Sensitivity and specificity of teachers for vision screening among primary school children in South India.

AIMS: This study aims to determine the sensitivity and specificity of vision screening by school teachers among primary school children. SETTINGS AND DESIGN: Prospective nonrandomized clinical trial. SUBJECTS AND METHODS: The study was carried in primary school children of Madurai, Tamil Nadu from April 2007 to October 2007. Sixty-five primary school teachers from 57 schools around Madurai, Tamil Nadu, India, underwent a half-day training programme at the hospital. Each teacher on return to the school screened around a hundred children using the tumbling E. All screened children were subsequently screened by a team from the hospital. The optometrists used tumbling E (Snellen's 20/30 and Early Treatment of Diabetic Retinopathy Study (ETDRS) 20/32) to check the vision of all children. Any child complaining of defective vision or noted to have defective vision on screening underwent a comprehensive ophthalmic evaluation. The sensitivity and specificity of teacher screening was assessed based on the data obtained. RESULTS: Screening was completed for 5150 children. The prevalence of vision <20/30 was 2.82%. Teacher screening was noted to have a sensitivity of 24.8% and a specificity of 98.65%. Tumbling E ETDRS screening by the optometrist had the highest sensitivity of 94.48% and specificity of 97.09%. CONCLUSIONS: Our study shows that vision screening by trained optometrists is a very useful tool to identify visual impairment in primary school children. Measures need to be taken to improve the sensitivity of teacher screening before recommending its generalized use.

Outcome of delayed adjustable strabismus surgery in children using a bow-tie optional adjustable technique.

PURPOSE: The aim of this article is to study the feasibility of a delayed adjustable technique of strabismus surgery in children using an optional adjustable suture technique. METHODS: The retrospective study included patients <12 years of age. Recessions were done using an optional adjustable bow-tie technique and resections were done by the conventional technique. Patients were evaluated on the third postoperative day and adjustments done when needed. Statistical analysis was done using Microsoft Excel 2010®. RESULTS: The study included 11 patients with exotropia and 16 patients with esotropia. The mean age of the patients was 5.2 years (range 1-11 years). The mean preoperative distance deviation was 46.7 ± 10.4 prism diopters (PD) for exotropic patients and 47.1 ± 16.9 PD for esotropic patients. The mean preoperative near deviation was 46.6 ± 11 PD for exotropic patients and 52.4 ± 17.1 PD for esotropia. Two patients with exotropia (18.2%) and four patients with esotropia (25%) were adjusted under intravenous ketamine in the operating room under anesthetist supervision. No difficulty was encountered in advancing/recessing the muscles. The success rate at 1 month was 100% for exotropia and 87.5% for esotropia. The success rate at the final follow-up was 81.8% for patients with exotropia and 68.7% for patients with esotropia. CONCLUSIONS: This delayed optional adjustable strabismus surgery technique provides good short-term results and lower adjustment rates.

Safety and efficacy of radial versus femoral access for rotational Atherectomy: A systematic review and meta-analysis.

INTRODUCTION: Over the recent years, there has been increased interest in the use of transradial (TR) access for percutaneous coronary intervention (PCI), including rotational atherectomy (RA). However, a large proportion of operators seem to be reluctant to use TR access for complex PCI including rotational atherectomy for heavily calcified coronary lesions. METHODS: We searched MEDLINE, ClinicalTrials.gov and the Cochrane Library for studies comparing radial versus femoral access in patients undergoing RA. Studies were included if they reported at least one of the following outcomes in each group separately: major adverse cardiac events (MACE), major bleeding, stent thrombosis, myocardial infarction (MI), hospital length of stay, radiation exposure, procedure time, procedure success and all-cause mortality. Odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) were calculated and a p-value of <0.05 was considered as a level of significance. RESULTS: This meta-analysis included 5 retrospective studies with 3315 patients undergoing RA via radial access and 5838 patients via femoral access. Radial access was associated with lower major access site bleeding (OR: 0.45, 95% CI: 0.31-0.67, p < 0.001), and radiation exposure (MD: -16.1, 95%CI: -25.4--6.7 Gy cm2, p = 0.0007). There were no significant differences observed in all-cause in-hospital mortality (OR: 0.92, 95% CI: 0.69-1.23, p = 0.58); MACE (OR: 0.80, CI: 0.63, 1.02, p = 0.08), stent thrombosis (OR: 0.28, 95%CI: 0.06-1.33 p = 0.11); and MI (OR: 0.43, 95%CI: 0.15-1.24, p = 0.12). There were no significant differences in hospital stay, procedure time or procedure success between the two groups (p > 0.05). CONCLUSION: This meta-analysis of 9153 patients from observational studies demonstrates similar all-cause mortality, MACE, procedural success and procedural time during RA performed using TR access and TF access. However, TR access was associated with decreased access site bleeding and radiation exposure. Given the observational nature of these findings, a randomized controlled trial is warranted for further evidence.

