Non valvular atrial fibrillation stroke risk stratification by CHA2DS2-VASc score and short term outcomes

Background: Atrial fibrillation confers a high risk of stroke and is associated with significant mortality and morbidity. Many scoring systems for have been proposed stroke risk stratification in atrial fibrillation. Peripheral thromboembolism, heart failure and death. The main objective of the study was to estimate CHA2DS2VASc score in cases of non valvular atrial fibrillation, to asses short term outcome in AF (stroke, thromboembolism, heart failure and death and to find out association of CHA2DS2VASc score with outcomes.Methods: 64 cases (29 M, 35 F) of non valvular AF were included in this prospective observational study.CHA2DS2VASc score was calculated and cases were categorized into low (score 0), intermediate (score 1 ) and high risk (score 2 ) for development of stroke. Cases were clinically evaluated and investigated for type, etiology, complications and comorbidities.Results: CHA2DS2VASc score was determined in 64 cases of non valvular AF. In 3 cases (4.6%) it was zero indicating low risk for stroke, 8 cases (12.5%) had CHA2DS2VASc score as 1had intermediate risk, and 53 cases (82.8%) had score 2 or more indicating high stroke risk (p<0.01). 3 cases of non valvular atrial fibrillation (4.6%) presented with stroke and all of them had CHA2DS2VASc score>2. At the end of 3 months, total no. of cases with stroke was reported to be 5 (7.8 %). Stroke risk was significantly higher in cases of CHA2DS2VASc score>2 (p<0.01). Congestive heart failure was reported in 32 (50%) cases. Peripheral embolism was documented in 1 case (1.5%). Overall Mortality at the end of 3 months was reported to be 7 (10.9%) and cases with CHA2DS2VASc score ≥2 had 13% mortality. CHA2DS2VASc score ≥2 was significantly associated with mortality (p<0.01). All 3 Cases with CHA2DS2VASc score as zero were uncomplicated. 8 cases (12.5%) had score as 1 and, out of these 8 cases, CHF was reported in 2 cases (25%), while 6 (75%) were uncomplicated.CHA2DS2VASc score ≥2 was reported in 53 cases (82.3%). This group had complications in the form of CHF in 30 cases (56.6 %), thromboembolism in 1 (1.8%), and stroke in 5 (9.4%) cases. Cases of AF with CHA2DS2VASc score >2 demonstrated significantly high incidence for stroke as compared to those with score as zero or one (p<0.01).Conclusions: CHA2DS2VASc is a simple score to predict stroke risk in cases of non valvular atrial fibrillation and is easy to estimate. CHA2DS2VASc score ≥2; is associated with high incidence of stroke in cases of non valvular AF. CHA2DS2VASc score≥2 is associated with mortality as a short term adverse outcome in non valvular atrial fibrillation.

Synthesis, molecular docking and biological evaluation of new quinoline analogues as potent anti-breast cancer and antibacterial agents

1215-1222A new class of quinoline analogues have been synthesized from isatin through two steps in good yields. They have been further evaluated for their anticancer activity against a breast cancer cell line (MDA-MB-231) and antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 6538p and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). All synthesized compounds have been confirmed by spectral characterization viz. FT-IR, MS, HPLC, 1H and 13C NMR. Among them, compound 4h exhibits promising anti-breast cancer activity whereas compounds 4d, 4f, 4h and 4j exhibit moderate antibacterial activity against all the tested organisms. Molecular docking analysis demonstrates the interaction of compound 4h with the active site amino acid of Human Carbonic Anhydrase I, Protein Kinase A and Kinesin Spindle Protein (KSP)

Synthesis, molecular docking and biological evaluation of new quinoline analogues as potent anti-breast cancer and antibacterial agents

A new class of quinoline analogues have been synthesized from isatin through two steps in good yields. They have been further evaluated for their anticancer activity against a breast cancer cell line (MDA-MB-231) and antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 6538p and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). All synthesized compounds have been confirmed by spectral characterization viz. FT-IR, MS, HPLC, 1H and 13C NMR. Among them, compound 4h exhibits promising anti-breast cancer activity whereas compounds 4d, 4f, 4h and 4j exhibit moderate antibacterial activity against all the tested organisms. Molecular docking analysis demonstrates the interaction of compound 4h with the active site amino acid of Human Carbonic Anhydrase I, Protein Kinase A and Kinesin Spindle Protein (KSP).

