Gift of Vision - Doorstep-to-Doorstep Outreach Eye Care Model, Sankara Model of Accessible and Affordable Eye Care, and its Impact on the Elderly.

SUMMARY: Vision loss among the elderly is a major health-care problem. Vision impairment is associated with a decreased ability to perform activities of daily living and an increased risk for depression. Cataract is a common cause of vision impairment among the elderly, but surgery is often effective in restoring vision. We describe the Sankara model of Gift of Vision, the doorstep-to-doorstep model of community eye care that offers high quantity-high-quality eye care. Our model demonstrates how a cost-effective one-time intervention such as a cataract surgery not only restores vision but also their quality of life.

Automated image quality appraisal through partial least squares discriminant analysis.

PURPOSE: Automatic retinal fundus image quality analysis is one of the most essential preliminary stages in automatic computer-aided retinal disease diagnosis system, which allows good-quality fundus images for accurate disease prediction through localization and segmentation of retinal regions. This paper presents new feature extraction methods using full-reference and no-reference image quality metrics for image quality classification. METHODS: Basic image features, reference and no-reference features are extracted from the fundus image and applied through different classification techniques to determine the image quality for further diagnosis. In this paper, human-made categorization including good and non-good-quality fundus image classification is constructed by considering major features of retinal fundus images are illumination, clarity, image intensity, contrast and region visibility. The proposed system presented fundus image quality classification by automatic extraction of features from fundus images through image processing techniques and automatic classification of image quality through different classification algorithm. RESULTS: This system was thoroughly investigated on 2674 retinal fundus images from publically available datasets, namely MESSIDOR, Drishti-GS1, DRIVE, HRF, DRIONS-DB, DIARETDB0, DIARETDB1, IDRiD, INSPIRE-AVR, CHASE-DB1, ONHSD, DRIMDB and e-ophtha-EX with better performance results in terms of sensitivity, accuracy, precision and F1 score of 99.36%, 96.79%, 96.29% and 97.79%, respectively. CONCLUSION: The proposed system results were compared to the existing state-of-the-art approaches and outperform existing methods for image quality assessment representing the efficiency and robustness of our system is most suitable for automatic image analysis during retinal disease diagnosis.

Detection of Wolbachia Phage (WO) in Indian Lac Insect [Kerria lacca (Kerr.)] and Its Implications.

Wolbachia, a maternally inherited bacterium induces reproductive alterations in its hosts such as feminization of males, male killing and parthenogenesis. It is the most diverse endosymbiont infecting more than 70% of the insects ranging from pests to pollinators. Kerria lacca-a hemipteran is a sedentary, oriental insect known to produce lac-the only resin of animal origin. The present study was conducted to screen the presence of Wolbachia and its associated phages in the two infrasubspecific forms (four insect lines) of K. lacca viz. kusmi and rengeeni differing from each other on the basis of host preference. Wolbachia and its associated phage were found to be prevalent in all the insect lines analyzed. We, hereby, report the presence of WO-phage (Wolbachia phage) for the first time in K. lacca. Further, phylogenetic data differentiated the kusmi and rengeeni infrasubspecific forms into two different groups on the basis of WO-phage sequences.

Free volume study on the origin of dielectric constant in a fluorine-containing polyimide blend: poly(vinylidene fluoride-co-hexafluoro propylene)/poly(ether imide).

The dielectric constant of fluorinated polymides, their blends, and composites is known to decrease with the increase in free volume due to a decrease in the number of polarizable groups per unit volume. Herein, we report an interesting finding on the origin of dielectric constant in a polymer blend prepared using a fluorine-containing polymer and a polyimide probed in terms of its available free volume, which is distinct from the generally observed behavior in fluorinated polyimides. For this study, a blend of poly(vinylidene fluoride-co-hexafluoro propylene) and poly(ether imide) was chosen and the interaction between them was studied using FTIR, XRD, TGA, and SEM. The blend was investigated by positron annihilation lifetime spectroscopy (PALS), Doppler broadening (DB), and dielectric analysis (DEA). With the increase in the free volume content in the blend, surprisingly, the dielectric constant also increases and is attributed to additional space available for the polarizable groups to orient themselves to the applied electric field. The results obtained would pave the way for more effective design of polymeric electrical charge storage devices.

