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BackgroundThis study examined whether biological mechanisms linking dementia caregiving with an increased risk of coronary heart disease can be modified by psychosocial interventions and which caregivers might benefit the most from an intervention.MethodsSpousal dementia caregivers were randomized to 12-week treatment with either a behavioral activation intervention (ie, Pleasant Events Program [PEP]; n = 60), or an active control Information and Support (IS; n = 63) condition. Indicators of caregiving stress were assessed pretreatment and circulating cardiovascular biomarkers were measured pre- and posttreatment.ResultsThere were no significant changes in biomarker levels from pre- to posttreatment both by treatment condition and across all caregivers. Regardless of the treatment condition, exploratory regression analysis revealed that caregivers were more likely to show significant decreases in C-reactive protein (CRP) and D-dimer when their spouse had severe functional impairment; in interleukin (IL)-6 and CRP when they had greater distress due to care recipient's problem behaviors; in tumor necrosis factor (TNF)-α when they had higher levels of negative affect; and in IL-6, CRP, TNF-α, and D-dimer when they had higher personal mastery. Within the PEP group, caregivers with higher negative affect and those with higher positive affect were more likely to show a reduction in von Willebrand factor and D-dimer, respectively. Within the IS group, caregivers whose spouse had severe functional impairment were more likely to show a decrease in IL-6.ConclusionsUnlike the average caregiver, caregivers high in burden/distress and resources might benefit from psychosocial interventions to improve cardiovascular risk, although these observations need confirmation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

ObjectiveOlder adults are among the most frequent users of emergency departments (EDs). Nonspecific symptoms, such as fatigue and widespread pain, are among the most common symptoms in patients admitted at the ED. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) are inflammation biomarkers associated with chronic stress (i.e., dementia caregiving) and nonspecific symptoms. This study aimed to determine whether IL-6 and TNF-α were prospectively associated with ED risk in dementia caregivers (CGs).MethodsParticipants were 85 dementia CGs, who reported during three assessments (3, 9, and 15 months after enrollment) if they had visited an ED for any reason. Cox proportional hazards models were used to examine the relations between resting circulating levels of IL-6 and TNF-α obtained at enrollment and subsequent risk for an ED visit, adjusting for age, sex, use of ED 1 month before enrollment, physical and mental health well-being, body mass index, and CG demands.Results(log) IL-6 significantly predicted ED visits during the 15-month follow-up (B = 1.96, SE = 0.82, p = .017). For every (log) picogram per milliliter increase in IL-6, the risk of visiting an ED was 7.10 times greater. TNF-α was not associated with subsequent ED visits. Exploratory analyses suggested that CGs with levels of IL-6 above the 80th percentile and experiencing high CG demands were at highest risk of an ED visit.ConclusionsIL-6 levels and CG demands may be useful for predicting vulnerability for future ED visits. Although further studies should be conducted to replicate and extend these findings, interventions that successfully modify inflammation markers, including the underlying pathophysiology related to stress and/or comorbid illnesses, may be useful in preventing costly and detrimental outcomes in this population.

To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted. These multiomic, molecular, physiological, and behavioral datasets provide a valuable roadmap of the putative health risks for future human spaceflight.

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 μM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease.

BackgroundCaregivers of a family member with a chronic disability or illness such as dementia are at increased risk for chronic disease. There are many factors that contribute to dementia caregiver vulnerability and these factors can be challenging to assess in clinical settings. Self-rated health (SRH) is an independent measure of survival and physical health in the elderly. As an inclusive measure of health, SRH has been proposed as a reliable way to assess a patient's general health in primary care. Therefore, we sought to identify determinants of poor/fair SRH versus categories of at least good SRH in informal caregivers.MethodsIn a cross-sectional study, we examined 134 elderly (≥55 years) providing in-home care for a spouse with dementia who rated their own health with a single-item question: "In general, would you say your health is excellent, very good, good, fair or poor?". In a multivariable model, we compared caregivers with poor/fair SRH to those with good, very good, or excellent SRH on demographics, health characteristics (health behaviors, physical health indicators, psychosocial factors) and caregiving-specific stress (a composite index/total of four caregiving-specific stressors: years of caregiving, dementia severity, care recipient functional impairment and perceived caregiver burden).ResultsCompared with caregivers who rated their own health as either good (31.3%), very good (38.8%) or excellent (14.2%), caregivers with poor/fair SRH (15.7%) were more likely to have lower physical function and total greater caregiving-specific stress. More years of caregiving, severe dementia and care recipient functional impairment, but not perceived caregiver burden, were also more likely among caregivers with poor/fair SRH. Additionally, high negative affect and low positive affect were more likely in caregivers with poor/fair vs. good or excellent and very good or excellent SRH, respectively.ConclusionsCaregivers with poor/fair SRH were characterized by higher levels of medical comorbidity, low physical function, high negative, but low positive affect and longer duration of caregiving, as well as more severe dementia and greater functional impairment of the care recipient. These findings suggest that caregivers need to be more closely evaluated and targeted for preventive interventions in clinical practice.Trial registrationClinicalTrials.gov registration number: NCT02317523 .

