The Mindful Reappraisal of Pain Scale (MRPS): Validation of a New Measure of Psychological Mechanisms of Mindfulness-Based Analgesia.

Objectives: Mindfulness is theorized to decrease the affective amplification of chronic pain by facilitating a shift from emotionally-laden, catastrophic pain appraisals of nociceptive input to reappraising chronic pain as an innocuous sensory signal that does not signify harm. Understanding of these hypothetical psychological mechanisms of mindfulness-based analgesia has been limited by a lack of direct measures. We conducted a series of psychometric and experimental studies to develop and validate the Mindful Reappraisal of Pain Sensations Scale (MPRS). Methods: After item generation, we conducted exploratory and confirmatory factor analyses of the MRPS in samples of opioid-treated chronic pain patients both before (n=450; n=90) and after (n=222) participating in Mindfulness-Oriented Recovery Enhancement (MORE). We then examined the convergent and divergent validity of the MRPS. Finally, in data from a randomized clinical trial (n=250), the MRPS was tested as a mediator of the effects of MORE on reducing chronic pain severity. Results: Exploratory and confirmatory factor analyses demonstrated the single-factor structure of the MRPS. The MRPS also evidenced convergent and divergent validity. Mindfulness training through MORE significantly increased MRPS scores relative to supportive psychotherapy (F4,425.03 = 16.15, p < .001). Changes in MRPS scores statistically mediated the effect of MORE on reducing chronic pain severity through 9-month follow-up. Conclusions: Taken together, these studies demonstrate that the MRPS is a psychometrically sound and valid measure of novel analgesic mechanisms of mindfulness including attentional disengagement from affective pain appraisals and interoceptive exposure to pain sensations.

FGF2, LIF, and IGF1 (FLI) supplementation during human in vitro maturation enhances markers of gamete competence.

STUDY QUESTION: Does a chemically defined maturation medium supplemented with FGF2, LIF, and IGF1 (FLI) improve in vitro maturation (IVM) of cumulus-oocyte complexes (COCs) obtained from children, adolescents, and young adults undergoing ovarian tissue cryopreservation (OTC)? SUMMARY ANSWER: Although FLI supplementation did not increase the incidence of oocyte meiotic maturation during human IVM, it significantly improved quality outcomes, including increased cumulus cell expansion and mitogen-activated protein kinase (MAPK) expression as well as enhanced transzonal projection retraction. WHAT IS KNOWN ALREADY: During OTC, COCs, and denuded oocytes from small antral follicles are released into the processing media. Recovery and IVM of these COCs is emerging as a complementary technique to maximize the fertility preservation potential of the tissue. However, the success of IVM is low, especially in the pediatric population. Supplementation of IVM medium with FLI quadruples the efficiency of pig production through improved oocyte maturation, but whether a similar benefit occurs in humans has not been investigated. STUDY DESIGN, SIZE, DURATION: This study enrolled 75 participants between January 2018 and December 2021 undergoing clinical fertility preservation through the Fertility & Hormone Preservation & Restoration Program at the Ann & Robert H. Lurie Children's Hospital of Chicago. Participants donated OTC media, accumulated during tissue processing, for research. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants who underwent OTC and include a pediatric population that encompassed children, adolescents, and young adults ≤22 years old. All participant COCs and denuded oocytes were recovered from media following ovarian tissue processing. IVM was then performed in either a standard medium (oocyte maturation medium) or one supplemented with FLI (FGF2; 40 ng/ml, LIF; 20 ng/ml, and IGF1; 20 ng/ml). IVM outcomes included meiotic progression, cumulus cell expansion, transzonal projection retraction, and detection of MAPK protein expression. MAIN RESULTS AND THE ROLE OF CHANCE: The median age of participants was 6.3 years, with 65% of them classified as prepubertal by Tanner staging. Approximately 60% of participants had been exposed to chemotherapy and/or radiation prior to OTC. On average 4.7 ± 1 COCs and/or denuded oocytes per participant were recovered from the OTC media. COCs (N = 41) and denuded oocytes (N = 29) were used for IVM (42 h) in a standard or FLI-supplemented maturation medium. The incidence of meiotic maturation was similar between cohorts (COCs: 25.0% vs 28.6% metaphase II arrested eggs in Control vs FLI; denuded oocytes: 0% vs 5.3% in Control vs FLI). However, cumulus cell expansion was 1.9-fold greater in COCs matured in FLI-containing medium relative to Controls and transzonal projection retraction was more pronounced (2.45 ± 0.50 vs 1.16 ± 0.78 projections in Control vs FLIat 16 h). Additionally, MAPK expression was significantly higher in cumulus cells obtained from COCs matured in FLI medium for 16-18 h (chemiluminescence corrected area 621,678 vs 2,019,575 a.u., P = 0.03). LIMITATIONS, REASONS FOR CAUTION: Our samples are from human participants who exhibited heterogeneity with respect to age, diagnosis, and previous treatment history. Future studies with larger sample sizes, including adult participants, are warranted to determine the mechanism by which FLI induces MAPK expression and activation. Moreover, studies that evaluate the developmental competence of eggs derived from FLI treatment, including assessment of embryos as outcome measures, will be required prior to clinical translation. WIDER IMPLICATIONS OF THE FINDINGS: FLI supplementation may have a conserved beneficial effect on IVM for children, adolescents, and young adults spanning the agricultural setting to clinical fertility preservation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Department of Obstetrics and Gynecology startup funds (F.E.D.), Department of Surgery Faculty Practice Plan Grant and the Fertility & Hormone Preservation & Restoration Program at the Ann & Robert H. Lurie Children's Hospital of Chicago (M.M.L. and E.E.R.). M.M.L. is a Gesualdo Foundation Research Scholar. Y.Y.'s research is supported by the internal research funds provided by Colorado Center of Reproductive Medicine. Y.Y., L.D.S., R.M.R., and R.S.P. have a patent pending for FLI. The remaining authors have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Mindfulness-Oriented Recovery Enhancement for Addictive Behavior, Psychiatric Distress, and Chronic Pain: A Multilevel Meta-Analysis of Randomized Controlled Trials.

