Changes in amount and intensity of physical activity over time in breast cancer survivors.

BACKGROUND: Physical activity is associated with decreased breast cancer recurrence and mortality, as well as fewer treatment-related symptoms. Nevertheless, most breast cancer survivors do not meet physical activity guidelines. The purpose of this manuscript is to characterize physical activity trends over time in breast cancer survivors. METHODS: Mayo Clinic Breast Disease Registry participants received surveys at baseline and at 1 and 4 years after diagnosis; breast cancer recurrence and/or metastatic disease were exclusion criteria. Participants were considered to be meeting guidelines if they self-reported at least 150 minutes of moderate-intensity (eg, fast walking) and/or strenuous (eg, jogging) physical activity per week. Statistical analyses include analysis of covariance methods, paired t tests, conditional logistic regression models, and McNemar tests of homogeneity. RESULTS: A total of 171 participants were included in the analysis. The amount of total physical activity decreased over time (P = .07). Mild-intensity physical activity (eg, easy walking) decreased most over time (P = .05). Among participants aged 18-49 years, mild-intensity (P = .05) and moderate-intensity (P = .02) physical activity decreased over time. Strenuous-intensity physical activity levels decreased over time among participants with a normal body mass index (P = .002) and with obesity (P = .01). CONCLUSIONS: We found a trend-level decrease in total physical activity over time, driven mostly by a decrease in mild-intensity physical activity. Young breast cancer survivors are especially likely to reduce their physical activity over time. Further research on implementing physical activity guidelines in clinical practice is warranted.

Primary hepatic Epstein-Barr virus-positive diffuse large B-cell lymphoma associated with azathioprine immunosuppression: a case report.

BACKGROUND: Hepatic masses are relatively common findings, and the diagnostic approach often begins by identifying patient and mass characteristics that are risk factors for malignancy. Chronic immunosuppression is a known risk factor for various malignancies, and azathioprine in particular has been reported in association with solid and hematologic malignancies, including diffuse large B-cell lymphoma. CASE PRESENTATION: A 46-year-old white woman presented to clinic with several weeks of gastrointestinal symptoms and was found to have a hepatic mass on imaging. Her history was notable for neuromyelitis optica spectrum disorder on chronic immunosuppression with azathioprine. It was initially thought to be an inflammatory adenoma. On 6-month follow-up imaging, the mass had grown rapidly in size and was surgically resected. Further workup determined the mass to be an iatrogenic immunodeficiency-associated Epstein-Barr virus-positive diffuse large B-cell lymphoma confined to the liver. Azathioprine was discontinued and the patient underwent treatment with rituximab with no evidence of recurrence 2 years after the initiation of treatment. CONCLUSIONS: This case report describes the first time hepatic Epstein-Barr virus-positive diffuse large B-cell lymphoma has been reported with azathioprine, which highlights the unique sequelae of chronic immunosuppression, including atypical hematologic malignancies, and the importance of considering chronic immunosuppression in the diagnostic evaluation of a hepatic mass.

Factors Associated With Physical Activity Levels in Patients With Breast Cancer.

Physical activity (PA) is associated with improvement in breast cancer treatment-related symptoms and survival, yet most breast cancer survivors do not meet national PA guidelines. This study aimed to identify characteristics of participants that were associated with an increased likelihood of meeting PA guidelines. Adults with breast cancer seen at Mayo Clinic (Rochester, MN) were surveyed regarding their PA participation, and those who self-reported at least 150 minutes of moderate and/or strenuous aerobic PA weekly on average were considered to be "meeting guidelines". Three thousand participants returned PA data. Younger age, completion of the survey 7-12 years after diagnosis, absence of recurrence, no bilateral mastectomy, absence of metastatic disease, and lower BMI at the time of survey completion were associated with PA participation (P < .05 in univariate and multivariate analyses). Findings were similar when a threshold of 90 minutes was applied. These results may inform the development of targeted PA-facilitating interventions.

Hot flash clinical trial baseline measurements: how long is needed?

OBJECTIVES: Classically, hot flash studies included a baseline period of 1 week or longer. The objective of this study was to compare the accuracy of a 1-day baseline diary to a traditional 1-week diary. METHODS: Raw data from 5 pilot studies and 15 phase III randomised controlled trials (RCTs), all of which used a 1-week baseline period, were obtained. Descriptive statistics were used to describe day-by-day variations in hot flash frequencies and scores, during the baseline week. Additional analyses evaluated whether the conclusions from any of the individual pilot studies would have been changed if only a 1-day baseline period had been used. For the RCTs, p values were recalculated using mixed models, adjusting for the baseline value by including it as a covariate. RESULTS: A total of 2573 participants were included. On average, participants had 8.5 hot flashes per day on day 1. Mean hot flash frequencies and scores on subsequent days (days 2-7) were within 6% of day 1 values. When comparing a 1-day to a 1-week baseline period, there was an absolute difference of only 0.29 hot flashes per day (SD 2.25). Reanalysis for each pilot study revealed that no individual study conclusions would have been altered by a shorter baseline. For the RCTs, a shorter baseline period changed the results of only 1 of 24 comparisons from statistically significant to not significant, or vice versa. CONCLUSIONS: A 1-day hot flash diary appears to accurately reflect the true frequency and severity of baseline symptoms in appropriately sized cohorts.

Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency.

Maternal iron deficiency anemia, obesity, and diabetes are prevalent during pregnancy. All are associated with neonatal brain iron deficiency (ID) and neurodevelopmental impairment. Exosomes are extracellular vesicles involved in cell-cell communication. Contactin-2 (CNTN2), a neural-specific glycoprotein, and brain-derived neurotrophic factor (BDNF) are important in neurodevelopment and found in exosomes. We hypothesized that exosomal CNTN2 and BDNF identify infants at risk for brain ID. Umbilical cord blood samples were measured for iron status. Maternal anemia, diabetes, and body mass index (BMI) were recorded. Cord blood exosomes were isolated and validated for the exosomal marker CD81 and the neural-specific exosomal marker CNTN2. Exosomal CNTN2 and BDNF levels were quantified by ELISA. Analysis of CNTN2 and BDNF levels as predictors of cord blood iron indices showed a direct correlation between CNTN2 and ferritin in all neonates (n = 79, ß = 1.75, p = 0.02). In contrast, BDNF levels inversely correlated with ferritin (ß = -1.20, p = 0.03), with stronger association in female neonates (n = 37, ß = -1.35, p = 0.06), although there is no evidence of a sex-specific effect. Analysis of maternal risk factors for neonatal brain ID as predictors of exosomal CNTN2 and BDNF levels showed sex-specific relationships between infants of diabetic mothers (IDMs) and CNTN2 levels (Interaction p = 0.0005). While male IDMs exhibited a negative correlation (n = 42, ß = -0.69, p = 0.02), female IDMs showed a positive correlation (n = 37, ß = 0.92, p = 0.01) with CNTN2. A negative correlation between BNDF and maternal BMI was found with stronger association in female neonates (per 10 units BMI, ß = -0.60, p = 0.04). These findings suggest CNTN2 and BNDF are respective molecular markers for male and female neonates at risk for brain ID. This study supports the potential of exosomal markers to assess neonatal brain status in at-risk infants.

Conditioned object preference: an alternative approach to measuring reward learning in rats.

Pavlovian conditioned approach behavior can be directed as much toward discrete cues as it is toward the environmental contexts in which those cues are encountered. The current experiments characterized a tendency of rats to approach object cues whose prior exposure had been paired with reward (conditioned object preference, COP). To demonstrate the phenomenon, rats were conditioned to associate cocaine or saline with two different objects. Rats acquired a preference, assessed using investigation times directed toward each object, for the cocaine-paired object following conditioning. Furthermore, high levels of object investigation during cocaine conditioning predicted stronger preferences for the cocaine-paired object in the test phase. Conditioned approach diminished across extinction but was reinstated through a priming injection of cocaine. To determine whether preferences are affected by reward value, rats were conditioned using three objects paired with 0, 5, or 20 mg/kg of cocaine. This produced object preferences in the post-test that scaled with cocaine dose used for conditioning. Finally, we explored whether contextual cues modulate expression of COP by testing rats for renewal of cocaine seeking. When conditioning was conducted in one context and extinction training in a second context, COP was renewed when the rats were retested in the original context. Thus, conditioned object preferences are readily acquired, easily measured, and amenable to a number of standard Pavlovian conditioning manipulations. This task promises to become a valuable addition to the panoply of behavioral tools available to test mechanisms underlying adaptive and maladaptive reward processing.

Dorsal Horn Circuits for Persistent Mechanical Pain.

Persistent mechanical hypersensitivity that occurs in the setting of injury or disease remains a major clinical problem largely because the underlying neural circuitry is still not known. Here we report the functional identification of key components of the elusive dorsal horn circuit for mechanical allodynia. We show that the transient expression of VGLUT3 by a discrete population of neurons in the deep dorsal horn is required for mechanical pain and that activation of the cells in the adult conveys mechanical hypersensitivity. The cells, which receive direct low threshold input, point to a novel location for circuit initiation. Subsequent analysis of c-Fos reveals the circuit extends dorsally to nociceptive lamina I projection neurons, and includes lamina II calretinin neurons, which we show also convey mechanical allodynia. Lastly, using inflammatory and neuropathic pain models, we show that multiple microcircuits in the dorsal horn encode this form of pain.