Voluntary wheel running as a promising strategy to promote autonomic resilience to social stress in females: Vagal tone lies at the heart of the matter.

Social stress is a major risk factor for comorbid conditions including cardiovascular disease and depression. While women exhibit 2-3× the risk for these stress-related disorders compared to men, the mechanisms underlying heightened stress susceptibility among females remain largely unknown. Due to a lack in understanding of the pathophysiology underlying stress-induced comorbidities among women, there has been a significant challenge in developing effective therapeutics. Recently, a causal role for inflammation has been established in the onset and progression of comorbid cardiovascular disease/depression, with women exhibiting increased sensitivity to stress-induced immune signaling. Importantly, reduced vagal tone is also implicated in stress susceptibility, through a reduction in the vagus nerve's well-recognized anti-inflammatory properties. Thus, examining therapeutic strategies that stabilize vagal tone during stress may shed light on novel targets for promoting stress resilience among women. Recently, accumulating evidence has demonstrated that physical activity exerts cardio- and neuro-protective effects by enhancing vagal tone. Based on this evidence, this mini review provides an overview of comorbid cardiovascular and behavioral dysfunction in females, the role of inflammation in these disorders, how stress may impart its negative effects on the vagus nerve, and how exercise may act as a preventative. Further, we highlight a critical gap in the literature with regard to the study of females in this field. This review also presents novel data that are the first to demonstrate a protective role for voluntary wheel running over vagal tone and biomarkers of cardiac dysfunction in the face of social stress exposure in female rats.

Cross-Sectional and Individual Relationships between Physical Activity and Glycemic Variability.

Introduction/Purpose: Overweight or obese adults spend more time sedentary and less time performing physical activity (PA) and are at an increased risk for developing impaired glycemic health. Free-living environments may provide insight into glycemic health in addition to clinical assessments. The purpose of this study was to examine the relationship between PA and glycemic health assessed by continuous glucose monitoring (CGM). Methods: Twenty-eight overweight or obese adults each wore an accelerometer and CGM over the same 7 consecutive days. Average daily time (minutes and metabolic-equivalent minutes (MET-minutes)) and associated energy expenditure performing light (LPA), moderate-to-vigorous (MVPA), total PA, and standard deviation (SD) across days were calculated. Average daily 24-h and waking glycemia, mean glucose concentration, glycemic variability measured as the continuous overlapping net glycemic action, mean amplitude of glycemic excursions, and mean of daily difference were assessed. Results: LPA MET-minutes per day was positively associated with 24-h and waking glycemia time-in-range and negatively associated with 24-h and waking time in hyperglycemia. Total PA time and the SD of MVPA and total PA time were negatively associated with 24-h mean glucose concentration. Individual-level analysis identified that most participants (50%-71%) expressed negative associations between LPA and MVPA time with 24-h mean glucose concentration, mean amplitude of glycemic excursion, and 4-h continuous overlapping net glycemic action. Conclusions: Expectedly, greater total PA time and intensity-specific PA time were associated with lower 24-h and waking mean glucose concentration, greater glycemia time-in-range, and less time in hyperglycemia. The relationship between glucose concentrations and PA time SD was unexpected, whereas most participants expressed hypothesized relationships, which necessitates further exploration.

Understanding chemotherapy-induced intestinal mucositis and strategies to improve gut resilience.

Intestinal mucositis remains one of the most debilitating side effects related to chemotherapy. The onset and persistence of mucositis is an intricate physiological process involving cross-communication between the specific chemotherapeutic drug, the immune system, and gut microbes that results in a loss of mucosal integrity leading to gut-barrier dysfunction. Intestinal mucositis has a severe impact on a patient's quality of life and negatively influences the outcome of treatment. Most importantly, intestinal mucositis is a major contributor to the decreased survival rates and early onset of death associated with certain chemotherapy treatments. Understanding the pathophysiology and symptomology of intestinal mucositis is important in reducing the negative consequences of this condition. Prophylaxis, early diagnosis, and proper symptom management are essential to improved survival outcomes in patients with cancer. This review focuses on the pathobiology of intestinal mucositis that accompanies chemotherapy treatments. In addition, we will discuss the therapeutic potential of select strategies that have shown promise in mitigating chemotherapies' off-target effects without hampering their anticancer efficacy.NEW & NOTEWORTHY Intestinal mucositis, or damage to the intestinal mucosa, is a common side effect of chemotherapy. In this review, we describe the pathobiology of intestinal mucositis that is associated with chemotherapy treatments. In addition, we discuss the efficacy of several potential therapeutic strategies that have shown some potential in alleviating chemotherapies' off-target effects.