Objectives: Mindfulness-Oriented Recovery Enhancement (MORE) is an integrative intervention designed to ameliorate addiction, chronic pain, and psychiatric symptoms. Although multiple randomized controlled trials (RCTs) have examined the clinical efficacy of MORE, no study has quantitatively synthesized this body of research. Thus, we conducted a meta-analysis of RCTs examining the effects of MORE on addictive behaviors, craving, opioid dose, pain, and psychiatric symptoms. Methods: Relevant manuscripts were identified through comprehensive searches of four bibliographic databases. Two- and three-level random-effects models were used to generate synthesized effect size estimates, and meta-regressions were performed to examine whether study and sample characteristics influenced the magnitude of aggregate effect sizes. Results: Our search identified 16 manuscripts reporting data from eight RCTs (N = 816). Moderate to small effects in favor of MORE were observed for addictive behaviors (SMC = - .54, p = .007), craving (SMC = - .42, p = .010), opioid dose (MC = - 17.95, p < .001), chronic pain (SMC = - .60, p < .001), and psychiatric symptoms (SMC = - .34, p < .001). MORE's effects on psychiatric symptoms and craving were not moderated by participant race, gender, age, or income. Conclusions: Study findings provide empirical evidence of MORE's efficacy for a wide diversity of individuals, and as such, MORE should now be disseminated broadly throughout the healthcare system. Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-022-01964-x.

Mindful Lawyering: a Pilot Study on Mindfulness Training for Law Students.

Objectives: Many US law schools are now offering elective courses in mindfulness training to alleviate disproportionately high levels of anxiety, depression, stress, and disordered alcohol use among law students. To date, empirical evidence on the effectiveness of these courses has been lacking. The aim of this pilot study was to explore the feasibility and impact of a 13-week mindfulness course, "Mindful Lawyering," specifically tailored to law students. The primary hypothesis was that mindfulness training would be significantly correlated with improvements in well-being and mindfulness. Methods: The design was a non-randomized, quasi-experimental study involving 64 law students. The mindfulness group was 31 students taking Mindful Lawyering; the comparison group was 33 students taking other law school courses. Outcome measures were the Depression, Anxiety, and Stress Scale; the Positive and Negative Affect Scale; the Alcohol Use Disorders Identification Test; and the Five Facet Mindfulness Questionnaire. Results: Results provide promising evidence to support the hypothesis. The mindfulness group showed significantly greater improvement on measures of stress (p < .001, d = 1.15), anxiety (p < .001, d = . 90), depression (p = .012, d = .66), negative affect (p = .002, d = .81), disordered alcohol use (p = .011, d = .67), and mindfulness (p < .001, d = 1.32) from pre to post relative to the comparison group. The course was well accepted and feasible for law students. Conclusions: Findings from the current study suggest that mindfulness training may occasion improvements in the well-being of law students. More research is needed to replicate these findings in larger, randomized samples of law students. Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-022-01965-w.

