Women's Cortisol Stress Responsivity, Sexual Arousability, and Sexual History.

Life history theory and the adaptive calibration model state that characteristics of one's early environment influence individual differences in both neuroendocrine reactivity to stress and sexual risk-taking behavior. However, few studies have directly examined the relationship between neuroendocrine reactivity to stress and risky sexual behavior. This study used multilevel modeling to test whether cortisol reactivity and recovery in response to laboratory stress were associated with women's history of sexual behavior and their sexual arousability in response to laboratory sexual stimuli. Participants were 65 women (35% heterosexual, 44% bisexual, and 21% lesbian) who completed two laboratory sessions, two weeks apart. Women's self-reported sexual arousability to sexual stimuli interacted with their sexual abuse history to predict their trajectories of cortisol stress reactivity and recovery. Cortisol reactivity and recovery were not associated with women's sexual risk taking, such as the age of sexual debut, sociosexuality, or lifetime number of sexual partners.

Investigating Clinical Benefits of a Novel Sleep-Focused Mind-Body Program on Gulf War Illness Symptoms: A Randomized Controlled Trial.

OBJECTIVE: Mind-Body Bridging (MBB) has been shown to be effective for improving disturbed sleep. In this prospective randomized controlled trial, we evaluated the efficacy of sleep-focused MBB compared with sleep education control (SED) for improving sleep in previously deployed Gulf War veterans. METHODS: US military service members with sleep and physical health complaints who were deployed in 1990-1991 were randomized to receive three weekly sessions of either MBB (n = 33) or SED (n = 27) between 2012 and 2015. The primary outcome of Medical Outcomes Study Sleep Scale was completed at baseline, weekly during treatment, postintervention, and 3-month follow-up. Secondary outcome measures for posttraumatic stress disorder, depression, fatigue, quality of life, symptom severity, and mindfulness were completed at baseline, postintervention and 3-month follow-up. Salivary samples were collected at five time points per day at each visit for cortisol and α-amylase assessment. Clinician-administered assessments of sleep and co-occurring conditions were conducted at baseline and postintervention. RESULTS: MBB was significantly more efficacious than SED in reducing disturbed sleep at follow-up (F(1,180.54) = 4.04, p = .046). In addition, self-reported posttraumatic stress disorder (F(1,56.42) = 4.50, p = .038) for the treatment effect, depression (F(1,93.70) = 4.44, p = .038), and fatigue symptoms (F(1,68.58) = 3.90, p = .050) at follow-up improved in MBB compared with those in SED. Consistently higher percentages of veterans in MBB reported improvements of sleep, pain, and composite sleep/general co-occurring symptoms at the postclinical evaluation, as compared with veterans in SED. Finally, the mean waking level of salivary α-amylase in the MBB declined to a greater extent than that in the SED, at follow-up (F(1,88.99) = 3.78, p = .055), whereas no effects were found on cortisol. CONCLUSIONS: Sleep-focused MBB can improve sleep and possibly also co-occurring symptoms in Gulf War veterans. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01543997.

Dynamic reflexivity in action: an armchair walkthrough of a qualitatively driven mixed-method and multiple methods study of mindfulness training in schoolchildren.

Dynamic reflexivity is central to enabling flexible and emergent qualitatively driven inductive mixed-method and multiple methods research designs. Yet too often, such reflexivity, and how it is used at various points of a study, is absent when we write our research reports. Instead, reports of mixed-method and multiple methods research focus on what was done rather than how it came to be done. This article seeks to redress this absence of emphasis on the reflexive thinking underpinning the way that mixed- and multiple methods, qualitatively driven research approaches are thought about and subsequently used throughout a project. Using Morse's notion of an armchair walkthrough, we excavate and explore the layers of decisions we made about how, and why, to use qualitatively driven mixed-method and multiple methods research in a study of mindfulness training (MT) in schoolchildren.

Associations between oxytocin and cortisol reactivity and recovery in response to psychological stress and sexual arousal.

