Physical Activity During Breast Cancer Therapy Associates With Preserved Exercise Capacity and Cardiac Function (WF97415).

Background: Cancer treatment increases cardiovascular disease risk, but physical activity (PA) may prevent cardiovascular disease. Objectives: This study examined whether greater PA was associated with better submaximal exercise capacity and cardiac function during cancer therapy. Methods: Participants included 223 women with stage I to III breast cancer (BC) before and 3 months after undergoing treatment and 126 control participants. Leisure-time PA (LTPA) was reported using the Godin-Shephard LTPA questionnaire. Cardiac function was assessed by cardiac magnetic resonance. Submaximal exercise capacity was determined by 6-minute walk distance. Results: BC participants reported similar baseline LTPA scores (24.7; 95% CI: 21.7-28.0) as control participants (29.4; 95% CI: 25.0-34.2). The BC group declined to 16.9 (95% CI: 14.4-19.6) at 3 months relative to 30.8 (95% CI: 26.2-35.8) in control participants. Among BC participants, more LTPA was related to better exercise capacity (ß ± SE: 7.1 ± 1.6; 95% CI: 4.0-10.1) and left ventricular (LV) circumferential strain (-0.16 ± 0.07; 95% CI: -0.29 to -0.02). Increased LTPA over the 3 months was associated with decreased likelihood of treatment-induced cardiac dysfunction according to LV circumferential strain classifications (OR: 0.98; 95% CI: 0.97-0.998). BC participants reporting insufficient LTPA according to PA guidelines exhibited deteriorations in exercise capacity (adjusted mean difference ± SE: -29 ± 10 m; P = 0.029), LV end-systolic volume (5.8 ± 1.3 mL; P < 0.001), LV ejection fraction (-3.2% ± 0.8%; P = 0.002), and LV circumferential strain (2.5% ± 0.5%; P < 0.001), but BC participants meeting LTPA guidelines did not exhibit these adverse changes. Conclusions: PA declined during BC therapy; however, PA participation was associated with attenuated declines in exercise capacity and cardiac function that are often observed in this population. (Understanding and Predicting Breast Cancer Events After Treatment [WF97415 UPBEAT]; NCT02791581).

Longitudinal associations among physical activity and sitting with endocrine symptoms and quality of life in breast cancer survivors: A latent growth curve analysis.

PURPOSE: Adjuvant endocrine therapy (AET) often causes debilitating endocrine symptoms that compromise quality of life (QOL) in women diagnosed with hormone receptor positive breast cancer (BC). We examined whether greater levels of physical activity (PA) or prolonged sitting were associated with reduced side effects or worse side effects of AET, respectively. METHODS: We used parallel process latent growth curve models to examine longitudinal patterns in PA and sitting behaviors, and their association with endocrine symptoms and QOL over 3 years of follow-up in 554 female BC survivors undergoing AET. RESULTS: At baseline, women were a mean age of 59 years, mostly white (72%), with overweight/obesity (67%), and approximately 50% were within 1 year of diagnosis. Unconditional models showed significant increases in PA (p < 0.01) over time but no change in sitting. Endocrine symptoms, general and BC-specific QOL all significantly worsened over time (p < 0.01). Parallel process models showed no cross-sectional or longitudinal associations between PA and endocrine symptoms. Higher levels of baseline PA were associated with higher baseline QOL scores (p = 0.01) but changes in PA were not associated with changes in QOL. Conversely, more sitting at baseline was associated with worse endocrine symptoms, general and BC specific QOL (ps <0.01). At baseline, having better QOL scores was associated with increases in sitting (ps <0.01), while having worse endocrine symptoms was associated with a slower rate of increase in sitting (p < 0.01). Increases in sitting time were also associated with a slower rate of increase in endocrine symptoms (p = 0.017). Model fit statistics (x2, CFI, TLI, SRMR) were acceptable. CONCLUSION: Both PA and sitting behaviors are important for the management of symptoms and in maintaining QOL in BC survivors. Women with already high symptom burden do not increase sitting time further but having better general and BC specific QOL to begin with means a greater decline over time.

Acute, but not chronic, aerobic exercise alters the impact of ex vivo LDL and fatty acid stimulation on monocytes and macrophages from healthy, young adults.