Mindfulness-Based Interventions for Perioperative Pain Management and Opioid Risk Reduction Following Surgery: A Stepped Care Approach.

Surgical procedures often improve health and function but can sometimes also result in iatrogenic effects, including chronic pain and opioid misuse. Due to the known risks of opioids and the physical, emotional, and financial suffering that often accompanies chronic pain, there has been a call for greater use of complementary non-pharmacological treatments like mindfulness-based interventions. Mindfulness can be broadly described as an attentional state involving moment-by-moment meta-awareness of thoughts, emotions, and body sensations. An expanding number of randomized clinical trials have found strong evidence for the value of mindfulness techniques in alleviating clinical symptomology relevant to surgical contexts. The purpose of this review is to examine the empirical evidence for the perioperative use of mindfulness interventions. We present a mindfulness-based stepped care approach that first involves brief mindfulness to treat preoperative pain and anxiety and prevent development of postoperative chronic pain or opioid misuse. More extensive mindfulness-based interventions are then provided to patients who continue to experience high pain levels or prolonged opioid use after surgery. Finally, we review psychophysiological mechanisms of action that may be integral to the analgesic and opioid sparing effects of mindfulness.

Willingness and Accessibility of a Hypnosis Intervention for Anxiety Among a Low Socioeconomic Status Population.

Objective: This survey study aimed to investigate the willingness and accessibility of a hypnosis intervention for anxiety among low socioeconomic status patients in a primary care setting. Methods: Participants were asked to complete a one-page survey during a scheduled office visit with their primary care provider. Survey questions included participants' interest in hypnosis as a treatment for anxiety, how many sessions they would be willing/able to attend, how they would prefer access to a recorded hypnosis intervention, and items relating to anxiety, including the Generalized Anxiety Disorder-7 measure. Results: Two hundred participants (71.5% female) completed the survey with a mean age of 43.16 (standard deviation = 15.78). Over half (54.6%) of the survey participants reported that they experience anxiety, and 74% of the participants indicated that they would be interested in hypnosis if it were recommended by their provider for anxiety. Discussion: Given the high prevalence of anxiety among survey participants, there exists a clear need for effective and accessible treatment options. These results demonstrate the willingness of individuals to use hypnosis for anxiety and to engage in remote hypnosis interventions.

Hypnotizability Norms may not be Representative of the General Population: Potential Sample and Self-Selection Bias Considerations.

The analysis of the methods sections of 66 normalization tests of hypnotizability scales reveals that out of 33,338 subjects, 58.57% were college and university students, and the majority of these were students of psychology. Of all subjects, 7.45% were younger school children, 27.63% were patients treated with hypnosis, and out of these, 85.26% were patients of 1 single therapist. Only 0.51% were trainees of dental or nursing schools, 0.13% were prisoners, and 5.71% were other adults. These figures suggest a sample-selection bias. As 83.08% of these subjects were told beforehand that they were to undergo a hypnosis study, a self-selection bias is also implied in the data. It can be presumed that those interested in hypnosis participated, whereas others who had no interest in hypnosis may have refrained. It is concluded that some of the published norms of hypnotizability tests may not be adequately representative of the general population. Many hypnosis studies, whether clinical or experimental, which are based on hypnotizability, may be afflicted by these biases.

Mindfulness-oriented recovery enhancement improves negative emotion regulation among opioid-treated chronic pain patients by increasing interoceptive awareness.

