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1.  Familial and Perceived Risk of Breast Cancer in Relation to Use of Complementary Medicine 
To examine use of complementary and alternative medicine (CAM) by women with varying levels of familial and perceived risk of breast cancer with the goal of preventing breast cancer.
Cross-sectional data on CAM use were collected on 2198 women (mean age 63) personally unaffected by breast cancer in the Minnesota Breast Cancer Family Study. CAM use was compared across women at high, moderate, or average risk based on family history, as well as across categories of perceived risk of breast cancer. CAM use was also examined in relation to screening and general health behaviors, worry about breast cancer, and optimism.
Half (49.5%) of the women reported using at least one CAM modality with the intent of preventing breast cancer. Univariate analyses indicated that greater overall CAM use was related to greater perceived risk (p = .018), more general health behaviors (p < .0001), more breast cancer screening behaviors (p = .0002), greater optimism (p = .0002) and higher educational attainment (p < .0001). Multivariate analysis revealed that general health behaviors (p < .0001), education (p = .0027), and optimism (p = .037) were significant predictors of CAM use when in the same model with perceived risk and breast cancer screening behaviors.
Many women use CAM with the goal of preventing breast cancer. General health promoting behaviors, education, and optimism predict CAM use. Evidence-based guidance is needed for the public and health care providers on the potential and limitations of specific CAM approaches to impact cancer risk.
PMCID: PMC3959885  PMID: 18541615
2.  Cerebral cavernous malformations arise independent of the Heart of Glass receptor 
Background and Purpose
The Heart of Glass (HEG) receptor binds KRIT1 and functions with KRIT1, CCM2 and PDCD10 in a common signaling pathway required for heart and vascular development. Mutations in KRIT1, CCM2 and PDCD10 also underlie human cerebral cavernous malformation (CCM), and postnatal loss of these genes in the mouse endothelium results in rapid CCM formation. Here we test the role of HEG in CCM formation in mice and humans.
We constitutively or conditionally deleted Heg and/or Ccm2 genes in genetically modified mice. Mouse embryos, brain and retina tissues were analyzed to assess CCM lesion formation.
CCMs form in postnatal mice with Ccm2−/− but not Heg−/− or Heg−/−;Ccm2+/−endothelial cells. Consistent with these findings, human patients with CCM who lack exonic mutations in KRIT1, CCM2 or PDCD10 do not have mutations in HEG.
These findings suggest that the HEG-CCM signaling functions during cardiovascular development and growth, while CCMs arise due to loss of HEG-independent CCM signaling in the endothelium of the central nervous system after birth.
PMCID: PMC4006321  PMID: 24643410
3.  Mechanisms of Systemic Adaptation to Univentricular Fontan Conversion 
After univentricular Fontan conversion, systemic venous pressure serves as the sole driving force for transpulmonary blood flow. Consequently, systemic venous return is markedly altered and ventricular filling is subnormal. The mechanisms and time course of systemic adaptation to Fontan conversion are incompletely understood. We hypothesized that acute elevation in systemic venous pressure induces an adaptive response similar to conversion to a univentricular Fontan circulation.
Adjustable vessel occluders were placed around the superior and inferior vena cavae in juvenile sheep. After one-week recovery, occluders were tightened to acutely increase and maintain systemic venous pressure at 15 mmHg (n=6), simulating one-stage Fontan conversion. Control animals (n=4) received identical surgery, but venous pressure was not manipulated.
Cardiac index decreased significantly (3.9±1.0 to 2.7±0.7 ml/min/m2, P<0.001), then normalized to Control at 2 weeks. Circulating blood volume increased (100±9.4 vs. 85.5±8.4 ml/kg, P=0.034) as a persistent response. Cardiac reserve improved, and was not different from Control, by week 3. Resting heart rate decreased in both groups. Oxygen extraction (A-VO2 difference) and neurohormonal mediators increased transiently, then normalized by week 2.
