Outcomes of Left Main Revascularization in Patients with Anemia: Gulf Left Main Registry.

INTRODUCTION: The aim of this study was to evaluate the effects of baseline anemia and anemia following revascularization on outcomes in patients with unprotected left main coronary artery (ULMCA) disease. METHODS: This was a retrospective, multicenter, observational study conducted between January 2015 and December 2019. The data on patients with ULMCA who underwent revascularization through percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) were stratified by the hemoglobin level at baseline into anemic and non-anemic groups to compare in-hospital events. The pre-discharge hemoglobin following revascularization was categorized into very low (<80 g/L for men and women), low (≥80 and ≤119 g/L for women and ≤129 g/L for men), and normal (≥130 g/L for men and ≥120 g/L for women) to assess impact on follow-up outcomes. RESULTS: A total of 2,138 patients were included, 796 (37.2%) of whom had anemia at baseline. A total of 319 developed anemia after revascularization and moved from being non-anemic at baseline to anemic at discharge. There was no difference in hospital major adverse cardiac and cerebrovascular event (MACCE) and mortality between CABG and PCI in anemic patients. At a median follow-up time of 20 months (interquartile range [IQR]: 27), patients with pre-discharge anemia who underwent PCI had a higher incidence of congestive heart failure (CHF) (p < 0.0001), and those who underwent CABG had significantly higher follow-up mortality (HR: 9.85 (95% CI: 2.53-38.43), p = 0.001). CONCLUSION: In this Gulf LM study, baseline anemia had no impact upon in-hospital MACCE and total mortality following revascularization (PCI or CABG). However, pre-discharge anemia is associated with worse outcomes after ULMCA disease revascularization, with significantly higher all-cause mortality in patients who had CABG, and a higher incidence of CHF in PCI patients, at a median follow-up time of 20 months (IQR: 27).

Left Main Coronary Artery Revascularization in Patients with Impaired Renal Function: Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting.

INTRODUCTION: The evidence about the optimal revascularization strategy in patients with left main coronary artery (LMCA) disease and impaired renal function is limited. Thus, we aimed to compare the outcomes of LMCA disease revascularization (percutaneous coronary intervention [PCI] vs. coronary artery bypass grafting [CABG]) in patients with and without impaired renal function. METHODS: This retrospective cohort study included 2,138 patients recruited from 14 centers between 2015 and 2,019. We compared patients with impaired renal function who had PCI (n= 316) to those who had CABG (n = 121) and compared patients with normal renal function who had PCI (n = 906) to those who had CABG (n = 795). The study outcomes were in-hospital and follow-up major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Multivariable logistic regression analysis showed that the risk of in-hospital MACCE was significantly higher in CABG compared to PCI in patients with impaired renal function (odds ratio [OR]: 8.13 [95% CI: 4.19-15.76], p < 0.001) and normal renal function (OR: 2.59 [95% CI: 1.79-3.73]; p < 0.001). There were no differences in follow-up MACCE between CABG and PCI in patients with impaired renal function (HR: 1.14 [95% CI: 0.71-1.81], p = 0.585) and normal renal function (HR: 1.12 [0.90-1.39], p = 0.312). CONCLUSIONS: PCI could have an advantage over CABG in revascularization of LMCA disease in patients with impaired renal function regarding in-hospital MACCE. The follow-up MACCE was comparable between PCI and CABG in patients with impaired and normal renal function.

Therapeutic Potential of Albumin Nanoparticles Encapsulated Visnagin in MDA-MB-468 Triple-Negative Breast Cancer Cells.