Surface topography of polylactic acid nanofibrous mats: influence on blood compatibility.

Fabricating nanofibrous scaffolds with robust blood compatibility remains an unmet challenge for cardiovascular applications since anti-thrombogenic surface coatings did not withstand physiological shear force. Hence, the present study envisages the influence of smooth and porous topographies of poly(lactic acid) (PLA) nanofibers on hemocompatibility as it could offer time-independent blood compatibility. Further, recent studies have evolved to integrate various contrasting agents for augmenting the prognostic properties of tissue engineered scaffolds; an attempt was also made to synthesize Curcumin-superparamagnetic iron oxide nanoparticle complex (Cur-SPION) as a contrasting agent and impregnated into PLA nanofibers for evaluating the blood compatibility. Herein, electrospun nanofibers of PLA with different topographies (smooth and porous) were fabricated and characterized for surface morphology, zeta potential, fluorescence, and crystallinity. The scaffolds with smooth, porous and rough surface topographies were thoroughly investigated for its hemocompatibility by evaluating hemolysis percentage, platelet adhesion, in vitro kinetic clotting time, serum protein adsorption, plasma recalcification time (PRT), capture and release of erythrocytes. Although the nanofibers of all three groups showed acceptable hemolytic percentage (HP < 5%), the adhered RBCs on Cur-SPION based fibers undergo morphological transformation from biconcave discocytes to echinocytes with cube-like protrusions. On the contrary, no morphological changes were observed in RBCs cultured on smooth and porous nanofibers. Porous fibers exhibited excellent anti-thrombogenic property and adhered lesser platelets and maintained the discoidal morphology of native platelets. Cur-SPION integrated PLA nanofibers showed inactivated platelets with anti-thrombogenic activity compared to smooth nanofibers. In conclusion, PLA nanofibers porous topography did not affect the RBC membrane integrity and maintained discoidal morphology of platelets with superior anti-thrombogenic activity. However, smooth and Cur-SPION integrated PLA nanofibers were found to activate the platelets and deform the RBC membrane integrity, respectively. Hence, the nanofibers with porous structures provide an ideal topography for time-independent hemocompatibility.

New Algorithm for the Prediction of Cardiovascular Risk in Symptomatic Adults with Stable Chest Pain.

PURPOSE OF REVIEW: To review the landmark studies in predicting obstructive coronary artery disease (CAD) in symptomatic patients with stable chest pain and identify better prediction tools and propose a simplified algorithm to guide the health care providers in identifying low risk patients to defer further testing. RECENT FINDINGS: There are a few risk prediction models described for stable chest pain patients including Diamond-Forrester (DF), Duke Clinical Score (DCS), CAD Consortium Basic, Clinical, and Extended models. The CAD Consortium models demonstrated that DF and DCS models overestimate the probability of CAD. All CAD Consortium models performed well in the contemporary population. PROMISE trial secondary data results showed that a clinical tool using readily available ten very low-risk pre-test variables could discriminate low-risk patients to defer further testing safely. In the contemporary population, CAD Consortium Basic or Clinical model could be used with more confidence. Our proposed simple algorithm would guide the physicians in selecting low risk patients who can be managed conservatively with deferred testing strategy. Future research is needed to validate our proposed algorithm to identify the low-risk patients with stable chest pain for whom further testing may not be warranted.