Glycemic variability: Importance, relationship with physical activity, and the influence of exercise.

Glycemic variability is a more sensitive assessment of glycemic health as opposed to traditional clinical measurements. It considers all blood glucose concentrations over a given period to better account for glucose oscillations that occur and provides clinicians with insight into how individuals regulate and/or maintain their glycemic health. The advancement of continuous glucose monitoring (CGM) allows for the measurement of free-living glucose concentrations while providing a more reliable assessment of treatment of dysregulated glycemic. CGM coupled with management of lifestyle behavioral factors, such as reduced sedentary behavior and increased physical activity and regular exercise, potentially offers a previously untapped method for promoting improved glycemic health through greater regulation of glucose concentrations. The aim of this review is to critically evaluate the evidence regarding the measurement of glycemic variability and summarize the current understanding of the relationship between glycemic variability, sedentary behavior, physical activity, the influence of a single exercise session or repeated exercise sessions, and exercise training. This review considers information pertaining to the strengths and limitations for measuring glycemic variability and provides insight into future study designs aimed at evaluating the relationship between sedentary behavior and physical activity with, as well as the influence of exercise on, glycemic variability as a primary outcome.

An acute naproxen dose does not affect core temperature or Interleukin-6 during cycling in a hot environment.

Non-steroidal anti-inflammatory drugs' anti-pyretic and anti-inflammatory effects has led some individuals to theorize these medications may blunt core body temperature (Tc) increases during exercise. We utilized a double-blind, randomized, and counterbalanced cross-over design to examine the effects of a 24-h naproxen dose (3-220 â€‹mg naproxen pills) and placebo (0 â€‹mg naproxen) on Tc and plasma interleukin-6 (IL-6) concentrations during cycling in a hot or ambient environment. Participants (n â€‹= â€‹11; 6 male, 5 female; age â€‹= â€‹27.8 â€‹± â€‹6.5 years, weight â€‹= â€‹79.1 â€‹± â€‹17.9 â€‹kg, height â€‹= â€‹177 â€‹± â€‹9.5 â€‹cm) completed 4 conditions: 1) placebo and ambient (Control); 2) placebo and heat (Heat); 3) naproxen and ambient (Npx); and 4) naproxen and heat (NpxHeat). Dependent measures were taken before, during, and immediately after 90 â€‹min of cycling and then 3 â€‹h after cycling. Overall, Tc significantly increased pre- (37.1 â€‹± â€‹0.4 â€‹°C) to post-cycling (38.2 â€‹± â€‹0.3 â€‹°C, F 1.7,67.3 â€‹= â€‹150.5, p â€‹< â€‹0.001) and decreased during rest (37.0 â€‹± â€‹0.3 â€‹°C, F 2.0,81.5 â€‹= â€‹201.6, p â€‹< â€‹0.001). Rate of change or maximum Tc were not significantly different between conditions. IL-6 increased pre- (0.54 â€‹± â€‹0.06 â€‹pg/ml) to post-exercise (2.46 â€‹± â€‹0.28 â€‹pg/ml, p â€‹< â€‹0.001) and remained significantly higher than pre-at 3 â€‹h post- (1.17 â€‹± â€‹0.14 â€‹pg/ml, 95% CI â€‹= â€‹-1.01 to -0.23, p â€‹= â€‹0.001). No significant IL-6 differences occurred between conditions. A 24-h, over-the-counter naproxen dose did not significantly affect Tc or IL-6 among males and females cycling in hot or ambient environments.

Alterations in Glycemic Variability, Vascular Health, and Oxidative Stress following a 12-Week Aerobic Exercise Intervention-A Pilot Study.