BACKGROUND: Elevated low-density lipoprotein (LDL) and triglyceride concentrations are associated with future cardiovascular risk in young adults. Conversely, chronic physical activity is generally accepted to reduce CVD risk. Atherosclerosis is a major underlying cause of CVD, and atherogenesis is mediated by peripheral monocytes and monocyte-derived macrophages. The study aimed to determine if an individual's physical activity level impacts the phenotype of monocytes and monocyte-derived macrophages when stimulated with LDL and fatty acid ex vivo. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from healthy, young adults of differing physical activity levels before and after a single bout of moderate intensity exercise (25 min at 60% of VO2peak). PBMCs were stimulated with LDL and palmitate ex vivo prior to differentiation into macrophages. Monocyte subset percentages and monocyte-derived macrophage expression of phenotypic (CD86, CD206) and functional (CCR2, ERK 1/2) markers were evaluated by flow cytometry. RESULTS: Compared to baseline, ex vivo LDL and palmitate stimulation decreased (p = 0.038) non-classical monocyte percentage from 24.7 ± 3.2 to 21.5 ± 2.6% in all participants. When ex vivo lipid stimulation was preceded by acute exercise, non-classical monocyte percentage was similar to baseline levels (p = 0.670, 25.8 ± 2.15%). Macrophage CD86/CD206 was increased from 1.30 ± 0.14 to 1.68 ± 0.19 when preceded by acute exercise in all participants. No differences were observed between participants of differing physical activity levels. CONCLUSIONS: Findings suggest that acute exercise modulates monocyte phenotype after LDL and palmitate stimulation in a protective manner, however, chronic physical activity does not alter monocyte/macrophage responses to any experimental condition in this population.

NLRP3-mediated inflammation in cardio-oncology: sterile yet harmful.

Despite significant advances and the continuous development of novel, effective therapies to treat a variety of malignancies, cancer therapy-induced cardiotoxicity has been identified as a prominent cause of morbidity and mortality, closely competing with secondary malignancies. This unfortunate limitation has prompted the inception of the field of cardio-oncology with its purpose to provide the necessary knowledge and key information on mechanisms that support the use of the most efficacious cancer therapy with minimal or no interruption while paying close attention to preventing cardiovascular related morbidity and mortality. Several mechanisms that contribute to cancer therapy-induced cardiotoxicity have been proposed and studied. These mainly involve mitochondrial dysfunction and reactive oxygen species-induced oxidative stress, lysosomal damage, impaired autophagy, cell senescence, DNA damage, and sterile inflammation with the formation and activation of the NLRP3 inflammasome. In this review, we focus on describing the principal mechanisms for different classes of cancer therapies that lead to cardiotoxicity involving the NLRP3 inflammasome. We also summarize current evidence of cardio-protection with inflammasome inhibitors in the context of heart disease in general, and further highlight the potential application of this evidence for clinical translation in at risk patients for the purpose of preventing cancer therapy associated cardiovascular morbidity and mortality.

Racial disparities in treatment-related cardiovascular toxicities amongst women with breast cancer: a scoping review.

PURPOSE: Black women often experience poorer breast cancer-related outcomes and higher mortality than white women. A contributor to this disparity may relate to the disproportionate burden of cancer treatment-related cardiovascular (CV) toxicities. The objective of this review is to identify studies that report racial differences in CV toxicity risk. METHODS: Medline and Embase were searched for studies that assessed CV toxicities as the outcome(s) and included Black and White women with breast cancer. Studies were selected based on inclusion/exclusion criteria and through the use of multiple reviewers. RESULTS: The review included 13 studies following a review of 409 citations and 49 full-text articles. All studies were retrospective and 8/13 utilized data from the Surveillance, Epidemiology, and End Results-Medicare linked database. Trastuzumab was the most frequently studied treatment. The proportion of Black women in these studies ranged from 5.5 to 63%. A majority of studies reported a higher risk of CV toxicity amongst Black women when compared to white women (93%). Black women had up to a two times higher risk of CV toxicity (HR, 2.73 (CI, 1.24 to 6.01)) compared to white women. Only one study evaluated the role of socioeconomic factors in explaining racial differences in CV toxicity; however, the disparity remained even after adjusting for these factors. CONCLUSIONS: There is a critical need for more longitudinal studies that evaluate multilevel factors (e.g., psychosocial, biological) that may help to explain this disparity. IMPLICATIONS FOR CANCER SURVIVORS: Black cancer survivors may require additional surveillance and mitigation strategies to decrease disproportionate burden of CV toxicities.

