Diagnostic accuracy of indigenously developed computer-based binocular vision assessment.

CONTEXT: The increased prevalence of nonstrabismic binocular vision anomalies (NSBVA) has given rise to the need for cost-effective screening and diagnostic tools. AIMS: The aim of the study is to assess the efficacy of an indigenously developed computer-based binocular vision assessment software (Train Your Eyes®) in screening NSBVA. SUBJECTS AND METHODS: Subjects who visited the binocular vision clinic of a tertiary eye care center with asthenopic symptoms between January 2019 and January 2020 were included in the study. Patients with other ocular comorbidities and stereopsis poorer than 500 arc seconds were excluded. All subjects underwent a comprehensive eye examination followed by binocular vision assessment using both the manual and computer-based methods. STATISTICAL ANALYSIS USED: Receiver operating characteristic (ROC) curves were utilized to choose the cut-off points that maximize the sensitivity and specificity. RESULTS: The mean (standard deviation) age of 88 subjects was 22 (4.5) years with 34 males. Based on the conventional manual assessment, 71 (81%) were diagnosed to have NSBVA and 17 (19%) had normal binocular vision. Based on the ROC analysis, the following cut-off points are proposed: 14 prism diopter (PD) for near positive fusional vergence amplitudes, 4.5 PD for near negative fusional vergence amplitudes, 4.5 cycles per minute (cpm) for binocular accommodative facility, and 3.5 cpm for monocular accommodative facility. All the binocular vision parameters demonstrated statistical significance in the ROC analysis (P < 0.05). CONCLUSIONS: The software-based screening tool was found to be highly sensitive in identifying NSBVA and thus could be used as a potential screening tool in the clinic and community.

Diagnosis and Management of Post Traumatic Recurrent Unilateral Accommodative Spasm-A Case Report.

Spasm of accommodation refers to constant contraction of the ciliary muscles of the eye, which fail to relax. Neurological issues, head injury, and psychogenic factors can lead to spasm of accommodation, which is generally bilateral. This case report describes the clinical presentation of traumatic, unilateral accommodative spasm in an army person. A 26-year-old male presented with complaints of diminution of near vision in the left eye noticed accidentally. History revealed a blunt injury in the eyebrow region of the left eye two months back. His best corrected visual acuity was 6/6, 0.8 M (N6) in the right eye and 6/9, 2.5 M (N18) in the left eye. Accommodative response was documented using an open-field autorefractometer that showed asymmetry in the accommodation response and pupillary diameter between the two eyes. One percent Atropine sulfate eye ointment - twice a day for 3 days - was prescribed. On the fourth day, the spasm was resolved in the left eye. Pre- and post-Atropine administration, lens thickness measurements were documented, which showed significant changes. Accommodative facility exercise was initiated after the pharmacological management. Unilateral accommodative spasm is rare and needs careful investigations. Objective assessment of accommodative response and lens thickness measurement play a vital role in confirming the diagnosis.

A Rare Survival in Celphos Poisoning.

Aluminium phosphide poisoning releases phosphine gas which causes inhibition of cytochrome oxidase, inhibition of electron transport chain and thereby myocardial suppression. It is known to cause various electric abnormalities in the heart from ST-T depression to fatal tachyarrhythmias. Here we present a case of celphos poisoning presenting with both supraventricular tachycardia and ventricular tachycardia.

Crystal structure of benzimidazolium salicylate.

In the anion of the title mol-ecular salt, C7H7N2 (+)·C7H5O3 (-) (systematic name: 1H-benzimidazol-3-ium 2-hy-droxy-ben-zo-ate), there is an intra-molecular O-H⋯O hydrogen bond that generates an S(6) ring motif. The CO2 group makes a dihedral angle of 5.33 (15)° with its attached ring. In the crystal, the dihedral angle between the benzimidazolium ring and the anion benzene ring is 75.88 (5)°. Two cations bridge two anions via two pairs of N-H⋯O hydrogen bonds, enclosing an R (4) 4(16) ring motif, forming a four-membered centrosymmetric arrangement. These units are linked via C-H⋯O hydrogen bonds, forming chains propagating along the b-axis direction. The chains are linked by C-H⋯π and π-π inter-actions [inter-centroid distances = 3.4156 (7) and 3.8196 (8) Å], forming a three-dimensional structure.

Crystal structure of 2,5-di-methyl-anilinium salicylate.

The title mol-ecular salt, C8H12N(+)·C7H5O3 (-) arose from the proton-transfer reaction between 2,5-xylidine and salicylic acid. In the anion, the dihedral angle between the planes of the aromatic ring and the -CO2 (-) group is 11.08 (8)°; this near planarity is consolidated by an intra-molecular O-H⋯O hydrogen bond. In the crystal, the components are connected by N-H⋯O hydrogen bonds, with all three O atoms in the anion acting as acceptors; the result is a [100] chain. The structure also features weak C-H⋯O bonds and aromatic π-π stacking [centroid-to-centroid distance = 3.7416 (10) Å] inter-actions, which lead to a three-dimensional network.

Synthesis and potential cytotoxic activity of new phenanthrylphenol-pyrrolobenzodiazepines.

New phenanthrylphenol-pyrrolobenzodiazepine (PP-PBD) conjugates have been synthesized and evaluated for their biological activity. One of the compounds 4a has been evaluated for its antiproliferative activity on 57 human tumour cell lines. The growth inhibition of 4a-c has been determined by MTT viability assay on MCF-7 cell line. Among them, 4c showed most potent growth inhibition. Based on this, an attempt was made to rationalize their mechanism of action through cell cycle analysis and DNA interaction studies. The effect of the lead compound 4c on MCF-7 cell growth associated with cell cycle arrest in G1 phase, followed by apoptosis. Our findings suggested the phenanthrylphenol-PBD conjugate 4c, which is a cyclin D1 inhibitor could be considered as a promising lead compound against breast cancer for further investigation.

