Effects of Cyclical Changes in Environmental Salinity on Osmoregulatory Parameters in the Mozambique Tilapia

M.S. University of Hawaii at Manoa 2016.Includes bibliographical references.Many euryhaline teleost fish, including the Mozambique tilapia, Oreochromis mossambicus, are native to waters in which salinity varies tidally between that of freshwater (FW) and seawater (SW). Acclimation to changes in environmental salinity is regulated largely by the neuroendocrine system, which directs ion extrusion or ion uptake response via the gill and other osmoregulatory tissues. In teleosts, prolactin (PRL) is critical to FW acclimation, stimulating ion uptake mechanisms. Osmoregulation in euryhaline teleosts has been studied extensively in steady state FW and SW, and after one-way transfers between FW and SW. It is unclear, however, how euryhaline fish respond to cyclical salinity changes. Mozambique tilapia were reared in FW, SW, and under a tidal regimen (TR), characterized by salinity changes between FW (TF) and SW (TS) every 6 hours (h), and transferred from FW or SW to TR to investigate adaptive ability to TR. TR fish were also sampled every 3 h in a 24-hour period to observe osmoregulatory parameters throughout the TR cycle. Regardless of the rearing regimen, plasma osmolality changed in direct relation to salinity, rising in SW and falling in FW, while plasma PRL was inversely related to salinity. In fish reared in TR, branchial gene expression of effectors of ion transport and PRL receptors was more similar to those of fish reared in SW than to those in FW. When fish were transferred from either FW or SW to TR, all measured osmoregulatory parameters were identical to those of fish reared in TR by 7 days. In TR fish sampled multiple times over a 24-hour period the greater resolution in sampling revealed several nuances within the overall patterns of salinity and regimen-dependent changes in osmoregulatory parameters. These findings indicate that life-long acclimation to SW and FW does not preclude adaptation to TR at the adult stage. The results also show that throughout a 24-hour period, TR fish are able to compensate for broad and frequent changes in external salinity while maintaining osmoregulatory parameters within a narrow range. These are the first known studies to investigate environmental adaptation of adult Mozambique tilapia to TR, and to characterize osmoregulatory parameters in TR fish over multiple iterations of TF & TS during a full diurnal cycle. As such, these studies have further characterized the effects of TR-acclimation at a more advanced life stage than addressed by previous reports, and have yielded greater insights to rearing in an environment that approximates the native habitat of the Mozambique tilapia

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events