Adaptation to global elevation in systemic venous pressure to Fontan levels is complete within 2 weeks. Increased blood volume and reduced heart rate are persistent responses. Increased oxygen extraction and neurohormonal upregulation are temporary responses which normalize with recovery of cardiac output. With improved physiologic understanding of systemic adaptation to Fontan conversion, approaches to single ventricle palliation can be more objectively assessed and optimized.
PMCID: PMC2925053  PMID: 20483432
4.  Anxiety sensitivity and catastrophizing: Associations with pain and somatization in non-clinical children 
Journal of health psychology  2009;14(8):1085-1094.
This study examined the relationships among anxiety sensitivity (AS), catastrophizing, somatization, and pain in 240 non-clinical children (121 girls; mean age = 12.7 years). Children with pain problems (n = 81; 33.8%) reported greater AS and catastrophizing (p’s < .01) relative to children without pain problems. AS but not catastrophizing was significantly associated with current pain. However, both AS and catastrophizing were significantly associated with somatization. AS and catastrophizing represent related but partially distinct cognitive constructs that may be targeted by interventions aimed at alleviating pain and somatization in children.
PMCID: PMC2770141  PMID: 19858329
Children; pain; somatization; catastrophizing; anxiety sensitivity
5.  Sex differences in the relationship between maternal negative life events and children’s laboratory pain responsivity 
Prior research has demonstrated links between psychosocial factors, including negative life events (NLE) and pain in children. The present study examined sex differences in the relationship between mother-reported NLE, child NLE, mother somatization and children’s laboratory pain responses for heat, cold and pressure pain tasks. We predicted that maternal NLE would be moderately associated with girls’ pain responses, but would not be associated with boys’ pain responses.
Participants were 176 non-clinical children (89 boys) aged 8–18 years (mean = 12.2, SD = 2.7) and their mothers. Mothers and children completed questionnaires assessing their perceptions of NLE experienced in the previous 12 months.
Contrary to predictions, maternal NLE were related to pain responses in both boys and girls, although in opposite directions. Thus, increased maternal stress was associated with increased pain responses in girls but with decreased pain responses in boys. In addition, the impact of maternal NLE was only apparent for heat and pain tasks, indicating differential effects for various types of pain.
The current findings underscore the importance of family variables in understanding sex differences in children’s pain. Future research is needed to examine the mechanisms within the parent-child relationship that contribute to sex-differentiated pain outcomes, particularly under conditions of exacerbated parental stress.
PMCID: PMC2813770  PMID: 19668092
negative life events; children’s laboratory pain; sex differences
6.  Gender role expectations of pain: relationship to experimental pain perception 
Pain  2002;96(3):335-342.
The primary purpose of this study was to investigate the influence of an individual’s Gender Role Expectations of Pain (GREP) on experimental pain report. One hundred and forty-eight subjects (87 females and 61 males) subjects underwent thermal testing and were asked to report pain threshold, pain tolerance, VAS ratings of pain intensity and unpleasantness, and a computerized visual analogue scales (VAS) rating of pain intensity during the procedure. Subjects completed the GREP questionnaire to assess sex-related stereotypic attributions of pain sensitivity, pain endurance, and willingness to report pain. Consistent with previous research, significant sex differences emerged for measures of pain threshold, pain tolerance, and pain unpleasantness. After statistically controlling for age, GREP scores were significant predictors of threshold, tolerance, and pain unpleasantness, accounting for an additional 7, 11, and 21% of the variance, respectively. Sex remained a significant predictor of pain tolerance in hierarchical regression analyses after controlling for GREP scores. Results provide support for two competing but not mutually exclusive hypotheses related to the sex differences in experimental pain. Both psychosocial factors and first-order, biological sex differences remain as viable explanations for differences in experimental pain report between the sexes. It appears that GREP do play a part in determining an individual’s pain report and may be contributing to the sex differences in the laboratory setting.