Breast cancer is among the most recurrent malignancies, and its prevalence is rising. With only a few treatment options available, there is an immediate need to search for better alternatives. In this regard, nanotechnology has been applied to develop potential chemotherapeutic techniques, particularly for cancer therapy. Specifically, albumin-based nanoparticles are a developing platform for the administration of diverse chemotherapy drugs owing to their biocompatibility and non-toxicity. Visnagin, a naturally derived furanochromone, treats cancers, epilepsy, angina, coughs, and inflammatory illnesses. In the current study, the synthesis and characterization of albumin visnagin (AV) nanoparticles (NPs) using a variety of techniques such as transmission electron microscopy, UV-visible, Fourier transform infrared, energy dispersive X-ray composition analysis, field emission scanning electron microscopy, photoluminescence, X-Ray diffraction, and dynamic light scattering analyses have been carried out. The MTT test, dual AO/EB, DCFH-DA, Annexin-V-FITC/PI, Propidium iodide staining techniques as well as analysis of apoptotic proteins, antioxidant enzymes, and PI3K/Akt/mTOR signaling analysis was performed to examine the NPs' efficacy to suppress MDA-MB-468 cell lines. The NPs decreased cell viability increased the amount of ROS in the cells, disrupted membrane integrity, decreased the level of antioxidant enzymes, induced cell cycle arrest, and activated the PI3K/Akt/mTOR signaling cascade, ultimately leading to cell death. Thus, AV NPs possesses huge potential to be employed as a strong anticancer therapy alternative.

PNPLA3 and TM6SF2 genetic variants and hepatic fibrosis and cirrhosis in Pakistani chronic hepatitis C patients: a genetic association study.

BACKGROUND: The present study investigates if common missense functional variants p.I148M and p.E167K in PNPLA3 and TM6SF2 genes, respectively, associate with development of hepatic fibrosis and cirrhosis in a geographically novel cohort of Pakistani chronic hepatitis C (CHC) patients. METHODS: In total, 502 Pakistani CHC patients [242 males, median age 40 years, 220 with significant hepatic fibrosis, including 114 with cirrhosis] were genotyped for PNPLA3 and TM6SF2 variants using TaqMan genotyping assays. Associations between genotypes, biochemical and clinical parameters were evaluated. RESULTS: Genotypic distributions for PNPLA3 and TM6SF2 polymorphisms conformed to Hardy-Weinberg equilibrium and did not associate with fibrosis grades ≥ F2 or cirrhosis in any of the genetic models tested (all p = > 0.05). PNPLA3 and TM6SF2 variants did not modulate baseline characteristics and serum markers of liver injury in CHC patients. Similarly, increasing number of risk alleles of PNPLA3 and TM6SF2 polymorphisms had no trend effect on serum liver enzyme activities or proportion of CHC patients with significant or advanced fibrosis or cirrhosis (p = > 0.05). The same trend of no association with hepatic fibrosis or cirrhosis persisted in the multivariate logistic regression models adjusting for age, gender, body mass index and HCV viral load (p = > 0.05). CONCLUSIONS: PNPLA3 and TM6SF2 variants do not appear to modulate development of hepatic fibrosis or cirrhosis in present CHC patients of Pakistani origin, and may be of more relevance in liver pathology involving abnormalities in hepatic fat accumulation. These results also reflect the divergent associations observed for different genetic modifiers of hepatic fibrosis and cirrhosis in distinct ethnicities.

Lipofection of Single Guide RNA Targeting MMP8 Decreases Proliferation and Migration in Lung Adenocarcinoma Cells.

Background and Objectives: Matrix metalloproteinases (MMP) have been implicated as major determinants of tumour growth and metastasis, which are considered two of the main hallmarks of cancer. The interaction of MMP8 and other signalling molecules within and adjacent tumoral tissues, including immune cells, are rather elusive, particularly of adenocarcinoma cell type. In this study, we aimed to investigate the role of MMP8 in non-small cell lung cancer proliferation and invasiveness potential. Materials and Methods: We individually lipofected with two different single guide RNA (sgRNAs) that specifically targeted on MMP8, with CRISPR-Cas 9 protein into the cells. Results: Our results clearly indicated that the lipofection of these complexes could lead to reduced ability of A549 cells to survive and proliferate to form colonies. In addition, when compared to non-transfected cells, the experimental cell groups receiving sgRNAs demonstrated relatively decreased migration rate, hence, wider wound gaps in scratch assay. The quantitative real time-polymerase chain reaction (qRT-PCR) demonstrated significant reduction in the MAP-K, survivin and PI3-K gene expression. MMP8 might have protective roles over tumour growth and spread in our body. Conclusions: The delivery of sgRNAs targeting on the MMP8 gene could induce tumour cell death and arrest cell migratory activity.

