Inhibition of Mg2+ binding and DNA religation by bacterial topoisomerase I via introduction of an additional positive charge into the active site region

Among bacterial topoisomerase I enzymes, a conserved methionine residue is found at the active site next to the nucleophilic tyrosine. Substitution of this methionine residue with arginine in recombinant Yersinia pestis topoisomerase I (YTOP) was the only substitution at this position found to induce the SOS response in Escherichia coli. Overexpression of the M326R mutant YTOP resulted in ∼4 log loss of viability. Biochemical analysis of purified Y. pestis and E. coli mutant topoisomerase I showed that the Met to Arg substitution affected the DNA religation step of the catalytic cycle. The introduction of an additional positive charge into the active site region of the mutant E. coli topoisomerase I activity shifted the pH for optimal activity and decreased the Mg2+ binding affinity. This study demonstrated that a substitution outside the TOPRIM motif, which binds Mg2+directly, can nonetheless inhibit Mg2+ binding and DNA religation by the enzyme, increasing the accumulation of covalent cleavage complex, with bactericidal consequence. Small molecules that can inhibit Mg2+ dependent religation by bacterial topoisomerase I specifically could be developed into useful new antibacterial compounds. This approach would be similar to the inhibition of divalent ion dependent strand transfer by HIV integrase in antiviral therapy

Telemedicine for glaucoma: Guidelines and recommendations

Background: Glaucoma is the leading cause of irreversible blindness worldwide. Access to glaucoma specialists is challenging and likely to become more difficult as the population ages.Introduction: Using telemedicine for glaucoma (teleglaucoma) has the potential to increase access to glaucoma care by improving efficiency and decreasing the need for long-distance travel for patients.Results:Teleglaucoma programs can be used for screening, diagnostic consultation, and long-term treatment monitoring. Key components of teleglaucoma programs include patient history, equipment, intraocular pressure measurement, pachymetry, anterior chamber imaging/gonioscopy, fundus photography, retinal nerve fiber layer imaging, medical record and imaging software, and skilled personnel.Discussion: Teleglaucoma has tremendous potential to improve patient access to high-quality cost-effective glaucoma care.Conclusions: We have reviewed some special considerations needed to address the complexity of providing guideline-concordant glaucoma care

A Comparison of Resource Use and Costs of Caring for Patients With Exfoliation Syndrome Glaucoma Versus Primary Open-Angle Glaucoma

To characterize differences in resource utilization and cost of managing enrollees with exfoliation glaucoma (XFG) compared to primary open-angle glaucoma (POAG). Retrospective utilization and cost comparison using Medicare claims data. We identified Medicare beneficiaries with XFG or POAG and ≥5 years of continuous enrollment from January 2008 to December 2014. We distinguished newly diagnosed cases from those with preexisting disease. We compared ophthalmic resource utilization and costs over 2 years of follow-up for persons with newly diagnosed and preexisting XFG vs those with POAG. Main outcome measures were number of clinic visits, diagnostic procedures, medication fills, laser and incisional surgery, and mean eye care costs per beneficiary. Among 192 eligible enrollees (median age 77.6 years) with newly diagnosed XFG and 7339 enrollees (median age 77.3 years) with newly diagnosed POAG, those with XFG had more office visits (mean, 9.1 vs 7.9; P = .001), cataract surgery (34.9% vs 19.0%; P < .0001), and glaucoma surgery (28.7% vs 19.7%, P = .002). They also experienced 27% higher mean total eye care costs ($3260 vs$2562, P = .0001) over 2 years of follow-up. Among 2745 enrollees (median age 80.5 years) with preexisting XFG and 89 036 persons (median age 79.5) with preexisting POAG, persons with XFG had more office visits (mean 9.3 vs 7.3; P < .0001), perimetry (85.3% vs 79.8%; P < .0001), cataract surgery (23.4% vs 12.3%; P < .0001), laser trabeculoplasty (18.6% vs 9.6%; P < .0001), and trabeculectomy (8.1 vs 1.8%; P < .0001) and experienced 37% higher total mean eye care costs ($3764 vs$2739; P < .0001). Healthcare resource utilization and costs are substantially higher for managing patients with XFG compared to POAG

Trends in Glaucoma Surgeries Performed by Glaucoma Subspecialists versus Nonsubspecialists on Medicare Beneficiaries from 2008 through 2016

To characterize the use of laser and incisional glaucoma surgeries among Medicare beneficiaries from 2008 through 2016 and to compare the use of these surgeries by glaucoma subspecialists versus nonsubspecialists. Retrospective, observational analysis. Medicare beneficiaries (n = 1 468 035) undergoing ≥1 laser or incisional glaucoma surgery procedure during 2008 through 2016. Claims data from a 20% sample of enrollees in fee-for-service Medicare throughout the United States were analyzed to identify all laser and incisional glaucoma surgeries performed from 2008 through 2016. We assessed use of traditional incisional glaucoma surgery techniques (trabeculectomy and glaucoma drainage implant [GDI] procedure) and microinvasive glaucoma surgery (MIGS). Enrollee and procedure counts were multiplied by 5 to estimate use throughout all of Medicare. Linear regression was used to compare trends in use of glaucoma surgeries between ophthalmologists who could be characterized as glaucoma subspecialists versus nonsubspecialists. Numbers of laser and incisional glaucoma surgeries performed overall and stratified by glaucoma subspecialist status. The number of Medicare beneficiaries undergoing any glaucoma therapeutic procedure increased by 10.6%, from 218 375 in 2008 to 241 565 in 2016. The total number of traditional incisional glaucoma surgeries decreased by 11.7%, from 37 225 to 32 885 (P = 0.02). The total number of MIGS procedures increased by 426% from 13 705 in 2012 (the first year MIGS codes were available) to 58 345 in 2016 (P = 0.001). Throughout the study period, glaucoma subspecialists performed most of the trabeculectomies (76.7% in 2008, 83.1% in 2016) and GDI procedures (77.7% in 2008, 80.6% in 2016). Many MIGS procedures were performed by nonsubspecialists. The proportions of endocyclophotocoagulations, iStent (Glaukos; San Clemente, CA) insertions, goniotomies, and canaloplasties performed by glaucoma subspecialists in 2016 were 22.0%, 25.2%, 56.9%, and 62.8%, respectively. From 2008 through 2016, a large shift in practice from traditional incisional glaucoma surgeries to MIGS procedures was observed. Although glaucoma subspecialists continue to perform most traditional incisional glaucoma surgeries, many MIGS procedures are performed by nonsubspecialists. These results highlight the importance of training residents in performing MIGS procedures and managing these patients perioperatively. Future studies should explore the impact of this shift in care on outcomes and costs