Situational Restriction of Elevation in Adduction Relieved by Faden on the Medial Rectus.

We describe a patient with situational restriction of elevation in adduction in his left eye. Clinical examination pointed to instability of the left medial rectus pulley. This was corrected by Faden on the medial rectus. The importance of this relatively new concept in identifying and treating orbital pulley instability is discussed.

Discovery of 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one (7ao) as a potent selective inhibitor of Polo like kinase 2 (PLK2).

Several families of protein kinases have been shown to play a critical role in the regulation of cell cycle progression, particularly progression through mitosis. These kinase families include the Aurora kinases, the Mps1 gene product and the Polo Like family of protein kinases (PLKs). The PLK family consists of five members and of these, the role of PLK1 in human cancer is well documented. PLK2 (SNK), which is highly homologous to PLK1, has been shown to play a critical role in centriole duplication and is also believed to play a regulatory role in the survival pathway by physically stabilizing the TSC1/2 complex in tumor cells under hypoxic conditions. As a part of our research program, we have developed a library of novel ATP mimetic chemotypes that are cytotoxic against a panel of cancer cell lines. We show that one of these chemotypes, the 6-arylsulfonyl pyridopyrimidinones, induces apoptosis of human tumor cell lines in nanomolar concentrations. The most potent of these compounds, 7ao, was found to be a highly specific inhibitor of PLK2 when profiled against a panel of 288 wild type, 55 mutant and 12 lipid kinases. Here, we describe the synthesis, structure activity relationship, in vitro kinase specificity and biological activity of the lead compound, 7ao.

Recurrent spontaneous coronary artery dissection: First case report in men with three episodes of spontaneous coronary dissection in separate vascular territories.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. In the literature, more than 1,200 cases of SCAD have been reported, with a low rate of recurrent spontaneous coronary artery dissection (r-SCAD) described in only 63 cases. Among these patients with r-SCAD, just three cases had three separate episodes of dissection and all were in women. We report the first case of r-SCAD in men, with three episodes of dissection in different coronary arteries and review the published literature on predisposing factors for r-SCAD and its management.

Visual outcome and incidence of glaucoma in patients with microspherophakia.

INTRODUCTION: A number of ocular complications have been reported in microspherophakia. The literature however is limited to small case reports and the incidence of these complications is largely unknown. Our study describes a series of patients who presented to our hospital from 1998 to 2008. MATERIAL AND METHODS: Data on the clinical and surgical findings of patients presented to us from 1998 to 2008 with microspherophakia were retrieved from the medical records and the results analyzed. RESULTS: Thirty-six eyes of 18 patients were reviewed. The mean age at presentation was 16±10 years. All patients had varying degrees of lenticular myopia with a mean of -11.07±5.03 D. Glaucoma developed in 16 eyes (44.4%). Half of them had high IOP at presentation. Despite medical and surgical management IOP remained high in five eyes at the last follow-up. Sixteen eyes (44.4%) required lensectomy for dislocated crystalline lens. Lensectomy did not have any impact on the intraocular pressures. Homocysteinuria was the most common systemic association noted. CONCLUSION: Microspherophakia is associated with a high incidence of lenticular myopia, subluxation of the crystalline lens and glaucoma. Management of glaucoma is difficult with the IOP remaining high in spite of combined medical and surgical management.

Discovery of 8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a potent inhibitor of cyclin-dependent kinase 4 (CDK4) and AMPK-related kinase 5 (ARK5).

The success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for developing multikinase inhibitors with low toxicity profiles. With this goal in mind, we analyzed more than 150 novel cyano pyridopyrimidine compounds and identified structure-activity relationship trends that can be exploited in the design of potent kinase inhibitors. One compound, 8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x), was found to be the most active, inducing apoptosis of tumor cells at a concentration of approximately 30-100 nM. In vitro kinase profiling revealed that 7x is a multikinase inhibitor with potent inhibitory activity against the CDK4/CYCLIN D1 and ARK5 kinases. Here, we report the synthesis, structure-activity relationship, kinase inhibitory profile, in vitro cytotoxicity, and in vivo tumor regression studies by this lead compound.

