MTT assay revealed that the conductive substrate provides a higher cellular activity to the platform with respect to non-conductive substrates. Such platforms are the harbingers of the emerging new generation, which can revolutionize the tissue engineering satisfying an enhanced tissue regeneration.

Iron hypothesis and coronary artery disease in geriatric patients.

Context and aims: Iron is a pro-oxidant factor in the pathogenesis of CAD. The association of body iron status was investigated relative to the occurrence and severity of CAD.Design and methods: The subjects consisted of 110 males and 115 females who were classified as either a CAD case or a control according to the results of coronary angiography.Results: A new parameter, the "serum free iron index," was defined as the ratio of serum iron to UIBC. The level of ferritin showed significant increase [97.2 (67.0-171.2) µg/L vs. 85.6 (52.5-129.4), p = .034], whereas serum total iron, free iron index, transferrin, UIBC and iron saturation were unchanged in CAD patients relative to control group. Among the indices of body iron only serum ferritin had significant association with the likelihood (OR of 1.004 (1.000-1.007), p = .04) and severity of CAD [χ2(3)= 7.99, p = .01], but the correlation was lessened in the presence of classical risk factors. Serum ferritin had also the highest and significant efficiency to predict CAD (AUC = 0.61, p = .020).Conclusions: Serum ferritin as a marker of intracellular iron has significant association with CAD; nevertheless, the correlation is not independent. Since iron deficiency is prevalent in elderly patients, iron hypothesis needs to expand to the both sides of iron deficiency and toxicity.

The Effect of Warm Footbath on the Quality of Sleep on Patients with Acute Coronary Syndrome in Cardiac Care Unit.

Introduction: This study aimed to determine the effect of warm footbath before bedtime on the quality of sleep on patients with acute Coronary Syndrome in Cardiac Care Unit. Methods: This study was conducted on 120 patients admitted to CCU at Mazandaran Heart Center and randomly divided into two groups of intervention and control. In the intervention group, warm footbath was performed after the second night in hospital before bed time by 41 C water for 20 minutes for three consecutive nights; in contrast, the control group did not receive anything of this sort. The next day, St Mary's Hospital Sleep Questionnaire was completed to evaluate sleep quality. Then, the obtained data were analyzed using SPSS software and Friedman, Wilcoxon exact statistical tests. Results: The quality of sleep in the first night of hospitalization was different from the third night after the intervention in both groups and the improvement process of sleep quality was observed in both groups. Most patients had moderate impairments (23-36), which had not changed during the intervention. In intervention groups, 8 patients had severe sleep disorders (greater than 37), which declined to 1 after three nights of intervention. While, in the control group this number fell from 10 patients with severe sleep disorders to 5. Warm footbath had a great positive impact on patients suffering from severe sleep disorders (P<0.05). Conclusion: Although warm footbath did not improve the quality of sleep in all patients, it reduced the number of patients who had severe sleep disturbances.

Self-gelling electroactive hydrogels based on chitosan-aniline oligomers/agarose for neural tissue engineering with on-demand drug release.

Designing biomimetic scaffolds is an intellectual challenge of the realm of regenerative medicine and tissue engineering. An electroactive substrate should meet multidisciplinary mimicking the mechanical, electrical, and electrochemical properties of neural tissues. Hydrogels have been known platforms to regulate neural interface modulus, but the lack of conductivity always hampered their applications; hence, developing conductive hydrogels with on-demand drug release has become a concern of tissue engineering. In this work, electroactive hydrogels based on chitosan-aniline oligomer and agarose with self-gelling properties were synthesized, and their electrical, thermal, and electrochemical properties were characterized by Fourier transform infrared (FTIR), cyclic voltammetry (CV), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), and four probe method . The conductivity of the as-prepared aniline oligomer-based hydrogel was ∼10-4 S/cm; which fell within the range of conductivities appropriate for applications in tissue engineering. The aniline oligomer played a key role in controlling the hydrogel properties by regulating the glass transition temperature and thermal properties. In addition, the swelling and degradation rates were decreased because of the hydrophobic properties of the aniline oligomer. The swelling capacity of the pristine hydrogel was ∼800%, while that of the conductive hydrogel decreased to ∼300%. The conductivity of the hydrogel was regulated by modifying the macromolecular architecture through aniline oligomer incorporation thanks to its conductivity on-demand drug release was observed by electrical stimulation, in which a large amount of the drug was released by voltage application. Biocompatibility analysis of the designed hydrogel was indicative of the conductivity enhancement, as reflected in the growth and proliferation of cellular activity.