Psychiatrists' Illustration of Awe in Empathic Listening Assessments: A Pilot Study.

Background "Awe" is typically an inspiring emotional response to perceptually vast stimuli signifying the transcendence beyond all cognitive frames of reference when we encounter the unexpected. Physicians' experience of awe in clinical care interactions has not been studied in an empirical, evidence-based way. We aim to present a focused study of awe in a psychiatrist's empathic listening (EL) assessments and propose an evidence-based framework to study it. Methodology This is an exploratory case series of a psychiatrist's EL interactions (mean duration/x̄ of 46.17 minutes) with six patients (two males and four females) aged 32-72 years (x̄ =54.67, σ = 16.64). Using the method of autoethnography, the verbal and nonverbal aspects of the EL assessments were analyzed and open-coded to generate qualitative data. Results The study revealed that the data in all the case studies could be classed into two thematic groups, namely, mindfulness and transpersonal mindfulness. The emotions of "awe" and "non-agency" were ubiquitous in all six case studies both for the psychiatrist and patients. Conclusions Recognizing the awe and non-agency in EL interaction is essential in conceptualizing the "mindfulness-to-transcendence" framework and the first step toward the evidence-based study of transcendence/metaphysics in phenomenological psychiatry.

A novel method of assessing balance and postural sway in patients with hypermobile Ehlers-Danlos syndrome.

Patients with hypermobile Ehlers-Danlos syndrome (hEDS) frequently suffer from poor balance and proprioception and are at an increased risk for falls. Here we present a means of assessing a variety of balance and postural conditions in a fast and non-invasive manner. The equipment required is commercially available and requires limited personnel. Patients can be repeatedly tested to determine balance and postural differences as a result of disease progression and aging, or a reversal following balance/exercise interventions.

Prevalence of gastrointestinal, cardiovascular, autonomic and allergic manifestations in hospitalized patients with Ehlers-Danlos syndrome: a case-control study.

OBJECTIVE: Previous observations suggest an association between Ehlers-Danlos syndrome (EDS) and gastrointestinal (GI), cardiovascular, immune, and autonomic nervous system dysfunction. We sought to determine whether a hospital diagnosis of EDS is associated with a higher prevalence of these manifestations vs hospitalized patients without EDS. We also evaluated hospital outcomes. METHODS: A total of 6,021 cases and matched controls were acquired from the 2016 National Inpatient Sample. In total, 2,007 EDS patients were identified via ICD-10 code. After bivariate analyses, multivariate logistic regression models were used to adjust for potential confounders. RESULTS: GI conditions were found in 44% of EDS patients vs 18% of controls [odds ratio (OR) = 3.57, 95% CI: 3.17, 4.02, P < 0.0001], with irritable bowel syndrome, gastroparesis and coeliac disease strongly associated with EDS. Autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope and orthostatic hypotension was found in 20% of EDS patients vs 6% of controls (OR = 4.45, 95% CI: 3.71, 5.32, P < 0.0001). EDS patients were more likely to have food allergy (OR = 3.88, 95% CI: 2.65, 5.66, P < 0.0001) and cardiovascular complications such as mitral valve disorders, aortic aneurysm and dysrhythmias (OR = 6.16, 95% CI: 4.60, 8.23, P < 0.0001). These conditions remained highly associated with EDS after considering confounders. EDS patients were 76% more likely to have longer than average hospitalizations (OR = 1.76, 95% CI: 1.54, 2.02, P < 0.0001). CONCLUSION: GI, cardiovascular, autonomic and allergic manifestations are significantly more prevalent in EDS patients compared with hospitalized patients without EDS. Physicians should consider EDS in patients with unexplained GI, cardiovascular, autonomic and allergic conditions and exercise precautions when treating EDS patients in a hospital setting.

High-intensity exercise improves pulmonary function and exercise tolerance in a patient with TSC-LAM.