Best practices for the development, scale-up, and post-approval change control of IR and MR dosage forms in the current quality-by-design paradigm.

In this whitepaper, the Manufacturing Technical Committee of the Product Quality Research Institute provides information on the common, best practices in use today in the development of high-quality chemistry, manufacturing and controls documentation. Important topics reviewed include International Conference on Harmonization, in vitro-in vivo correlation considerations, quality-by-design approaches, process analytical technologies and current scale-up, and process control and validation practices. It is the hope and intent that this whitepaper will engender expanded dialog on this important subject by the pharmaceutical industry and its regulatory bodies.

Prediction of cancer rescue p53 mutants in silico using Naïve Bayes learning methodology.

This research is focussed on predicting through Naïve Bayes learning, the possible p53 rescue mutants from amino-acid substitutions at the second, third and fourth site recombination that could reinstate normal p53 activity. The Naïve Bayes probability values of the amino-acid substitutions at the respective site-wise recombination were utilized to formulate the proposed Genetic Mutant Marker Extraction (GMME) technique that could unearth the hot spot cancer, strong rescue and weak rescue mutants. The p53 mutation records depicting the amino-acid substitutions obtained by yeast assays comprising of nearly 16,700 records, available at the University of California, Machine Learning Repository, were utilized as the training dataset for the GMME technique. The proposed GMME technique revealed the hot spot cancer mutants, strong rescue and weak rescue mutants leading to the detection of probable genetic markers for Cancer prediction from the surface regions 96-289 constituting the second, third and fourth site recombinations. Thus far, computational approaches have been able to predict rescue markers at region-specific mutations (96-105, 114-123, 130-156 and 223- 232) with respect to the second site recombination for three hot spot cancer mutants only viz, P152L, R158L and G245S. The GMME technique aimed at predicting possible rescue markers for p53 mutants at the second, third and fourth site recombinations revealing novel rescue markers for fourteen hot spot cancer mutants. Moreover, the GMME technique can be extended effectively to increasing number of recombinant sites that can be efficiently utilized to predict novel rescue markers.

Improved classification of lung cancer tumors based on structural and physicochemical properties of proteins using data mining models.

Detecting divergence between oncogenic tumors plays a pivotal role in cancer diagnosis and therapy. This research work was focused on designing a computational strategy to predict the class of lung cancer tumors from the structural and physicochemical properties (1497 attributes) of protein sequences obtained from genes defined by microarray analysis. The proposed methodology involved the use of hybrid feature selection techniques (gain ratio and correlation based subset evaluators with Incremental Feature Selection) followed by Bayesian Network prediction to discriminate lung cancer tumors as Small Cell Lung Cancer (SCLC), Non-Small Cell Lung Cancer (NSCLC) and the COMMON classes. Moreover, this methodology eliminated the need for extensive data cleansing strategies on the protein properties and revealed the optimal and minimal set of features that contributed to lung cancer tumor classification with an improved accuracy compared to previous work. We also attempted to predict via supervised clustering the possible clusters in the lung tumor data. Our results revealed that supervised clustering algorithms exhibited poor performance in differentiating the lung tumor classes. Hybrid feature selection identified the distribution of solvent accessibility, polarizability and hydrophobicity as the highest ranked features with Incremental feature selection and Bayesian Network prediction generating the optimal Jack-knife cross validation accuracy of 87.6%. Precise categorization of oncogenic genes causing SCLC and NSCLC based on the structural and physicochemical properties of their protein sequences is expected to unravel the functionality of proteins that are essential in maintaining the genomic integrity of a cell and also act as an informative source for drug design, targeting essential protein properties and their composition that are found to exist in lung cancer tumors.

Prediction of P53 mutants (multiple sites) transcriptional activity based on structural (2D&3D) properties.