Determination of serum tumor necrosis factor-alpha (TNF-α) levels in metabolic syndrome patients from Saudi population.

OBJECTIVES: To detect the relationship between serum tumor necrosis factor-alpha (TNF-α) and metabolic syndrome (MetS) components in patients of the Saudi population. METHODS: This cross-sectional study was carried out at Jouf University Saudi Arabia from September 2019 to August 2020 and comprised of 183 individuals (91 cases and 92 controls). The blood samples were drawn from the patients visiting two tertiary care settings of Al Jouf province. Biochemical analysis was conducted on various instruments, and serum TNF-α was measured by the ELISA method. RESULTS: The levels of serum glucose fasting, lipid profile, HbA1c and body mass index (BMI) were raised significantly in cases of MetS than controls (p = 0.001). Serum TNF-α was significantly higher in patients (58.04 ± 15.44) than controls (48.81 ± 10.30). It was correlated with the BMI, blood HbA1c, serum fasting glucose (SFG) and serum high density lipoprotein (HDL). The weak positive correlation was found with BMI (r = 0.18; p = 0.01), serum glucose (r = 0.21; p = 0.007) and HbA1c (r = 0.14; p = 0.04), but found negative association with serum HDL (r = -0.18; p = 0.01). CONCLUSION: The serum TNF-α was raised in metabolic syndrome patients than the healthy controls. It was positively associated with high BMI, serum fasting glucose, and HbA1c and found linked and negatively linked to low HDL levels in MetS patients in the Saudi population.

The Biology of Toll-Like Receptor 9 and Its Role in Cancer.

Toll-like receptor 9 (TLR9) plays a fundamental role in innate immune responses through pathogen-associated and danger-associated molecular pattern recognition. Ligand recognition by TLR9 results in activation of several signaling pathways, including those involving nuclear factor-kappa B, mitogen-activated protein kinases, and interfer-on-regulatory factors, which promote secretion of proinflammatory cytokines and type I interferons. TLR9 is expressed by immune-mediated cells and in clinical specimens and cell lines of various human cancers. TLR9 appears to act as a double-edged sword in cancer, with some studies indicating that it is associated with increased malignancy and others indicating that it contributes to immune response against cancer. At present, the mechanisms underlying the role of TLR9 in cancer pathophysiology are not completely clear, although various TLR9 agonists and antagonists are being tested in in vitro and in vivo cancer models as well as clinical trials. This review summarizes the current state of knowledge regarding TLR9 features, isoforms, structure, ligands, and signaling, and discusses the roles of TLR9 in cancer pathogenesis. Recent efforts to utilize TLR9 agonists and antagonists as potential anticancer immunotherapy agents are also highlighted.

Molecular Analysis of the Antibiotic Resistant NDM-1 Gene in Clinical Isolates of Enterobacteriaceae.

BACKGROUND: The emergence of the New Dehli metallo-beta-lactamase (NDM) gene in Enterobacteriaceae is responsible for multidrug resistance responsible for severe infections and serious morbidity in patients. Our study aimed to define the molecular characteristics and antibiogram of the NDM-1 producing Enterobacteriaceae. METHODS: We isolated 370 individual enterobacteria from the clinical specimens collected from the two tertiary hospitals in Sakaka, Saudi Arabia. Bacterial isolation was performed using standard microbiological techniques and the Phoenix and Microscan WalkAway Plus automated analyzers. Bacterial strains were characterized by phenotypic methods and PCR, and DNA sequencing was used for the molecular characterization of NDM genes. RESULTS: The blaNDM gene was detected among the 68 members of the Enterobacteriaceae including a single case of rarely reported Cedecea lapagei. Of these 68, 43 isolates (63.2%) were blaNDM-1 and 25 (36.8%) were blaNDM variants. A statistically significant relationship between the NDM-1 and Klebsiella pneumoniae (p = 0.004) was seen, and the relationship between the NDM variants was significantly associated with Citrobacter freundii (p = 0.02) and Escherichia coli (p = 0.03). The in vitro minimum inhibitory concentrations (MICs) of NDM-producing Enterobacteriaceae revealed a very high rate of antibiotic resistance against several groups of antibiotics. These bacterial strains were less resistant to two aminoglycosides, gentamicin (39; 57.3%) and amikacin (27; 39.7%), and showed minimum resistance to tigecycline (25; 36.8%). CONCLUSIONS: The emergence of a large number of NDM-1 enterobacteria in our study identifies a substantial public concern, both within hospitals and the wider community, and leaves us a narrow choice of therapeutic options: the aminoglycosides, co-trimoxazole, and tigecycline.

