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Aim To evaluate the impact of ultra-rapid FLASH mouse whole brain irradiation on hippocampal dendritic spines and neuroinflammation, factors associated with cognitive impairment after brain irradiation. Methods We administered 30 Gy whole brain irradiation to C57BL6/J mice in sub-second (FLASH) vs. 240 s conventional delivery time keeping all other parameters constant, using a custom configured clinical linac. Ten weeks post-irradiation, we evaluated spatial and non-spatial object recognition using novel object location and object recognition testing. We measured dendritic spine density by tracing Golgi-stained hippocampal neurons and evaluated neuroinflammation by CD68 immunostaining, a marker of activated microglia, and expression of 10 pro-inflammatory cytokines using a multiplex immunoassay. Results At ten weeks post-irradiation, compared to unirradiated controls, conventional delivery time irradiation significantly impaired novel object location and recognition tasks whereas the same dose given in FLASH delivery did not. Conventional delivery time, but not FLASH, was associated with significant loss of dendritic spine density in hippocampal apical dendrites, with a similar non-significant trend in basal dendrites. Conventional delivery time was associated with significantly increased CD68-positive microglia compared to controls whereas FLASH was not. Conventional delivery time was associated with significant increases in 5 of 10 pro-inflammatory cytokines in the hippocampus (and non-significant increases in another 3), whereas FLASH was associated with smaller increases in only 3. Conclusion Reduced cognitive impairment and associated neurodegeneration were observed with FLASH compared to conventional delivery time irradiation, potentially through decreased induction of neuroinflammation, suggesting a promising approach to increasing therapeutic index in radiation therapy of brain tumors.

Gemfibrozil and L-carnitine are involved in fatty acid metabolism. We assessed the impact of administering gemfibrozil together with L-carnitine on the performance, lipid redistribution, intramuscular fat, and carcass quality in broiler chickens. Day-old male Ross 308 chicks were randomly divided among nine treatments, with three replicates per treatment. There were of 10 chicks in each replicate. The experiment involved a 3×3 factorial arrangement of treatments, with three levels of L-carnitine, in combination with three levels of gemfibrozil. Body weight, feed intake and feed conversion ratio (FCR) were obtained weekly from 3 to 6 weeks of age. At the end of the experimental period, the chicks were sacrificed and carcass and blood samples were obtained for various measures. There were interactions between L-carnitine and gemfibrozil on weight gain, feed intake, FCR, full and empty abdominal carcass weights, breast and wing weights, abdominal fat weight, heart weight and triglyceride concentration (P>0.05). The presence of dietary L-carnitine and gemfibrozil together reduced the weight gain, feed intake, abdominal fat weight and triglyceride concentration. Conversely, combinations of L-carnitine and gemfibrozil significantly increased the heart weight. There were no effects of L-carnitine and gemfibrozil on eviscerated carcass weight nor on liver weight. Dietary L-carnitine and gemfibrozil together influence measures of performance, fat distribution and carcass quality in broiler chickens.

Experiments were performed to investigate the activity of hepatic Phe hydroxylase (PAH) and plasma amino acid concentrations under conditions of Phe imbalance or toxicity in chicks fed on experimental diets from 7 to 14 or 16 d of age. In experiment 1, Phe imbalance was created by adding 10% of a mixture of indispensable amino acids lacking Phe (IAA - Phe) to a basal diet containing 0.46% Phe. The activity of PAH was not significantly affected by the imbalance. Correcting the imbalance by adding 1.12% Phe to the diet prevented the growth impairment and increased the activity of PAH. In experiment 2, growth was reduced by the addition of excess (2%) Phe to the basal diet. Correcting the excess by adding the IAA - Phe to the diet prevented the growth reduction. The activity of PAH was not significantly affected by 2% Phe, but it increased in chicks fed the corrected diet. The levels of PAH mRNA were not affected by the dietary treatments. A factorial arrangement of treatments with 3 dietary levels of Phe (0.46, 1.58, and 2.46%) with or without the IAA - Phe was used in experiment 3. The effects on growth were similar to those of the same treatments in experiments 1 and 2. The addition of Phe significantly increased hepatic PAH activity, but there was no detectable main effect of the IAA - Phe and no interaction. Plasma Phe concentration was increased by dietary Phe and decreased by the IAA - Phe mixture. We conclude that hepatic PAH activity in chicks variably increases in response to Phe or a 10% dietary supplement of indispensable amino acids including Phe but does not increase in response to IAA - Phe when the amino acids are added to a diet that is marginally adequate in Phe. The increased activity does not involve changes in PAH mRNA. The effects of IAA - Phe on plasma Phe concentrations appear to be independent of hepatic PAH activity as measured in vitro.

Two experiments were performed to study Phe imbalance and toxicity in 1-wk-old Babcock B380 chicks resulting from the addition of either a mixture of indispensable amino acids lacking Phe (IAA – Phe) or excess Phe to a diet that was nutritionally adequate in Phe. Chicks received a preexperimental semipurified diet for 1 wk and experimental diets from 7 to 14 d of age. In the first experiment, the chicks were given diets with Phe levels at 0.24, 0.29, 0.34, 0.39, 0.44, and 0.49% of the diet to determine the Phe requirement. The requirement of the chicks for Phe, based on weight gain and feed efficiency, was determined to be 0.39% of the diet. In experiment 2, the IAA – Phe (10% of the diet) or excess Phe (2% of the diet) was added to a diet containing 0.44% Phe. Chicks given the IAA – Phe or excess Phe had significantly slower growth rates than chicks given the basal diet (P ≥ 0.05). The activities of the major hepatic enzyme of Phe catabolism, Phe hydroxylase (PAH), were significantly higher than that of chicks fed the basal diet when the chicks were fed the diets containing IAA – Phe plus 1.1% Phe (P ≥ 0.05) but not when chicks were fed the diet containing IAA – Phe alone. The activity of PAH in chicks given the excess (2%) Phe was nearly 4 times the activity of PAH in chicks given the basal diet. Adding IAA – Phe to the diet containing excess Phe also resulted in higher PAH activity than was observed in chicks fed the basal diet, although the activity was significantly lower than observed for chicks receiving the diet containing excess Phe alone (P ≥ 0.05). It is concluded that hepatic PAH activity in chicks increases primarily in response to its substrate, Phe. A dietary amino acid load without Phe reduces this response to excess Phe.

probability of tumors, organ toxicity and overall prognosis of the SIB and SqIB treatments of head and neck cancer using the selective radiobiological models. Similar agreements were also reported in the SqIB treatments of head and neck cancer. A large cohort group of study is warranted to increase to power of observations to these models which will strengthen our conclusions. That can help to take preventive measures for the critical organs in such types of treatments, as well as in ranking different types of treatment techniques. Author Disclosure: A. Pyakuryal: None. S. Pandit: None. G. Narayanasamy: None. S. Jang: None. S. Lee: None. T.T. Sio: None.