Prevalence of Cardiovascular Diseases Among Breast Cancer Survivors: Findings From the NHANES 2003-2018.

PURPOSE: To examine the prevalence of cardiovascular diseases (CVD) among breast cancer (BC) survivors. DESIGN: Cross-sectional observational study using the data from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. SETTING: United States (US). SUBJECTS: A nationally representative sample of US women with a history of BC. MEASURES: Self-reported CVD status (i.e., coronary artery disease (CAD), heart failure, and stroke) and time of the CVD diagnosis were used to categorize BC survivors into three groups: No CVD, preexisting CVD, and post-acquired CVD after BC diagnosis. ANALYSIS: The prevalence of CVD among BC survivors were estimated by demographic characteristics. Complex sampling design of the NHANES was accounted to estimate the population-level prevalence. RESULTS: A total of 658 BC survivors were identified, representing 3.01% (≈3.4 million) of the US women aged ≥18 years old. Of those, ≈6% (≈.2 million) had preexisting CVD and ≈11% (≈.4 million) had at least one CVD diagnosed after BC diagnosis, with an average time elapsed ranging from ≈5 years for heart failure to ≈9 years for CAD and stroke. The prevalence of CVD among BC survivors differed by demographic characteristics including age, education, marital status, menopausal, and physical activity levels. CONCLUSION: Our findings suggest that BC survivors are at risk of suffering from CVD and public health strategies for the long-term management of CVD risk factors in this vulnerable population group is recommended.

Sex differences in monocyte CCR2 expression and macrophage polarization following acute exercise.

Monocyte chemokine receptor 2 (CCR2) and phosphorylated extra-cellular regulated kinase 1 & 2 (ERK1/2) impact macrophage differentiation and progression of atherosclerosis. Whereas aerobic exercise favorably modulates the immune system and reduces atherosclerotic risk, it is unknown whether sex differences exist in the monocyte/macrophage response to acute aerobic exercise. AIMS: To determine the impact of an acute bout of moderate intensity aerobic exercise on monocyte and macrophage CCR2 expression, ERK1/2 phosphorylation, and macrophage polarization in pre-menopausal women and men. MATERIALS AND METHODS: Blood samples were collected in 24 people (Women/Men; n = 12) prior to (PRE), immediately after a bout of moderate intensity cycle ergometry (POST), and 2 h (2H) following exercise. Monocyte and macrophage CCR2 and phosphorylated ERK1/2 as well as macrophage CD86 and CD206 were analyzed by flow cytometry. KEY FINDINGS: PRE classical monocyte CCR2 expression was greater in women compared to men (Women: 20546.2 ± 2306.4 vs. Men: 14437.6 ± 1201.9 AUF; p = 0.028) and was reduced in women at 2H (PRE: 20546.2 ± 2306.4 vs. 2H: 15856.9 ± 1314.4 AUF; p = 0.027). POST classical monocyte CCR2 expression was inversely associated (r = -0.697, p = 0.012) with POST classical monocyte ERK1/2 phosphorylation in women only. The percentage of CCR2+ macrophages was lower in women at POST (Women: 62.0 ± 8.9 vs. Men: 83.6 ± 3.1; p = 0.031) and at 2H (Women: 60.3 ± 8.4 vs. Men: 83.5 ± 3.0%; p = 0.016). SIGNIFICANCE: These data suggest that a single bout of moderate intensity aerobic exercise differentially impacts monocyte CCR2 expression and macrophage polarization in women compared to men.

Lean Mass Abnormalities in Heart Failure: The Role of Sarcopenia, Sarcopenic Obesity, and Cachexia.