Progress on Thin Film Freezing Technology for Dry Powder Inhalation Formulations

The surface drying process is an important technology in the pharmaceutical, biomedical, and food industries. The final stage of formulation development (i.e., the drying process) faces several challenges, and overall mastering depends on the end step. The advent of new emerging technologies paved the way for commercialization. Thin film freezing (TFF) is a new emerging freeze-drying technique available for various treatment modalities in drug delivery. TFF has now been used for the commercialization of pharmaceuticals, food, and biopharmaceutical products. The present review highlights the fundamentals of TFF along with modulated techniques used for drying pharmaceuticals and biopharmaceuticals. Furthermore, we have covered various therapeutic applications of TFF technology in the development of nanoformulations, dry powder for inhalations and vaccines. TFF holds promise in delivering therapeutics for lung diseases such as fungal infection, bacterial infection, lung dysfunction, and pneumonia

Molecular insights into Coumarin analogues as antimicrobial agents: Recent developments in drug discovery

A major global health risk has been witnessed with the development of drug-resistant bacteria and multidrug-resistant pathogens linked to significant mortality. Coumarins are heterocyclic compounds belonging to the benzophenone class enriched in different plants. Coumarins and their derivatives have a wide range of biological activity, including antibacterial, anticoagulant, antioxidant, anti-inflammatory, antiviral, antitumour, and enzyme inhibitory effects. In the past few years, attempts have been reported towards the optimization, synthesis, and evaluation of novel coumarin analogues as antimicrobial agents. Several coumarin-based antibiotic hybrids have been developed, and the majority of them were reported to exhibit potential antibacterial effects. In the present work, studies reported from 2016 to 2020 about antimicrobial coumarin analogues are the focus. The diverse biological spectrum of coumarins can be attributed to their free radical scavenging abilities. In addition to various synthetic strategies developed, some of the structural features include a heterocyclic ring with electron-withdrawing/donating groups conjugated with the coumarin nucleus. The suggested structure−activity relationship (SAR) can provide insight into how coumarin hybrids can be rationally improved against multidrug-resistant bacteria. The present work demonstrates molecular insights for coumarin derivatives having antimicrobial properties from the recent past. The detailed SAR outcomes will benefit towards leading optimization during the discovery and development of novel antimicrobial therapeutics

Graphene nanoribbons with mixed cove-cape-zigzag edge structure

A recently developed bottom-up synthesis strategy enables the fabrication of graphene nanoribbons with well-defined width and non-trivial edge structures from dedicated molecular precursors. Here we discuss the synthesis and properties of zigzag nanoribbons (ZGNRs) modified with periodic cove-cape-cove units along their edges. Contrary to pristine ZGNRs, which show antiferromagnetic correlation of their edge states, the edge-modified ZGNRs exhibit a finite single particle band gap without localized edge states. We report the on-surface synthesis of such edge-modified ZGNRs and discuss tunneling conductance dI/dV spectra and dI/dV spatial maps that reveal a noticeable localization of electronic states at the cape units and the opening of a band gap without presence of edge states of magnetic origin. A thorough ab initio investigation of the electronic structure identifies the conditions under which antiferromagnetically coupled, edge-localized states reappear in the electronic structure. Further modifications of the ribbon structure are proposed that lead to an enhancement of such features, which could find application in nanoelectronics and spintronics

Exoplanets with ELT-METIS. I. Estimating the direct imaging exoplanet yield around stars within 6.5 parsecs