Molecular Detection of blaIMP Genes in Metallo-Beta-Lactamase Producing Clinical Gram-Negative Isolates.

BACKGROUND: The use of carbapenem antibiotics in the treatment of serious Gram-negative bacterial infections is under threat due to the emergence of the blaIMP gene amongst the bacterial pathogens. METHODS: The present descriptive cross-sectional study aimed to determine the occurrence of the blaIMP gene and minimum inhibitory concentrations (MICs) of the bacterial pathogens. The carbapenem-resistant isolates were screened out for the detection of MBLs by using the modified Hodge test and disk potentiation method. MBL producing strains were tested for the presence of the blaIMP gene by using PCR technique. The MICs of the blaIMP gene positive bacterial isolates were detected on the Vitek 2 system (bioMerieux). RESULTS: The primary source of MBLs and blaIPM gene carrying bacterial pathogens was blood (38.5%). We isolated 104 bacterial isolates in the initial screening of carbapenem resistance. Metallo-beta-lactamases (MBLs) were detected in 76 (73%) of the isolates which predominantly included 27 (26%) Klebsiella pneumoniae, 20 (19.2%) Acinetobacter baumannii, 16 (15.4%) Pseudomonas aeruginosa, and 11 (10.6%) E. coli while the other Gram-nega-tive MBL producing bacteria were few in number. The blaIPM gene was detected in 1 (1.3%) case of Acinetobacter baumannii and 1 (1.3%) case of Stenotrophomonas maltophilia. These strains were found to be multi-drug resistant with high MICs (≥ 8 to ≥ 256 µg/mL) against the majority of the drugs. CONCLUSIONS: The emergence of the blaIPM gene is a matter of serious concern as it left us with limited treatment options of minocycline, tigecycline, and levofloxacin. The horizontal transfer of blaIPM gene in other Gram-negative isolates can lead the epidemics of multidrug resistance.

The role of AdipoR1 and AdipoR2 in liver fibrosis.

Activation of the adiponectin (APN) signaling axis retards liver fibrosis. However, understanding of the role of AdipoR1 and AdipoR2 in mediating this response is still rudimentary. Here, we sought to elucidate the APN receptor responsible for limiting liver fibrosis by employing AdipoR1 and AdipoR2 knock-out mice in the carbon tetrachloride (CCl4) model of liver fibrosis. In addition, we knocked down receptor function in primary hepatic stellate cells (HSCs) in vitro. Following the development of fibrosis, AdipoR1 and AdipoR2 KO mice had no quantitative difference in fibrosis by Sirius red staining. However, AdipoR2 KO mice had an enhanced fibrotic signature with increased Col1-α1, TGFß-1, TIMP-1, IL-10, MMP-2 and MMP-9. Knockdown of AdipoR1 or AdipoR2 in HSCs followed by APN treatment demonstrated that AdipoR1 and AdipoR2 did not affect proliferation or TIMP-1 gene expression, while AdipoR2 modulated Col1-α1 and α-SMA gene expression, HSC migration, and AMPK activity. These finding suggest that AdipoR2 is the major APN receptor on HSCs responsible for mediating its anti-fibrotic effects.

Adiponectin reduces hepatic stellate cell migration by promoting tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion.

