Hepatocyte nuclear factor 1 alpha influences pancreatic cancer growth and metastasis.

Hepatocyte nuclear factor 1 homeobox alpha (HNF1α) is a transcription factor involved in endodermal organogenesis and pancreatic precursor cell differentiation and development. Earlier studies have reported a role for HNF1α in pancreatic ductal adenocarcinoma (PDAC) but it is controversial. The mechanism by which it impacts PDAC is yet to be explored in depth. In this study, using the online databases we observed that HNF1α is upregulated in PDAC, which was also confirmed by our immunohistochemical analysis of PDAC tissue microarray. Silencing HNF1α reduced the proliferative, migratory, invasive and colony forming capabilities of pancreatic cancer cells. Key markers involved in these processes (pPI3K, pAKT, pERK, Bcl2, Zeb, Snail, Slug) were significantly changed in response to alterations in HNF1α expression. On the other hand, overexpression of HNF1α did not induce any significant change in the aggressiveness of pancreatic cancer cells. Our results demonstrate that reduced expression of HNF1α leads to inhibition of pancreatic cancer growth and progression, which indicates that it could be a potential oncogene and target for PDAC.

The role of ventral striatum in reward-based attentional bias.

INTRODUCTION: Models of attention suggest that endogenous and exogenous factors can bias attention. However, recent data suggest that reward can also enhance attention towards relevant stimulus features as a function of involuntary biases. In this study, we utilized the additional singleton task to determine the neural circuitry that biases perceptual processing as a function of reward history. METHODS: Participants searched for a unique shape amongst an array of differently shaped objects. All shapes, including the target shape, had the same color except one distractor shape. Participants randomly received a low or high reward after correct trials. From one trial to the next, target colors could stay the same or swap with the distractor color. Interestingly, and despite the irrelevancy of reward magnitude for task accuracy, the difference in reaction time between swap and non-swap trials usually is more pronounced following a high compared to a low reward. RESULTS: In the current study, we showed that reward modulated attention is larger for individuals with enhanced reward magnitude sensitivity in the ventral striatum. In addition, connectivity data shows that ventral striatum was more positively connected with visual cortex during high reward non-swap trials compared to high reward swap trials for participants showing stronger reward modulated attention. CONCLUSIONS: This suggests that involuntary reward modulated attention might be implemented by direct influences of the ventral striatum on visual cortex.

The processing of animacy information is disrupted as a function of callous-unemotional traits in youth with disruptive behavior disorders.

Atypical amygdala responses to emotional stimuli have been consistently reported in youth with Disruptive Behavior Disorders (DBDs; Conduct Disorder/Oppositional Defiant Disorder). However, responding to animacy stimuli has not been systematically investigated. Yet, the amygdala is known to be responsive to animacy stimuli and impairment in responsiveness to animacy information may have implications for social cognitive development. Twenty-nine youth with DBDs and 20 typically developing youth, matched for IQ, age (Mage  = 14.45, SD = 2.05) and gender, completed a dot probe task during fMRI. Stimuli consisted of negative/faces, negative/objects, neutral/faces and neutral/objects images. Youth with DBDs, relative to typically developing youth, showed: i) reduced amygdala and lateral temporal cortex responses to faces relative to objects. Moreover, within the group of youth with DBDs, increasing callous-unemotional traits were associated with lesser amygdala responses to faces relative to objects. These data suggest that youth with DBDs, particularly those with high levels of CU traits exhibit dysfunction in animacy processing in the amygdala. This dysfunction may underpin the asociality reported in these youth.

Outbursts of anger as a trigger of acute cardiovascular events: a systematic review and meta-analysis.

AIM: Short-term psychological stress is associated with an immediate physiological response and may be associated with a transiently higher risk of cardiovascular events. The aim of this study was to determine whether brief episodes of anger trigger the onset of acute myocardial infarction (MI), acute coronary syndromes (ACS), ischaemic and haemorrhagic stroke, and ventricular arrhythmia. METHODS AND RESULTS: We performed a systematic review of studies evaluating whether outbursts of anger are associated with the short-term risk of heart attacks, strokes, and disturbances in cardiac rhythm that occur in everyday life. We performed a literature search of the CINAHL, Embase, PubMed, and PsycINFO databases from January 1966 to June 2013 and reviewed the reference lists of retrieved articles and included meeting abstracts and unpublished results from experts in the field. Incidence rate ratios and 95% confidence intervals were calculated with inverse-variance-weighted random-effect models. The systematic review included nine independent case-crossover studies of anger outbursts and MI/ACS (four studies), ischaemic stroke (two studies), ruptured intracranial aneurysm (one study), and ventricular arrhythmia (two studies). There was evidence of substantial heterogeneity between the studies (I(2) = 92.5% for MI/ACS and 89.8% for ischaemic stroke). Despite the heterogeneity, all studies found that, compared with other times, there was a higher rate of cardiovascular events in the 2h following outbursts of anger. CONCLUSION: There is a higher risk of cardiovascular events shortly after outbursts of anger.

The impact of marijuana use on glucose, insulin, and insulin resistance among US adults.

BACKGROUND: There are limited data regarding the relationship between cannabinoids and metabolic processes. Epidemiologic studies have found lower prevalence rates of obesity and diabetes mellitus in marijuana users compared with people who have never used marijuana, suggesting a relationship between cannabinoids and peripheral metabolic processes. To date, no study has investigated the relationship between marijuana use and fasting insulin, glucose, and insulin resistance. METHODS: We included 4657 adult men and women from the National Health and Nutrition Examination Survey from 2005 to 2010. Marijuana use was assessed by self-report in a private room. Fasting insulin and glucose were measured via blood samples after a 9-hour fast, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance. Associations were estimated using multiple linear regression, accounting for survey design and adjusting for potential confounders. RESULTS: Of the participants in our study sample, 579 were current marijuana users and 1975 were past users. In multivariable adjusted models, current marijuana use was associated with 16% lower fasting insulin levels (95% confidence interval [CI], -26, -6) and 17% lower HOMA-IR (95% CI, -27, -6). We found significant associations between marijuana use and smaller waist circumferences. Among current users, we found no significant dose-response. CONCLUSIONS: We found that marijuana use was associated with lower levels of fasting insulin and HOMA-IR, and smaller waist circumference.