The G protein ␣ subunits Gpa1, Gpa2, and Gpa3 mediate signal transduction and are important in the growth and virulence of Cryptococcus neoformans. To understand how Gpa1 functions without a conventional G subunit, we characterized a resistance to inhibitors of cholinesterase 8 (Ric8) homolog from C. neoformans, which shares amino acid sequence homology with other Ric8 proteins that exhibit guanine nucleotide exchange factor (GEF) activity toward G␣. We found that the ric8 mutant was reduced in capsule size and melanin formation, which could be suppressed by cyclic AMP (cAMP) supplementation or by introducing the activated GPA1 Q284L allele. Consistent with the fact that Ric8 participates in cAMP signaling to regulate virulence, the ric8 mutant was attenuated in virulence toward mice. Interestingly, disruption of RIC8 also resulted in opposing effects on pheromone signaling, as the ric8 mutant showed reduced mating but an enhanced ability to induce the pheromone response in the mating partner. To identify Ric8 functional mechanisms, we examined the interactions between Ric8 and the three G␣ proteins. Ric8 interacted with Gpa1 and Gpa2, but not Gpa3. The presence of Gpa1 Q284L negatively affected its interaction with Ric8, whereas the activated Gpa2 Q203L allele abolished the interaction. Collectively, these findings suggest that Ric8 functions as a GEF to facilitate the activation of Gpa1-cAMP signaling and to promote Gpa2, affecting mating efficiency. Our study highlights the distinct and conserved characteristics associated with G protein signaling and contributes to our overall understanding of how G protein ␣ subunits function with or without a canonical G partner in C. neoformans.
Background: Unused or rarely used instruments in standard surgical trays can unnecessarily increase costs. Prior studies have demonstrated the practicality and cost savings of reduced instrument tray sizes in various subspecialties. This study describes results and estimated cost savings from a reduced instrument tray used for vitrectomy surgery at a large, tertiary academic medical center. Methods: Common usage patterns of vitrectomy instruments by one retina surgeon were reviewed and a reduced instrument vitrectomy tray was created and implemented in successive vitrectomy surgeries. Need for opening the previously utilized larger tray was recorded. Estimated cost savings of the new trays were calculated based upon per instrument sterilization, processing, and instrument replacement costs. Results: New vitrectomy trays including just 7 instruments (89% reduction compared to original trays) were created and implemented in 189 successive cases. The original tray was never opened. Estimated cost savings from saved sterilization and processing resources is approximately $9588 per year. Assuming 5-and 10-year lifespan per instrument, annual cost avoidance is projected at $7886 and $15,772, respectively. Other indirect benefits relevant to healthcare quality were also noted. Conclusion: A reduced instrument tray can be successfully implemented for vitrectomy surgery and can result in significant indirect benefits as well as direct cost savings from reduced sterilization costs. Our study highlights the substantial impact made by evaluating the usage pattern and making appropriate instrument tray changes for just one retina surgeon. Applying these same methods to other surgeons and specialties can have significant implications on healthcare costs and quality.
Purpose Despite the common misconception that tuberculosis is an uncommon disease in developed countries such as the United States, cases have become increasingly more prevalent. We aim to further the ophthalmologic understanding of this disease through the presentation of clinical findings in nine cases of presumed ocular tuberculosis seen at our institution. Methods Retrospective case review of all patients diagnosed with tuberculosis with encounters at Saint Louis University Hospital and SLUCare between 1/1/2011 and 3/1/2021. Results Nine patients, 6 females and 3 males ages 18-60 years, were included in this study. All cases (100%) presented with a variety of ocular involvement including anterior uveitis, panuveitis, optic nerve edema, sequential papillitis, granulomatous uveitis, peripheral vasculitis, and possible choroidal granuloma. Known history of tuberculosis exposure was only obtained in 22% of patients. Conclusion The low proportion of patients with known history of tuberculosis exposure and manifestations of ocular tuberculosis highlights the general lack of presumption of diagnosis amongst our population. Patients without known exposure and without extraocular manifestations are most at risk for being misdiagnosed and left untreated for tuberculosis. It is important to address this issue with studies leading to more precise diagnostic guidelines and protocols so that patients will be treated in a timely manner to prevent irreversible visual damage secondary to intraocular inflammation as well as potential systemic manifestations of tuberculosis.
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