The role of body composition in patients with heart failure (HF) has been receiving much attention in the last few years. Particularly, reduced lean mass (LM), the best surrogate for skeletal muscle mass, is independently associated with abnormal cardiorespiratory fitness (CRF) and muscle strength, ultimately leading to reduced quality of life and worse prognosis. While in the past, reduced CRF in patients with HF was thought to result exclusively from cardiac dysfunction leading to reduced cardiac output at peak exercise, current evidence supports the concept that abnormalities in LM may also play a critical role. Abnormalities in the LM body composition compartment are associated with the development of sarcopenia, sarcopenic obesity, and cachexia. Such conditions have been implicated in the pathophysiology and progression of HF. However, identification of such conditions remains challenging, as universal definitions for sarcopenia, sarcopenic obesity, and cachexia are lacking. In this review article, we describe the most common body composition abnormalities related to the LM compartment, including skeletal and respiratory muscle mass abnormalities, and the consequences of such anomalies on CRF and muscle strength in patients with HF. Finally, we discuss the potential nonpharmacologic therapeutic strategies such as exercise training (ie, aerobic exercise and resistance exercise) and dietary interventions (ie, dietary supplementation and dietary patterns) that have been implemented to target body composition, with a focus on HF.

Impact of physical activity on monocyte subset CCR2 expression and macrophage polarization following moderate intensity exercise.

Coronary artery disease (CAD) is an immune-mediated disease in which CCR2 attracts classical, intermediate, and non-classical monocytes to the arterial intima where they differentiate to macrophages. Balance between pro-inflammatory M1 and anti-inflammatory M2 macrophages contributes to CAD prevention. Moderate to vigorous intensity physical activity (MVPA) elicits an immune response and reduces the incidence of CAD, however, the impact of prior MVPA on monocyte subset CCR2 expression and macrophage polarization following acute exercise is unknown. Purpose: To determine the impact of physical activity status on monocyte subset CCR2 surface expression and macrophage polarization in response to an acute bout of moderate intensity cycle ergometry. Methods: 24 healthy women and men (12 high physically active [HIACT]: ≥1500 METmin/wk MVPA & 12 low physically active [LOACT]: <600 METmin/wk MVPA) underwent an acute moderate intensity (60% VO2peak) bout of cycle ergometry for 30 â€‹min. Blood samples were collected prior to (PRE), immediately (POST), 1 â€‹h (1H), and 2 â€‹h (2H) following exercise. Monocyte CCR2 and macrophage CD86 (M1) and CD206 (M2) were analyzed by flow cytometry. Results: Intermediate monocyte CCR2 decreased in response to exercise in the HIACT group (PRE: 11409.0 â€‹± â€‹1084.0 vs. POST: 9524.3 â€‹± â€‹1062.4; p â€‹= â€‹0.034). Macrophage CD206 was lower in the LOACT compared to the HIACT group at 1H (HIACT: 67.2 â€‹± â€‹5.6 vs. LOACT: 50.1 â€‹± â€‹5.2%; p â€‹= â€‹0.040). Macrophage CD206 at 1H was associated with both PRE (r â€‹= â€‹0.446, p â€‹= â€‹0.043) and POST (r â€‹= â€‹0.464, p â€‹= â€‹0.034) non-classical monocyte CCR2. Conclusion: These data suggest that regular moderate to vigorous physical activity positively impacts both monocytes and macrophages following acute moderate intensity exercise and that this impact may contribute to the prevention of coronary artery disease.

Excess Blood Flow Response to Acute Resistance Exercise in Individuals Who are Obese or Nonobese.

Lipford, GF, Evans, RK, Acevedo, EO, Wolfe, LG, and Franco, RL. Excess blood flow response to acute resistance exercise in individuals who are obese or nonobese. J Strength Cond Res 31(11): 3120-3127, 2017-Resistance exercise (RE) is a commonly recommended treatment option for obese individuals. However, little is known regarding alterations in vasodilatory responses to RE, which could impair exercise tolerance. No studies to date have compared microvascular vasodilatory capacity, assessed by excess blood flow (EBF), responses in individuals who are obese or nonobese following acute RE. The purpose of the study was to evaluate EBF before and up to 24-hour after a single RE bout in obese (n = 18, 38.1 ± 7.64% body fat) and nonobese (n = 10, 23.6 ± 4.03% body fat) individuals who volunteered to participate. Each subject completed a leg flexion and knee extension one repetition maximum (1RM) test, and subsequently completed 4 sets of 8 repetitions at 85% of 1RM. Excess blood flow, adiponectin, and tumor necrosis factor α (TNF-α) were evaluated at baseline (PRE-RE), immediately after (POST-RE), and 1 (POST-1) and 24 (POST-24) hours after exercise. A repeated-measures analysis of variance revealed a significant interaction for EBF between the 2 groups (p = 0.029). The estimated marginal means plot suggested that obese individuals had a significant increase in POST-RE EBF in comparison with PRE-RE EBF (428.54 ± 261.59 vs. 547.00 ± 311.15 ml/100 ml/min·s; p = 0.046). In addition, EBF significantly decreased at POST-24 in comparison with POST-RE in the obese individuals (547.00 ± 311.15 vs. 389.33 ± 252.32 ml/100 ml/min·s; p = 0.011). Changes in EBF were not related to adiponectin or TNF-α. An acute bout of RE resulted in an opposite EBF response between nonobese and obese individuals immediately after RE. Furthermore, only the obese individuals displayed a significant increase in EBF immediately after RE, which was significantly reduced 24 hours after the RE bout. Microvascular vasodilatory capacity may alter the adaptive exercise response associated with RE, requiring alterations to frequency, intensity, and/or duration that are specific to populations of various body composition profiles.

