Multiple ammonia-induced episodes of hepatic encephalopathy provoke neuronal cell loss in bile-duct ligated rats.

Background & Aims: Hepatic encephalopathy (HE) is defined as a reversible syndrome and therefore should resolve following liver transplantation (LT). However, neurological complications have been reported in up to 47% of LT recipients, which have been documented to be associated with a history of overt HE pre-LT. We hypothesise that multiple episodes of HE lead to permanent cell injury and exacerbate neurological dysfunction. Our goal was to evaluate the impact of cumulative HE episodes on neurological status and brain integrity in rats with chronic liver disease. Methods: Episodes of overt HE (loss of righting reflex) were induced following injection of ammonium acetate in bile duct ligation (BDL) rats (BDL-Ammonia) every 4 days starting at week 3 post-BDL. Neurobehaviour was evaluated after the last episode. Upon sacrifice, plasma ammonia, systemic oxidative stress, and inflammation markers were assessed. Neuronal markers including neuron-specific nuclear antigen and SMI311 (anti-neurofilament marker) and apoptotic markers (cleaved caspase-3, Bax, and Bcl2) were measured. Total antioxidant capacity, oxidative stress marker (4-hydroxynonenal), and proinflammatory cytokines (tumour necrosis factor-alpha and interleukin-1ß) were measured in brain (hippocampus, frontal cortex, and cerebellum). Proteomic analysis was conducted in the hippocampus. Results: In hippocampus of BDL-Ammonia rats, cleaved caspase-3 and Bax/Bcl2 ratio were significantly increased, whereas NeuN and SMI311 were significantly decreased compared with BDL-Vehicle rats. Higher levels of oxidative stress-induced post-translational modified proteins were found in hippocampus of BDL-Ammonia group which were associated with a lower total antioxidant capacity. Conclusions: Ammonia-induced episodes of overt HE caused neuronal cell injury/death in BDL rats. These results suggest that multiple bouts of HE can be detrimental on the integrity of the brain, translating to irreversibility and hence neurological complications post-LT. Impact and implications: Hepatic encephalopathy (HE) is defined as a reversible neuropsychiatric syndrome resolving following liver transplantation (LT); however, ∼47% of patients demonstrate neurological impairments after LT, which are associated with a previous history of overt HE pre-LT. Our study indicates that multiple episodes of overt HE can cause permanent neuronal damage which may lead to neurological complications after LT. Nevertheless, preventing the occurrence of overt HE episodes is critical for reducing the risk of irreversible neuronal injury in patients with cirrhosis.

Wintering Snow Buntings Elevate Cold Hardiness to Extreme Levels but Show No Changes in Maintenance Costs.

AbstractResident temperate passerines adjust their phenotypes to cope with winter constraints, with peak performance in metabolic traits typically occurring during the coldest months. However, it is sparsely known whether cold-adapted northern species make similar adjustments when faced with variable seasonal environments. Life in near-constant cold could be associated with limited flexibility in traits underlying cold endurance. We investigated this by tracking individual physiological changes over five consecutive winters in snow buntings (Plectrophenax nivalis), an Arctic-breeding migratory passerine typically confronted with nearly constant cold. Buntings were held in an outdoor aviary and exposed to seasonal temperature variation typical of temperate zone climates. We measured phenotypic changes in body composition (body, fat, and lean mass, pectoralis muscle thickness), oxygen transport capacity (hematocrit), metabolic performance (basal metabolic rate [BMR] and summit metabolic rate [Msum]), thermogenic endurance (time to reach Msum), and cold tolerance (temperature at Msum). Snow buntings showed flexibility in functions underlying thermogenic capacity and cold endurance comparable to that observed in temperate resident passerines wintering at similar latitudes. Specifically, they increased body mass (13%), fat mass (246%), hematocrit (23%), pectoralis muscle thickness (8%), and Msum (27%). We also found remarkable cold tolerance in these birds, with individuals reaching Msum in helox at temperatures equivalent to less than -90°C in air. However, in contrast with resident temperate passerines, lean mass decreased by 12%, and there was no clear increase in maintenance costs (BMR). Our results show that the flexibility of traits underlying thermal acclimatization in a cold-adapted northern species is comparable to that of temperate resident species living at lower latitudes and is therefore not limited by life in near-constant cold.

Assessment of combined use of ArcCheck® detector and portal dosimetry for delivery quality assurance of head and neck and prostate volumetric-modulated arc therapy.