Prediction of secondary site mutations that reinstate mutated p53 to normalcy has been the focus of intense research in the recent past owing to the fact that p53 mutants have been implicated in more than half of all human cancers and restoration of p53 causes tumor regression. However laboratory investigations are more often laborious and resource intensive but computational techniques could well surmount these drawbacks. In view of this, we formulated a novel approach utilizing computational techniques to predict the transcriptional activity of multiple site (one-site to five-site) p53 mutants. The optimal MCC obtained by the proposed approach on prediction of one-site, two-site, three-site, four-site and five-site mutants were 0.775,0.341,0.784,0.916 and 0.655 respectively, the highest reported thus far in literature. We have also demonstrated that 2D and 3D features generate higher prediction accuracy of p53 activity and our findings revealed the optimal results for prediction of p53 status, reported till date. We believe detection of the secondary site mutations that suppress tumor growth may facilitate better understanding of the relationship between p53 structure and function and further knowledge on the molecular mechanisms and biological activity of p53, a targeted source for cancer therapy. We expect that our prediction methods and reported results may provide useful insights on p53 functional mechanisms and generate more avenues for utilizing computational techniques in biological data analysis.

Three new species of Kerria (Hemiptera: Coccoidea: Tachardiidae) from India.

Three new species of Kerria Targioni-Tozzetti from India, namely Kerria pennyae Ahmad & Ramamurthy sp. nov. on Schleichera oleosa from Orissa, Kerria dubeyi Ahmad & Ramamurthy sp. nov. on Ficus bengalensis from Bangalore and Kerria varshneyi Ahmad & Ramamurthy sp. nov. on Ziziphus mauritiana from Punjab are described and illustrated, and a key is provided to species of Kerria known from India.

Three new species of Kerria (Hemiptera: Sternorrhyncha: Coccoidea: Tachardiidae), a redesciption of K. yunnanensis Ou & Hong, and a revised key to species of Kerria.

Three new species of lac insect, Kerria Targioni-Tozzetti viz., Kerria manipurensis Ahmad & Ramamurthy sp. nov., Kerria maduraiensis Ahmad & Ramamurthy sp. nov., and Kerria thrissurensis Ahmad & Ramamurthy sp. nov. are described and illustrated. Kerria yunnanensis Ou & Hong is illustrated and redescribed, and a key to the known species of Kerria is provided. The usefulness of star pores as a diagnostic character in the subgeneric divisions of Kerria is also discussed.

Genotype-phenotype studies of VCP-associated inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia.

Valosin containing protein (VCP) disease associated with inclusion body myopathy, Paget disease of the bone and frontotemporal dementia is a progressive autosomal dominant disorder caused by mutations in Valosin containing protein gene. To establish genotype-phenotype correlations we analyzed clinical and biochemical markers from a database of 190 members in 27 families harboring 10 missense mutations. Individuals were grouped into three categories: symptomatic, presymptomatic carriers and noncarriers. The symptomatic families were further divided into ten groups based on their VCP mutations. There was marked intra and inter-familial variation; and significant genotype-phenotype correlations were difficult to establish because of small numbers. Nevertheless when comparing the two most common mutations, R155C mutation was found to be more severe, with an earlier onset of myopathy and Paget (p = 0.03). Survival analysis of all subjects revealed an average life span after diagnosis of myopathy and Paget of 18 and 19 years respectively, and after dementia only 6 years. R155C had a reduced survival compared to the R155H mutation (p = 0.03).We identified amyotrophic lateral sclerosis (ALS) was diagnosed in 13 individuals (8.9%) and Parkinson's disease in five individuals (3%); however, there was no genotypic correlation. This study represents the largest dataset of patients with VCP disease and expands our understanding of the natural history and provides genotype-phenotype correlations in this unique disease.

Comparison of the Sensititre YeastOne colorimetric antifungal panel with CLSI microdilution for antifungal susceptibility testing of the echinocandins against Candida spp., using new clinical breakpoints and epidemiological cutoff values.

