Magnetic Resonance (MR) Metabolic Imaging in Glioma

This review is focused on describing the use of magnetic resonance (MR) spectroscopy for metabolic imaging of brain tumors. We will first review the MR metabolic imaging findings generated from preclinical models, focusing primarily on in vivo studies, and will then describe the use of metabolic imaging in the clinical setting. We will address relatively well‐established ¹H MRS approaches, as well as ³¹P MRS, ¹³C MRS and emerging hyperpolarized ¹³C MRS methodologies, and will describe the use of metabolic imaging for understanding the basic biology of glioma as well as for improving the characterization and monitoring of brain tumors in the clinic.     

Inducible expression of dominant negative insulin-like growth factor I receptor in MCF-7 breast cancer cells

The insulin-like growth factor I receptor (IGF-IR) is expressed in many cell types and is critical for normal growth and development. In the healthy mammary gland, the role of IGF-IR is not fully elucidated. However, IGF-IR, which is primarily expressed in the mammary epithelial cells, is known to play an obligatory role in cellular transformation, facilitating the progression to breast cancer. We have utilized the tetracycline regulatory (tet-on) system to generate an in vitro model system to allow us to further investigate IGF-I/IGF-IR function in mammary epithelial cells. A plasmid construct containing a mutant IGF-I receptor (IGF-IR-DN) fused to the tetracycline operator (tetOPh_CMV-IGF-IR-DN) was stably transfected into MCF-7 human breast cancer cells. The conditional regulation of the IGF-IR-DN gene expression was studied in four independent clonal lines. The translated IGF-IR-DN protein was detected only in the stably transfected doxycycline-induced cells, and its expression was up-regulated (three- to sixfold) following induction. IGF-I stimulated cell proliferation diminished (twofold) in doxycycline-induced cells compared to uninduced cells, demonstrating that the transgene construct was functional and ruling out any pleiotropic effect that may be attributed to doxycycline. Interestingly, autophosphorylation of the IGF-IR and phosphorylation of the downstream substrate, insulin receptor substrate-1 (IRS-1), was not inhibited in doxycycline/IGF-I treated cells, suggesting the possibility that activation of downstream substrates other than the IRS-1 may be critical for optimal cell proliferation. This novel in vitro model should allow us to more directly examine the role of IGF-I/IGF-IR signaling and function in mammary epithelial cells.     

Opioid drug poisonings in Ohio adolescents and young adults, 2002–2014

Context: Opioids represent a drug class that adolescents and young adults intentionally misuse and abuse. When taken on their own or with other substances in this manner, opioids pose an increased risk of overdose and potential death.

Objective: To determine trends of opioid drug poisonings among adolescents and young adults in Ohio from 2002 to 2014 using Poison Control Center (PCC) data.

Methods: Data were obtained from Ohio PCCs from 2002 to 2014 for opioid drug poisonings amongst 10–29 year olds. Trends were evaluated with Poisson regression. Ohio counties with higher opioid drug poisoning rates were identified using age-adjusted resident population estimates. Chi-square tests were conducted to compare these county rates to the Ohio rate.

Results: Both unintentional and intentional Ohio PCC opioid drug poisonings peaked in 2009, and there were significant declines through 2014. Almost 40% of intentional opioid drug poisonings were for young adults aged 18–24 years. Suspected suicide poisonings were 64.9% female, misuse poisonings were 54.5% male, and abuse poisonings were 60.1% male. Commonly reported substances included tramadol, heroin, and acetaminophen combinations with hydrocodone or oxycodone. Benzodiazepines and ethanol were the most common substances reported in conjunction with opioids. The top four Ohio counties with significantly higher opioid drug poisoning rates than the state average in 2014 were Hamilton, Mahoning, Butler, and Fairfield.

Conclusion: This study enhances the understanding of Ohio’s opioid epidemic so that future prevention efforts and legislation can better target needed resources. Both males and females would benefit from opioid education early in their lives.     

Changes in the Occurrence,Severity, and Distress of Symptoms in Patients With Gastrointestinal Cancers Receiving Chemotherapy

Context

Studies on multiple dimensions of the symptom experience of patients with gastrointestinal cancers are extremely limited.

Contextual Information Drives the Reconsolidation-Dependent Updating of Retrieved Fear Memories

Stored memories enter a temporary state of vulnerability following retrieval known as ‘reconsolidation'', a process that can allow memories to be modified to incorporate new information. Although reconsolidation has become an attractive target for treatment of memories related to traumatic past experiences, we still do not know what new information triggers the updating of retrieved memories. Here, we used biochemical markers of synaptic plasticity in combination with a novel behavioral procedure to determine what was learned during memory reconsolidation under normal retrieval conditions. We eliminated new information during retrieval by manipulating animals'' training experience and measured changes in proteasome activity and GluR2 expression in the amygdala, two established markers of fear memory lability and reconsolidation. We found that eliminating new contextual information during the retrieval of memories for predictable and unpredictable fear associations prevented changes in proteasome activity and glutamate receptor expression in the amygdala, indicating that this new information drives the reconsolidation of both predictable and unpredictable fear associations on retrieval. Consistent with this, eliminating new contextual information prior to retrieval prevented the memory-impairing effects of protein synthesis inhibitors following retrieval. These results indicate that under normal conditions, reconsolidation updates memories by incorporating new contextual information into the memory trace. Collectively, these results suggest that controlling contextual information present during retrieval may be a useful strategy for improving reconsolidation-based treatments of traumatic memories associated with anxiety disorders such as post-traumatic stress disorder.