INTRODUCTION: While exercise has been shown to improve respiratory symptoms, exercise tolerance, and bone mineral density in many populations, no supervised exercise training interventions have been undertaken in patients with lymphangioleiomyo-matosis (LAM). MATERIAL AND METHODS: One patient with TSC-LAM (tuberous sclerosis complex lymphangioleiomyomatosis) participated in two weekly sessions (50-60 min) of supervised aerobic exercise at 80-85% heart rate max for one year. Treadmill ergometry (VO2peak), spirometry (FEV1, FVC, FEV1/FVC, peak flow), and bone mineral density testing were performed prior to every 3 months. RESULTS: After one year of supervised aerobic exercise training we saw dramatic increases in the patient's VO2max (20%), FEV1 (9.5%), FEV1/FVC (9.1%) and peak flow (47%). CONCLUSIONS: The results from this study indicate that supervised exercise training can improve exercise tolerance and pulmonary function in a patient with lymphangioleiomyomatosis. Further research is needed, including longitudinal studies with larger sample sizes, to determine long-term effects and consistency of these findings. Aerobic exercise may offer a viable alternative or com-pliment to pharmacological interventions in the treatment of lymphangioleiomyomatosis. We show that high-intensity exercise training can markedly and safely improve pulmonary function in a patient with TSC-LAM. While we did not record quality of life or mood states, our patient did report improved self-confidence as well as enhanced mood.

A single bout of dynamic exercise by healthy adults enhances the generation of monocyte-derived-dendritic cells.

The ex vivo generation of monocyte-derived-dendritic cells (mo-DCs) has facilitated the use of DCs in immunotherapy research. However, low blood monocyte numbers frequently limit the manufacture of sufficient numbers of mo-DCs for subsequent experimental and clinical procedures. Because exercise mobilizes monocytes to the blood, we tested if acute dynamic exercise by healthy adults would augment the generation of mo-DCs without compromising their differentiation or function. We compared mo-DC generation from before- and after-exercise blood over 8-days of culture. Function was assessed by FITC-dextran uptake and the stimulation of autologous cytomegalovirus (pp65)-specific-T-cells. Supporting the hypothesis, we found a near fourfold increase in number of mo-DCs generated after-exercise. Furthermore, relative FITC-dextran uptake, differentiation rate, and stimulation of pp65-specific-T-cells did not differ between before- and after-exercise mo-DCs. We conclude that exercise enhances the ex vivo generation of mo-DCs without compromising their function, and so may overcome some limitations associated with manufacturing these cells for immunotherapy.

ß2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model.

ß(2)-Adrenoceptor (ß2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent ß2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the ß2AR, epinephrine. In this study, we demonstrate that activation of the ß2AR by epinephrine is paradoxically required for development of the asthma phenotype. In an antigen-driven model, mice sensitized and challenged with ovalbumin showed marked elevations in three cardinal features of the asthma phenotype: inflammatory cells in their bronchoalveolar lavage fluid, mucin over production, and airway hyperresponsiveness. However, genetic depletion of epinephrine using mice lacking the enzyme to synthesize epinephrine, phenylethanolamine N-methyltransferase, or mice that had undergone pharmacological sympathectomy with reserpine to deplete epinephrine, had complete attenuation of these three cardinal features of the asthma phenotype. Furthermore, administration of the long-acting ß2AR agonist, formoterol, a drug currently used in asthma treatment, to phenylethanolamine N-methyltransferase-null mice restored the asthma phenotype. We conclude that ß2AR agonist-induced activation is needed for pathogenesis of the asthma phenotype. These findings also rule out constitutive signaling by the ß2AR as sufficient to drive the asthma phenotype, and may help explain why chronic administration of ß2AR agonists, such as formoterol, have been associated with adverse outcomes in asthma. These data further support the hypothesis that chronic asthma management may be better served by treatment with certain "ß-blockers."

Acute aerobic exercise in humans increases cytokine expression in CD27(-) but not CD27(+) CD8(+) T-cells.

