Knowledge, attitude, and practice about red eye among the general population visiting a tertiary care hospital in rural setting, Tamil Nadu, India.

Background: Red eye is a common symptom in patients visiting the ophthalmology outpatient department (OPD). However, not all with red eye are due to infection and some can be threatening to visual loss. This study aimed to explore the knowledge, attitude, and practice (KAP) among the general public regarding red eye attending a tertiary care hospital, Tamil Nadu.

Solutions to bridge the theory-practice gap in nursing education in the UAE: a qualitative study.

Background: The theoretical knowledge of nursing underpins the practice, while the practice environment determines the circumstances within which the theoretical knowledge is applied. The biggest challenge facing nursing as an academic field is the theory-practice gap, which is a universal issue in nursing. This study aimed to raise solutions to close the gap between theory and practice in nursing education through the eyes of nursing students in UAE.

Managing the theory-practice gap in nursing education and practice: Hearing the voices of nursing students in the United Arab Emirates.

Aim: The aim of this study is to explore factors contributing to the theory-practice gap in nursing education in the United Arab Emirates.

Background: The gap between what is taught in nursing classrooms and what is practised in clinical settings creates challenges for nursing students, practitioners, managers and educators. This has important implications for the United Arab Emirates and other developing countries as their healthcare systems require a permanent nursing taskforce that is well supplied with ready to practice graduates.

Controlled electrochemical synthesis of new rare earth metal lutetium hexacyanoferrate on reduced graphene oxide and its application as a salicylic acid sensor.

The hexangular star building-like lutetium hexacyanoferrate (LuHCF) structure with an average size of ca. 8.0 ± 0.

Highly sensitive and selective determination of pyrazinamide at poly-L-methionine/reduced graphene oxide modified electrode by differential pulse voltammetry in human blood plasma and urine samples.

In this current study we used electrochemically active film which contains poly-L-methionine (PMET) and electrochemically reduced graphene oxide (ERGO) on glassy carbon electrode (GCE) for pyrazinamide (PZM) detection. The electrocatalytic response of analyte at PMET/ERGO/GCE film was measured using both cyclic voltammetry (CV) and differential pulse voltammetry (DPV). In addition, electrochemical impedance studies revealed that the smaller R(ct) value observed at PMET/ERGO film modified GCE which authenticates its good conductivity and faster electron transfer rate.

Electropolymerization of curcumin on glassy carbon electrode and its electrocatalytic application for the voltammetric determination of epinephrine and p-acetoaminophenol.

Here in, we report the simultaneous voltammetric determination of epinephrine (EP) and p-acetoaminophenol (AP) on a poly curcumin (1,7 Bis ((4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5 dione), poly CM) modified glassy carbon electrode (GCE) for the first time. The CM was polymerized on to the GCE surface by simple electro polymerization process. A low peak to peak (ΔEp) separation of 60 mV was observed, indicating fast electron transfer between poly CM and the electrode surface.

Direct electrochemistry of glucose oxidase at electrochemically reduced graphene oxide-multiwalled carbon nanotubes hybrid material modified electrode for glucose biosensor.

Direct electrochemistry of glucose oxidase (GOx) at an electrochemically reduced graphene oxide-multiwalled carbon nanotubes hybrid (ERGO-MWCNT) modified glassy carbon electrode (GCE) has been reported. The π-π stacking interaction operating between the MWCNT and graphene oxide (GO) has been revealed by UV-Vis absorption spectroscopy. GOx was well immobilized onto the ERGO-MWCNT hybrid film, as a result direct electrochemistry of GOx has been achieved.

Discovery and characterization of atropisomer PH-797804, a p38 MAP kinase inhibitor, as a clinical drug candidate.

PH-797804 ((aS)-3-{3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl}-N,4-dimethylbenzamde) is a diarylpyridinone inhibitor of p38 mitogen-activated protein (MAP) kinase derived from a racemic mixture as the more potent atropisomer (aS), first proposed by molecular modeling and subsequently confirmed by experiments. Due to steric constraints imposed by the pyridinone carbonyl group and the 6- and 6'-methyl substituents of PH-797804, rotation around the connecting bond of the pyridinone and the N-phenyl ring is restricted. Density functional theory predicts a remarkably high rotational energy barrier of >30 kcal mol(-1), corresponding to a half-life of more than one hundred years at room temperature.

Discovery of PH-797804, a highly selective and potent inhibitor of p38 MAP kinase.