PMCID: PMC2535906  PMID: 11973007
Pain; Gender; Sex differences; Experimental pain; Thermal pain
7.  Role of Anticipatory Anxiety and Anxiety Sensitivity in Children’s and Adolescents’ Laboratory Pain Responses 
Journal of pediatric psychology  2004;29(5):379-388.
To examine relationships among trait anxiety sensitivity, state task-specific anticipatory anxiety, and laboratory pain responses in healthy children and adolescents.
Participants (N=118, 49.2% female, ages 8-18 years) completed a measure of anxiety sensitivity and rated anticipatory anxiety prior to undergoing thermal, pressure, and cold pain tasks. Linear and logistic regressions were used to test the hypothesis that anxiety sensitivity and anticipatory anxiety would predict incremental variance in pain response after controlling for sex, age, and anxious symptoms.
Anticipatory anxiety accounted for 35-38% of unique variance in pain report across tasks, and 10% of unique variance in thermal tolerance. Anxiety sensitivity was unrelated to pain responses.
Task-specific anxiety is an important predictor of pain report and, in certain cases, pain tolerance. Interventions designed to reduce task-specific anticipatory anxiety may help reduce pain responses in children and adolescents.
PMCID: PMC2373257  PMID: 15187176
laboratory pain; anxiety; anxiety sensitivity; children; adolescents
8.  Parent and child anxiety sensitivity: Relationship to children’s experimental pain responsivity 
Anxiety sensitivity (AS) or fear of anxiety sensations has been linked to childhood learning history for somatic symptoms, suggesting that parental AS may impact children’s responses to pain. Using structural equation modeling (SEM), we tested a conceptual model in which parent AS predicted child AS, which in turn predicted a hypothesized latent construct consisting of children’s pain intensity ratings for three laboratory pain tasks (cold pressor, thermal heat and pressure). This conceptual model was tested in 211 non-clinical parent-child pairs (104 girls, mean age = 12.4 years; 178 mothers). Our model was supported in girls only indicating that the sex of the child moderated the hypothesized relationships. Thus, parent AS was related to child laboratory pain intensity via its contribution to child AS in girls but not in boys. In girls, 42% of the effect of parent AS on laboratory pain intensity was explained via child AS. In boys, there was no clear link between parent AS and child AS, although child AS was predictive of experimental pain intensity across sex. Our results are consistent with the notion that parent AS may operate via healthy girls’ own fear of anxiety symptoms to influence their responses to laboratory pain stimuli.
Perspective-The present study highlights sex differences in the links among parent and child anxiety sensitivity (AS; fear of anxiety sensations) and children’s experimental pain responses. Among girls, childhood learning history related to somatic symptoms may be a particularly salient factor in the development of AS and pain responsivity.
PMCID: PMC1540407  PMID: 16632321
anxiety sensitivity; laboratory pain; children; adolescents; parent; sex differences
9.  Pain and Use of Complementary and Alternative Medicine in a National Sample of Persons Living with HIV 
The current study investigated the relationship of pain to use of complementary and alternative medicine (CAM) in a U.S. nationally representative sample of 2466 persons with HIV using data from the HIV Cost and Services Utilization Study (HCSUS). Pain was conceptualized as a need characteristic within the context of predisposing, enabling, and need (PEN) characteristics following Andersen's Behavioral Model of Health Services Use. Multivariate analyses were used to examine the association of baseline PEN characteristics with CAM use by follow-up (approximately 6 months later), including use of five specific CAM domains. Change in pain from baseline to follow-up was also examined in relation to CAM use. Baseline pain was a strong predictor of CAM use, and increased pain over time was associated with use of unlicensed or underground drugs with potential for harm. These results highlight the importance of medical efforts to control pain in persons living with HIV.
PMCID: PMC1420635  PMID: 16310616
Complementary medicine; alternative medicine; human immunodeficiency virus; pain

Results 1-9 (9)