ObjectiveCaregiving stress is associated with increased risk of cardiovascular disease (CVD). Inability to adequately regulate blood pressure is a possible underlying mechanism explaining this risk. We examined the relationship between length of caregiving and cardiovagal baroreflex sensitivity (cBRS) to better understand the link between caregiving and CVD risk.MethodsA total of 146 elderly individuals (≥55years) participated in this study, of whom 96 were providing in-home care to a spouse with dementia and 50 were healthy controls married to a non-demented spouse (i.e., non-caregivers). Among the caregivers, 56 were short-term caregivers (caring

ObjectiveElevated blood pressure is a significant public health concern, particularly given its association with cardiovascular disease risk, including stroke. Caring for a loved one with Alzheimer disease has been associated with physical health morbidity, including higher blood pressure. Engagement in adaptive coping strategies may help prevent blood pressure elevation in this population. This 5-year longitudinal study examined whether greater participation in pleasant leisure activities was associated with reduced blood pressure in caregivers.MethodsParticipants were 126 in-home spousal Alzheimer's caregivers (M [SD] age = 74.2 [7.9] years) that completed five yearly assessments. Linear mixed-effects models analysis was used to examine the longitudinal relationship between pleasant leisure activities and caregivers' blood pressure, after adjusting for demographic and health characteristics.ResultsGreater engagement in pleasant leisure activities was associated with reduced mean arterial blood pressure (B = -0.08, SE = 0.04, p = .040). Follow-up analyses indicated that engagement in activities was significantly associated with reduced diastolic (B = -0.07, SE = 0.03, p = .030) but not systolic blood pressure (B = -0.10, SE = 0.06, p = .114). In addition, mean arterial blood pressure was significantly reduced when caregiving duties ended because of placement of care recipients in nursing homes (B = -3.10, SE = 1.11, p = .005) or death of the care recipient (B = -2.64, SE = 1.14, p = .021).ConclusionsGreater engagement in pleasant leisure activities was associated with lowered caregivers' blood pressure over time. Participation in pleasant leisure activities may have cardiovascular health benefits for Alzheimer's caregivers.

ObjectivesClinical outcomes are worse for patients with heart failure (HF) and elevated depression symptoms. Depression-related sympathoimmune dysregulation may be one mechanism leading to poorer HF prognosis. Sympathetically mediated adrenergic activity is known to regulate immune activity via β-adrenergic receptors (β-ARs). However, studies show conflicting relationships between leukocyte β-AR sensitivity and depression symptoms. The aim of this study was to determine in patients with HF the relationship of leukocyte β-AR sensitivity with two diverse measures of depression, self-report questionnaire versus clinical diagnostic interview.MethodsPatients with HF (N = 73, mean [standard deviation] age = 56.3 [13.0]) completed the Beck Depression Inventory-1A and a modified Structured Clinical Interview for the DSM-IV. Leukocyte β-AR sensitivity was determined from isoproterenol-stimulated cyclic adenosine monophosphate levels; plasma norepinephrine and epinephrine were also assessed.ResultsPatients with major depression determined by Structured Clinical Interview for the DSM-IV had significantly higher β-AR sensitivity than did nondepressed patients (F(6,72) = 9.27, p = .003, η = 0.12). The Beck Depression Inventory-1A revealed a more complex relationship. Minimal, mild, and moderate-to-severe depression symptom groups had significant differences in β-AR sensitivity (F(7,72) = 7.03, p = .002, η = 0.18); mild symptoms were associated with reduced β-AR sensitivity and moderate-to-severe symptoms with higher β-AR sensitivity compared with patients with minimal depressive symptoms.ConclusionsClinical depression was associated with elevated β-AR sensitivity in patients with HF. By deconstructing depression measurements, a greater depth of information may be garnered to potentially reveal subtypes of depression symptoms and their relation to β-AR sensitivity.

