Reversal of endocrine resistance in breast cancer: interrelationships among 14-3-3ζ, FOXM1, and a gene signature associated with mitosis

Introduction  

Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. 14-3-3 ζ/YWHAZ, a member of the 14-3-3 family of conserved proteins, is over-expressed in several types of cancer, and our previous work showed that high expression of 14-3-3ζ in ER-positive breast cancers was associated with a poor clinical outcome for women on tamoxifen. Therefore, we now probe the role of 14-3-3ζ in endocrine resistance, and we examine the functional dimensions and molecular basis that underlie 14-3-3ζ activities.     

Disturbances in Melatonin, Cortisol and Core Body Temperature Rhythms after Major Surgery

Background It has been suggested that circadian rhythm disturbances are present after major surgery and that this may play a role in the development of postoperative sleep disturbances, fatigue, cognitive dysfunction and cardiovascular morbidity. The objective of this study was to examine the profile of melatonin, cortisol and core body temperature rhythms before and after major surgery. Methods Blood samples (melatonin and cortisol) and core body temperature readings were collected every hour in the 24-h period prior to surgery and the 48 h after surgery from 11 patients undergoing major abdominal surgery. All patients had private rooms. Light exposure was controlled and monitored. Phase markers [50% dim light melatonin onset (DLMO 50%) and offset (DLMOff 50%), cortisol and core body temperature acrophase] for the three circadian rhythm profiles were calculated before and after surgery. The correlation between the melatonin rhythm and time of surgery, duration of surgery and opioid use was examined. Results A median delay in the onset of melatonin was seen on the first postoperative day [median DLMO 50% 22:46 hours (range: 21:15–01:08 hours) on the preoperative day compared with 23:54 hours (range: 19:09–02:46 hours) on the first postoperative day; P ≤ 0.05] . A significant positive correlation existed between the duration of surgery and the time of melatonin onset (r = 0.67, P ≤ 0.05) . There was a significantly reduced basal secretion of melatonin immediately after surgery, with a subsequent significant increase in maximum melatonin values on the second postoperative night. A median delay of up to 4 h was seen in the timing of the peak of the temperature rhythm on the second postoperative day. Both cortisol secretion and core body temperature were increased after surgery and did not return to preoperative values in the 48 h of the postoperative study period. No significant correlation between opioid dose and the basal or maximum melatonin levels or the time of melatonin onset was found. Conclusion We found disturbances in three circadian markers after major surgery. The clinical consequences of postoperative circadian disturbances should be investigated further in the future.     

Evaluating the Impact of an Anti-stigma Intervention on Pharmacy Students’ Willingness to Counsel People Living with Mental Illness

Third-year pharmacy students (n?=?88) participated in an anti-stigma intervention program consisting of presentations, videos, discussion and active-learning exercises. Willingness to counsel (WTC) people with mental illness (MI) was evaluated using immediate pre and post-tests comparing diabetes, depression and schizophrenia. At pre-test, WTC diabetes was highest (higher?=?increased WTC) while schizophrenia was the lowest. There were no statistically significant differences between pre/post-test WTC for diabetes and depression, while schizophrenia WTC increased significantly (p?<?0.05). At post-test, diabetes WTC was significantly higher than depression and schizophrenia (p?<?0.0001). Regression results for WTC depression showed that comfortability and gender were significant (p?<?0.05) predictors. Regression results for WTC schizophrenia showed that comfortability was a significant (p?<?0.05) predictor. As highly accessible healthcare providers, pharmacists have the potential to positively impact healthcare, but this depends on WTC. Colleges of pharmacy may consider instituting policies that support experiential education involving counseling people living with MI, as this may increase comfortability.     

Increasing body image flexibility in a residential eating disorder facility: Correlates with symptom improvement

Objective: The purpose of this study was to examine the effects of changes in body image psychological flexibility over the course of treatment on various outcome variables. Method: Participants included 103 female, residential patients diagnosed with an eating disorder. Pretreatment and posttreatment data were collected that examined body image psychological flexibility, general psychological flexibility, symptom severity, and other outcome variables. Results: Changes in body image psychological flexibility significantly predicted changes in all outcome measures except for obsessive-compulsive symptoms after controlling for body mass index, depression, and anxiety. Additionally, these results were maintained after controlling for general psychological flexibility, contributing to the incremental validity of the BI-AAQ. Discussion: This study suggests that changes in body image psychological flexibility meaningfully predict changes in various treatment outcomes of interest, including eating disorder risk, quality of life, and general mental health. Findings indicate that body image psychological flexibility might be a viable target for eating disorder treatment.