The Ipn Regulates Anxiety Independently Of Drug Addiction

ABSTRACT THE INTERPEDUNCULAR NUCLEUS REGULATES ANXIETY Ian A. McLaughlin Dr. Mariella De Biasi This work is devoted to better understanding how a component of one of the principle anatomical intersections of cognitive, emotional, and motivational signaling regulates anxiety and addiction. The majority of my work focused on the interpeduncular nucleus (IPN). The IPN and its principle source of afferent signals, the medial habenula (MHb), comprise a junction of signaling within the diencephalic conduction system (DDC). Along with the medial forebrain bundle, the DDC is a highly conserved pathway by which signals from the limbic forebrain reach the midbrain and hindbrain. Work in our lab and others has implicated the MHb-IPN axis in the aversive affective and somatic withdrawal syndrome that manifests following cessation of chronic exposure to habit-forming drugs, including alcohol, nicotine, and opioids. Given that functional role, I sought to establish if this pathway regulates affect independently of chronic drug exposure. In addition to my primary work, additional experiments I performed contributed to the growing understanding of how this pathway functions within the context of addiction. In particular, I contributed to studies focused on how the presence of the α5 nicotinic acetylcholine receptor subunit (nAChRs) in the IPN and its neighboring structure, the ventral tegmental area (VTA), influences predispositions to alcohol and nicotine addictions in animal models. Using in vivo chemogenetics, viral tracing and receptor subunit rescue, microdialysis, and behavioral analyses, I worked to evaluate how perturbations of signaling within the IPN or VTA affected mouse behavior. Overall, I have found that the IPN does indeed regulate affect independently of chronic drug exposure, and that signaling via the α5 nAChR subunit within both the IPN and VTA significantly regulates drug-taking behavior

Reducing Tobacco Use and Access Through Strengthened Minimum Price Laws

Higher prices reduce consumption and initiation of tobacco products. A minimum price law that establishes a high statutory minimum price and prohibits the industry’s discounting tactics for tobacco products is a promising pricing strategy as an alternative to excise tax increases. Although some states have adopted minimum price laws on the basis of statutorily defined price “markups” over the invoice price, existing state laws have been largely ineffective at increasing the retail price. We analyzed 3 new variations of minimum price laws that hold great potential for raising tobacco prices and reducing consumption: (1) a flat rate minimum price law similar to a recent enactment in New York City, (2) an enhanced markup law, and (3) a law that incorporates both elements

The OGF-OGFr axis utilizes the p21 pathway to restrict progression of human pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the 4th leading cause of death from cancer in the U.S. The opioid growth factor (OGF; [Met⁵]-enkephalin) and the OGF receptor form an inhibitory growth regulatory system involved in the pathogenesis and treatment of pancreatic cancer. The OGF-OGFr axis influences the G₀/G₁phase of the cell cycle. In this investigation, we elucidate the pathway of OGF in the cell cycle.</p> <p>Results</p> <p>Using BxPC-3 cells, OGF decreased phosphorylation of retinoblastoma (Rb) protein without changing total Rb. This change was correlated with reduced cyclin-dependent kinase protein (Cdk) 2 kinase activity, but not total Cdk2. OGF treatment increased cyclin-dependent kinase inhibitor (CKI) p21 protein expression in comparison to controls, as well levels of p21 complexed with Cdk2. Naloxone abolished the increased expression of p21 protein by OGF, suggesting a receptor-mediated activity. p21 specific siRNAs blocked OGF's repressive action on proliferation in BxPC-3, PANC-1, and Capan-2 cells; cells transfected with negative control siRNA had no alteration in p21 expression, and therefore were inhibited by OGF.</p> <p>Conclusion</p> <p>These data are the first to reveal that the target of cell proliferative inhibitory action of OGF in human pancreatic cancer is a p21 CKI pathway, expanding strategies for diagnosis and treatment of these neoplasias.</p

Investigating Temporal Features of Carotid Intima-Media Thickness from Ultrasound Imaging with Recurrent Neural Networks

Measuring carotid intima-media thickness (cIMT) of the Common Carotid Artery (CCA) via B-mode ultrasound imaging is a non-invasive yet effective way to monitor and assess cardiovascular risk. Recent studies using Convolutional Neural Networks (CNNs) to automate the process have mainly focused on the detection of regions of interest (ROI) in single frame images collected at fixed timepoints and have not exploited the temporal information captured in ultrasound imaging. This paper presents a novel framework to investigate the temporal features of cIMT, in which Recurrent Neural Networks (RNN) were deployed for ROI detection using consecutive frames from ultrasound imaging. The cIMT time series can be formed from estimates of cIMT in each frame of an ultrasound scan, from which additional information (such as min, max, mean, and frequency) on cIMT time series can be extracted. Results from evaluation show the best performance for ROI detection improved 4.75% by RNN compared to CNN-based methods. Furthermore, the heart rate estimated from the cIMT time series for seven patients was highly correlated with the patient’s clinical records, which suggests the potential application of the cIMT time series and related features for clinical studies in the future.<br/

Does the Medical College Admission Test (MCAT) predict licensing examination performance in the Canadian context?

Background: Research on the predictive validity of the Medical College Admissions Test (MCAT) on licensing examination performance is varied in its conclusions, with only a few studies examining this relationship in a Canadian context. We assessed the predictive validity of the MCAT on successful performance on the Medical Council of Canada Qualifying Examination (MCCQE) Part 1 by students attending the Cumming School of Medicine.   Methods: Prospective data were collected on MCAT score and sub-section scores, MCCQE decision, multiple mini interview (MMI) performance, gender, and age. The cohort was divided into a derivation cohort (2013 and 2014) and validation cohort (2015 and 2016). Students were dichotomized into pass or fail on MCCQE. Multiple logistic regression in which our dependent variable was MCCQE Part I examination success at the first attempt was used, and potential explanatory variables were age, gender, MCAT total score, and sub-scores for the biological sciences (MCAT-BS), physical sciences, and verbal reasoning, GPA, and MMI ratings.Results: For the derivation cohort MCAT-BS was associated with success on the MCCQE Part I. The odds ratio for this association of 1.37 (95% confidence interval [1.01, 1.85], p = 0.04). When we applied the MCAT-BS to our validation cohort the odds ratio of MCCQE Part I examination success was 1.42 [1.10, 1.83], p = 0.007) and the area under the ROC curve was 0.66 [0.54, 0.79]).Conclusion: The MCAT-BS predicted successful performance on the MCCQE Part 1 Examination in the Canadian setting