OBJECTIVE: Long-term opioid therapy presents health risks for people with chronic pain. Some chronic pain patients escalate their opioid dose to regulate negative emotions. Therefore, emotion regulatory strategies like reappraisal are key treatment targets for this population. Mindfulness has been shown to enhance reappraisal, but the mechanisms of action are unknown. This study was a secondary analysis of data from a randomized, controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE) to test a specific postulate of the Mindfulness-to-Meaning Theory: that mindfulness-based interventions promote reappraisal, via interoceptive self-regulation, as a means of decreasing emotional distress. METHODS: Ninety-five patients with opioid-treated chronic pain (age = 56.8 ±â€¯11.7, 66% female) were randomized to 8 weeks of MORE or Support Group (SG) psychotherapy. An interoceptive awareness latent variable was constructed from the Multidimensional Assessment of Interoceptive Awareness (MAIA). Next, interoceptive self-regulation was assessed as a mediator of the effect of MORE on post-treatment reappraisal, and then reappraisal was examined as a mediator of change in distress through 3-month follow-up. RESULTS: MORE participants had greater improvements in interoceptive awareness than the SG as measured by the interoceptive awareness latent variable (ß = 0.310, p = 0.008) and by the self-regulation MAIA subscale (ß = 0.335, p = 0.001). The effect of MORE on treatment-induced increases in reappraisal was mediated by increased interoceptive self-regulation (indirect effect: ß = 0.110, p = 0.030). In turn, decreases in distress through 3-month follow-up were mediated by increases in reappraisal (indirect: ß = -0.136, p = 0.031). CONCLUSION: MORE facilitated reappraisal of distress by enhancing interoceptive self-regulation, supporting a central mechanistic causal pathway specified by the Mindfulness-to-Meaning Theory.

Effect of Hypnosis on Anxiety: Results from a Randomized Controlled Trial with Women in Postmenopause.

Anxiety is common, yet often under-treated, among women in postmenopause. This study examined the effect of a hypnotic intervention designed to reduce hot flashes, on anxiety levels of postmenopausal women. Anxiety was assessed using the State-Trait Anxiety Inventory, the Hospital Anxiety and Depression Scale-Anxiety subscale, and a visual analog scale. Additionally, hypnotizability was tested as a moderator of anxiety reductions. Significant reductions in anxiety were found from baseline to endpoint and follow-up and hypnosis was superior to the control condition. Additionally, ratings of Current Anxiety decreased from pre-session to post-session at each weekly visit and the pre-session scores reduced continuously. Hypnotizability was found to moderate anxiety reductions, but regardless of hypnotizability level participants, on average, experienced significant symptom improvement from baseline scores. These data provide initial support for the use of hypnosis to reduce symptoms of anxiety among postmenopausal women.Trial registration: This study was registered at ClinicalTrials.gov on February 11, 2011 under Identifier number NCT01293695 ( https://clinicaltrials.gov/ct2/show/NCT01293695?term=Elkins&cond=hot+flashes&draw=2&rank=2 ).

Mindful Self-Hypnosis for Self-Care: An Integrative Model and Illustrative Case Example.

The combination of mindfulness and self-hypnosis could provide a tool that is easily implemented by individuals who want to care for their well-being in times of high stress. Each discipline has been shown to be effective in relieving stress, and integration could further facilitate change while creating a tool that is highly accessible. There are many similarities between the two practices, such as focusing of attention and the emphasis on mind-body connection. However, important distinctions in psychological (e.g., self-monitoring) and neural (e.g., functional connectivity) elements are noted. A theory of how integrated mindful self-hypnosis may create change is presented. An illustrative case example of mindful self-hypnosis practice and a self-hypnosis transcript are provided.

Brief Report: Knowledge of, Interest in, and Willingness to Try Behavioral Interventions in Individuals With Parkinson's Disease.

Purpose/Objective • Behavioral interventions hold enormous promise for managing a variety of motor and nonmotor symptoms in Parkinson's disease (PD). Despite this, prior studies have suggested that the utilization of these interventions is relatively low. The current study seeks to understand factors that could relate to the utilization of PD behavioral strategies. Specifically, the study evaluates the self-described knowledge of, interest in, and willingness to participate in behavioral interventions in a community-dwelling sample of individuals with PD. Research Method/Design • Forty-five individuals with PD completed a survey that assessed knowledge, interest, and willingness to participate in 5 behavioral interventions: hypnosis, relaxation training, mindfulness/meditation, computerized "brain games," and counseling. In addition, participants self-reported their quality of life across several domains; these domain scores were correlated with overall ratings of interest and willingness to participate in behavioral interventions. Results • Self-reported knowledge of behavioral interventions was low, but interest and willingness to participate was moderate to high across modalities. Statistically significant correlations were noted between perceived knowledge of the techniques and interest (r = 0.29, P = .05) as well as willingness to participate (r = 0.32, P = .03) in these techniques. Interest and willingness were also correlated with self-reported bodily discomfort (r = 0.36, P = .02). Conclusions/Implications • The participants of the current sample were interested and willing to participate in behavioral interventions but had limited knowledge of the potential for these techniques to manage their symptoms. The reported high level of willingness to participate in behavioral interventions suggests that it is feasible to provide behavioral interventions in this population.