Previous research suggests a dynamic regulatory relationship between oxytocin and cortisol, but the specific nature of this relationship and its context-specificity have not been fully specified. In the present study, we repeatedly assessed both salivary oxytocin and salivary cortisol during two experimental sessions (one inducing sexual arousal and one inducing psychological stress), conducted two weeks apart with the same group of 63 female participants. Baseline cortisol and baseline oxytocin were significantly correlated in both sessions. Cortisol levels showed significantly different patterns of change during the stress assessment than during the sexual arousal assessment, but oxytocin showed similar patterns of change across both assessments. Greater cortisol stress reactivity predicted higher oxytocin levels immediately after the stressor, but a different pattern emerged during the arousal assessment: Greater oxytocin arousal reactivity predicted attenuated post-arousal reductions in cortisol. For both cortisol and oxytocin, individual differences in women's reactivity to sexual arousal did not predict their reactivity to psychological stress. These findings contribute new insights regarding associations between cortisol and oxytocin reactivity and recovery in different psychological contexts.

The Arkansas aging initiative: an innovative approach for addressing the health of older rural Arkansans.

The Donald W. Reynolds Institute on Aging at the University of Arkansas for Medical Sciences in Little Rock is addressing one of the most pressing policy issues facing the United States: how to care for the burgeoning number of older adults. In 2001, the Institute created the Arkansas Aging Initiative, which established seven satellite centers on aging across the state using $1.3 to $2 million dollars annually from the state's portion of the Master Tobacco Settlement. These centers on aging assist the state's population of older adults, many of whom reside in rural areas, live in poverty, and suffer from poor health. The centers provide multiple avenues of education for the community, health care providers, families, and caregivers. The Arkansas Aging Initiative, in partnership with local hospitals, also makes geriatric primary and specialty care more accessible through senior health clinics established across rural Arkansas. In 2005, older adults made more than 36,000 visits to these clinics. All sites have attracted at least one physician who holds a Certificate of Added Qualifications in geriatrics and one advanced practice nurse. Other team members include geriatric medical social workers, pharmacists, nutritionists, and neuropsychologists. This initiative also addresses other policy issues, including engaging communities in building partnerships and programs crucial to maximizing their limited resources and identifying opportunities to change reimbursement mechanisms for care provided to the growing number of older adults. We believe this type of program has the potential to create a novel paradigm for nationwide implementation.

Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways.

Osteoblasts and adipocytes originate from a common progenitor, which arises from bone marrow mesenchymal stroma/stem cells (mMSC). Aging causes a decrease in the number of bone-forming osteoblasts and an increase in the number of marrow adipocytes. Here, we demonstrate that, during aging, the status of mMSC changes with respect to both their intrinsic differentiation potential and production of signaling molecules, which contributes to the formation of a specific marrow microenvironment necessary for maintenance of bone homeostasis. Aging causes a decrease in the commitment of mMSC to the osteoblast lineage and an increase in the commitment to the adipocyte lineage. This is reflected by changes in the expression of phenotype-specific gene markers. The expression of osteoblast-specific transcription factors, Runx2 and Dlx5, and osteoblast markers, collagen and osteocalcin, is decreased in aged mMSC. Conversely, the expression of adipocyte-specific transcription factor PPAR-gamma2, shown previously to regulate osteoblast development and bone formation negatively and to regulate marrow adipocyte differentiation positively, is increased, as is a gene marker of adipocyte phenotype, fatty acid binding protein aP2. Furthermore, production of an endogenous PPAR-gamma activator(s) that stimulates adipocyte differentiation and production of autocrine/paracrine factor(s) that suppresses the osteoblastic phenotype are also increased. In addition, expression of different components of TGF-beta and BMP2/4 signaling pathways is altered, suggesting that activities of these two cytokines essential for bone homeostasis change with aging.

Dispositional mindfulness predicts attenuated waking salivary cortisol levels in cancer survivors: a latent growth curve analysis.