Exercise alters the percentage of CD8(+) T-cells in the bloodstream expressing type I and type II cytokines. It is unknown if this reflects a change in cytokine expression within individual cells, or whether these observations result from the exercise-induced shift in the proportions of early/intermediate (CD27(+)) and late (CD27(-)) differentiated cells, which have vastly different cytokine profiles. 16 males cycled for 60 min at 95% maximal steady state. Mononuclear cells isolated from blood collected before, immediately after, and 1 h after exercise were cultured overnight with and without phytohaemagglutinin stimulation. CD8(+) T-cells were assessed for differentiation markers and intracellular cytokine expression by flow cytometry. The numbers and percentage of CD27(-)CD8(+) T-cells increased immediately after exercise and fell below pre-exercise values 1 h later. At 1 h after exercise, an increased number and percentage of CD8(+) T-cells expressing IL-2, IFN-γ, TNF-α, IL-6, IL-4, and IL-10 was observed in both stimulated and unstimulated cells. The cytokine response to exercise was confined to CD27(-)CD8(+) T-cells, although cytokine expression among CD8(+) T-cells was highest when the proportion of CD27(-)CD8(+) T-cells was lowest. Moreover, the cytokine response to exercise could be predicted by the number of late cells in resting blood: cytokine expression was highest among those with low resting proportions of late cells. We conclude that exercise-induced changes in the percentage of CD8(+) T-cells expressing cytokines are not due to proportional shifts in early/intermediate and late differentiated T-cells. Exercise may prime late-differentiated blood CD8(+) T-cells to initiate effector functions in preparation for their extravasation into the tissues.

Relationship between systemic inflammation and delayed-type hypersensitivity response to Candida antigen in older adults.

Research has shown that aging is associated with increased systemic inflammation as well as a reduction in the strength of immune responses. However, little evidence exists linking the decrease in cell-mediated immunity in older adults with other health parameters. We sought to examine the relationship between cell-mediated immunity as measured in vivo by the delayed-type hypersensitivity (DTH) response to candida antigen and demographic and physiological variables in older (65-80 y.o.) adults. Candida antigen response was not related to gender or obesity, or to a number of other physiological variables including fitness and body composition. However, positive responders had significantly lower serum C-reactive protein levels (CRP, p<0.05) vs. non-responders. Furthermore, subjects with CRP<4.75 mg•L(-1) had greater odds of developing a positive response compared to those with CRP>4.75 mg•L(-1). Therefore, positive responses to candida antigen in older adults appears to be related to lower levels of systemic inflammation.

Exercise and the aging immune system.

Aging is associated with a decline in the normal functioning of the immune system that is described by the canopy term "immunosenescence". This contributes to poorer vaccine responses and the increased incidence of infection and malignancy seen in the elderly. Regular exercise has been associated with enhanced vaccination responses, lower numbers of exhausted/senescent T-cells, increased T-cell proliferative capacity, lower circulatory levels of inflammatory cytokines ("inflamm-aging"), increased neutrophil phagocytic activity, lowered inflammatory response to bacterial challenge, greater NK-cell cytotoxic activity and longer leukocyte telomere lengths in aging humans, all of which indicate that habitual exercise is capable of regulating the immune system and delaying the onset of immunosenescence. This contention is supported by the majority of animal studies that report improved immune responses and outcomes to viral infections and malignancies due to exercise training. However, whether or not exercise can reverse, as well as prevent, immunosenescence is a contentious issue, particularly because most longitudinal exercise training studies do not report the same positive effects of exercise on immunity that have been widely reported in studies with a cross-sectional design. In this review, we summarize some of the known effects of exercise on immunosenescence, discuss avenues for future research, and provide potential mechanisms by which exercise may help rejuvinate the aging immune system.

Effects of exercise on weight loss and monocytes in obese mice.

Obesity causes innate immune dysfunction, contributing to increased disease risk. Weight loss from a combination of caloric restriction and exercise is the most effective treatment of obesity. We compared forced and voluntary exercise as weight-loss treatments in diet-induced obese (DIO) mice and assessed the effects of weight loss on monocyte concentration and cell-surface expression of Toll-like receptor (TLR) 2, TLR4, CD80, and CD86. DIO CD1 male mice were allocated randomly to 1 of 3 groups (n = 6 per group): voluntary wheel running (VEX); forced treadmill running (FEX); and sedentary (S). A fourth (control) group (CN, n = 6) of nonDIO mice was included also. During the 8-wk weight-loss treatment, all 4 groups consumed a low-fat (10% fat) diet. Nonlethal saphenous vein blood samples collected at baseline, week 4, and week 8 were analyzed by flow cytometry to assess monocyte concentration and functional receptor expression. The VEX and FEX groups lost significantly more body weight (36% and 27%, respectively) over the 8 wk of treatment than did other groups. VEX mice ran 4.4 times more than did FEX animals. VEX mice had higher monocyte concentrations (48% and 58%, respectively) than did the CN and FEX groups. Compared with baseline, week 8 cell-surface expression of TLR2 (22%), TLR4 (33%), and CD86 (18%) was increased in VEX mice. At week 4, CD80 expression was 42% greater for VEX than S mice. The present study confirms that short-term exercise and low-fat diet consumption cause significant weight loss and altered immune profiles.