Hypnosis for Hot Flashes and Associated Symptomsin Women with Breast Cancer.

Women with breast cancer experience a host of physical and psychological symptoms, including hot flashes, sleep difficulties, anxiety, and depression. Therefore, treatment for women with breast cancer should target these symptoms and be individualized to patients' specific presentations. The current article reviews the common symptoms associated with breast cancer in women, then examines clinical hypnosis as a treatment for addressing these symptoms and improving the quality of life of women with breast cancer. Clinical hypnosis is an effective, nonpharmaceutical treatment for hot flashes and addressing many symptoms typically experienced by breast cancer patients. A case example is provided to illustrate the use of clinical hypnosis for the treatment of hot flashes with a patient with breast cancer.

Feasibility of Music and Hypnotic Suggestion to Manage Chronic Pain.

The authors investigated the feasibility and possible effects of hypnotic suggestion and music for chronic pain. Ten people completed the 2-week intervention that consisted of daily listening to hypnotic suggestions combined with music. Averaged subjective pain intensity, pain bothersomeness, overall distress, anxiety, and depression decreased from baseline to endpoint. Participants rated pre- and postlistening pain intensity and pain bothersomeness decreased for each session. Information provided during end-of-study interviews indicated all participants were satisfied with treatment and felt they benefited from being in the study. Means and standard deviations are reported for outcome measures and a case study is provided. This preliminary study supports the use of a combined hypnotic suggestion and music intervention for chronic pain.

Cell-specific abnormalities of glutamate transporters in schizophrenia: sick astrocytes and compensating relay neurons?

Excitatory amino-acid transporters (EAATs) bind and transport glutamate, limiting spillover from synapses due to their dense perisynaptic expression primarily on astroglia. Converging evidence suggests that abnormalities in the astroglial glutamate transporter localization and function may underlie a disease mechanism with pathological glutamate spillover as well as alterations in the kinetics of perisynaptic glutamate buffering and uptake contributing to dysfunction of thalamo-cortical circuits in schizophrenia. We explored this hypothesis by performing cell- and region-level studies of EAAT1 and EAAT2 expression in the mediodorsal nucleus of the thalamus in an elderly cohort of subjects with schizophrenia. We found decreased protein expression for the typically astroglial-localized glutamate transporters in the mediodorsal and ventral tier nuclei. We next used laser-capture microdissection and quantitative polymerase chain reaction to assess cell-level expression of the transporters and their splice variants. In the mediodorsal nucleus, we found lower expression of transporter transcripts in a population of cells enriched for astrocytes, and higher expression of transporter transcripts in a population of cells enriched for relay neurons. We confirmed expression of transporter protein in neurons in schizophrenia using dual-label immunofluorescence. Finally, the pattern of transporter mRNA and protein expression in rodents treated for 9 months with antipsychotic medication suggests that our findings are not due to the effects of antipsychotic treatment. We found a compensatory increase in transporter expression in neurons that might be secondary to a loss of transporter expression in astrocytes. These changes suggest a profound abnormality in astrocyte functions that support, nourish and maintain neuronal fidelity and synaptic activity.

Systematic review of leisure therapy and its effectiveness in managing functional outcomes in stroke rehabilitation.

BACKGROUND: Evidence suggests that the incorporation of leisure activities in adult stroke rehabilitation can contribute to improved physical, cognitive, and psychological outcomes. However, differences in study design and treatment delivery may affect these findings. Furthermore, the magnitude of therapeutic change associated with leisure therapy is unclear, with few quantitative reviews available. OBJECTIVE: To synthesize and evaluate the empirical evidence examining leisure therapy in stroke rehabilitation. METHODS: Eight independent studies (N = 615 participants) were identified from a comprehensive database search. Study quality was evaluated using the Oxford Levels of Evidence. Pre- and posttreatment data for participants who received leisure therapy, in comparison with peers who received standard care or no treatment, were evaluated by calculating Cohen's d effect sizes and 95% confidence intervals. RESULTS: No studies met the criteria for the highest level of methodological rigor, although all used randomization procedures. Leisure therapy contributed to significant short-term improvements in psychological outcomes, namely quality of life and mood (d range, 2.10 to 0.54), in addition to leisure-specific outcomes, including increased participation in and satisfaction with leisure activities (d range, 0.81 to 1.23). Longer term effects of treatment could not be determined, with one study providing data and reporting nonsignificant effects (d range, -0.07 to 0.17). CONCLUSIONS: There is some evidence that leisure therapy offers an opportunity to enhance short-term treatment gains in community-based stroke rehabilitation. Further controlled research is needed to establish its longer term effects and assist the development of evidence-based guidelines for this treatment.