PURPOSE: Cancer survivors experience significant stress and diminished well-being long after treatment. Dispositional mindfulness is linked with salutary coping with stress and enhanced well-being, with potentially beneficial effects on stress-related hormones. In the present study, we evaluated dispositional mindfulness as a predictor of changes in waking salivary cortisol levels among a sample of cancer survivors. METHODS: Mindfulness, well-being, and saliva samples were collected at baseline and at 4- and 12-week follow-ups. Latent growth curve analysis was conducted to examine baseline dispositional mindfulness as a predictor of changes in waking salivary cortisol over time, and regression analyses examined associations between well-being and cortisol. RESULTS: Findings indicated that cancer survivors who reported lower baseline levels of dispositional mindfulness exhibited increases in waking cortisol over time, whereas those who reported higher baseline dispositional mindfulness showed comparatively stable waking cortisol over the study period. Furthermore, increases in waking cortisol were associated with decreased well-being over the study period. CONCLUSIONS: This study provides preliminary evidence that cancer survivors with higher levels of dispositional mindfulness may be buffered from deleterious changes in cortisol secretion. IMPLICATIONS FOR CANCER SURVIVORS: Enhanced dispositional mindfulness may promote salutary neuroendocrine function among cancer survivors and thereby improve well-being during the survivorship process.

An Exploratory Study of the Effects of Mind-Body Interventions Targeting Sleep on Salivary Oxytocin Levels in Cancer Survivors.

Cancer survivors experience high levels of distress, associated with a host of negative psychological states, including anxiety, depression, and fear of recurrence, which often lead to sleep problems and reduction in quality of life (QOL) and well-being. As a neuropeptide hormone associated with affiliation, calmness, and well-being, oxytocin may be a useful biological measure of changes in health outcomes in cancer survivors. In this exploratory study, which comprised a subset of participants from a larger study, we evaluated (a) the feasibility and reliability of salivary oxytocin (sOT) levels in cancer survivors and (b) the effects of 2 sleep-focused mind-body interventions, mind-body bridging (MBB) and mindfulness meditation (MM), compared with a sleep hygiene education (SHE) control, on changes in sOT levels in 30 cancer survivors with self-reported sleep disturbance. Interventions were conducted in 3 sessions, once per week for 3 weeks. Saliva samples were collected at baseline, postintervention (~1 week after the last session), and at the 2-month follow-up. In this cancer survivor group, we found that intra-individual sOT levels were fairly stable across the 3 time points, of about 3 months' duration, and mean baseline sOT levels did not differ between females and males and were not correlated with age. Correlations between baseline sOT and self-report measures were weak; however, several of these relationships were in the predicted direction, in which sOT levels were negatively associated with sleep problems and depression and positively associated with cancer-related QOL and well-being. Regarding intervention effects on sOT, baseline-subtracted sOT levels were significantly larger at postintervention in the MBB group as compared with those in SHE. In this sample of cancer survivors assessed for sOT, at postintervention, greater reductions in sleep problems were noted for MBB and MM compared with that of SHE, and increases in mindfulness and self-compassion were observed in the MBB group compared with those in SHE. The findings in this exploratory study suggest that sOT may be a reliable biological measure over time that may provide insight into the effects of mind-body interventions on health outcomes in cancer survivors.

Blood pressure, salivary cortisol, and inflammatory cytokine outcomes in senior female cancer survivors enrolled in a tai chi chih randomized controlled trial.

PURPOSE: Older cancer survivors are a vulnerable population due to an increased risk for chronic diseases (e.g., cardiovascular disease) compounded with treatment late-effects and declines in physical functioning. Therefore, interventions that reduce chronic disease risk factors (i.e., blood pressure, chronic inflammation, and cortisol) are important in this population. Tai chi chih (TCC) is a mind-body exercise associated with reductions in chronic disease risk factors, but has not been examined with older cancer survivors. In a feasibility randomized controlled trial of TCC, we examined secondary outcomes of blood pressure, salivary cortisol, and inflammatory cytokines (interleukin (IL)-6, IL-12, tumor necrosis factor-α, IL-10, IL-4) due to their implications in chronic diseases. METHODS: Sixty-three senior female cancer survivors (M age = 67 years, SD = 7.15) with physical functioning limitations (SF-12 physical functioning ≤80 or role-physical ≤72) were randomized to 12-weeks (60-min, three times a week) of TCC or Health Education control (HEC) classes. Resting blood pressure, 1-day salivary cortisol samples, and fasting plasma samples for cytokine multiplex assays were collected at baseline and 1-week post-intervention. RESULTS: Controlling for baseline values, the TCC group had significantly lower systolic blood pressure (SBP, p = 0.002) and cortisol area-under-curve (AUC, p = 0.02) at post-intervention than the HEC group. There was no intervention effect on inflammatory cytokines (p's > 0.05). CONCLUSIONS: This TCC feasibility trial was associated with significant reductions in SBP and cortisol AUC in senior female cancer survivors. Larger, definitive trials are needed to confirm these findings. IMPLICATIONS FOR CANCER SURVIVORS: Senior survivors' have an increased risk for chronic diseases; however, TCC interventions may help reduce associated risk factors.