BackgroundDepressive symptoms and fatigue frequently overlap in clinical samples and the general population. The link of depressive symptoms and fatigue with increased risk of cardiovascular disease has been partly explained by shared biological mechanisms including sympathetic overactivity. Prolonged sympathetic overactivity downregulates the responsiveness of the β-adrenergic receptor (β-AR), a receptor that mediates several end-organ sympathetic responses.PurposeThe authors studied whether depression and fatigue are related to reduced β-AR responsiveness within the human body (in vivo) in an ethnically diverse sample of African and Caucasian Americans.MethodsThe chronotropic25 dose (CD25) was used to determine in vivo β-AR responsiveness in 93 healthy participants. Psychometric measures included the Center of Epidemiological Studies-Depression Scale and the Multidimensional Fatigue Symptom Inventory.ResultsHierarchical regression analyses (adjusted for age, gender, body mass index, blood pressure, smoking, and ethnicity) revealed that mental fatigue was significantly related to reduced β-AR responsiveness (i.e., higher CD25 values) in the whole sample. Moderation analyses indicated significant ethnicity × depression/fatigue interactions. Depressive symptoms, total fatigue, emotional fatigue, mental fatigue, and physical fatigue were related to reduced β-AR responsiveness in Caucasian American but not in African Americans.ConclusionsOur findings suggest that symptoms of depression and fatigue are related to decreased in vivo β-AR responsiveness in Caucasian Americans. The lack of this association in African Americans highlights the importance for considering ethnicity as a potential moderator in research focusing on associations between psychological variables and cardiovascular function.

ObjectivesThis study aimed to further elucidate the biobehavioral mechanisms linking dementia caregiving with an increased cardiovascular disease risk. We hypothesized that both elevated depressive symptoms and a behavioral correlate of depression, low leisure satisfaction, are associated with systemic inflammation.MethodWe studied 121 elderly Alzheimer's disease caregivers who underwent 4 annual assessments for depressive symptoms, leisure satisfaction, and circulating levels of inflammatory markers. We used mixed-regression analyses controlling for sociodemographic and health-relevant covariates to examine longitudinal relationships between constructs of interest.ResultsThere were inverse relationships between total leisure satisfaction and tumor necrosis factor-α (TNF-α; p = .047), interleukin-8 (IL-8; p < .001), and interferon-γ (IFG; p = .020) but not with IL-6 (p = .21) and C-reactive protein (p = .65). Lower enjoyment from leisure activities was related to higher levels of TNF-α (p = .045), IL-8 (p < .001), and IFG (p = .002), whereas lower frequency of leisure activities was related only to higher IL-8 levels (p = .023). Depressive symptoms were not associated with any inflammatory marker (all p values > .17). Depressive symptoms did not mediate the relationship between leisure satisfaction and inflammation.DiscussionLower satisfaction with leisure activities is related to higher low-grade systemic inflammation. This knowledge may provide a promising way of improving cardiovascular health in dementia caregivers through behavioral activation treatments targeting low leisure satisfaction.

Background: Surf therapy combines physical activity with social support to provide a healing environment. Objective: This exploratory pre-to post-intervention study examined the effects of a novel surf therapy program for women who experienced abuse, trauma, and/or mental illness on emotional regulation, resilience, body acceptance, and gratitude. Methods: Twenty-seven women (ages 25 to 54; mean 36.32 + SD 7.79) participated in an 8-week Groundswell Surf Therapy Program held in four different coastal cities in California. Standardized self-report questionnaires were administered prior to and following the therapy program, including the Body Acceptance Scale, the Connor-Davidson Resilience Scale (CD-RISC), the Affective Style Questionnaire, and the Gratitude Questionnaire-Six-Item Form (GQ-6) in a pre-post study design. Data were analyzed by repeated measures analysis of variance (ANOVA). Results: Body acceptance [ P < 0.001; partial Eta squared = 0.472] and resilience were increased [ P = 0.005; partial Eta squared = 0.319] following the surf therapy intervention. Emotional regulation was examined according to three subscales, with the adjust [ P < 0.001; partial Eta squared = 0.397] and tolerate [ P < 0.001; partial Eta squared = 0.299] subscales increasing following the intervention, and the conceal subscale [ P = 0.459; partial Eta squared = 0.031] remaining unchanged. Gratitude scores were unchanged [ P = 0.425; partial Eta squared = 0.026]. Conclusion: A surf therapy program rooted in somatic and trauma-informed models was associated with improved resilience, emotional regulation, and body acceptance in at-risk women. [ABSTRACT FROM AUTHOR]

Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e., Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps < 0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps < 0.05). Poorer subjective sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.

ContextDementia care giving can lead to increased stress, physical and psychosocial morbidity, and mortality. Anecdotal evidence suggests that hospice care provided to people with dementia and their caregivers may buffer caregivers from some of the adverse outcomes associated with family caregiving in Alzheimer's Disease (AD).ObjectivesThis pilot study examined psychological and physical outcomes among 32 spousal caregivers of patients with AD. It was hypothesized that caregivers who utilized hospice services would demonstrate better outcomes after the death of their spouse than caregivers who did not utilize hospice.MethodsThe charts of all spousal caregivers enrolled in a larger longitudinal study from 2001 to 2006 (N=120) were reviewed, and participants whose spouse had died were identified. Of these, those who received hospice care (n=10) were compared to those who did not (n=22) for various physiological and psychological measures of stress, both before and after the death of the care recipient. An Analysis of Covariance (ANCOVA), with postdeath scores as the dependent variable and pre-death scores as covariates, was used for all variables.ResultsSignificant group differences were found in postdeath depressive symptoms (HAM-D; F(1,29)=6.10, p0.5 between groups.ConclusionsThese data suggest that hospice enrollment may ameliorate the detrimental psychological effects in caregivers who have lost a spouse with Alzheimer's Disease. Based on these pilot data, further prospective investigation is warranted.

Dementia caregiving is associated with elevations in depressive symptoms and increased risk for cardiovascular diseases (CVD). This study evaluated the efficacy of the Pleasant Events Program (PEP), a 6-week Behavioral Activation intervention designed to reduce CVD risk and depressive symptoms in caregivers. One hundred dementia family caregivers were randomized to either the 6-week PEP intervention (N = 49) or a time-equivalent Information-Support (IS) control condition (N = 51). Assessments were completed pre- and post-intervention and at 1-year follow-up. Biological assessments included CVD risk markers Interleukin-6 (IL-6) and D-dimer. Psychosocial outcomes included depressive symptoms, positive affect, and negative affect. Participants receiving the PEP intervention had significantly greater reductions in IL-6 (p = .040), depressive symptoms (p = .039), and negative affect (p = .021) from pre- to post-treatment. For IL-6, clinically significant improvement was observed in 20.0% of PEP participants and 6.5% of IS participants. For depressive symptoms, clinically significant improvement was found for 32.7% of PEP vs 11.8% of IS participants. Group differences in change from baseline to 1-year follow-up were non-significant for all outcomes. The PEP program decreased depression and improved a measure of physiological health in older dementia caregivers. Future research should examine the efficacy of PEP for improving other CVD biomarkers and seek to sustain the intervention's effects.

The sympathetic nervous system not only regulates cardiovascular and metabolic responses to stress but also is altered by stress. The sympathoneural and sympathoadrenomedullary systems are modified by different metabolic pathways and have different responses to short- and to long-term stressors. Stress also induces nonneuronal catecholamine enzymes, primarily through corticosteroids. Catecholamine synthetic enzymes are induced by different pathways in response to short- and long-term acting stressors, like cold exposure or immobilization, and differently in the sympathetic ganglia and the adrenal medulla. However, a long-term exposure to one stressor can increase the response to a second, different stressor. Tyrosine hydroxylase gene transcription increases after only 5min of immobilization through phosphorylation of CREB, but this response is short lived. However, repeated stress gives a longer-lived response utilizing transcription factors such as Egr-1 and Fra-2. Glucocorticoids and ACTH also induce sympathoneural enzymes leading to distinct patterns of short-term and long-lived activation of the sympathetic nervous system. Nonneuronal phenylethanolamine N-methyltransferase (PNMT) develops early in the heart and then diminishes. However, intrinsic cardiac adrenergic cells remain and nonneuronal PNMT is present in many cells of the adult organism and increases in response to glucocorticoids. Both stress-induced and administered glucocorticoids induce fetal PNMT and hypertension. Human stressors such as caring for an ill spouse or sleep apnea cause a persistent increase in blood norepinephrine, increased blood pressure, and downregulated catecholamine receptors. Hypertension is associated with a loss of slow-wave sleep, when sympathetic nerve activity is lowest. These findings indicate that stress-induced alteration of the sympathetic nervous system occurs in man as in experimental animals.