Rapid morphological characterization of isolated mitochondria using Brownian motion.

Mitochondrial morphology has been associated with numerous pathologies including cancer, diabetes, obesity and heart disease. However, the connection is poorly understood-in part due to the difficulty of characterizing the morphology. This impedes the use of morphology as a tool for disease detection/monitoring. Here, we use the Brownian motion of isolated mitochondria to characterize their size and shape in a high throughput fashion. By using treadmill exercise training, mitochondria from heart and gastrocnemius of Balb/c mice were modulated in size and used to investigate the protocol. Consistent with previous reports, the heart mitochondria of untrained mice increased 5% in diameter immediately after a single bout of moderate exercise (1.091 ± 0.004 µm) as compared to completely sedentary controls (1.040 ± 0.022 µm). In addition, no change was observed in the size of gastrocnemius mitochondria (1.025 ± 0.018 µm), which was also in agreement with previous studies. The method was also successfully applied to smaller Saccharomyces cerevisiae mitochondria.

A review focused on the psychological effectiveness of tai chi on different populations.

As a popular exercise form, Tai Chi (TC) has been investigated to determine its contributions to an active and healthy lifestyle. There are an increasing number of researchers who focus on exploring the potential physiological and psychological benefits of TC but only a few systematic reviews of these benefits to a variety of populations. The purpose of this paper is to comprehensively evaluate the reported psychological benefits associated with practicing TC. Although many investigators have reported possible psychological benefits of TC for children, young adults, older healthy adults, and for a variety of patient populations, many of the reports suffer one or more methodological flaws. These flaws include inadequate study design, including lack of control groups, small sample sizes, unsophisticated statistical techniques, or publication without rigorous peer review. After reviewing the results of the existing literature regarding the potential psychological benefits of TC, we recommend that future investigations be conducted with additional adherence to the traditional scientific process.

NK-cells have an impaired response to acute exercise and a lower expression of the inhibitory receptors KLRG1 and CD158a in humans with latent cytomegalovirus infection.

NK-cells and γδ T-cells are cytotoxic effectors of the immune system that are preferentially mobilized into the blood compartment in response to acute stress and exercise. While infection history is known to alter the phenotype and exercise-responsiveness of CD8+ T-cells, the influence of latent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections on the phenotypes and exercise-responsiveness of NK-cells and γδ T-cells are unknown. Twenty healthy males (age: 28.4±5.4 years) cycled for 30 min at 85% peak power. Blood lymphocytes isolated before, immediately after, and 1 h after exercise were surface stained for CD3, CD4, CD8, CD56, CD57, CD158a, KLRG1, and γδ-TCR antigens by four-color flow cytometry. CMV and EBV serostatus (pos/neg) was determined by ELISA. CMVpos had lower proportions of NK-cells expressing inhibitory receptors (KLRG1+ and CD158a+) and higher proportions of terminally differentiated NK-cells (KLRG1-/CD57+) compared to CMVneg. CMVpos mobilized far fewer (132 cells/µL vs. 245 cells/µL) NK-cells in response to exercise despite having similar baseline NK-cell counts and physiological responses to exercise as CMVneg, although terminally differentiated NK-cells were equally responsive to exercise regardless of CMV serostatus (p=0.658). EBVpos had higher proportions of CD8+ NK-cells, but cellular responses to exercise were not influenced by EBV. The frequency and exercise-responsiveness of γδ T-cells was not affected by CMV or EBV serostatus (p>0.05). In conclusion, latent CMV infection is associated with lowered numbers of NK-cells expressing inhibitory receptors and a blunted mobilization of NK-cells in response to acute exercise. This may indicate a compromised immune response to "fight-or-flight" situations in those infected with CMV.

Repeated bouts of aerobic exercise enhance regulatory T cell responses in a murine asthma model.

