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BackgroundResearch on traumatic brain injury (TBI) highlights the significance of counteracting its metabolic impact via exogenous fuels to support metabolism and diminish cellular damage. While ethyl pyruvate (EP) treatment shows promise in normalizing cellular metabolism and providing neuroprotection, there is a gap in understanding the precise metabolic pathways involved. Metabolomic analysis of the acute post-injury metabolic effects, with and without EP treatment, aims to deepen our knowledge by identifying and comparing the metabolite profiles, thereby illuminating the injury's effects and EP's therapeutic potential.MethodsIn the current study, an untargeted metabolomics approach was used to reveal brain metabolism changes in rats 24 h after a controlled cortical impact (CCI) injury, with or without EP treatment. Using principal component analysis (PCA), volcano plots, Random Forest and pathway analysis we differentiated the brain metabolomes of CCI and sham injured animals treated with saline (Veh) or EP, identifying key metabolites and pathways affected by injury. Additionally, the effect of EP on the non-injured brain was also explored.ResultsPCA showed a clear separation of the four study groups (sham-Veh, CCI-Veh, sham-EP, CCI-EP) based on injury. Following CCI injury (CCI-Veh), 109 metabolites belonging to the amino acid, carbohydrate, lipid, nucleotide, and xenobiotic families exhibited a twofold change at 24 h compared to the sham-Veh group, with 93 of these significantly increasing and 16 significantly decreasing (p

PurposeGastrointestinal stromal tumors (GIST) commonly arise in different regions of the stomach and are driven by various mutations (most often in KIT, PDGFRA, and SDHx). We hypothesized that the anatomic location of gastric GIST is associated with unique genomic profiles and distinct driver mutations.Experimental designWe compared KIT versus non-KIT status with tumor location within the National Cancer Database (NCDB) for 2,418 patients with primary gastric GIST. Additionally, we compiled an international cohort (TransAtlantic GIST Collaborative, TAGC) of 236 patients and reviewed sequencing results, cross-sectional imaging, and operative reports. Subgroup analyses were performed for tumors located proximally versus distally. Risk factors for KIT versus non-KIT tumors were identified using multivariate regression analysis. A random forest machine learning model was then developed to determine feature importance.ResultsWithin the NCDB cohort, non-KIT mutants dominated distal tumor locations (P < 0.03). Proximal GIST were almost exclusively KIT mutant (96%) in the TAGC cohort, whereas 100% of PDGFRA and SDH-mutant GIST occurred in the distal stomach. On multivariate regression analysis, tumor location was associated with KIT versus non-KIT mutations. Using random forest machine learning analysis, stomach location was the most important feature for predicting mutation status.ConclusionsWe provide the first evidence that the mutational landscape of gastric GIST is related to tumor location. Proximal gastric GIST are overwhelmingly KIT mutant, irrespective of morphology or age, whereas distal tumors display non-KIT genomic diversity. Anatomic location of gastric GIST may therefore provide immediate guidance for clinical treatment decisions and selective confirmatory genomic testing when resources are limited.

The aim of the current study was to determine effects of mild traumatic brain injury (TBI), with or without blockade of purinergic ATP Y1 (P2Y1) receptors or store-operated calcium channels, on extracellular levels of ATP, glutamate, glucose and lactate. Concentrations of ATP, glutamate, glucose and lactate were measured in cerebral microdialysis samples obtained from the ipsilateral cortex and underlying hippocampus of rats with mild unilateral controlled cortical impact (CCI) or sham injury. Immediately after CCI, a large release of ATP was observed in the cortex (3.53-fold increase of pre-injury value) and hippocampus (2.97-fold increase of pre-injury value), with ATP returning to the baseline levels within 20 min post-injury and remaining stable for during the 3-h sampling period. In agreement with the results of previous studies, there was a significant increase in glutamate 20 min after CCI, which was concomitant with a decrease in extracellular glucose (20 min) and an increase in lactate (40-60 min) in both brain regions after CCI. Addition of a selective P2Y1 receptor blocker (MRS2179 ammonium salt hydrate) to the microdialysis perfusate significantly lowered pre-injury ATP and glutamate levels, and eliminated the post-CCI peaks. Addition of a blocker of store-operated calcium channels [2-aminoethoxy diphenylborinate (2-APB)] to the microdialysis perfusate significantly lowered pre-injury ATP in the hippocampus, and attenuated the post-CCI peak in both the cortex and hippocampus. 2-APB treatment significantly increased baseline glutamate levels, but the values post-injury did not differ from those in the sham group. Pre-injury glucose levels, but not lactate levels, were increased by MRS2179 and decreased by 2-APB. However, none of these treatments substantially altered the CCI-induced reduction in glucose and increase in lactate in the cortex. In conclusion, the results of the present study demonstrated that a short although extensive release of ATP immediately after experimental TBI can be significantly attenuated by blockade of P2Y1 receptors or store-operated calcium channels.

Little is known about how triple negative breast cancer (TNBC) is discussed on the visual social media platform, Instagram. A greater understanding of the experiences of TNBC survivors that are documented on this platform may inform us of how this group of survivors cope with this rare, but aggressive form of breast cancer. This study analyzed a random sample (N = 501) of Instagram posts using the hashtag #triplenegativebreastcancer. Using a quantitative content analysis, posts were coded for the presence of health belief model constructs as well as the presence of treatment-related experiences, social support, and hereditary breast cancer genetic mutations (BRCA 1/2). Our findings suggest that health organizations and agencies are not utilizing Instagram as a conduit of health communications about TNBC to reach individuals worldwide. This article provides insights into potential strategies that can be used by these entities to promote user engagement with posts about TNBC, such as utilizing health messaging that is episodic in nature, uses supportive and encouraging words, and provides information about chemotherapy.

Moral disengagement (MD) has been consistently associated with antisocial behavior (ASB) in prior research. Limited research tested the directionality of the bivariate relationship, and most studies focused only on the direction of MD predicting ASB, even though ASB could also influence MD based on the literature on attribution and behavioral influence on attitude. Moreover, the few studies testing reciprocal associations rarely controlled for stable individual differences and did not explicitly examine the age effect to allow for a clear developmental inference. We analyzed age-based self-report antisocial behavior and moral disengagement data across ages 16–23 from 1,349 juvenile offenders (86.43% male; 20.31% White, 41.29% Black, 33.65% Hispanic) in the Pathways to Desistance Project using a random intercept cross-lagged panel model. Controlling for stable individual differences in MD and ASB and their associations along with the autoregressive effects, there was a reciprocal relationship between MD and ASB from ages 16 to 18. However, from ages 19 to 21, only ASB significantly predicted MD in the following year. There was no significant cross-lagged effect from ages 21 to 23. Our findings highlight the dynamic relationship between MD and ASB from ages 16 to 23. Youth between 16 and 18 years old may be more pliable to change with treatment/intervention due to the two-way traffic of cognition and behavior, but we also caution against treatment efforts with a heavy focus on proactive criminal thinking involving moral disengagement to reduce offending behavior beyond age 18. Public Significance Statement: The mutual influences of MD and ASB from age 16 to 18 suggest that youth at these ages are more pliable to change, and the two-way traffic in their cognition and behavior may be opportune for intervention to start a positive feedback loop. Because of the lack of effect of MD on ASB beyond age 18, we caution against treatment efforts with a heavy focus on proactive criminal thinking (e.g., moral disengagement) to reduce offending behavior. [ABSTRACT FROM AUTHOR]