Objective. To investigate the relationship between coping and atherothrombotic biomarkers of an increased cardiovascular disease (CVD) risk in the elderly. Methods. We studied 136 elderly caregiving and noncaregiving men and women who completed the Ways of Coping Checklist to assess problem-focused coping, seeking social support (SSS), blamed self, wishful thinking, and avoidance coping. They had circulating levels of 12 biomarkers measured. We also probed for potential mediator and moderator variables (chronic stress, affect, health behavior, autonomic activity) for the relation between coping and biomarkers. Results. After controlling for demographic and CVD risk factors, greater use of SSS was associated with elevated levels of serum amyloid A (P = 0.001), C-reactive protein (CRP) (P = 0.002), vascular cellular adhesion molecule (VCAM)-1 (P = 0.021), and D-dimer (P = 0.032). There were several moderator effects. For instance, greater use of SSS was associated with elevated VCAM-1 (P < 0.001) and CRP (P = 0.001) levels in subjects with low levels of perceived social support and positive affect, respectively. The other coping styles were not significantly associated with any biomarker. Conclusions. Greater use of SSS might compromise cardiovascular health through atherothrombotic mechanisms, including elevated inflammation (i.e., serum amyloid A, CRP, VCAM-1) and coagulation (i.e., D-dimer) activity. Moderating variables need to be considered in this relationship.

Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive renal disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed both common and unusual variants in both the open reading frame and such regulatory regions as the proximal promoter and 30-UTR. In chromaffin cell-transfected CHGA 30-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 30-UTR displayed statistical associations with hypertension. Genetic variation in the proximal CHGA promoter predicted glomerular filtration rate in healthy twins. However, for hypertensive renal damage, both end-stage renal disease and rate of progression of earlier disease were best predicted by variants in the 30-UTR. Finally, mechanistic studies were undertaken initiated by the clue that CHGA promoter variation predicted circulating endothelin-1. In cultured endothelial cells, CHGA triggered co-release of not only the vasoconstrictor and pro-fibrotic endothelin-1, but also the pro-coagulant von Willebrand Factor and the pro-angiogenic angiopoietin-2. These findings, coupled with stimulation of endothelin-1 release from glomerular capillary endothelial cells by CHGA, suggest a plausible mechanism whereby genetic variation at the CHGA locus eventuates in alterations in human renal function. These results document the consequences of genetic variation at the CHGA locus for cardiorenal disease and suggest mechanisms whereby such variation achieves functional effects.

Although objective and subjective indicators of socioeconomic status (SES) are linked to cardiovascular disease (CVD), little is known about their relationship to endothelial dysfunction, which often precedes CVD.This study examined how objective and subjective SES relate to brachial artery flow-mediated dilation (FMD).FMD was assessed in 72 healthy adults (mean age 36 years). The MacArthur Scale of Subjective Social Status assessed perceived social standing in the USA (SSS-USA) and local community (SSS-Community). Objective SES measures included income and the Hollingshead Two-Factor Index of Social Position (education, occupation).Adjusted regressions revealed that SSS-Community positively correlated with FMD (p