Hepatic stellate cells (HSC) are central players in liver fibrosis that when activated, proliferate, migrate to sites of liver injury, and secrete extracellular matrix. Obesity, a known risk factor for liver fibrosis is associated with reduced levels of adiponectin, a protein that inhibits liver fibrosis in vivo and limits HSC proliferation and migration in vitro. Adiponectin-mediated activation of adenosine monophosphate-activated kinase (AMPK) inhibits HSC proliferation, but the mechanism by which it limits HSC migration to sites of injury is unknown. Here we sought to elucidate how adiponectin regulates HSC motility. Primary rat HSCs were isolated and treated with adiponectin in migration assays. The in vivo actions of adiponectin were examined by treating mice with carbon tetrachloride for 12 weeks and then injecting them with adiponectin. Cell and tissue samples were collected and analyzed for gene expression, signaling, and histology. Serum from patients with liver fibrosis was examined for adiponectin and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein. Adiponectin administration into mice increased TIMP-1 gene and protein expression. In cultured HSCs, adiponectin promoted TIMP-1 expression and through binding of TIMP-1 to the CD63/ß1-integrin complex reduced phosphorylation of focal adhesion kinase to limit HSC migration. In mice with liver fibrosis, adiponectin had similar effects and limited focal adhesion kinase phosphorylation. Finally, in patients with advanced fibrosis, there was a positive correlation between serum adiponectin and TIMP-1 levels. In sum, these data show that adiponectin stimulates TIMP-1 secretion by HSCs to retard their migration and contributes to the anti-fibrotic effects of adiponectin.

Reverse Vaccinology Approach to Identify Novel and Immunogenic Targets against Streptococcus gordonii.

Streptococcus gordonii is a gram-positive, mutualistic bacterium found in the human body. It is found in the oral cavity, upper respiratory tract, and intestines, and presents a serious clinical problem because it can lead to opportunistic infections in individuals with weakened immune systems. Streptococci are the most prevalent inhabitants of oral microbial communities, and are typical oral commensals found in the human oral cavity. These streptococci, along with many other oral microbes, produce multispecies biofilms that can attach to salivary pellicle components and other oral bacteria via adhesin proteins expressed on the cell surface. Antibiotics are effective against this bacterium, but resistance against antibodies is increasing. Therefore, a more effective treatment is needed. Vaccines offer a promising method for preventing this issue. This study generated a multi-epitope vaccine against Streptococcus gordonii by targeting the completely sequenced proteomes of five strains. The vaccine targets are identified using a pangenome and subtractive proteomic approach. In the present study, 13 complete strains out of 91 strains of S. gordonii are selected. The pangenomics results revealed that out of 2835 pan genes, 1225 are core genes. Out of these 1225 core genes, 643 identified as non-homologous proteins by subtractive proteomics. A total of 20 essential proteins are predicted from non-homologous proteins. Among these 20 essential proteins, only five are identified as surface proteins. The vaccine construct is designed based on selected B- and T-cell epitopes of the antigenic proteins with the help of linkers and adjuvants. The designed vaccine is docked against TLR2. The expression of the protein is determined using in silico gene cloning. Findings concluded that Vaccine I with adjuvant shows higher interactions with TLR2, suggesting that the vaccine has the ability to induce a humoral and cell-mediated response to treat and prevent infection; this makes it promising as a vaccine against infectious diseases caused by S. gordonii. Furthermore, validation of the vaccine construct is required by in vitro and in vivo trials to check its actual potency and safety for use to prevent infectious diseases caused by S. gordonii.

Nanocomposites of iron oxide, sodium alginate, and eugenol induce apoptosis via PI3K/Akt/mTOR signaling in Hep3 cells and in vivo hepatotoxicity in the zebrafish model.

Hepatic cancer is among the most recurrently detected malignancies worldwide and one of the main contributors to cancer-associated mortality. With few available therapeutic choices, there is an instant necessity to explore suitable options. In this aspect, Nanotechnology has been employed to explore prospective chemotherapeutic approaches, especially for cancer treatment. Nanotechnology is concerned with the biological and physical properties of nanoparticles in the therapeutic use of drugs. In the current work, formulation, and characterization of α-Fe2O3-Sodium Alginate-Eugenol nanocomposites (FSE NCs) using several approaches like SEM and TEM, UV-visible, FTIR, and PL spectroscopy, XRD, EDAX, and DLS studies have been performed. With an average size of 50 nm, the rhombohedral structure of NCs was identified. Further, their anticancer activity against Hep3B liver cancer cell lines has been performed by cell viability, dual staining, DCFH-DA, Annexin-V/-FITC/PI, cell cycle analysis methods, and PI3K/Akt/mTOR signaling proteins were studied to assess the anticancer effects of the NCs in Hep3B cells. Also, anti-cancer activity on animal modeling in-vivo using zebra fishes to hematological parameters, liver enzymes, and histopathology study effectiveness was noticed. Moreover, the NCs reduced the viability, elevated the ROS accumulation, diminished the membrane integrity, reduced the antioxidants, blocked the cell cycle, and triggered the PI3K/Akt/mTOR signaling axis that eventually resulted in cell death. As a result, FSE NCs possess huge potential for use as a possible anticancer candidate.