The state of being overweight or obese leads to an increased risk of development of cardiometabolic disease. Increases in glycemic variability have been associated with greater induction of oxidative stress and declined vascular health, which may be exacerbated by higher weight status and improved through exercise. The purpose of this study was to examine the impact of a twelve-week aerobic exercise intervention on continuous glucose monitor (CGM) assessed glucose concentrations and glycemic variability, and biomarkers of vascular health and oxidative stress in overweight or obese adults. Eight adults (Age = 48.9 ± 5.2 years; BMI = 29.4 ± 8.3 kg/m2) completed a twelve-week aerobic exercise intervention. Participants walked three times per week at moderate intensity for ~150 minutes each week. All participants wore a CGM for seven consecutive days at baseline and post-intervention. On the final day of monitoring, a fasting blood sample was collected, and an oral glucose tolerance test (OGTT) was performed. Intra- and inter-day glycemic variability was assessed as the mean amplitude of glycemic excursions, continuous overlapping net glycemic action of one-, two-, and four-hour, and the mean observation of daily differences. Plasma concentrations of nitric oxide (NO) and myeloperoxidase (MPO) were measured, and their ratio was calculated (NO:MPO). No CGM-assessed glucose concentrations or measures of glycemic variability changed from baseline to post-intervention. MPO concentration decreased (24.8 ± 8.2 ng/mL to 16.4 ± 4.6 ng/mL, p < 0.01), the NO:MPO ratio improved (3.5:1 to 6.4:1, p < 0.01) following the twelve-week intervention. Individual level changes in body weight and V̇O2peak were found. In conclusion, twelve weeks of aerobic exercise reduced oxidative stress and improved the propensity to vasodilate but did not alter CGM-assessed glucose concentrations or glycemic variability in this group of overweight or obese non-diabetic adults. These findings may be due to individual changes in body weight or V̇O2peak, which necessitates further research to explore their influence on these outcomes of interest.

A 24 hour naproxen dose on gastrointestinal distress and performance during cycling in the heat.

Using a double-blind, randomized and counterbalanced, cross-over design, we assessed naproxen's effects on gastrointestinal (GI) distress and performance in eleven volunteers (6 male, 5 female). Participants completed 4 trials: 1) placebo and ambient); 2) placebo and heat; 3) naproxen and ambient; and 4) naproxen and heat. Independent variables were one placebo or 220 mg naproxen pill every 8 h (h) for 24 h and ambient (22.7 ±â€¯1.8°C) or thermal environment (35.7 ±â€¯1.3°C). Participants cycled 80 min at a steady heart rate then 10 min for maximum distance. Perceived exertion was measured throughout cycling. Gastrointestinal distress was assessed pre-, during, post-, 3 h post-, and 24 h post-cycling using a GI index for upper, lower, and systemic symptoms. No statistically significant differences occurred between conditions at any time for GI symptoms or perceived exertion, distance, or heart rate during maximum effort. A 24 h naproxen dose did not significantly affect performance or cause more frequent or serious GI distress when participants were euhydrated and cycling at moderate intensity in a thermal environment.

The influence of exercise training dose on fasting acylated ghrelin concentration in older women.

This study investigated if exercise dose affected acylated ghrelin response to exercise training, and how body weight or fat mass changes might affect the responses. Non-obese older women (n = 49) were randomly assigned to 4-month moderate-intensity aerobic exercise of one of two doses (8 or 14 kcal kg-1 body weight weekly). Following exercise training, fasting acylated ghrelin concentrations changed differently between the two groups (p for group × time interaction = 0.050). It decreased in the moderate-dose (Cohen's d = 0.52, p = 0.019), but did not change in the low-dose exercise group. Adjustment for weight or fat changes did not affect these results. Therefore, exercise training dose can have specific effects on acylated ghrelin that are not dependent on weight or fat loss. However, whether the different acylated ghrelin changes are associated with differing degree of subsequent weight maintenance worth further investigation.

Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer.

We examined the role of macrophages in inflammation associated with colorectal cancer (CRC). Given the emerging evidence on immune-microbiota interactions in CRC, we also sought to examine the interaction between macrophages and gut microbiota. To induce CRC, male C57BL/6 mice ( n = 32) received a single injection of azoxymethane (AOM), followed by three cycles of dextran sodium sulfate (DSS)-supplemented water in weeks 1, 4, and 7. Prior to the final DSS cycle ( week 7) and twice weekly until euthanasia, mice ( n = 16/group) received either 200 µl ip of clodronate-filled liposomes (CLD) or phosphate-buffered saline (PBS) encapsulated liposomes to deplete macrophages. Colon tissue was analyzed for polyp burden, macrophage markers, transcription factors, and inflammatory mediators. Stool samples were collected, and DNA was isolated and subsequently sequenced for 16S rRNA. Clodronate liposomes decreased tumor number by ∼36% and specifically large (≥1 mm) tumors by ∼36% ( P < 0.05). This was consistent with a decrease in gene expression of EMR1 in the colon tissue and polyp tissue as well as expression of select markers associated with M1 (IL-6) and M2 macrophages (IL-13, IL-10, TGFß, CCL17) in the colon tissue ( P < 0.05). Similarly, there was a decrease in STAT3 and p38 MAPK and ERK signaling in colon tissue. Clodronate liposomes increased the relative abundance of the Firmicutes phylum ( P < 0.05) and specifically Lactobacillaceae and Clostridiaceae families, which have been associated with reduced CRC risk. Overall, these data support the development of therapeutic strategies to target macrophages in CRC and provide support for further evaluation of immune-microbiota interactions in CRC. NEW & NOTEWORTHY We found that macrophage depletion during late-stage tumorigenesis is effective at reducing tumor growth. This was associated with a decrease in macrophage markers and chemokines in the colon tissue and a decrease in transcription factors that are linked to colorectal cancer. The macrophage-depleted group was found to have an increased abundance of Firmicutes, a phylum with documented anti-tumorigenic effects. Overall, these data support the development of therapeutic strategies to target macrophages in colorectal cancer.