A commercially prepared dried colorimetric microdilution panel (Sensititre Yeast One, TREK Diagnostic Systems, Cleveland, OH, USA) was compared in 3 different laboratories with the Clinical and Laboratory Standards Institute (CLSI) reference microdilution method by testing 2 quality control strains, 25 reproducibility strains, and 404 isolates of Candida spp. against anidulafungin, caspofungin, and micafungin. Reference CLSI BMD MIC end points and YeastOne colorimetric end points were read after 24 h of incubation. Excellent (100%) essential agreement (within 2 dilutions) between the reference and colorimetric MICs was observed. Categorical agreement (CA) between the 2 methods was assessed using the new species-specific clinical breakpoints (CBPs): susceptible (S), ≤0.25 µg/mL; intermediate (I), 0.5 µg/mL; and resistant (R), ≥1 µg/mL, for C. albicans, C. tropicalis, and C. krusei, and ≤2 µg/mL (S), 4 µg/mL (I), and ≥8 µg/mL (R) for C. parapsilosis and all 3 echinocandins. The new CBPs for anidulafungin and caspofungin and C. glabrata are ≤0.12 µg/mL (S), 0.25 µg/mL (I), and ≥0.5 µg/mL (R), whereas those for micafungin are ≤0.06 µg/mL (S), 0.12 µg/mL (I), and ≥0.25 µg/mL (R). Due to the lack of CBPs for any of the echinocandins and C. lusitaniae, the epidemiological cutoff values (ECVs) were used for this species to categorize the isolates as wild-type (WT; MIC ≤ECV) and non-WT (MIC >ECV), respectively, for anidulafungin (≤2 µg/mL/>2 µg/mL), caspofungin (≤1 µg/mL/>1 µg/mL), and micafungin (≤0.5 µg/mL/>0.5 µg/mL). CA ranged from 93.6% (caspofungin) to 99.6% (micafungin) with less than 1% very major or major errors. The YeastOne colorimetric method remains comparable to the CLSI BMD reference method for testing the susceptibility of Candida spp. to the echinocandins when using the new (lower) CBPs and ECVs. Further study using defined fks mutant strains of Candida is warranted.

Mouthparts and stylet penetration of the lac insect Kerria lacca (Kerr) (Hemiptera:Tachardiidae).

Hitherto less known aspects on mouthpart morphology and penetration mechanism of the lac insect Kerria lacca have been explored. Unique details of the mouthparts, i.e. morphology of labium and stylets and salivary sheath have been brought out. The gross morphology of the mouthparts though resembled other plant sucking homopterans; a two-segmented labium with symmetrically distributed six pairs of contact-chemoreceptors on its surface was distinct; the mandibular stylets had serrations on its extreme apical region, while the maxillary stylets had their external surface smooth with parallel longitudinal grooves on their inner surface. Formation of flanges, salivary sheath and penetration pathway observed along with probing and penetration of the stylets intracellularly up to the phloem cells, as illustrated herein, are the addition to the existing knowledge on the structural details of the mouthparts and the feeding behavior thereupon.

Clinical evaluation of the Sensititre YeastOne colorimetric antifungal panel for antifungal susceptibility testing of the echinocandins anidulafungin, caspofungin, and micafungin.

A commercially prepared, dried colorimetric microdilution panel (Sensititre YeastOne Trek Diagnostic Systems, Cleveland, OH) was compared in three different laboratories with the Clinical and Laboratory Standards Institute (CLSI) reference microdilution method by testing 2 quality control strains, 25 reproducibility strains, and 404 isolates of Candida spp. against anidulafungin, caspofungin, and micafungin. Reference MIC endpoints and YeastOne colorimetric endpoints were read after 24 h of incubation. YeastOne endpoints were determined to be the lowest concentration at which the color in the well changed from red (positive, indicating growth) to blue (negative, indicating no growth). Excellent essential agreement (within 2 dilutions) between the reference and colorimetric MICs was observed. Overall agreement was 100% for all three agents. Categorical agreement ranged from 99.3% (anidulafungin) to 100% (caspofungin, micafungin) and interlaboratory reproducibility was 99%. The YeastOne colorimetric method appears to be comparable to the CLSI reference method for testing the susceptibility of Candida spp. to the echinocandins anidulafungin, caspofungin, and micafungin.

Low effluent nutrient technologies for wastewater treatment.