The critical impacts of cytokine storms in respiratory disorders.

Cytokine storm (CS) refers to the spontaneous dysregulated and hyper-activated inflammatory reaction occurring in various clinical conditions, ranging from microbial infection to end-stage organ failure. Recently the novel coronavirus involved in COVID-19 (Coronavirus disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been associated with the pathological phenomenon of CS in critically ill patients. Furthermore, critically ill patients suffering from CS are likely to have a grave prognosis and a higher case fatality rate. Pathologically CS is manifested as hyper-immune activation and is clinically manifested as multiple organ failure. An in-depth understanding of the etiology of CS will enable the discovery of not just disease risk factors of CS but also therapeutic approaches to modulate the immune response and improve outcomes in patients with respiratory diseases having CS in the pathogenic pathway. Owing to the grave consequences of CS in various diseases, this phenomenon has attracted the attention of researchers and clinicians throughout the globe. So in the present manuscript, we have attempted to discuss CS and its ramifications in COVID-19 and other respiratory diseases, as well as prospective treatment approaches and biomarkers of the cytokine storm. Furthermore, we have attempted to provide in-depth insight into CS from both a prophylactic and therapeutic point of view. In addition, we have included recent findings of CS in respiratory diseases reported from different parts of the world, which are based on expert opinion, clinical case-control research, experimental research, and a case-controlled cohort approach.

Does Gender Affect the Outcomes of Myocardial Revascularization for Left-Main Coronary Artery Disease?

Currently, gender is not considered in the choice of the revascularization strategy for patients with unprotected left main coronary artery (ULMCA) disease. This study analyzed the effect of gender on the outcomes of percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG) in patients with ULMCA disease. Females who had PCI (n = 328) were compared with females who had CABG (n = 132) and PCI in males (n = 894) was compared with CABG (n = 784). Females with CABG had higher overall hospital mortality and major adverse cardiovascular events (MACE) than females with PCI. Male patients with CABG had higher MACE; however, mortality did not differ between males with CABG vs PCI. In female patients, follow-up mortality was significantly higher in CABG patients, and target lesion revascularization was higher in patients with PCI. Male patients had no difference in mortality and MACE between groups; however, MI was higher with CABG, and congestive heart failure was higher with PCI. In conclusion, women with ULMCA disease treated with PCI could have better survival with lower MACE compared with CABG. These differences were not evident in males treated with either CABG or PCI. PCI could be the preferred revascularization strategy in women with ULMCA disease.

Single Versus Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting for Unprotected Left-Main Coronary Disease.

BACKGROUND: The use of dual antiplatelet therapy (DAPT) after coronary revascularization for left-main disease is still debated. The study aimed to characterize patients who received dual versus single antiplatelet therapy (SAPT) after coronary artery bypass grafting (CABG) for unprotected left-main disease and compare the outcomes of those patients. RESULTS: This multicenter retrospective cohort study included 551 patients who were grouped into 2 groups: patients who received SAPT (n = 150) and those who received DAPT (n = 401). There were no differences in age ( P = 0.451), gender ( P = 0.063), smoking ( P = 0.941), diabetes mellitus ( P = 0.773), history of myocardial infarction ( P = 0.709), chronic kidney disease ( P = 0.615), atrial fibrillation ( P = 0.306), or cerebrovascular accident ( P = 0.550) between patients who received SAPT versus DAPT. DAPTs were more commonly used in patients with acute coronary syndrome [87 (58%) vs. 273 (68.08%); P = 0.027], after off-pump CABG [12 (8%) vs. 73 (18.2%); P = 0.003] and in patients with radial artery grafts [1 (0.67%) vs. 32 (7.98%); P < 0.001]. While SAPTs were more commonly used in patients with low ejection fraction [55 (36.67%) vs. 61 (15.21%); P < 0.001] and in patients with postoperative acute kidney injury [27 (18%) vs. 37 (9.23%); P = 0.004]. The attributed treatment effect of DAPT for follow-up major adverse cerebrovascular and cardiac events was not significantly different from that of SAPT [ß, -2.08 (95% confidence interval (CI), -20.8-16.7); P = 0.828]. The attributed treatment effect of DAPT on follow-up all-cause mortality was not significantly different from that of SAPT [ß, 4.12 (CI, -11.1-19.32); P = 0.595]. There was no difference in bleeding between groups ( P = 0.666). CONCLUSIONS: DAPTs were more commonly used in patients with acute coronary syndrome, after off-pump CABG, and with radial artery grafts. SAPTs were more commonly used in patients with low ejection fraction and acute kidney injury. Patients on DAPT after CABG for left-main disease had comparable major adverse cerebrovascular and cardiac events and survival to patients on SAPT, with no difference in bleeding events.

