Sex differences and the role of estrogen, estrous cycle, and DRG neurons in a mouse model of cancer pain

University of Minnesota Ph.D. dissertation. April 2014. Major: Comparative and Molecular Biosciences. Advisors: Dr. Alvin J. Beitz & Dr. Alice A. Larson. 1 computer file (PDF); v, 121 pages.While conflicting views exist in the literature regarding sex differences in cancer pain, recent studies show that women are more likely to experience greater cancer pain than men. Transient receptor potential (TRP) are considered critical receptors in tumor-induced peripheral sensitization while cycling sex steroid hormones are considered critical factors in sex-dependent differences in cancer pain. Whether sex differences in cancer pain are due to estrogens affect on TRP receptors has yet to be determined. Utilizing a mouse model of bone cancer, we compared tumor-induced mechanical allodynia and thermal (heat and cold) hyperalgesia in intact, gonadectomized, and estradiol-replaced males and females. Tumor-induced changes in TRP and estrogen receptor mRNA levels were assessed. We also examined the anti-nociceptive effects of a topical application of a TRPM8 agonist (menthol) and subcutaneous injected TRPV1 antagonist on tumor-induced nociception. We found no sex differences in tumor-induced mechanical allodynia, but, there was greater mechanical allodynia in females during proestrus/estrus than during diestrus. Estradiol replacement in gonadectomized females increased tumor-induced mechanical allodynia, but decreased allodynia in gonadectomized males. Collectively, females were more sensitive to tumor-induced cold hyperalgesia than males. Tumor-induced cold sensitivity was increased in all gonadectomized animals regardless of estradiol replacement. GPR30 mRNA was greater in females during diestrus than proestrus/estrus. TRPV1 mRNA was lower in diestrus females but greater during proestrus/estrus. Estradiol replacement had in inverse effect on TRPV1 mRNA expression in gonadectomized females, but had no effect in gonadectomized males. TRPM8 mRNA was greater in females than males, while TRPA1 mRNA was greater in males than in females. The TRPV1 antagonist induced antinociception in proestrus/estrus females, but this effect was reduced in estradiol replaced gonadectomized males. Menthol-induced antinociception was reduced in gonadectomized females, but restored with estradiol replacement. These findings suggest that estrogen mediates sex differences in tumor-induced mechanical allodynia and cold hyperalgesia, TRP expression, menthol-induced antinociception as well as TRPV1 antagonist antinociception. Collectively, this verifies that estrogen is, in part, responsible for contrasting sensitivity of males and females to cancer pain

Determinants of caregiving experiences and mental health of partners of cancer patients

BACKGROUND. Research regarding informal caregiving showed considerable individual variation in responses to cancer caregiving. The current longitudinal study examined determinants of caregiver outcomes in terms of caregiver experiences at 3 months and caregiver's mental health at 6 months after hospital discharge. It included both negative and positive dimensions of caregiving outcomes.METHODS. One hundred forty-eight patients with newly diagnosed colorectal carcinoma and their partners were included. Caregiver experiences were assessed by the Caregiver Reaction Assessment Scale, which contains four negative subscales (disrupted schedule, financial problems, lack of family support, and loss of physical strength) and one positive subscale (self-esteem). The mental health of the caregiver was assessed in terms of depression and quality of life. Possible determinants of the caregiver's experiences and mental health were categorized according to characteristics of the caregiver, the patient, and the care situation. Caregiving experiences were studied as a fourth additional category of possible determinants of the caregiver's mental health.RESULTS. Each domain of the caregiving experience was explained by different factors, with total explained variances ranging between 11-46%. Negative caregiver experiences were associated with a low income, living with only the patient, a distressed relationship, a high level of patient dependency, and a high involvement in caregiving tasks. Caregivers with a low level of education and caregivers of patients with a stoma were able to derive more self-esteem from caregiving. Although caregiving may lead to depression, especially in those experiencing loss of physical strength, caregivers may sustain their quality of life by deriving self-esteem from caregiving.CONCLUSIONS. It is important that professionals involved in the ongoing care of cancer patients and their families be aware of the increasing demands made on caregivers and the specific problems and uplifts they perceive in caregiving. Professional caregivers are urged to involve informal caregivers with care explicitly and continuously. However, specific attention to those caregivers who live only with the patient, those with a low income, those with a distressed relationship, and those with a high level of patient dependency and care involvement is warranted. Cancer 1999;86:577-88. (C) 1999 American Cancer Society.</p

Porosity measurements of interstellar ice mixtures using optical laser interference and extended effective medium approximations