PURPOSE: To assess the efficiency of combined use of ArcCheck® detector (AC) and portal dosimetry (PDIP) for delivery quality assurance of head and neck and prostate volumetric-modulated arc therapy. MATERIALS AND METHODS: Measurement processes were studied with the Gamma index method according to three analysis protocols. The detection sensitivity to technical errors of each individual or combined measurement processes was studied by inserting collimator, dose and MLC opening error into five head and neck and five prostate initial treatment plans. A total of 220 plans were created and 660 analyses were conducted by comparing measurements to error free planned dose matrix. RESULTS: For head and neck localization, collimator errors could be detected from 2° for AC and 3° for PDIP. Dose and MLC errors could be detected from 2% and 0.5 mm for AC and PDIP. Depending on the analysis protocol, the detection sensitivity of total simulated errors ranged from 54% to 88% for AC vs 40% to 74% for PDIP and 58% to 92% for the combined process. For the prostate localization, collimator errors could be detected from 4° for AC while they could not be detected by PDIP. Dose and MLC errors could be detected from 3% and 0.5 mm for AC and PDIP. The detection sensitivity of total simulated errors ranged from 30% to 56% for AC vs 16% to 38% for PDIP and 30% to 58% for combined process. CONCLUSION: The combined use of the two measurement processes did not statistically improve the detectability of technical errors compared to use of single process.

Basal and maximal metabolic rates differ in their response to rapid temperature change among avian species.

In birds, acclimation and acclimatization to temperature are associated with changes in basal (BMR), summit (Msum) and maximal (MMR) metabolic rates but little is known about the rate at which species adjust their phenotype to short-term temperature variations. Our aims were (1) to determine the pattern of metabolic adjustments following a rapid temperature change, (2) to determine whether performance varies at similar rates during exposure to warm or cold environments, and (3) to determine if BMR, Msum and MMR change at comparable rates during thermal acclimation. We measured these parameters in white-throated sparrows (Zonotrichia albicollis), black-capped chickadees (Poecile atricapillus), and snow buntings (Plectrophenax nivalis) after acclimation to 10 °C (day 0) and on the 4th and 8th days of acclimation to either -5 or 28 °C. Birds changed their metabolic phenotype within 8 days with patterns differing among species. Sparrows expressed the expected metabolic increases in the cold and decreases at thermoneutrality while performance in chickadees and buntings was not influenced by temperature but changed over time with inverse patterns. Our results suggest that BMR varies at comparable rates in warm and cold environments but changes faster than Msum and MMR, likely due to limitations in the rate of change in organ size and function. They also suggest that maximal metabolic capacity is lost faster in a warm environment than it is gained in a cold environment. With the expected increase in temperature stochasticity at northern latitudes, a loss of thermogenic capacity during warm winter days could, therefore, be detrimental if birds are slow to readjust their phenotype with the return of cold days.

Norway maple displays greater seasonal growth and phenotypic plasticity to light than native sugar maple.

Norway maple (Acer platanoides L), which is among the most invasive tree species in forests of eastern North America, is associated with reduced regeneration of the related native species, sugar maple (Acer saccharum Marsh) and other native flora. To identify traits conferring an advantage to Norway maple, we grew both species through an entire growing season under simulated light regimes mimicking a closed forest understorey vs. a canopy disturbance (gap). Dynamic shade-houses providing a succession of high-intensity direct-light events between longer periods of low, diffuse light were used to simulate the light regimes. We assessed seedling height growth three times in the season, as well as stem diameter, maximum photosynthetic capacity, biomass allocation above- and below-ground, seasonal phenology and phenotypic plasticity. Given the north European provenance of Norway maple, we also investigated the possibility that its growth in North America might be increased by delayed fall senescence. We found that Norway maple had significantly greater photosynthetic capacity in both light regimes and grew larger in stem diameter than sugar maple. The differences in below- and above-ground biomass, stem diameter, height and maximum photosynthesis were especially important in the simulated gap where Norway maple continued extension growth during the late fall. In the gap regime sugar maple had a significantly higher root : shoot ratio that could confer an advantage in the deepest shade of closed understorey and under water stress or browsing pressure. Norway maple is especially invasive following canopy disturbance where the opposite (low root : shoot ratio) could confer a competitive advantage. Considering the effects of global change in extending the potential growing season, we anticipate that the invasiveness of Norway maple will increase in the future.