Patients with obstructive sleep apnea (OSA) have been described to have increased levels of inflammatory cytokines (particularly TNF-α) and have severely disturbed sleep architecture. Serum inflammatory markers, even in normal individuals, have been associated with abnormal sleep architecture. Not much is known about the role the TNF receptor plays in the inflammation of OSA nor if it is associated with changes in sleep architecture or arousals during the night. We hypothesized that the TNF receptor might play an important role in the inflammation as well as sleep architecture changes in patients with OSA.Thirty-six patients with diagnosed (AHI > 15) but untreated OSA were enrolled in this study. Baseline polysomnograms as well as TNF-α and soluble TNF receptor I (sTNF-RI) serum levels were obtained on all patients. We evaluated the association between serum levels of TNF-α and sTNF-RI with various polysomongraphic characteristics, including sleep stages and EEG arousals.sTNF-RI levels were significantly correlated with snore arousals (r value 0.449, p value 0.009), spontaneous movement arousals (r value 0.378, p value 0.025), and periodic limb movement arousals (r value 0.460, p value 0.008). No statistically significant correlations were observed with TNF-α to any polysomnographic variables. To control for statistical significance with multiple comparisons, a MANOVA was performed with TNF-α and sTNF-RI as dependent variables and sleep architecture measures and arousals as independent variables. The model for sTNF-RI was statistically significant (F value 2.604, p value 0.03), whereas the model for TNF-α was not, suggesting sleep quality significantly affects sTNF-RI. Hierarchal linear regression analysis demonstrated that sTNF-RI was independently associated with spontaneous movement arousal index scores after controlling for age, body mass index, and sleep apnea severity.These findings suggest that sTNF-RI is associated with arousals during sleep, but not with other measures in patients with OSA.

The objective of this study was to examine differences in catecholamine (CA) response to exercise between children who had received a diagnosis of attention-deficit/hyperactivity disorder (ADHD) and age- and gender-matched controls. On the basis of the notion of a CA dysfunction in ADHD, we reasoned that the normal robust increase in circulating CA seen in response to exercise would be blunted in children with ADHD. To test this, we recruited 10 treatment-naïve children with newly diagnosed ADHD and 8 age-matched controls (all male) and measured CA response to an exercise test in which the work was scaled to each subject's physical capability. After exercise, epinephrine and norepinephrine increased in both control and ADHD subjects (p = 0.006 and p = 0.002, respectively), but the responses were substantially blunted in the ADHD group (p = 0.018) even though the work performed did not differ from controls. Circulating dopamine increased significantly in the control subjects (p < 0.016), but no increase was noted in the subjects with ADHD. Finally, a significant attenuation in the lactate response to exercise was found in ADHD (between groups, p < 0.005). Our data suggest that CA excretion after exercise challenges in children with ADHD is deficient. This deficiency can be detected using a minimally invasive, nonpharmacologic challenge.

We hypothesized that brief exercise of a small muscle group would lead to local rather than systemic alterations in cytokines, peripheral blood mononuclear cells, and mediators of angiogenesis. Fifteen men and eight women (age range 22-36 yr old) performed 10 min of unilateral wrist flexion exercise. Blood was sampled from venous catheters in the resting and exercising arm at baseline, at the end of exercise, and at 10, 30, 60, and 120 min after exercise. Lactate was significantly elevated in the exercising arm (+276 +/- 35%; P < 0.0005) with no change in the resting arm. In contrast, increases in both arms were observed for interleukin-6 (+139 +/- 51%; P < 0.0005), growth hormone (+1,104 +/- 284%; P < 0.003), natural killer cells (+81 +/- 9%; P < 0.0005), and lymphocytes expressing CD62L, CD11a, and CD54. There were no significant differences in these increases between the resting and exercising arm. Catecholamines increased in both arms [epinephrine peak increase, +226 +/- 36% (P < 0.001); norepinephrine peak increase, +90 +/- 15% (P < 0.01)]. Fibroblast growth factor-2 initially decreased with exercise in both arms, and this was followed by a rebound increase. Vascular endothelial growth factor demonstrated a small but significant increase in both arms (+124 +/- 31%; P < 0.05). Brief, low-intensity exercise leads to a systemic rather than local response of mediators that could be involved in inflammation, repair, or angiogenic adaptation to physical activity.

In adults, exercise is a powerful and natural stimulator of immune cells and adhesion molecules. Far less is known about these exercise responses during childhood and whether or not exercise in real-life activities of healthy children might influence immune responses. We compared laboratory exercise (10 x 2 min periods of heavy, constant intensity, cycle ergcometer exercise with 1 min rests between exercise in nine subjects, aged 9-15 years) with field exercise (90 min soccer practice in nine different subjects, aged 9-11 years). Blood was sampled before both protocols, 5 min after the 30 min laboratory protocol, and 10-15 min after the 90 min field protocol. Both field and laboratory exercise protocols led to significant (P