The effect of acute physical and mental stress on soluble cellular adhesion molecule concentration.

AIMS: This study investigated the impact of acute physical and mental stress on serum concentrations of vascular cell adhesion molecule (VCAM)-1 and CX3CL1/fractalkine. MATERIALS AND METHODS: Male volunteers (n=20; 21.3±0.55years of age) completed a graded treadmill test to exhaustion and a 20-minute mental stress task (Stroop Color-Word Test, mental arithmetic) on separate, non-consecutive days. Heart rate (HR) was measured at baseline and throughout exercise and mental stress. Blood was collected at baseline (PRE), immediately following (POST) and 30min after (POST30) exercise and mental stress. Soluble VCAM-1 and fractalkine were quantified in participant serum via enzyme-linked immunosorbent assays. KEY FINDINGS: Both treadmill exercise and the mental stress task significantly increased participant HR; although, exercise resulted in a substantially greater increase in participant HR compared to mental stress (197.82±11.99 vs. 38.67±3.10% [p<0.001]). VCAM-1 (815.74±139.55 vs. 738.67±131.59ng/mL [p=0.002]) and fractalkine (1.032±0.33 vs. 0.59±0.20ng/mL [p<0.001]) were significantly elevated in participant serum POST maximal exercise before returning to values similar to baseline at POST30. The acute mental stress task did not significantly alter serum VCAM-1 or fractalkine at any time point. SIGNIFICANCE: In conclusion, maximal aerobic exercise results in a significant elevation of the soluble adhesion molecules VCAM-1 and fractalkine in the serum of adult males that does not occur following laboratory-induced mental stress. The findings of the current investigation may suggest a novel protective role for acute aerobic exercise in vascular health via exercise-induced CAM proteolysis.

G protein-coupled receptor kinase-2 in peripheral blood mononuclear cells following acute mental stress.

AIMS: This study investigated G-protein-coupled receptor kinase-2 (GRK2) density in peripheral blood mononuclear cells (PBMC) and its relationship to plasma pro-inflammatory cytokine concentrations following acute mental stress. MAIN METHODS: Apparently healthy males (n=20; 21.3±0.55years) participated in an acute mental stress task. Heart rate was measured at baseline and throughout mental stress. Plasma epinephrine (EPI), norepinephrine (NE), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were assessed via enzyme-linked immunosorbent assays before, immediately following, and 30, 60 and 120min after the mental stress task. GRK2 density was measured by western blot technique at the same time points. KEY FINDINGS: Acute mental stress elicited significant elevations in HR, and plasma EPI and NE. Additionally, GRK2 density increased significantly across time following the stress task. Post hoc analyses revealed that GRK2 density was significantly elevated at 30 and 60min following acute stress. A significant positive correlation was observed between GRK2 density and plasma EPI, while a significant negative correlation was revealed between GRK2 density and TNF-α across all time points. SIGNIFICANCE: Acute mental stress significantly increased GRK2 density in PBMCs of young adult males. Furthermore, although plasma IL-6 and TNF-α did not change following mental stress, it remains unknown whether a longer time period was needed to observe a pro-inflammatory state associated with the desensitization of ß-adrenergic receptor activity. Our findings that GRK2 expression is promptly increased in PBMC following an acute stress task, may suggest a link between stress and intracellular inflammatory signaling.