Impact of preoperative intra-aortic balloon pump on outcomes in coronary artery bypass grafting for unprotected left-main coronary artery disease.

Background: Preoperative intra-aortic balloon pump (IABP) before coronary artery bypass grafting (CABG) could improve operative outcomes by augmenting the diastolic coronary blood flow. Data on preoperative IABP use in patients with left-main coronary artery (LMCA) disease are limited. This study aimed to characterize patients who received preoperative IABP before CABG for LMCA and evaluate its effect on postoperative outcomes. Methods: This multicenter retrospective cohort study that included consecutive 914 patients who underwent CABG for unprotected LMCA disease from January 2015 to December 2019 in 14 tertiary referral centers. Patients were grouped according to the preoperative IABP insertion into patients with IABP (n=101) and without IABP (n=813). Propensity score matching adjusting for preoperative variables, with 1:1 match and a caliber of 0.03 identified 80 matched pairs. The primary outcomes used in propensity score matching were cardiac mortality and major adverse cardiac and cerebrovascular events (MACCE). Results: IABP was commonly inserted in patients with previous myocardial infarction (MI), chronic kidney disease, peripheral arterial disease, and congestive heart failure. IABP patients had higher EuroSCORE [ES >8%: 95 (11.86%) vs. 40 (39.60%), P<0.001] and SYNTAX {29 [interquartile range (IQR) 25-35] vs. 33 (IQR 26-36); P=0.02} scores. Preoperative cardiogenic shock and arrhythmia were more prevalent in patients with IABP, while acute coronary syndrome was more prevalent in patients without IABP. After matching, there was no difference in vasoactive inotropic score between groups [3.5 (IQR 1-7.5) vs. 6 (IQR 1-13.5), P=0.06], and lactate levels were nonsignificantly higher in patients with IABP [2.4 (IQR 1.4-4.5) vs. 3.1 (IQR 1.05-7.75), P=0.05]. There were no differences between groups in acute kidney injury [20 (25%) vs. 26 (32.5%), P=0.34], cerebrovascular accidents [3 (3.75%) vs. 4 (5%), P>0.99], heart failure [5 (6.25%) vs. 7 (8.75%), P=0.75], MI [7 (8.75%) vs. 8 (10%), P>0.99], major adverse cardiac and cerebrovascular events [10 (12.5%) vs. 17 (21.25%), P=0.21], and cardiac mortality [6 (7.50%) vs. 14 (17.50%), P=0.09]. Patients who received IABP had longer ventilation times [8.5 (IQR 6-23) vs. 15.5 (IQR 5-50.5) h, P=0.03] and intensive care unit (ICU) stays [3 (IQR 2-5) vs. 4 (IQR 2-7.5) days, P=0.01]. Conclusions: Preoperative IABP in patients with LMCA might not be associated with reduced cardiac mortality or hospital complications. IABP could increase the duration of mechanical ventilation and ICU stay, and its use should be individualized for each patient.

Development of a tetravalent subunit vaccine against dengue virus through a vaccinomics approach.