Oral epithelial cells transplanted on to corneal surface tend to adapt to the ocular phenotype.

To understand the response of oral epithelial cells, transplanted on corneal surface to the ocular cues in vivo. The corneal button obtained after penetrating keratoplasty (PK) of an eye of a patient with total limbal stem cell deficiency (LSCD), previously treated with cultured oral mucosal epithelial transplantation (COMET) was examined by immunohistochemistry for the expression of keratins, p63, p75, PAX6, Ki-67, CD31, and CD34. COMET followed by optical-PK has improved visual acuity to 20/40 and rendered a stable ocular surface. The excised corneal tissue showed the presence of stratified epithelium with vasculatures. The epithelial cells of the corneal button expressed K3, K19, Ki-67, p63, p75 and the cornea-specific PAX6 and K12. This study confirms that the oral cells, transplanted to corneal surface, survive and stably reconstruct the ocular surface. They maintain their stemness at the ectopic site and acquire some of the corneal epithelial-like characters.

Cataract surgery in juvenile xanthogranuloma: case report and a brief review of literature.

There is limited literature on the management of cataracts in juvenile xanthogranuloma (JXG). A 2-month-old girl presented to us with hyphema, secondary glaucoma OU and skin nodules suggestive of JXG. She developed bilateral cataracts during her follow-up and was treated successfully with cataract surgery and aphakic rehabilitation.

Design, synthesis, and biological evaluation of (E)-N-aryl-2-arylethenesulfonamide analogues as potent and orally bioavailable microtubule-targeted anticancer agents.

A series of novel (E)-N-aryl-2-arylethenesulfonamides (6) were synthesized and evaluated for their anticancer activity. Some of the compounds in this series showed potent cytotoxicity against a wide spectrum of cancer cell-lines (IC50 values ranging from 5 to 10 nM) including all drug resistant cell-lines. Nude mice xenograft assays with compound (E)-N-(3-amino-4-methoxyphenyl)-2-(2',4',6'-trimethoxyphenyl)ethenesulfonamide (6t) showed dramatic reduction in tumor size, indicating their in vivo potential as anticancer agents. A preliminary drug development study with compound 6t is predicted to have increased blood-brain barrier permeability relative to many clinically used antimitotic agents. Mechanistic studies indicate that 6t and some other analogues disrupted microtubule formation, formation of mitotic spindles, and arrest of cells in mitotic phase. Compound 6t inhibited purified tubulin polymerization in vitro and in vivo and circumvented drug resistance mediated by P-glycoprotein. Compound 6t specifically competed with colchicine binding to tubulin and with similar avidity as podophylltoxin, indicating its binding site on tubulin.

Hydrothiolation of benzyl mercaptan to arylacetylene: application to the synthesis of (E) and (Z)-isomers of ON 01910·Na (Rigosertib®), a phase III clinical stage anti-cancer agent.

A stereoselective and efficient method for free radical addition of benzyl thiol to aryl acetylene in the presence of Et3B-hexane has been developed for the synthesis of (Z) and (E)-styryl benzyl sulfides where base catalyzed hydrothiolations have failed. The scope of this reaction was successfully extended for the synthesis of (E)-ON 01910·Na, a phase III clinical stage anti-cancer agent and its inactive geometrical isomer (Z)-ON 01910·Na. It is interesting to note that all the E-isomers synthesized have shown better cytotoxicity profile on cancer cells compared to the Z-isomers.

(Z)-1-aryl-3-arylamino-2-propen-1-ones, highly active stimulators of tubulin polymerization: synthesis, structure-activity relationship (SAR), tubulin polymerization, and cell growth inhibition studies.

Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for antiproliferative activity in cell-based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI(50) values. Flow cytometry studies showed that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M block, these compounds caused microtubule stabilization like paclitaxel and induced apoptosis via activation of the caspase family. The observations made in this investigation demonstrate that (Z)-1-Aryl-3-arylamino-2-propen-1-one (10) represents a new class of microtubule-stabilizing agents.