Sympathetic Activity Assessed during Exercise Recovery in Young Obese Females.

OBJECTIVE: To evaluate differences in sympathetic activity, as assessed by an exercise recovery index (ERI; heart rate/oxygen consumption [VO2] plateau), between black and white obese female adolescents. An additional aim was to determine the association of ERI with insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]), cardiovascular fitness per fat-free mass (VO2 per fat-free mass), systolic blood pressure (SBP), and percent body fat (%FAT) in both black and white obese adolescents. STUDY DESIGN: Sixty-one females volunteered to participate in this study. HOMA-IR, SBP, and %FAT were assessed during resting conditions in black (n = 49, 13.7 ± 1.6 years, 38.1 ± 6.1 kg/m(2)) and white (n = 12, 13.3 ± 2.2 years, 34.3 ± 4.9 kg/m(2)) obese adolescents. An ERI was calculated during a 5-minute passive recovery period immediately following a graded treadmill exercise test to exhaustion. RESULTS: The ERI was significantly greater in black compared with white obese adolescent females (29.8 ± 6.4 vs 24.1 ± 3.1 bpm·mLO2(-1)·min(-1), P = .004). Using multiple linear regression modeling, there was a significant independent association between ERI and VO2 per fat-free mass (r = -0.310, P = .027) and %FAT (r = 0.326, P = .020) in black obese adolescents after controlling for HOMA-IR and SBP. CONCLUSIONS: These results suggest that black obese adolescent females have greater sympathetic activity, as assessed by an ERI, than white obese adolescent females. These findings support the need for weight management efforts aimed at both reducing %FAT and improving fitness in obese adolescents, specifically black females. TRIAL REGISTRATION: Registered with Clinicaltrials.gov: NCT00562293.

Sex differences in pulmonary oxygen uptake kinetics in obese adolescents.

OBJECTIVE: To determine whether sex differences exist in the pulmonary oxygen uptake (VO2) uptake on-kinetic response to moderate exercise in obese adolescents. We also examined whether a relationship existed between the VO2 on-transient response to moderate intensity exercise, steady-state VO2, and peak VO2 between obese male and female adolescents. STUDY DESIGN: Male (n = 12) and female (n = 28) adolescents completed a graded exercise test to exhaustion on a treadmill. Data from the initial 4 minutes of treadmill walking were used to determine the time constant. RESULTS: The time constant was significantly different (P = .001) between obese male and female adolescents (15.17 ± 8.45 seconds vs 23.07 ± 8.91 seconds, respectively). No significant relationships were observed between the time constant and variables of interest in either sex. CONCLUSIONS: Sex differences exist in VO2 uptake on-kinetics during moderate exercise in obese adolescents, indicating an enhanced potential for male subjects to deliver and/or use oxygen. It may be advantageous for female subjects to engage in a longer warm-up period before the initiation of an exercise regimen to prevent an early termination of the exercise session.

Forearm blood flow response to acute exercise in obese and non-obese males.

Chronic exercise is thought to improve endothelium-dependent vasodilation; however, few studies have evaluated the effects of acute exercise on microvascular vasodilatory capacity (MVC). Moreover, no studies have compared MVC responses in obese and non-obese individuals following acute exercise. To evaluate MVC, utilizing forearm blood flow (FBF) and excess blood flow (EBF) before and up to 48 h after a single exercise bout to elicit peak oxygen consumption (VO2 peak) in obese and non-obese males. Twelve obese (37.0 ± 1.1 kg/m(2)) and 12 non-obese (21.9 ± 0.3 kg/m(2)) males volunteered to participate. FBF measures, before and during reactive hyperemia (RH), were obtained prior to (PRE-E), immediately after (POST-E), and at 1 (POST-1), 2 (POST-2), 24 (POST-24), and 48 (POST-48) hours after exercise. EBF, was calculated as the difference between FBF, before and during RH. Blood samples were obtained to evaluate the response of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), which are potential modifiers of MVC. FBF before and during RH were significantly (P < 0.05) increased in both groups POST-E. The EBF magnitude of change from PRE-E was significantly (P < 0.05) elevated in non-obese when compared with obese males. Although not related to MVC, concentrations of IL-6 significantly decreased between POST-2 and POST-24 in both groups. An acute bout of exercise designed to elicit VO2 peak significantly increased forearm MVC in non-obese and obese males, although the magnitude of change in EBF from PRE-E to POST-E was greater in non-obese males.

LPS-stimulated tumor necrosis factor-alpha and interleukin-6 mRNA and cytokine responses following acute psychological stress.

The purpose of this study was to examine the effect of acute psychological stress on LPS-stimulated TNF-α and IL-6 mRNA expression. Twenty-one healthy male subjects participated in 20 min of acute stress. Blood samples for norepinephrine and LPS-stimulated TNF-α and IL-6 cytokines and mRNA were drawn prior to, immediately after and 1-h after stress. Stress-induced increases in anxiety scores, cortisol, plasma norepinephrine, and heart rate demonstrated that the experimental protocol elicited an acute stress response. LPS-stimulated TNF-α mRNA decreased significantly immediately post-stress and partially recovered at 1h post-stress, whereas LPS-stimulated IL-6 mRNA exhibited a significant change across time, with an increase immediately after stress and a decrease 1h after stress. Trends in LPS-stimulated TNF-α and IL-6 cytokine concentrations followed the patterns of mRNA expression. A negative correlation of body mass index (BMI) and percent change of LPS-stimulated TNF-α mRNA was observed immediately post-stress, and BMI positively correlated with percent change of LPS-stimulated IL-6 cytokine levels immediately following stress. These findings demonstrated that acute psychological stress affects LPS-stimulated IL-6 and TNF-α gene expression. These results also indicate that BMI may impact the effects of psychological stress on cytokine responses to immune challenge. Further examination of the effects of stress on synthesis of other cellular cytokines and investigation of the association of BMI and stress responses will provide a more clear representation of the cytokine responses to acute psychological stress. In addition, studies examining the influence of gender on the response of immune cell subsets to acute stress and the possible mediating effect of BMI are warranted.

Effects of mental challenge on neurovascular responses in healthy male subjects.

The purpose of this study was to examine the effects of mental challenge on total antioxidant capacity (TAC), forearm blood flow (FBF), vascular reactivity (VR), and the release of norepinephrine (NE). Furthermore, this study also examined the possible relationships of NE with FBF and VR following the mental challenge. Twenty healthy male subjects participated in twenty minutes of mental stress task (Stroop Color-Word Task [SCW] and mental arithmetic task [MA]). Our results showed that HR and NE increased significantly immediately following the mental challenge, whereas total antioxidant capacity did not change. Furthermore, the area-under-the-curves (AUCs) for both FBF at baseline and during reactive hyperemia, and VR elicited a significant change across time immediately post-stress. The percent change in the HR was partially correlated with the percent change in the VR immediately post-stress (p=0.08). Additionally, the percent change in the NE was positively correlated with TAC immediately post-stress, whereas NE only demonstrated a partial relationship with FBF at baseline immediately following the mental challenge (p=0.10). These findings suggest that forearm vasodilation following the mental challenge may be mediated by the antioxidant defense and sympathetic activation. Further studies are warranted to elucidate the mechanisms that explain the responses and relationships presented in this investigation.

Evaluation of a 6-month multi-disciplinary healthy weight management program targeting urban, overweight adolescents: effects on physical fitness, physical activity, and blood lipid profiles.

This study evaluated preliminary physical fitness, physical activity, and blood lipid profile data obtained from overweight adolescents upon enrolling in a healthy weight management program and following 6 months of program participation. One hundred and sixty-eight participants (13.4+/-1.8 years, 37.9+/-8.3 kg/m(2), 59.5% female and 76.2% African-American) enrolled in the program. The intervention addressed factors related to nutrition, physical activity, and other behaviors related to weight management. Sixty-four participants (38.1%) completed 6 months of program participation. While there was no significant reduction in body mass or body mass index (BMI), BMI z-score was reduced by 1.2% (p < 0.05), cardiorespiratory fitness was increased by 10.8% (p = 0.001), body fat percentage was reduced by 2.6% (p = 0.001), total cholesterol was reduced by 7.2% (p < 0.001), and low density lipoprotein (LDL-C) was reduced by 8.4% (p < 0.001) at 6 months. Continued development and evaluation of programs designed to prevent and treat child and adolescent overweight is warranted to address this major public health issue.