We have reported previously that moderate intensity aerobic exercise training attenuates airway inflammation in a murine asthma model. Recent studies implicate regulatory T (Treg) cells in decreasing asthma-related airway inflammation; as such, the current study examined the effect of exercise on Treg cell function in a murine asthma model. Mice were sensitized with ovalbumin (OVA) prior to the start of exercise training at a moderate intensity 3x/week for 4weeks; exercise was performed as treadmill running (13.5m/min, 0% grade). Mice were OVA challenged repeatedly throughout the exercise protocol. At protocol completion, mice were analyzed for changes in the number and suppressive function of CD4(+)CD25(+)Foxp3(+) cells isolated from lungs, mediastinal lymph nodes, and spleens. Results show that exercise increased significantly the number of Foxp3(+) cells within the lungs and mediastinal lymph nodes, but not the spleens, of OVA-treated mice as compared with sedentary controls. Exercise also enhanced the suppression function of CD4(+)CD25(+)Foxp3(+) Treg cells derived from OVA-treated mice as compared with sedentary controls. Specifically, Treg cells from exercised, OVA-treated mice more effectively suppressed CD4(+)CD25(-) cell proliferation and Th2 cytokine production in vitro. Enhanced suppression was associated with increased protein levels of TGF-beta and lesser amounts of IL-10 and IL-17; however, blocking TGF-beta had no effect on suppressive functions. These data demonstrate that exercise-mediated increases in Treg cell function may play a role in the attenuation of airway inflammation. Further, these results indicate that moderate intensity aerobic exercise training may alter the Treg cell function within the asthmatic airway.

Epithelial cells as immune effector cells: the role of CD40.

Through the expression of inflammatory mediators and immune-related molecules, epithelial cells function as immune effector cells in a wide variety of tissues; the expression of the CD40 receptor on these cells contributes this role. Engagement of CD40 activates epithelial cells and results in their release of pro- and anti-inflammatory mediators as well as pro-fibrotic molecules. As such, epithelial CD40 has been implicated in the pathogenesis of inflammatory disorders, generation of self-tolerance, and rejection of allografts.

Cardiovascular exercise training extends influenza vaccine seroprotection in sedentary older adults: the immune function intervention trial.

OBJECTIVES: To determine whether cardiovascular exercise training resulted in improved antibody responses to influenza vaccination in sedentary elderly people who exhibited poor vaccine responses. DESIGN: Single-site randomized parallel-arm 10-month controlled trial. SETTING: University of Illinois at Urbana-Champaign. PARTICIPANTS: One hundred forty-four sedentary, healthy older (69.9 +/- 0.4) adults. INTERVENTIONS: Moderate (60-70% maximal oxygen uptake) cardiovascular exercise was compared with flexibility and balance training. MEASUREMENTS: The primary outcome was influenza vaccine response, as measured according to hemagglutination inhibition (HI) anti-influenza antibody titer and seroprotective responses (HI titer > or =40). Secondary measures included cardiovascular fitness and body composition. RESULTS: Of the 160 participants enrolled, 144 (90%) completed the 10-month intervention with excellent compliance ( approximately 83%). Cardiovascular, but not flexibility, exercise intervention resulted in improvements in indices of cardiovascular fitness, including maximal oxygen uptake. Although not affecting peak (e.g., 3 and 6 weeks) postvaccine anti-influenza HI titers, cardiovascular exercise resulted in a significant increase in seroprotection 24 weeks after vaccination (30-100% dependent on vaccine variant), whereas flexibility training did not. CONCLUSION: Participants randomized to cardiovascular exercise experienced improvements in influenza seroprotection throughout the entire influenza season, whereas those in the balance and flexibility intervention did not. Although there were no differences in reported respiratory tract infections, the exercise group exhibited reduced overall illness severity and sleep disturbance. These data support the hypothesis that regular endurance exercise improves influenza vaccine responses.

Higher antibody, but not cell-mediated, responses to vaccination in high physically fit elderly.