The USEPA (2001) water quality nutrient criteria will have a significant impact on water pollution control industry due to stringent N and P requirements. This paper presents an update of findings on successful total N (TN) and total P (TP) technologies being implemented at existing wastewater treatment plants (WWTP) to achieve low TN and TP effluents and some key challenges in achieving lower levels. Plants consistently achieving <5 mg TN/L and < 0.5 mg TP/L were identified from a worldwide literature search and plant data collection. Technology gaps and research needs to improve successful technologies to achieve very low TN and TP effluents are summarised in this paper. The dissolved and colloidal organic N have been identified as major challenges in achieving very low levels of TN. Technical and economic challenges to achieve very low TP effluents include alkalinity deficiency, high chemical usage, high sludge production and lack of sufficient influent BOD for biological P uptake.

Synthesis and anti-inflammatory activity of a series of N-substituted naproxen glycolamides: nitric oxide-donor naproxen prodrugs.

A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b, 5a, 5b, 7b, and 7c exhibited anti-inflammatory activity equivalent to that of the parent NSAID, naproxen-Na, in the rat carrageenan paw edema model. At equimolar doses relative to naproxen-Na, the NO-donor glycolamide derivatives 4a, 4b, 5a, 5b, 7b, and 7c were gastro-sparing in the rat. Naproxen formation from these NO-donor glycolamides varied among the structures examined, with the N-substituent on the amide group having a particular influence, and demonstrated their prodrug nature. Compound 7b was selected for exemplary demonstration that the glycolamide nitrates can be bioactivated to release NO. These data open the possibility that naproxen glycolamide nitrates may represent a safer alternative to naproxen as anti-inflammatory medicines.

Free volume study on calcification process in an intraocular lens after cataract surgery.

An opacified intraocular lens explanted from a patient in the postoperative period after phacoemulsification was investigated to find the cause of opacification. From the UV-visible and energy dispersive X-ray spectroscopy (EDS) measurements, the opacification in the present case seems to be due to calcification of the intraocular lens and not due to modification in the UV absorber material of the lens. The average free volume size of the intraocular lens both in unimplanted and explanted state were obtained from positron lifetime spectroscopy (PLS). Further, the combined FTIR and PLS results indicate that calcium gets into the free volume cavities of the intraocular lens matrix as a cationic moiety, may be in the form of Ca(++). The small decrease in glass transition temperature of the calcified lens seems to indicate the plasticizing action of calcium ions. The present results could be of some use in the design of the intraocular lens material in which calcification would be minimum.

3-(2-Methoxytetrahydrofuran-2-yl)pyrazoles: a novel class of potent, selective cyclooxygenase-2 (COX-2) inhibitors.

A series of 3-(2-methoxytetrahydrofuran-2-yl)pyrazoles (4-10) was synthesized. The compounds were evaluated for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activity in human whole blood (HWB). The compound, 5-(4-methanesulfonylphenyl)-3-(2-methoxytetrahydrofuran-2-yl)-1-p-tolyl-1H-pyrazole 5 showed potent and selective COX-2 inhibition (IC50 for COX-1: >100 microM and COX-2: 1.2 microM).

Synthesis and selective cyclooxygenase-2 inhibitory activity of a series of novel, nitric oxide donor-containing pyrazoles.

The synthesis of a series of novel pyrazoles containing a nitrate (ONO(2)) moiety as a nitric oxide (NO)-donor functionality is reported. Their COX-1 and COX-2 inhibitory activities in human whole blood are profiled. Our data demonstrate that pyrazole ring substituents play an important role in COX-2 selective inhibition, such that a cycloalkyl pyrazole (6b) was found to be a potent and selective COX-2 inhibitor. Other modifications at the 3 position of the central pyrazole ring (17b, 23b, 26b-I) enhanced COX-2 inhibitory potency. Among the pyrazoles synthesized, the oxime (23b) was identified as the most potent COX-2 selective inhibitor. Accordingly, 23b was profiled pharmacologically in the rat after oral administration and shown to possess potent antiinflammatory activity in the carrageenan-induced air-pouch model and less gastric toxicity than a standard COX-2 inhibitor when administered with background aspirin treatment. We suggest that the enhanced gastric tolerance of an NO-donor COX-2 selective inhibitor has the potential to augment the clinical profile of this drug class.