Activation of an adipogenic program in adult myoblasts with age.

Myoblasts isolated from mouse hindlimb skeletal muscle demonstrated increased adipogenic potential as a function of age. Whereas myoblasts from 8-month-old adult mice did not significantly accumulate terminal markers of adipogenesis regardless of culture conditions, myoblasts from 23-month-old mice accumulated fat and expressed genes characteristic of differentiated adipocytes, such as the fatty acid binding protein aP2. This change in differentiation potential was associated with a change in the abundance of the mRNA encoding the transcription factor C/EBPalpha, and in the relative abundance of PPARgamma2 to PPARgamma1 mRNAs. Furthermore, PPARgamma activity appeared to be regulated at the level of phosphorylation, being more highly phosphorylated in myoblasts isolated from younger animals. Although adipogenic gene expression in myoblasts from aged animals was activated, presumably in response to PPARgamma and C/EBPalpha, unexpectedly, myogenic gene expression was not effectively repressed. The Wnt signaling pathway may also alter differentiation potential in muscle with age. Wnt-10b mRNA was more abundantly expressed in muscle tissue and cultured myoblasts from adult compared with aged mice, resulting in stabilization of cytosolic beta-catenin, that may potentially contribute to inhibition of adipogenic gene expression in adult myoblasts. The changes reported here, together with those reported in bone marrow stroma with age, suggest that a default program may be activated in mesenchymal cells with increasing age resulting in a more adipogenic-like phenotype. Whether this change in differentiation potential contributes to the increased adiposity in muscle with age remains to be determined.

Medical and functional consequences of anemia in the elderly.

Anemia is a common problem in the elderly, accounting for significant morbidity and mortality in this population. It also has a negative effect on quality of life. Recent findings have shown that anemia can lead to cardiovascular and neurological complications, such as congestive heart failure and impaired cognitive function. In addition, anemia has been implicated in functional impairment and falls. Available data have shown that the successful management of this condition will not only improve patients' quality of life, but may also prevent the anemia from worsening.

Financial effect of a hospital outpatient senior clinic on an academic medical center.

OBJECTIVES: To estimate the billed charges generated for the university hospital (UH) by patients seen in a UH outpatient senior clinic over a 6-month period. To estimate the average billed charges per geriatric patient generated for the UH over the same 6-month period. DESIGN: Retrospective analysis. SETTING: Hospital-based outpatient senior clinic at a university medical center. PARTICIPANTS: Outpatients aged 65 and older. MEASUREMENTS: The total inpatient, outpatient, and professional fee charges generated for the UH by the senior health center (SHC) patients were estimated for a 6-month period, with the use of billing data from the professional and hospital billing systems. To estimate the multiplier effect and average charges per SHC patient per year, our analysis focused on professional charges generated directly in the SHC and professional fees and hospital charges generated by secondary referral (inpatient and outpatient). RESULTS: One thousand nine hundred ninety-eight patients were seen in the SHC during the 6-month period. For every $1 billed in professional charges in the SHC, $17 was billed elsewhere in the hospital system. Geriatric medicine professional charges generated by the 1,998 SHC patients over the 6-month period totaled $546,691. The 6-month charges by the rest of the hospital system for the same 1,998 patients included hospital inpatient charges of $4,684,195 for all departments; hospital outpatient charges (ancillary plus technical, including facility fees for the SHC) of $3,027,212; and professional fees of $1,606,287 for other departments, thereby producing a multiplier factor of 17. The average overall charges per geriatric patient per 6 months totaled $4,937, which included hospital inpatient, hospital outpatient, and professional fees. The UH generated an average of $3,860 in hospital charges per SHC patient per 6 months. The average hospital charges generated per established SHC patient per 6 months were $2,936. The average hospital charges for a new SHC patient were $7,187 per 6 months. The average professional charges were $1,078 per patient per 6 months. CONCLUSIONS: This study provides a reasonable estimate of the substantial multiplier, or "flow-through," effect of a senior clinic on its parent medical center. Although senior clinics may be a cost center when viewed in isolation, these clinics are actually revenue generators when viewed from the perspective of the entire health system.