The purpose of this study was to examine whether cardiovascular fitness, independent of confounding factors, was associated with immune responsiveness to clinically relevant challenges in older adults (60-76 yr). Thirteen sedentary, low-fit (LF; maximal O(2) uptake = 21.1 +/- 1.1 ml.kg(-1).min(-1)) and 13 physically active, high-fit (HF; maximal O(2) uptake = 46.8 +/- 3.4 ml.kg(-1).min(-1)) older adults participated in this study. Dietary intake was assessed, and a battery of psychosocial tests was administered. In vivo antibody and ex vivo proliferative and cytokine responses to influenza (Fluzone) and tetanus toxoid (TT) vaccination and delayed-type hypersensitivity skin tests were performed. HF elderly individuals displayed a higher antibody response to two of the three strains included in the Fluzone vaccine as measured by hemagluttination inhibition, but there was no difference between groups in influenza-specific ex vivo proliferation or IFN-gamma or IL-10 production. HF elderly individuals exhibited a lower IgG(1) response and a tendency for a higher IgG(2) response to the TT vaccine. There were, however, no differences in TT-specific ex vivo proliferation or IFN-gamma or IL-10 production. In contrast, HF subjects had higher proliferative responses to phytohemagluttinin. In addition, there were no differences in delayed-type hypersensitivity responses to fungal antigens between groups. These results suggest that, after accounting for confounding factors, HF elderly individuals have higher antibody responses to Fluzone vaccine and a Th2 skewing of the antibody response to TT. There was little evidence that HF mounted better cell-mediated immune responses to the Fluzone or TT vaccine measured in peripheral blood cells or to other recall antigens in vivo.

Moderate exercise early after influenza virus infection reduces the Th1 inflammatory response in lungs of mice.

We have previously shown that moderate exercise significantly increased survival after influenza virus (A/PR/8/34) infection in mice. We hypothesized that this brief duration of exercise would either increase innate immune defences and/or shift the immune response from a Th1 inflammatory to a Th2 anti-inflammatory response resulting in decreased lung pathology. Adult male BALB/cByJ mice (5-6 months old) were infected with 50 microL of A/PR/8/34 virus (40HAU) intranasally and randomized to either an exercise (EX) or sedentary (SED) group. EX mice performed 20-30 min of moderate exercise (8-12 m/min) on a motorized treadmill 4 hr post-infection and then exercised similarly for 4 consecutive days. SED mice were exposed to similar environmental conditions but did not exercise. Mice from both EX and SED groups were sacrificed 1, 3, or 5 days post-infection (p.i.) and lungs, mediastinal lymph nodes (MLNs) and spleens were harvested. EX significantly reduced total cellular infiltration and IFN-gamma gene expression in lungs at Days 3 and 5 p.i. and there was a qualitative shift in the expression of cytokines in the lung from a Th1 to a Th2 response. There was also a tendency toward a reduction in influenza M1 protein mRNA expression. There was no difference in IFN-beta protein levels between groups. These data suggest that moderate exercise when applied early after infection shifts the immune response away from a Th1 profile in mice infected with influenza virus. This exercise-induced shift in immune response may be responsible for improved survival after influenza virus infection.

Moderate exercise protects mice from death due to influenza virus.

We wanted to determine if different doses of exercise, performed in the initial days after infection when the host is mounting an immune response, altered mortality, and morbidity to influenza virus infection in mice. Forty hemagglutinating units of influenza virus (A/Puerto Rico/8/34) were administered intranasally to lightly anesthetized mice. Male Balb/cByJ mice were randomized to one of three groups: sedentary control (CON); moderate (MOD) exercise (20-30 min at 8-12 m/min); or prolonged (PRO) exercise (2.5 h at 8-12 m/min). Mice exercised on a treadmill 4 h post-infection and for three more consecutive days before symptom onset. Mortality, morbidity, bodyweight, and food intake were assessed. MOD had a significantly (p = .007) higher survival (18 of 22; 82%) rate when compared to CON (10 of 23; 43%). There was no difference in morbidity between MOD and CON, despite improved survival. PRO exhibited a survival rate of 30% (p = .29 vs. CON) and demonstrated significantly higher morbidity on several days. While all groups exhibited anorexia and significant body weight loss (approximately 30-35%) post-infection, exercise had little effect on these variables. We demonstrate that moderate exercise, performed in the initial days after influenza infection, significantly decreased mortality in mice. Prolonged exercise led to increased morbidity and tended to decrease survival.