Solution structure of a covalently bound pyrrolo[2,1-c][1,4]benzodiazepine-benzimidazole hybrid to a 10mer DNA duplex.

A pyrrolo[2,1-c][1,4]benzodiazepine-benzimidazole hybrid (PBD-BIMZ) derived from the tricyclic anticancer PBD antibiotics can covalently bind to a guanine base at its exocyclic 2-amino group in double-helical DNA. Through the formation of stable DNA adducts, these hybrids have previously been shown to have significant anticancer activity in a number of cell lines. Here, the three-dimensional solution structure of the complex formed between the self-complementary DNA decamer 5'-AACAATTGTT-3' and PBD-BIMZ has been investigated by two-dimensional NMR spectroscopy and NOE distance restraint molecular dynamics simulations. Refinements using an explicit solvation model yielded a complex structure that is in good agreement with the NMR structural data. Successful convergence is indicated by an average mutual root-mean-square deviation of <1 A for three final representative structures selected by clustering methods from the molecular dynamics trajectories at 300 K. The ligand binds in an (11S,11aS) configuration to one of the two symmetrically located guanine bases of the duplex and is oriented with its benzimidazole moiety toward the 5'-end of the modified guanine. It is accommodated within the minor groove covering the centrally located 6 bp. Conformational and helical parameters of the DNA adduct are typical of a B-like duplex, and more significant helical distortions by the covalent binding of PBD-BIMZ are mostly confined to the covalent binding site and the junction between complexed and noncomplexed DNA segments. In contrast to the overall well-determined conformation of the bound hybrid, its terminal N-methylpiperazine ring appears to adopt various conformations associated with increased flexibility.

Synthesis of new benzimidazole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates with efficient DNA-binding affinity and potent cytotoxicity.

The synthesis of new benzimidazole linked pyrrolobenzodiazepine conjugates is described. Some of these conjugates show significant DNA-binding affinity and, a representative compound 4c shows promising in vitro cytotoxicity against a number of human cancer cell lines.

Phosphonate-linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates: synthesis, DNA-binding affinity and cytotoxicity.

Pyrrolobenzodiazepine-diethylphosphonate conjugates have been designed and synthesized that link through two different types of spacers that are simple alkane chain and also a piperazine moiety side-armed with the alkane chains. These pyrrolobenzodiazepine conjugates have exhibited remarkable DNA-binding affinity and improved solubility in water, a representative compound 7d showing promising in vitro cytotoxicity.

Virtual screening in drug discovery -- a computational perspective.

Virtual screening emerged as an important tool in our quest to access novel drug like compounds. There are a wide range of comparable and contrasting methodological protocols available in screening databases for the lead compounds. The number of methods and software packages which employ the target and ligand based virtual screening are increasing at a rapid pace. However, the general understanding on the applicability and limitations of these methodologies is not emerging as fast as the developments of various methods. Therefore, it is extremely important to compare and contrast various protocols with practical examples to gauge the strength and applicability of various methods. The review provides a comprehensive appraisal on several of the available virtual screening methods to-date. Recent developments of the docking and similarity based methods have been discussed besides the descriptor selection and pharmacophore based searching. The review touches upon the application of statistical, graph theory based methods machine learning tools in virtual screening and combinatorial library design. Finally, several case studies are undertaken where the virtual screening technology has been applied successfully. A critical analysis of these case studies provides a good platform to estimate the applicability of various virtual screening methods in the new lead identification and optimization.

Pharmacophoric 2-hydroxyalkyl benzenesulfonamide: a single-step synthesis from benzenesulfonamide via hemiaminal.

ortho-Acylation attempt of benzenesulfonamide afforded the corresponding hemiaminal as major product. The in situ reduction of the reaction mixture, reported herein, directly provided 2-hydroxyalkyl benzenesulfonamide, an important pharmacophoric element for designing drug-like scaffolds. Its application is demonstrated through designing a novel series of 1,5-diarylpyrazoles for cyclooxygenase-2 (COX-2) inhibition.

Synthesis of C8-linked pyrrolo[2,1-c][1,4]benzodiazepine-benzimidazole conjugates with remarkable DNA-binding affinity.

Two types of benzimidazoles have been synthesized and linked to DC-81 at C8-position through different alkyl chain spacers. These PBD conjugates have exhibited remarkable DNA-binding affinity, and a representative compound shows promising in vitro anticancer activity.

Synthesis of C8-linked pyrrolo[2,1-c][1,4]benzodiazepine-acridone/acridine hybrids as potential DNA-binding agents.

Pyrrolobenzodiazepine hybrids linked to acridone/acridine ring systems at C8-position have been designed and prepared that exhibit significant DNA-binding affinity, and a representative compound shows promising in vitro anticancer activity.

Synthesis and DNA binding affinity of novel A-C8/C-C2-exo unsaturated alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers.

The synthesis of novel A-C8/C-C2-exo unsaturated alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers is reported and these dimers show significant DNA binding affinity and they also exhibit moderate anticancer activity.

Synthesis of novel C2 and C2-C8 linked pyrrolo[2,1-c][1,4]benzodiazepine-naphthalimide hybrids as DNA-binding agents.

Synthesis of C2 and C2-C8 linked pyrrolobenzodiazepine-naphthalimide hybrids have been prepared that exhibit significant DNA-binding affinity and cytotoxicity.