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Over the last few years, US Food and Drug Administration-approved drugs using RNA interference have come to the market. Many have treated liver-specific diseases utilizing N-acetyl galactosamine conjugation because of its effective delivery and limited off-target effects. The autosomal recessive disorder primary hyperoxaluria, specifically type 1, has benefited from these developments. Primary hyperoxaluria arises from mutations in the enzymes involved in endogenous oxalate synthesis. The severity of disease varies but can result in kidney failure and systemic oxalosis. Until recently, the treatment options were limited and focused primarily on supportive treatments, pyridoxine use in a subset of patients with primary hyperoxaluria type 1, and liver-kidney transplants in those who progressed to kidney failure. Two genes have been targeted with RNA interference; lumasiran targets glycolate oxidase and nedosiran targets lactate dehydrogenase A. Lumasiran was recently approved in the treatment of primary hyperoxaluria type 1 and nedosiran is in the approval process. Unfortunately, despite initial hopes that nedosiran may also be a treatment option for primary hyperoxaluria types 2 and 3, initial data suggest otherwise. The use of RNA interference liver-specific targeting for the treatment of primary hyperoxaluria type 1 will likely transform the natural history of the disease. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Primary hyperparathyroidism (1HPT) is associated with the risk of developing kidney stones. Our objective was to determine the prevalence of 1HPT amongst SF evaluated at a tertiary stone clinic and determine if it is cost-effective to screen for this condition. Methods: We retrospectively reviewed 742 adult SF seen by a single urologic surgeon from 2012 to 2017 all of who were screened for 1HPT with an intact serum PTH (iPTH) and calcium. The diagnosis of 1HPT was based on the presence of hypercalcemia with an inappropriately elevated iPTH or a high normal serum calcium and an inappropriately elevated iPTH. The diagnosis was confirmed by surgical neck exploration. Published cost data and stone recurrence rates were utilized to create a cost-effectiveness decision tree. Results obtained: Fifty-three (7.1%) were diagnosed with 1HPT. 15 (28%) had hypercalcemia and inappropriately elevated iPTH, 38 (72%) had high normal serum calcium levels and inappropriately elevated iPTH. The potential diagnosis was ignored/missed by primary care physicians in 9 (17.0%) based on a review of prior lab results. Cost modeling was undertaken for 5, 10, 15, and 20-year intervals after screening. Based on our prevalence data, historical risks for recurrence and published cost data for stone treatments, cost savings in screening are realized at 10 years. Conclusion: These results support screening for primary hyperparathyroidism in patients evaluated in a tertiary referral setting. [ABSTRACT FROM AUTHOR]

Two experiments investigated the ability to use olfactory cues in maze-learning tasks following cadmium exposure. In Experiment 1, two groups of rats-one exposed to a cadmium-saccharin solution, one exposed just to saccharin-received double-alternation, reward(R)-nonreward(N) runway training. When only olfactory cues could be used as discriminative stimuli (Phase 1), just the saccharin-exposed animals were capable of mastering the Rrnnrrnn pattern. When a tactile discriminative stimulus was added (Phase 2), both groups of animals displayed appropriate patterned responding. Removal of the tactile cue (Phase 3) resulted in the immediate disruption of patterned responding in the cadmium-exposed animals. In Experiment 2, when a peppermint odor was used as a discriminative stimulus for T-maze performance, cadmium-exposed animals were incapable of learning the discrimination. However, when a light served as the discriminative stimulus, cadmium-exposed subjects performed as well as control subjects. These results point to potential olfactory deficits resulting from cadmium ingestion. [ABSTRACT FROM AUTHOR]