Investigating efficacy of two brief mind-body intervention programs for managing sleep disturbance in cancer survivors: a pilot randomized controlled trial.

PURPOSE: After completing treatment, cancer survivors may suffer from a multitude of physical and mental health impairments, resulting in compromised quality of life. This exploratory study investigated whether two mind-body interventions, i.e., Mind-Body Bridging (MBB) and Mindfulness Meditation (MM), could improve posttreatment cancer survivors' self-reported sleep disturbance and comorbid symptoms, as compared to sleep hygiene education (SHE) as an active control. METHODS: This randomized controlled trial examined 57 cancer survivors with clinically significant self-reported sleep disturbance, randomly assigned to receive MBB, MM, or SHE. All interventions were conducted in three sessions, once per week. Patient-reported outcomes were assessed via the Medical Outcomes Study Sleep Scale and other indicators of psychosocial functioning relevant to quality of life, stress, depression, mindfulness, self-compassion, and well-being. RESULTS: Mixed effects model analysis revealed that mean sleep disturbance symptoms in the MBB (p = .0029) and MM (p = .0499) groups were lower than in the SHE group, indicating that both mind-body interventions improved sleep. In addition, compared with the SHE group, the MBB group showed reductions in self-reported depression symptoms (p = .040) and improvements in overall levels of mindfulness (p = .018), self-compassion (p = .028), and well-being (p = .019) at postintervention. CONCLUSIONS: This study provides preliminary evidence that brief sleep-focused MBB and MM are promising interventions for sleep disturbance in cancer survivors. Integrating MBB or MM into posttreatment supportive plans should enhance care of cancer survivors with sleep disturbance. Because MBB produced additional secondary benefits, MBB may serve as a promising multipurpose intervention for posttreatment cancer survivors suffering from sleep disturbance and other comorbid symptoms. IMPLICATIONS FOR CANCER SURVIVORS: Two brief sleep-focused mind-body interventions investigated in the study were effective in reducing sleep disturbance and one of them further improved other psychosocial aspects of the cancer survivors' life. Management of sleep problems in survivors is a high priority issue that demands more attention in cancer survivorship.

Reduction in salivary α-amylase levels following a mind-body intervention in cancer survivors--an exploratory study.

OBJECTIVE: The main aim of this exploratory study was to assess whether salivary α-amylase (sAA) and salivary cortisol levels would be positively modulated by sleep-focused mind-body interventions in female and male cancer survivors. METHODS: We conducted a randomized controlled trial in which 57 cancer survivors with self-reported sleep disturbance received either a Sleep Hygiene Education (SHE; n=18) control, or one of two experimental mind-body interventions, namely, Mind-Body Bridging (MBB; n=19) or Mindfulness Meditation (MM; n=20). Interventions were three sessions each conducted once per week for three consecutive weeks. Saliva cortisol and sAA were measured at baseline and 1 week after the last session. Participants also completed a sleep scale at the same time points when saliva was collected for biomarker measurement. RESULTS: Our study revealed that at post-intervention assessment, mean sAA levels upon awakening ("Waking" sample) declined in MBB compared with that of SHE. Mean Waking cortisol levels did not differ among treatment groups but declined slightly in SHE. Self-reported sleep improved across the three interventions at Post-assessment, with largest improvements in the MBB intervention. CONCLUSION: In this exploratory study, sleep focused mind-body intervention (MBB) attenuated Waking sAA levels, suggesting positive influences of a mind-body intervention on sympathetic activity in cancer survivors with sleep disturbance.