Aims. This article aims to provide an alternative method of measuring the porosity of multi-phase composite ices from their refractive indices and of characterising how the abundance of a premixed contaminant (e.g., CO2) affects the porosity of water-rich ice mixtures during omni-directional deposition. Methods. We combine optical laser interference and extended effective medium approximations (EMAs) to measure the porosity of three astrophysically relevant ice mixtures: H2O:CO2=10:1, 4:1, and 2:1. Infrared spectroscopy is used as a benchmarking test of this new laboratory-based method. Results. By independently monitoring the O-H dangling modes of the different water-rich ice mixtures, we confirm the porosities predicted by the extended EMAs. We also demonstrate that CO2 premixed with water in the gas phase does not significantly affect the ice morphology during omni-directional deposition, as long as the physical conditions favourable to segregation are not reached. We propose a mechanism in which CO2 molecules diffuse on the surface of the growing ice sample prior to being incorporated into the bulk and then fill the pores partly or completely, depending on the relative abundance and the growth temperature.Comment: 9 pages, 6 figures, 1 table. Accepted for publication in A&

THE FEASIBILITY AND ACCEPTABILITY OF BEHAVIORAL ACTIVATION IN AN ADOLESCENT CLINICAL SETTING

Purpose: During the COVID-19 pandemic, estimates of adolescent depression prevalence have significantly increased. Although 80% of youth with mental health problems do not access mental health (MH) services, most interact regularly with pediatricians, suggesting primary care is a promising setting for youth MH service delivery. Behavioral activation (BA) is a straightforward intervention focusing on increasing engagement in meaningful activities and has been shown to be effective in adolescent populations. This study examines the feasibility and acceptability of implementing BA delivered by nurses to adolescents with mild to moderate depressive symptoms in an ambulatory setting. Methods: We examined the feasibility and acceptability of BA to a sociodemographic-diverse adolescent population. To examine feasibility, we retrospectively analyzed the percentage of patients presenting with mild to moderate depressive symptoms on the patient health questionnaire-9 during a random four week period. We then conducted qualitative interviews with four parent-adolescent dyads, and two additional adolescents. A semi-structured interview guide was iteratively developed to assess perceived acceptability of BA and barriers and facilitators to engaging in the intervention. Interviews were recorded, transcribed, and coded by authors JDT and JF. A thematic analysis was completed to identify whether the program as designed was acceptable to the targeted population. Results: A records review found that out of 122 unique patients presenting for any clinic visit during the four week period, 44 (35%) met criteria for mild to moderate depressive symptoms. Of those who met criteria, youth were 17.45 years old (range = 12-22) with 61% identified as female. Results of the qualitative interviews suggest that participants perceived BA to be appropriate; themes emerged suggesting that both parents and youth noted nurse-delivered BA was similar to other types of therapies they had engaged with in other settings and that participants experienced nurses’ as able to protect confidentiality and someone they could be “vulnerable” with. Participants were mixed in how feasible they felt regular visits to the pediatrician’s office was, with some noting that transportation and time were major barriers for engaging in treatment. All participants noted that telehealth options (including meeting with a nurse provider over the phone or through web conferencing) were appropriate and would facilitate treatment access. Participants also noted that time, transportation and cost were significant barriers to engaging in valued activities (a central mechanism of BA), and several parents and youth noted that these barriers were exacerbated during the pandemic. Conclusion: Our data highlights the implementation potential for delivering BA by nurses in an adolescent ambulatory setting. Qualitative themes suggest this approach (especially delivered via telehealth) is feasible and acceptable for youth with mild to moderate depressive symptoms

The cooling rate of neutron stars after thermonuclear shell flashes

Thermonuclear shell flashes on neutron stars are detected as bright X-ray bursts. Traditionally, their decay is modeled with an exponential function. However, this is not what theory predicts. The expected functional form for luminosities below the Eddington limit, at times when there is no significant nuclear burning, is a power law. We tested the exponential and power-law functional forms against the best data available: bursts measured with the high-throughput Proportional Counter Array (PCA) on board the Rossi X-ray Timing Explorer. We selected a sample of 35 'clean' and ordinary (i.e., shorter than a few minutes) bursts from 14 different neutron stars that 1) show a large dynamic range in luminosity, 2) are the least affected by disturbances by the accretion disk and 3) lack prolonged nuclear burning through the rp-process. We find indeed that for every burst a power law is a better description than an exponential function. We also find that the decay index is steep, 1.8 on average, and different for every burst. This may be explained by contributions from degenerate electrons and photons to the specific heat capacity of the ignited layer and by deviations from the Stefan-Boltzmann law due to changes in the opacity with density and temperature. Detailed verification of this explanation yields inconclusive results. While the values for the decay index are consistent, changes of it with the burst time scale, as a proxy of ignition depth, and with time are not supported by model calculations.Comment: 10 pages, 7 figures, recommended for publication in A&