The synthesis and SAR studies of a novel N-aryl pyridinone class of p38 kinase inhibitors are described. Systematic structural modifications to the HTS lead, 5, led to the identification of (-)-4a as a clinical candidate for the treatment of inflammatory diseases. Additionally, the chiral synthesis and properties of (-)-4a are described.

Design, synthesis and activity of a potent, selective series of N-aryl pyridinone inhibitors of p38 kinase.

A series of N-aryl pyridinone inhibitors of p38 mitogen activated protein (MAP) kinase were designed and prepared based on the screening hit SC-25028 (1) and structural comparisons to VX-745 (5). The focus of the investigation targeted the dependence of potency and metabolic stability on the benzyloxy connectivity, the role of the C-6 position and the substitution pattern on the N-phenyl ring. Further optimization produced the highly selective and potent pyridinones 2 and 3.

Substituted N-aryl-6-pyrimidinones: a new class of potent, selective, and orally active p38 MAP kinase inhibitors.

A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat.

Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase.

The identification and evolution of a series of potent and selective p38 inhibitors is described. p38 inhibitors based on a N-benzyl pyridinone high-throughput screening hit were prepared and their SAR explored. Their design was guided by ligand bound co-crystals of p38alpha.

Structural bioinformatics-based prediction of exceptional selectivity of p38 MAP kinase inhibitor PH-797804.

PH-797804 is a diarylpyridinone inhibitor of p38alpha mitogen-activated protein (MAP) kinase derived from a racemic mixture as the more potent atropisomer (aS), first proposed by molecular modeling and subsequently confirmed by experiments. On the basis of structural comparison with a different biaryl pyrazole template and supported by dozens of high-resolution crystal structures of p38alpha inhibitor complexes, PH-797804 is predicted to possess a high level of specificity across the broad human kinase genome. We used a structural bioinformatics approach to identify two selectivity elements encoded by the TXXXG sequence motif on the p38alpha kinase hinge: (i) Thr106 that serves as the gatekeeper to the buried hydrophobic pocket occupied by 2,4-difluorophenyl of PH-797804 and (ii) the bidentate hydrogen bonds formed by the pyridinone moiety with the kinase hinge requiring an induced 180 degrees rotation of the Met109-Gly110 peptide bond.

R-isomers of Arg-Gly-Asp (RGD) mimics as potent alphavbeta3 inhibitors.

The integrin alpha(v)beta(3), vitronectin receptor, is expressed in a number of cell types and has been shown to mediate adhesion of osteoclasts to bone matrix, vascular smooth muscle cell migration, and angiogenesis. We recently disclosed the discovery of a tripeptide Arg-Gly-Asp (RGD) mimic, which has been shown to be a potent inhibitor of the integrin alpha(v)beta(3) and has excellent anti-angiogenic properties including its suppression of tumor growth in animal models. In other investigations involving RGD mimics, only compounds containing the S-isomers of the beta-amino acids have been shown to be potent.

Genetic and biochemical studies establish that the fungicidal effect of a fully depeptidized inhibitor of Cryptococcus neoformans myristoyl-CoA:protein N-myristoyltransferase (Nmt) is Nmt-dependent.

Cryptococcus neoformans is a fungal pathogen that causes chronic meningitis in 10% of patients with AIDS. Genetic and biochemical studies were conducted to determine whether myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a target for development of a new class of fungicidal drugs. A single copy of a conditional lethal C.

Novel biologically active nonpeptidic inhibitors of myristoylCoA:protein N-myristoyltransferase.

A new class of biologically active nonpeptidic inhibitors of Candida albicans NMT has been synthesized starting from the octapeptide ALYASKLS-NH2 (2). The synthetic strategy entailed the preparation of novel protected Ser-Lys mimics 9 and 12 from (S)- or (R)-3-iodotyrosine and then grafting key enzyme recognition elements in a stepwise manner. Like 2, compounds 16, 17, and 18 are competitive Candida NMT inhibitors that bind to the peptide recognition site of the enzyme.

Design and synthesis of novel imidazole-substituted dipeptide amides as potent and selective inhibitors of Candida albicans myristoylCoA:protein N-myristoyltransferase and identification of related tripeptide inhibitors with mechanism-based antifungal activity.

A new class of antifungal agents has been discovered which exert their activity by blockade of myristoylCoA: protein N-myristoyltransferase (NMT; EC 2.1.3.

Titration calorimetric analysis of AcylCoA recognition by myristoylCoA:protein N-myristoyltransferase.