Dengue virus infection (DVI) is a mosquito-borne disease that can lead to serious morbidity and mortality. Dengue fever (DF) is a major public health concern that affects approximately 3.9 billion people each year globally. However, there is no vaccine or drug available to deal with DVI. Dengue virus consists of four distinct serotypes (DENV1-4), each raising a different immunological response. In the present study, we designed a tetravalent subunit multi-epitope vaccine, targeting proteins including the structural protein envelope domain III (EDIII), precursor membrane proteins (prM), and a non-structural protein (NS1) from each serotype by employing an immunoinformatic approach. Only conserved sequences obtained through a multiple sequence alignment were used for epitope mapping to ensure efficacy against all serotypes. The epitopes were shortlisted based on an IC50 value <50, antigenicity, allergenicity, and a toxicity analysis. In the final vaccine construct, overall, 11 B-cell epitopes, 10 HTL epitopes, and 10 CTL epitopes from EDIII, prM, and NS1 proteins targeting all serotypes were selected and joined via KK, AAY, and GGGS linkers, respectively. We incorporated a 45-amino-acid-long B-defensins adjuvant in the final vaccine construct for a better immunogenic response. The vaccine construct has an antigenic score of 0.79 via VaxiJen and is non-toxic and non-allergenic. Our refined vaccine structure has a Ramachandran score of 96.4%. The vaccine has shown stable interaction with TLR3, which has been validated by 50 ns of molecular dynamics (MD) simulation. Our findings propose that a designed multi-epitope vaccine has substantial potential to elicit a strong immune response against all dengue serotypes without causing any adverse effects. Furthermore, the proposed vaccine can be experimentally validated as a probable vaccine, suggesting it may serve as an effective preventative measure against dengue virus infection.

An In Silico Deep Learning Approach to Multi-Epitope Vaccine Design: A Hepatitis E Virus Case Study.

Hepatitis E Virus (HEV) is a major cause of acute and chronic hepatitis. The severity of HEV infection increases manyfold in pregnant women and immunocompromised patients. Despite the extensive research on HEV in the last few decades, there is no widely available vaccine yet. In the current study, immunoinformatic analyses were applied to predict a multi-epitope vaccine candidate against HEV. From the ORF2 region, 41 conserved and immunogenic epitopes were prioritized. These epitopes were further analyzed for their probable antigenic and non-allergenic combinations with several linkers. The stability of the vaccine construct was confirmed by molecular dynamic simulations. The vaccine construct is potentially antigenic and docking analysis revealed stable interactions with TLR3. These results suggest that the proposed vaccine can efficiently stimulate both cellular and humoral immune responses. However, further studies are needed to determine the immunogenicity of the vaccine construct.

In-silico drug design for the novel Karachi-NF001 strain of brain-eating amoeba: Naegleria fowleri.

Naegleria fowleri (N. fowleri) is a free-living thermophilic amoeba of fresh water and soil. The amoeba primarily feeds on bacteria but can be transmitted to humans upon contact with freshwater sources. Furthermore, this brain-eating amoeba enters the human body through the nose and travels to the brain to cause primary amebic meningoencephalitis (PAM). N. fowleri has been reported globally since its discovery in 1961. Recently a new strain of N. fowleri named Karachi-NF001 was found in a patient who had traveled from Riyadh, Saudi Arabia to Karachi in 2019. There were 15 unique genes identified in the genome of the Karachi-NF001 strain compared to all the previously reported strains of N. fowleri worldwide. Six of these genes encode well-known proteins. In this study, we performed in-silico analysis on 5 of these 6 proteins, namely, Rab family small GTPase, NADH dehydrogenase subunit 11, two Glutamine-rich protein 2 proteins (locus tags: 12086 and 12110), and Tigger transposable element-derived protein 1. We conducted homology modeling of these 5 proteins followed by their active site identification. These proteins were subjected to molecular docking against 105 anti-bacterial ligand compounds as potential drugs. Subsequently, the 10 best-docked compounds were determined for each protein and ranked according to the number of interactions and their binding energies. The highest binding energy was recorded for the two Glutamine-rich protein 2 proteins with different locus tags, and results have shown that the protein-inhibitor complex was stable throughout the simulation run. Moreover, future in-vitro studies could validate the findings of our in-silico analysis and identify potential therapeutic drugs against N. fowleri infections.