A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice.

The purpose of this study was to examine the effect of a 40% high-fat diet (HFD) supplemented with a dietary attainable level of quercetin (0.02%) on body composition, adipose tissue (AT) inflammation, Non-Alcoholic Fatty-Liver Disease (NAFLD), and metabolic outcomes. Diets were administered for 16 weeks to C57BL/6J mice (n = 10/group) beginning at 4 weeks of age. Body composition and fasting blood glucose, insulin, and total cholesterol concentrations were examined intermittently. AT and liver mRNA expression (RT-PCR) of inflammatory mediators (F4/80, CD206 (AT only), CD11c (AT only) TLR-2 (AT only), TLR-4 (AT only), MCP-1, TNF-α, IL-6 (AT only), and IL-10 (AT only)) were measured along with activation of NFκB-p65, and JNK (western blot). Hepatic lipid accumulation, gene expression (RT-PCR) of hepatic metabolic markers (ACAC1, SREBP-1, PPAR-γ), protein content of Endoplasmic Reticulum (ER) Stress markers (BiP, phosphorylated and total EIF2α, phosphorylated and total IRE1α, CHOP), and hepatic oxidative capacity were assessed (western blot). Quercetin administration had no effect at mitigating increases in visceral AT, AT inflammation, hepatic steatosis, ER Stress, decrements in hepatic oxidative capacity, or the development of insulin resistance and hypercholesterolemia. In conclusion, 0.02% quercetin supplementation is not an effective therapy for attenuating HFD-induced obesity development. It is likely that a higher dose of quercetin supplementation is needed to elicit favorable outcomes in obesity.

Weight loss following diet-induced obesity does not alter colon tumorigenesis in the AOM mouse model.

Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity. Subsequently, azoxymethane (AOM) was used to promote colon and liver carcinogenesis. A subset of obese mice was then switched to a low-fat diet (LFD) containing 67.5% carbohydrate, 12.2% fat, and 20% protein to promote intentional weight loss. Body weight loss and excess fat reduction did not protect mice from colon cancer progression and liver dysplastic lesion in the AOM-chemical-cancer model even though these mice had improved blood glucose and leptin levels. Intentional weight loss in AOM-treated mice actually produced histological changes that resemble dysplastic alterations in the liver and presented a higher percentage of F4/80+CD206+ macrophages and activated T cells (CD4+CD69+) in the spleen and lymph nodes, respectively. In addition, the liver of AOM-treated mice exposed to a HFD during the entire period of the experiment exhibited a marked increase in proliferation and pNF-κB activation. Altogether, these data suggest that intentional weight loss following chemical-induced carcinogenesis does not affect colon tumorigenesis but may in fact negatively impact liver repair mechanisms.

High-fat diets rich in saturated fat protect against azoxymethane/dextran sulfate sodium-induced colon cancer.

High-fat-diet (HFD) consumption is associated with colon cancer risk. However, little is known about how the lipid composition of a HFD can influence prooncogenic processes. We examined the effects of three HFDs differing in the percentage of total calories from saturated fat (SF) (6, 12, and 24% of total caloric intake), but identical in total fat (40%), and a commercially available Western diet (26 and 41% saturated and total fat, respectively) on colon cancer development using the azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model. A second dose-response experiment was performed using diets supplemented with the saturated-fatty-acid (SFA)-rich coconut oil. In experiment 1, we found an inverse association between SF content and tumor burden. Furthermore, increased SF content was associated with reduced inflammation, increased apoptosis, and decreased proliferation. The second dose-response experiment was performed to test whether this effect may be attributed to the SF content of the diets. Consistent with the initial experiment, we found that high SF content was protective, at least in male mice; there was a decrease in mortality in mice consuming the highest concentration of SFAs. To explore a potential mechanism for these findings, we examined colonic mucin 2 (Muc2) protein content and found that the HFDs with the highest SF content had the greatest concentration of Muc2. Our data suggest that high dietary SF is protective in the AOM/DSS model of colon cancer, which may be due, at least in part, to the ability of SF to maintain intestinal barrier integrity through increased colonic Muc2.