Saccharomyces cerevisiae myristoylCoA:protein N-myristoyltransferase (Nmt1p) is an essential enzyme that catalyzes the transfer of myristic acid (C14:0) from myristoylCoA to the N-terminus of cellular proteins with a variety of functions. Nmts from an assortment of species display remarkable in vivo specificity for this rare acyl chain. To better understand the mechanisms underlying this specificity, we have used isothermal titration calorimetry as well as kinetic measurements to study the interactions of Nmt1p with acylCoA analogs having variations in chain length and/or conformation, analogs with alterations in the thioester bond, and analogs with or without a 3'-phosphate in their CoA moiety.

Conformationally constrained [p-(omega-aminoalkyl)phenacetyl]-L-seryl-L-lysyl dipeptide amides as potent peptidomimetic inhibitors of Candida albicans and human myristoyl-CoA:protein N-myristoyl transferase.

MyristoylCoA:protein N-myristoyltransferase (NMT) covalently attaches the 14-carbon saturated fatty acid myristate, via an amide bond, to the N-terminal glycine residues of a variety of cellular proteins. Genetic studies have shown that NMT is essential for the viability of the principal fungal pathogens which cause systemic infection in immunosuppressed humans and hence is a target for development of fungicidal drugs. We have generated a class of potent peptidomimetic inhibitors of the NMT from one such fungal pathogen, Candida albicans.

Scanning alanine mutagenesis and de-peptidization of a Candida albicans myristoyl-CoA:protein N-myristoyltransferase octapeptide substrate reveals three elements critical for molecular recognition.

Candida albicans produces a single myristoyl-CoA:protein N-myristoyltransferase (Nmt) that is essential for its viability. An ADP-ribosylation factor (Arf) is included among the few cellular protein substrates of this enzyme. An octapeptide (GLYASKLS-NH2) derived from a N-terminal Arf sequence was used as the starting point to identify elements critical for recognition by the acyltransferases's peptide-binding site.

N-myristoylation of Arf proteins in Candida albicans: an in vivo assay for evaluating antifungal inhibitors of myristoyl-CoA: protein N-myristoyltransferase.

Myristoyl-CoA: protein N-myristoyltransferase (Nmt) catalyses the covalent attachment of myristate to the N-terminal glycine of a small subset of cellular proteins produced during vegetative growth of Candida albicans. nmt447D is a mutant NMT allele encoding an enzyme with a Gly447-->ASP substitution and reduced affinity for myristoyl-CoA. Among isogenic NMT/NMT, NMT/ delta nmt and nmt delta/nmt447D strains, only nmt delta/nmt447D cells require myristate for growth on yeast/peptone/dextrose media (YPD) at 24 or 37 degrees C.

Selective peptidic and peptidomimetic inhibitors of Candida albicans myristoylCoA: protein N-myristoyltransferase: a new approach to antifungal therapy.

MyristoylCoA: protein N-myristoyltransferase (NMT) catalyzes the cotranslational covalent attachment of a rare cellular fatty acid, myristate, to the N-terminal Gly residue of a variety of eukaryotic proteins. The myristoyl moiety is often essential for expression of the biological functions for these proteins. Attachment of C14:0 alone provides barely enough hydrophobicity to allow stable association with membranes.

4-oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus I.

Candida albicans and Cryptococcus neoformans are major causes of systemic fungal infections, particularly in patients with acquired immunodeficiency syndrome. Metabolic labeling studies revealed that these organisms synthesize a small number of N-myristoylproteins, the most prominent being 20-kDa ADP-ribosylation factors (Arfs). C.

Substrate specificity of Saccharomyces cerevisiae myristoyl-CoA: protein N-myristoyltransferase. Analysis of fatty acid analogs containing carbonyl groups, nitrogen heteroatoms, and nitrogen heterocycles in an in vitro enzyme assay and subsequent identification of inhibitors of human immunodeficiency virus I replication.

Covalent attachment of myristic acid (C14:0) to the amino-terminal glycine residue of a variety of eukaryotic cellular and viral proteins can have a profound influence on their biological properties. The enzyme that catalyzes this modification, myristoyl-CoA-protein N-myristoyltransferase (NMT), has been identified as a potential target for antiviral and antifungal therapy. Its reaction mechanism is ordered Bi Bi with myristoyl-CoA binding occurring before binding of peptide and CoA release preceding release of myristoylpeptide.