Only high levels of dabigatran attenuate catheter thrombosis in vitro and in rabbits.

In patients with mechanical heart valves, thromboembolic events were more frequent with dabigatran, an oral thrombin inhibitor, than with warfarin. This observation raises the possibility that dabigatran may be less effective than conventional anticoagulants in patients with other blood-contacting devices, such as catheters. To address this, we compared the capacity of dabigatran and/or heparin to inhibit catheter-induced thrombin generation in vitro and to attenuate catheter occlusion in rabbits. Using a catheter-induced thrombin generation assay, concentrations of dabigatran over 100 ng/ml prolonged the lag time and time to peak thrombin, and reduced the peak thrombin concentration and endogenous thrombin potential in a concentration-dependent fashion. Compared with saline in a rabbit model of catheter thrombosis, dabigatran prolonged the mean time to catheter occlusion by 2.9- and 1.9-fold when plasma levels were 173 and 140 ng/ml, respectively; values comparable to median peak levels in humans given dabigatran 150 mg twice daily. In contrast, low-dose dabigatran, which produced a level of 60 ng/ml; a value comparable to the trough level of dabigatran in humans, did not prolong the time to occlusion. Whereas a 70 U/kg bolus of heparin prolonged the mean time to occlusion by 3.4-fold, a 15 U/kg bolus had no effect. When low-dose dabigatran was given in combination with 15 U/kg heparin, the mean time to occlusion was prolonged by 2.7-fold. These findings suggest that only peak levels of dabigatran are sufficient to prevent catheter-induced clotting unless supplemented heparin is given.

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels.

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (-)-α-bisabolol, farnesene, umbelliferone; 3-30 µM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (-)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (-)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 µM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (-)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium.

Cranial electrotherapy stimulation for the treatment of chronically symptomatic bipolar patients.

OBJECTIVE: The aim of this study was to determine if cranial electrotherapy stimulation (CES) is beneficial in chronically symptomatic bipolar (CSBP) subjects. METHODS: A retrospective chart review of all consecutive CSBP subjects who were prescribed CES collected demographic and clinical information. RESULTS: The Clinical Global Impression improved significantly [mean (SD), 2.7 (0.6) at baseline vs 2.0 (0.0), t = 0, P < 0.001], but mood symptoms change minimally. There were very few adverse effects of CES. CONCLUSIONS: Patients with CSBP continue to experience symptoms with CES but also are modestly improved.

Effects of developmental bisphenol A exposure on reproductive-related behaviors in California mice (Peromyscus californicus): a monogamous animal model.

Bisphenol A (BPA), a pervasive, endocrine disrupting compound (EDC), acts as a mixed agonist-antagonist with respect to estrogens and other steroid hormones. We hypothesized that sexually selected traits would be particularly sensitive to EDC. Consistent with this concept, developmental exposure of males from the polygynous deer mouse, Peromyscus maniculatus, to BPA resulted in compromised spatial navigational ability and exploratory behaviors, while there was little effect on females. Here, we have examined a related, monogamous species, the California mouse (Peromyscus californicus), where we predicted that males would be less sensitive to BPA in terms of navigational and exploratory behaviors, while displaying other traits related to interactions with females and territorial marking that might be vulnerable to disruption. As in the deer mouse experiments, females were fed either a phytoestrogen-free CTL diet through pregnancy and lactation or the same diet supplemented with BPA (50 mg/kg feed weight) or ethinyl estradiol (EE) (0.1 part per billion) to provide a "pure" estrogen control. After weaning, pups were maintained on CTL diet until they had reached sexual maturity, at which time behaviors were evaluated. In addition, territorial marking was assessed in BPA-exposed males housed alone and when a control male was visible in the testing arena. In contrast to deer mice, BPA and EE exposure had no effect on spatial navigational skills in either male or female California mice. While CTL females exhibited greater exploratory behavior than CTL males, BPA exposure abolished this sex difference. BPA-exposed males, however, engaged in less territorial marking when CTL males were present. These studies demonstrate that developmental BPA exposure can disrupt adult behaviors in a sex- and species-dependent manner and are consistent with the hypothesis that sexually selected traits are particularly vulnerable to endocrine disruption and should be a consideration in risk assessment studies.