Sex differences in the relationship of IL-6 signaling to cancer cachexia progression.

A devastating aspect of cancer cachexia is severe loss of muscle and fat mass. Though cachexia occurs in both sexes, it is not well-defined in the female. The Apc(Min/+) mouse is genetically predisposed to develop intestinal tumors; circulating IL-6 is a critical regulator of cancer cachexia in the male Apc(Min/+) mouse. The purpose of this study was to examine the relationship between IL-6 signaling and cachexia progression in the female Apc(Min/+) mouse. Male and female Apc(Min/+) mice were examined during the initiation and progression of cachexia. Another group of females had IL-6 overexpressed between 12 and 14 weeks or 15-18 weeks of age to determine whether IL-6 could induce cachexia. Cachectic female Apc(Min/+) mice lost body weight, muscle mass, and fat mass; increased muscle IL-6 mRNA expression was associated with these changes, but circulating IL-6 levels were not. Circulating IL-6 levels did not correlate with downstream signaling in muscle in the female. Muscle IL-6r mRNA expression and SOCS3 mRNA expression as well as muscle IL-6r protein and STAT3 phosphorylation increased with severe cachexia in both sexes. Muscle SOCS3 protein increased in cachectic females but decreased in cachectic males. IL-6 overexpression did not affect cachexia progression in female Apc(Min/+) mice. Our results indicate that female Apc(Min/+) mice undergo cachexia progression that is at least initially IL-6-independent. Future studies in the female will need to determine mechanisms underlying regulation of IL-6 response and cachexia induction.

Quercetin supplementation attenuates the progression of cancer cachexia in ApcMin/+ mice.

Although there are currently no approved treatments for cancer cachexia, there is an intensified interest in developing therapies because of the high mortality index associated with muscle wasting diseases. Successful treatment of the cachectic patient focuses on improving or maintaining body weight and musculoskeletal function. Nutraceutical compounds, including the natural phytochemical quercetin, are being examined as potential treatments because of their anti-inflammatory, antioxidant, and anticarcinogenic properties. The purpose of this study was to determine the effect of quercetin supplementation on the progression of cachexia in the adenomatous polyposis coli (Apc)(Min/+) mouse model of colorectal cancer. At 15 wk of age, C57BL/6 and male Apc(Min/+) mice were supplemented with 25 mg/kg of quercetin or vehicle solution mix of Tang juice and water (V) daily for 3 wk. Body weight, strength, neuromuscular performance, and fatigue were assessed before and after quercetin or V interventions. Indicators of metabolic dysfunction and inflammatory signaling were also assessed. During the treatment period, the relative decrease in body weight in the Apc(Min/+) mice gavaged with V (Apc(Min/+)V; -14% ± 2.3) was higher than in control mice gavaged with V (+0.6% ± 1.0), control mice gavaged with quercetin (-2% ± 1.0), and Apc(Min/+) mice gavaged with quercetin (Apc(Min/+)Q; -9% ± 1.3). At 18 wk of age, the loss of grip strength and muscle mass shown in Apc(Min/+)V mice was significantly attenuated (P < 0.05) in Apc(Min/+)Q mice. Furthermore, Apc(Min/+)V mice had an induction of plasma interleukin-6 and muscle signal transducer and activator of transcription 3 phosphorylation, which were significantly (P < 0.05) mitigated in Apc(Min/+)Q mice, despite having a similar tumor burden. Quercetin treatment did not improve treadmill run-time-to-fatigue, hyperglycemia, or hyperlipidemia in cachectic Apc(Min/+) mice. Overall, quercetin supplementation positively affected several aspects of cachexia progression in mice and warrants further exploration as a potential anticachectic therapeutic.

Dietary quercetin reduces chemotherapy-induced fatigue in mice.