Feasibility and acceptability of a Tai Chi Chih randomized controlled trial in senior female cancer survivors.

OBJECTIVE: The purpose of this randomized controlled trial (RCT) was to examine the feasibility and acceptability of a Tai Chi Chih (TCC) intervention in senior female cancer survivors with physical functioning limitations, and its effects on health-related quality of life (QOL). DESIGN: This was a two-armed, parallel group, RCT with 12-weeks of Tai Chi Chih or Health Education Control. METHODS: Sixty-three senior (M age = 67 years, SD = 7.15) female cancer survivors (83% breast cancer, stages I-III) with physical functioning limitations (SF-12 Health Survey role-physical & physical functioning subscales) were randomized to 12-weeks of TCC or Health Education control (HEC). Primary outcomes were feasibility and acceptability. Secondary outcomes included health-related QOL (SF-36 Health Survey), and participants' qualitative feedback on the intervention. RESULTS: Retention (TCC = 91%; HEC = 81%) and class attendance (TCC = 79%; HEC = 83%) rates, and satisfaction levels for both study arms were high, but did not significantly differ from one another. At one-week post-intervention, none of the SF-36 scores differed between the TCC and HEC groups. Within-group analyses revealed significant improvements in the mental component summary score in TCC (p = 0.01), but not in HEC. Qualitative analyses indicated that the TCC group felt they received mental and physical benefits, whereas HEC group reported on social support benefits and information received. CONCLUSION: The TCC intervention was found to be a feasible and acceptable modality for senior female cancer survivors. Future, larger definitive trials are needed to clarify TCC dosage effects on QOL in this vulnerable population.

Two sessions of sleep-focused mind-body bridging improve self-reported symptoms of sleep and PTSD in veterans: A pilot randomized controlled trial.

OBJECTIVE: Sleep disturbance is highly prevalent among veterans. As an alternative to sleep medications with their undesirable side effects, nonpharmacological mind-body interventions may be beneficial for sleep management in primary care. The aim of this pilot study was to investigate whether a novel mind-body intervention, mind-body bridging (MBB), focusing on sleep, could improve self-reported sleep disturbance and comorbid symptoms in veterans. METHODS: This pilot study was a randomized controlled trial at the Veterans Affairs Salt Lake City Health Care System in which 63 veterans with self-reported sleep disturbance received MBB or an active sleep education control. Both interventions were conducted in two sessions, once per week. Patient-reported outcomes included the following: primary-Medical Outcomes Study (MOS) Sleep Survey, MOS Short Form-36V; secondary-Center for Epidemiological Studies-Depression, PTSD Check List-Military, Five-Factor Mindfulness Questionnaire. RESULTS: At both Week 1 (1 week after the first session) and post-intervention assessments, while sleep disturbance decreased in both groups, MBB performed significantly better than did the control group. Furthermore, self-reported PTSD symptoms improved in MBB, while they remained unchanged in the control. Overall mindfulness increased in MBB, while it remained unchanged in the control. CONCLUSIONS: This study provides preliminary evidence that a brief sleep-focused MBB could be a promising intervention for sleep and potentially other comorbid symptoms (e.g., PTSD). MBB could help patients develop awareness skills to deal with sleep-related symptoms. Integration of MBB into primary care settings may enhance care of patients with sleep disturbance and co-morbid symptoms.

Opioid pharmacotherapy for chronic non-cancer pain in the United States: a research guideline for developing an evidence-base.

UNLABELLED: This document reports the consensus of an interdisciplinary panel of research and clinical experts charged with reviewing the use of opioids for chronic noncancer pain (CNCP) and formulating guidelines for future research. Prescribing opioids for chronic noncancer pain has recently escalated in the United States. Contrasting with increasing opioid use are: 1) The lack of evidence supporting long-term effectiveness; 2) Escalating misuse of prescription opioids including abuse and diversion; and 3) Uncertainty about the incidence and clinical salience of multiple, poorly characterized adverse drug events (ADEs) including endocrine dysfunction, immunosuppression and infectious disease, opioid-induced hyperalgesia and xerostomia, overdose, falls and fractures, and psychosocial complications. Chief among the limitations of current evidence are: 1) Sparse evidence on long-term opioid effectiveness in chronic pain patients due to the short-term time frame of clinical trials; 2) Insufficiently comprehensive outcome assessment; and 3) Incomplete identification and quantification of ADEs. The panel called for a strategic interdisciplinary approach to the problem domain in which basic scientists and clinicians cooperate to resolve urgent issues and generate a comprehensive evidence base. It offered 4 recommendations in 3 areas: 1) A research strategy for studying the effectiveness of long-term opioid pharmacotherapy; 2) Improvements in evidence-generation methodology; and 3) Potential research topics for generating new evidence. PERSPECTIVE: Prescribing opioids for CNCP has outpaced the growth of scientific evidence bearing on the benefits and harms of these interventions. The need for a strong evidence base is urgent. This guideline offers a strategic approach to creating a comprehensive evidence base to guide safe and effective management of CNCP.

Trends in funding for research on pain: a report on the National Institutes Of Health grant awards over the years 2003 to 2007.

UNLABELLED: In recent years, the National Institutes of Health (NIH) has experienced unprecedented reductions in its customary annual budget increases. Consequently, researchers, health care policy planners and others have a pressing need for accurate information on NIH funding patterns. We created a unique and objective system for compiling, classifying, and analyzing data on NIH grant awards and funding for research on pain, nausea, and dyspnea using naïve observers, cross-validation by multiple raters, and face validation by experts. We present results of our method and analyses for the period from 2003 to 2007. Following a 12% increase from 2003 to 2004, funding for pain research fell by 9.4% per year on average over the next 3 years. The percent of the total NIH budget going to support pain research increased to 0.78% in 2004 but fell to 0.61% in 2007. A piecewise regression model confirmed the declining trend represented a significant fit to the data (R(2)=0.98, p=0.024). Separate breakdowns by Institutes showed similar patterns. Analyses of nausea and dyspnea research support revealed small but steady increases over the same period. Declining support for pain research disproportionate to decreases in the NIH budget signals a need for measures to promote funding for meritorious applications. PERSPECTIVE: Results of 5 year trends in numbers of grants and funding for research in pain, nausea, and dyspnea by the NIH show overall declines for pain but slight increases for nausea and dyspnea. Declining support for pain research that exceeds the reductions in the total NIH budget signals a need for measures to increase pain research funding.

Oxytocin receptor binding in the hypothalamus during gestation in rats.

Central oxytocin receptors (OTR) may be involved in adaptations of the brain oxytocin (OT) system during gestation, which are critical for systemic release of OT during parturition and lactation. We used quantitative autoradiography to determine changes in OTR binding in numerous brain sites during the course of gestation in the rat. Furthermore, to evaluate the importance of ovarian steroids in mediating pregnancy-related changes in OTR binding, we measured binding in ovariectomized animals treated with progesterone and/or estrogen, and in pregnant animals treated with exogenous progesterone during late gestation. We found that OTR binding was significantly increased in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by midgestation (day 15) compared with control. In addition, there was a further significant increase in OTR binding in these nuclei by late gestation (day 20). The bed nucleus of the stria terminalis (BNST) and the medial preoptic area (MPOA) also showed significant gestation-associated increases in OTR binding, which were similar during mid- and late pregnancy. Treatment with exogenous progesterone throughout pregnancy did not alter the increase in OTR binding characteristic of late gestation in any of these brain sites. Finally, estrogen treatment in ovariectomized animals resulted in increased OTR binding in the SON, BNST, and MPOA, but not the PVN. These data demonstrate that OTR binding in the hypothalamus is increased during mid- and late-gestation, compared with ovariectomized control animals, which may be mediated by increased estradiol.