Direct imaging is a powerful exoplanet discovery technique that is complementary to other techniques and offers great promise in the era of 30 m class telescopes. Space-based transit surveys have revolutionized our understanding of the frequency of planets at small orbital radii around Sun-like stars. The next generation of extremely large ground-based telescopes will have the angular resolution and sensitivity to directly image planets with R < 4 R[SUB]⊕[/SUB] around the very nearest stars. Here, we predict yields from a direct imaging survey of a volume-limited sample of Sun-like stars with the Mid-Infrared ELT Imager and Spectrograph (METIS) instrument, planned for the 39 m European Southern Observatory Extremely Large Telescope (ELT) that is expected to be operational towards the end of the decade. Using Kepler occurrence rates, a sample of stars with spectral types A-K within 6.5 pc, and simulated contrast curves based on an advanced model of what is achievable from coronagraphic imaging with adaptive optics, we estimated the expected yield from METIS using Monte Carlo simulations. We find the METIS expected yield of planets in the N2 band (10.10−12.40 μm) is 1.14 planets, which is greater than comparable observations in the L (3.70−3.95 μm) and M (4.70−4.90 μm) bands. We also determined a 24.6% chance of detecting at least one Jovian planet in the background limited regime assuming a 1 h integration. We calculated the yield per star and estimate optimal observing revisit times to increase the yield. We also analyzed a northern hemisphere version of this survey and found there are additional targets worth considering. In conclusion, we present an observing strategy aimed to maximize the possible yield for limited telescope time, resulting in 1.48 expected planets in the N2 band.EPIC; NNEx

Exoplanets with ELT-METIS. I. Estimating the direct imaging exoplanet yield around stars within 6.5 parsecs

peer reviewedDirect imaging is a powerful exoplanet discovery technique that is complementary to other techniques and offers great promise in the era of 30 m class telescopes. Space-based transit surveys have revolutionized our understanding of the frequency of planets at small orbital radii around Sun-like stars. The next generation of extremely large ground-based telescopes will have the angular resolution and sensitivity to directly image planets with R < 4 R[SUB]⊕[/SUB] around the very nearest stars. Here, we predict yields from a direct imaging survey of a volume-limited sample of Sun-like stars with the Mid-Infrared ELT Imager and Spectrograph (METIS) instrument, planned for the 39 m European Southern Observatory Extremely Large Telescope (ELT) that is expected to be operational towards the end of the decade. Using Kepler occurrence rates, a sample of stars with spectral types A-K within 6.5 pc, and simulated contrast curves based on an advanced model of what is achievable from coronagraphic imaging with adaptive optics, we estimated the expected yield from METIS using Monte Carlo simulations. We find the METIS expected yield of planets in the N2 band (10.10−12.40 μm) is 1.14 planets, which is greater than comparable observations in the L (3.70−3.95 μm) and M (4.70−4.90 μm) bands. We also determined a 24.6% chance of detecting at least one Jovian planet in the background limited regime assuming a 1 h integration. We calculated the yield per star and estimate optimal observing revisit times to increase the yield. We also analyzed a northern hemisphere version of this survey and found there are additional targets worth considering. In conclusion, we present an observing strategy aimed to maximize the possible yield for limited telescope time, resulting in 1.48 expected planets in the N2 band.EPIC; NNEx

On-surface synthesis of graphene nanoribbons with zigzag edge topology

Graphene-based nanostructures exhibit a vast range of exciting electronic properties that are absent in extended graphene. For example, quantum confinement in carbon nanotubes and armchair graphene nanoribbons (AGNRs) leads to the opening of substantial electronic band gaps that are directly linked to their structural boundary conditions. Even more intriguing are nanostructures with zigzag edges, which are expected to host spin-polarized electronic edge states and can thus serve as key elements for graphene-based spintronics. The most prominent example is zigzag graphene nanoribbons (ZGNRs) for which the edge states are predicted to couple ferromagnetically along the edge and antiferromagnetically between them. So far, a direct observation of the spin-polarized edge states for specifically designed and controlled zigzag edge topologies has not been achieved. This is mainly due to the limited precision of current top-down approaches, which results in poorly defined edge structures. Bottom-up fabrication approaches, on the other hand, were so far only successfully applied to the growth of AGNRs and related structures. Here, we describe the successful bottom-up synthesis of ZGNRs, which are fabricated by the surface-assisted colligation and cyclodehydrogenation of specifically designed precursor monomers including carbon groups that yield atomically precise zigzag edges. Using scanning tunnelling spectroscopy we prove the existence of edge-localized states with large energy splittings. We expect that the availability of ZGNRs will finally allow the characterization of their predicted spin-related properties such as spin confinement and filtering, and ultimately add the spin degree of freedom to graphene-based circuitry.Comment: 15 pages, 4 figure

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline