Goodmanjonasson4637

Hyperthermia is a promising anticancer treatment used in combination with radiotherapy and chemotherapy. Temperatures above 41.5 °C are cytotoxic and hyperthermia treatments can target a localized area of the body that has been invaded by a tumor. However, non-lethal temperatures (39-41 °C) can increase cellular defenses, such as heat shock proteins. This adaptive survival response, thermotolerance, can protect cells against subsequent cytotoxic stress such as anticancer treatments and heat shock (>41.5 °C). Autophagy is another survival process that is activated by stress. This study aims to determine whether autophagy can be activated by heat shock at 42 °C, and if this response is mediated by reactive oxygen species (ROS). Autophagy was increased during shorter heating times ( less then 60 min) at 42 °C in cells. Levels of acidic vesicular organelles (AVO) and autophagy proteins Beclin-1, LC3-II/LC-3I, Atg7 and Atg12-Atg5 were increased. Heat shock at 42 °C increased levels of ROS. Increased levels of LC3 and AVOs at 42 °C were inhibited by antioxidants. Therefore, increased autophagy during heat shock at 42 °C ( less then 60 min) was mediated by ROS. Conversely, heat shock at 42 °C for longer times (1-3 h) caused apoptosis and activation of caspases in the mitochondrial, death receptor and endoplasmic reticulum (ER) pathways. Thermotolerant cells, which were developed at 40 °C, were resistant to activation of apoptosis at 42 °C. Autophagy inhibitors 3-methyladenine and bafilomycin sensitized cells to activation of apoptosis by heat shock (42 °C). Improved understanding of autophagy in cellular responses to heat shock could be useful for optimizing the efficacy of hyperthermia in the clinic.

Patient knowledge of radiation therapy (RT) before consult is typically limited, with many having misconceptions or fears. AUPM170 There exists a need to improve patient education in RT. Our purpose was to study the impact of patient education videos on patient-reported knowledge of RT, anxiety/fear, and satisfaction.

At our institution, we created 2 RT educational videos a general RT video and a breast cancer-specific video. Patients presenting for breast RT who agreed to participate (n = 107) were randomly assigned to receive a link to the videos (video group; n = 58) or not (no-video group; n = 49) before consultation. Pre- and postconsult surveys were administered assessing patient-reported measures on a 5-point Likert-type scale.

Patients in the video group reported significantly higher levels of confidence in their knowledge of radiation side effects, with 45.6.% at least somewhat confident versus 21.3% in the no-video group (P = .009; median on a 5-point Likert-type scale, 2 [interquartile range IQR, 2-3] versus 2 [IQR, 1-2], respectively [P = .012]). There was a trend toward higher knowledge of the radiation treatment process in the video group (median, 3 [IQR, 2-3] versus 2 [IQR, 2-3] for no-video group; P = .064). There were no significant differences in preconsult anxiety or fear between the groups, but of those who were assigned videos, 46.8% reported decreased anxiety afterward, and 66.0% felt more comfortable coming to a consult. While those in the no-video group hypothesized that a video would be helpful (median, 3; IQR, 3-4), those in the video group found them to be very helpful in real life (median, 4; IQR, 45; P = .0009). After the consult, all patients in both groups were satisfied.

Patient education videos increase patient-reported knowledge of RT and are found to be very helpful.

Patient education videos increase patient-reported knowledge of RT and are found to be very helpful.The nucleus accumbens (NAc) plays a crucial role in various mental activities, including positive and negative reinforcement. We previously hypothesized that a balance between dopamine (DA) and adenosine signals regulates the PKA-Rap1 pathway in medium spiny neurons expressing DA D1 receptors (D1R-MSNs) or D2 receptors (D2R-MSNs) and demonstrated that the PKA-Rap1 pathway in D1R-MSNs is responsible for positive reinforcement. Here, we show the role of the PKA-Rap1 pathway in accumbal D2R-MSNs in negative reinforcement. Mice were exposed to electric foot shock as an aversive stimulus. We monitored the phosphorylation level of Rap1gap S563, which leads to the activation of Rap1. Electric foot shocks increased the phosphorylation level of GluN1 S897 and Rap1gap S563 in the NAc. The aversive stimulus-evoked phosphorylation of Rap1gap S563 was detected in accumbal D2R-MSNs and inhibited by pretreatment with adenosine A2a receptor (A2aR) antagonist. A2aR antagonist-treated mice showed impaired aversive memory in passive avoidance tests. AAV-mediated inhibition of PKA, Rap1, or MEK1 in accumbal D2R-MSNs impaired aversive memory in passive avoidance tests, whereas activation of this pathway potentiated aversive memory. Optogenetic inactivation of mesolimbic DAergic neurons induced place aversion in real-time place aversion tests. Aversive response was attenuated by inhibition of PKA-Rap1 signaling in accumbal D2R-MSNs. These results suggested that accumbal D2R-MSNs regulate aversive behaviors through the A2aR-PKA-Rap1-MEK pathway. Our findings provide a novel molecular mechanism for regulating negative reinforcement.

Dysfunctional connectivity of resting-state functional networks has been observed in patients with major depressive disorder (MDD), particularly in cognitive function networks including the central executive network (CEN), default mode network (DMN) and salience network (SN). Findings from studies examining how aberrant functional connectivity (FC) changed after antidepressant treatment, however, have been inconsistent. Thus, the purpose of the present study was to explore potential mechanisms of altered cognitive function networks during resting-state between remitted major depressive disorder (rMDD) patients and healthy controls (HCs) and furthermore, the relationship between dysfunctional connectivity patterns in rMDD and clinical symptoms.

In this study, 19 HCs and 19 rMDD patients were recruited for resting-state functional magnetic resonance imaging (fMRI) scanning. FC was evaluated with independent component analysis for CEN, DMN and SN. Two sample t tests were conducted to compare differences between rMDD and HCs.