Mutations in Zebrafish lrp2 Result in Adult-Onset Ocular Pathogenesis That Models Myopia and Other Risk Factors for Glaucoma

The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, Bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals—but not all—develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease

CaRotid Artery Filtering Technique (CRAFT): A Technique for Carotid Artery Stenting with Intrinsic Embolic Protection.

PURPOSE: Carotid artery stenting (CAS) is an established treatment for symptomatic carotid artery stenosis as an alternative to carotid endarterectomy. A variety of techniques and devices have been devised to minimise periprocedural stroke risk using either proximal or distal embolic protection. This study presents a method of embolic protection during CAS-the CaRotid Artery Filtering Technique (CRAFT). MATERIALS AND METHODS: The CRAFT technique employs aspects of both proximal and distal embolic protection. The CASPER RX stent (MicroVention, Tustin, CA, USA), which is a double-layered, closed-cell, micromesh nitinol stent, is deployed across the carotid artery stenosis with the assistance of a FlowGate balloon guide catheter (Stryker Neurovascular, Fremont, CA, USA). The partially deployed stent acts as a distal filter while the balloon guide is deflated midway during stent deployment to prevent distal plaque embolisation, followed by completion of stent deployment and angioplasty. RESULTS: A total of 94 patients underwent CAS using the CRAFT technique between June 2016 and March 2021. Successful stent deployment was achieved in all patients. Preliminary results demonstrated acute stent occlusion in 6 patients (6.4%) and distal embolic stroke in 5 patients (5.3%). The median procedural fluoroscopy time was 34 minutes with an interquartile range of 22 to 55 minutes. CONCLUSION: The CRAFT technique of CAS presented by this study can be applied in the treatment of symptomatic carotid artery stenosis in both emergency and elective procedure settings with a high technical success and low distal embolic stroke risk

Synthesis of 3-(6-aryl-pyridin-2-yl)- and 8-(6-aryl-pyridin-2-yl) coumarins

869-871Mannich bases of 3-acetyl coumarin 1 and 4-methyl-7-methoxy-8-acetyl coumarin 4 on reaction with substituted phenacyl bromide pyridinium salts 2a-f in the presence of ammonium acetate in refluxing acetic acid afford the title 3-(6-aryl-pyridin-2-yl)- and 8-(6-aryl-pyridin-2-yl) coumarins (3a-f and 5a-f) in moderate to good yields

Efficiency Based Evaluation of Public Transport and Paratransit Systems with a View to Integrating Transportation

Rapid urbanization, increasing population, and a booming economy have stimulated growth in Indian cites, resulting in higher levels of dependence on private vehicles. This has raised serious issues over the sustainability of transport infrastructure in cities. Public transportation (PT) systems can help achieve sustainable transportation. But they face competition from intermediate public transport (IPT) or Paratransit. The existing PT and IPT systems, therefore, need to re-plan their operations to complement each other and deliver a wider network of services. To achieve this, an evaluation of both PT and IPT systems at microscopic levels is needed to facilitate their possible integration in a coordinated multimodal transportation system. The present paper attempts to evaluate the public and paratransit systems in the city of Surat in the Indian state of Gujarat using a data envelopment analysis (DEA) technique in DEAP software at the individual and system level. The operations, route design, and cost efficiency of both systems are evaluated to understand how well the existing set-up caters to demand. The arithmetic mean of operations, route design, and cost efficiencies of 26 routes of PT system were worked out to be 0.89, 0.94, and 0.69, while that of the 13 routes of the IPT system were 0.92, 0.97, and 0.88 respectively. The system investigation shows that analytically, only 8% of IPT routes were inefficient in all the three aspects, compared with 42% of PT routes. The performance of each route was analyzed, appropriate suggestions made, and the potential of these systems for designing an integrated transport system highlighted