Genomic alterations and abnormal expression of APE2 in multiple cancers.

Although APE2 plays essential roles in base excision repair and ATR-Chk1 DNA damage response (DDR) pathways, it remains unknown how the APE2 gene is altered in the human genome and whether APE2 is differentially expressed in cancer patients. Here, we report multiple-cancer analyses of APE2 genomic alterations and mRNA expression from cancer patients using available data from The Cancer Genome Atlas (TCGA). We observe that APE2 genomic alterations occur at ~17% frequency in 14 cancer types (n = 21,769). Most frequent somatic mutations of APE2 appear in uterus (2.89%) and skin (2.47%) tumor samples. Furthermore, APE2 expression is upregulated in tumor tissue compared with matched non-malignant tissue across 5 cancer types including kidney, breast, lung, liver, and uterine cancers, but not in prostate cancer. We also examine the mRNA expression of 13 other DNA repair and DDR genes from matched samples for 6 cancer types. We show that APE2 mRNA expression is positively correlated with PCNA, APE1, XRCC1, PARP1, Chk1, and Chk2 across these 6 tumor tissue types; however, groupings of other DNA repair and DDR genes are correlated with APE2 with different patterns in different cancer types. Taken together, this study demonstrates alterations and abnormal expression of APE2 from multiple cancers.

Comparison of Two Fluid Replacement Protocols During a 20-km Trail Running Race in the Heat.

Lopez, RM, Casa, DJ, Jensen, K, Stearns, RL, DeMartini, JK, Pagnotta, KD, Roti, MW, Armstrong, LE, and Maresh, CM. Comparison of two fluid replacement protocols during a 20-km trail running race in the heat. J Strength Cond Res 30(9): 2609-2616, 2016-Proper hydration is imperative for athletes striving for peak performance and safety, however, the effectiveness of various fluid replacement strategies in the field setting is unknown. The purpose of this study was to investigate how two hydration protocols affect physiological responses and performance during a 20-km trail running race. A randomized, counter-balanced, crossover design was used in a field setting (mean ± SD: WBGT 28.3 ± 1.9° C). Well-trained male (n = 8) and female (n = 5) runners (39 ± 14 years; 175 ± 9 cm; 67.5 ± 11.1 kg; 13.4 ± 4.6% BF) completed two 20-km trail races (5 × 4-km loop) with different water hydration protocols: (a) ad libitum (AL) consumption and (b) individualized rehydration (IR). Data were analyzed using repeated measures ANOVA. Paired t-tests compared pre-race-post-race measures. Main outcome variables were race time, heart rate (HR), gastrointestinal temperature (TGI), fluid consumed, percent body mass loss (BML), and urine osmolality (Uosm). Race times between groups were similar. There was a significant condition × time interaction (p = 0.048) for HR, but TGI was similar between conditions. Subjects replaced 30 ± 14% of their water losses in AL and 64 ± 16% of their losses in IR (p < 0.001). Ad libitum trial experienced greater BML (-2.6 ± 0.5%) compared with IR (-1.3 ± 0.5%; p < 0.001). Pre-race to post-race Uosm differences existed between AL (-273 ± 146 mOsm) and IR (-145 ± 215 mOsm, p = 0.032). In IR, runners drank twice as much fluid than AL during the 20-km race, leading to > 2% BML in AL. Ad libitum drinking resulted in 1.3% greater BML over the 20-km race, which resulted in no thermoregulatory or performance differences from IR.

Examining the influence of hydration status on physiological responses and running speed during trail running in the heat with controlled exercise intensity.

The purpose of this study was to determine the effects of dehydration at a controlled relative intensity on physiological responses and trail running speed. Using a randomized, controlled crossover design in a field setting, 14 male and female competitive, endurance runners aged 30 ± 10.4 years completed 2 (hydrated [HY] and dehydrated [DHY]) submaximal trail runs in a warm environment. For each trial, the subjects ran 3 laps (4 km per lap) on trails with 4-minute rests between laps. The DHY were fluid restricted 22 hours before the trial and during the run. The HY arrived euhydrated and were given water during rest breaks. The subjects ran at a moderate pace matched between trials by providing pacing feedback via heart rate (HR) throughout the second trial. Gastrointestinal temperature (T(GI)), HR, running time, and ratings of perceived exertion (RPE) were monitored. Percent body mass (BM) losses were significantly greater for DHY pretrial (-1.65 ± 1.34%) than for HY (-0.03 ± 1.28%; p < 0.001). Posttrial, DHY BM losses (-3.64 ± 1.33%) were higher than those for HY (-1.38 ± 1.43%; p < 0.001). A significant main effect of T(GI) (p = 0.009) was found with DHY having higher T(GI) postrun (DHY: 39.09 ± 0.45°C, HY: 38.71 ± 0.45°C; p = 0.030), 10 minutes post (DHY: 38.85 ± 0.48°C, HY: 38.46 ± 0.46°C; p = 0.009) and 30 minutes post (DHY: 38.18 ± 0.41°C, HY: 37.60 ± 0.25°C; p = 0.000). The DHY had slower run times after lap 2 (p = 0.019) and lap 3 (p = 0.025). The DHY subjects completed the 12-km run 99 seconds slower than the HY (p = 0.027) subjects did. The RPE in DHY was slightly higher than that in HY immediately postrun (p = 0.055). Controlling relative intensity in hypohydrated runners resulted in slower run times, greater perceived effort, and elevated T(GI), which is clinically meaningful for athletes using HR as a gauge for exercise effort and performance.