PURPOSE: While fatigue is the most commonly reported symptom of chemotherapy, there are currently no effective treatments for chemotherapy-induced fatigue (CIF). We used a mouse model to examine the benefits of quercetin on CIF as measured by voluntary wheel running activity and sought to determine whether quercetin may be associated with a decrease in inflammation and/or anemia. METHODS: Mice were assigned to 1 of 4 groups: placebo-vehicle (Plac-PBS), placebo-5-fluorouracil (Plac-5FU), quercetin-vehicle (Quer-PBS), or quercetin-5-fluorouracil (Quer-5FU). All mice were given a daily injection of either 60 mg/kg of 5-FU or phosphate buffered saline (PBS) for 5 days. Quercetin (0.02%) treatment was administered in the food 3 days prior to 5-FU administration and for the duration of the experiment (ie, days -2 to 14). A second group of mice was sacrificed at 5 and 14 days post initial injection for assessment of monocyte chemoattractant protein-1 (MCP-1) and anemia. RESULTS: Voluntary wheel running was reduced in both the Plac-5FU and Quer-5FU groups following 5-FU injection (P < .05). However, the Quer-5FU group recovered to baseline levels by approximately day 7, whereas the Plac-5FU group remained suppressed. MCP-1 was significantly elevated at 14 days in Plac-5FU (P < .001), but no changes were seen with Quer-5FU. Treatment with 5-FU resulted in anemia at both 5 days and 14 days; however, quercetin blocked this effect at 14 days (P < .001). CONCLUSION: These results demonstrate the beneficial effect of quercetin on improving recovery of voluntary physical activity following 5-FU treatment, which may be linked to a decrease in inflammation and anemia.

The application of the theory of planned behavior to help-seeking intention in a Chinese society.

PURPOSE: This study tested the efficacy of Ajzen's theory of planned behavior (TPB) in explaining intention to seek mental health services and compared the traditional TPB model with a TPB partial mediation model. It also aimed to understand factors related to intention to seek mental health services in Macao to inform local policies. METHOD: The present study consisted of two phases: (a) a pilot study to develop belief-based measures used in the main study, and (b) a cross-sectional study to investigate the application of TPB in understanding help-seeking intention. In the main study, 337 Macao residents (age range 18-65) participated in a survey conducted in the community. RESULTS: The TPB partial mediation model was better than the traditional TPB model in explaining help-seeking intention in Macao. The model also suggested that attitude, subjective norm, and perceived behavioral control were all significant predictors of help-seeking intention. However, symptom severity, prior help-seeking, and gender did not significantly directly predict help-seeking intention. CONCLUSION: Preference for the TPB partial mediation model may be culturally relevant. The implications of the findings are discussed in relation to the salient beliefs about help-seeking. Limitations and recommendations for future research are provided.

Influences of face, stigma, and psychological symptoms on help-seeking attitudes in Macao.

The purpose of this study was to examine the relationships between concerns about loss of face, stigma, psychological symptoms, and attitudes toward seeking mental health services such as counseling in Macao. Participants included 391 students attending the largest public university in Macao: 277 were from Macao and 114 were from Mainland China. Participants completed questionnaires measuring attitudes toward seeking professional psychological help, concerns about loss of face, self-stigma, public-stigma, and psychological symptoms. Results showed that positive attitudes toward help-seeking were significantly negatively correlated with self-stigma, public-stigma, and concerns about loss of face but there was no significant correlation with psychological symptoms. Psychological symptoms were positively correlated with face concerns, self-stigma, and public-stigma. Stigma (self and public) was found to be significantly positively associated with face concerns, but the correlations were weak. Findings also showed that Macao students had higher levels of distress, and endorsed greater self- and public-stigma than Mainland Chinese students; however, the groups did not differ in face concerns or attitudes toward help-seeking. Regression analysis indicated that group membership was not a significant predictor of help-seeking. Self-stigma was the strongest predictor of professional help-seeking. Age and sex were also found to be significant predictors. Results suggested that younger students were more likely to seek help and that female students reported greater levels of distress and tended to have more positive attitudes toward seeking psychological services than male students.

Indomethacin in combination with exercise leads to muscle and brain inflammation in mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used by athletes to reduce exercise-induced inflammation and pain. However, NSAID use has been linked to side effects, including mucosal damage in the gastrointestinal tract resulting in endotoxemia and inflammation. Incidentally, when NSAID use is combined with exercise there is some evidence that this effect may be exacerbated; however, this hypothesis has not been directly tested in a controlled experiment. We examined the combined effect of indomethacin (IND) and exercise on muscle and brain inflammation in mice. Male C57BL/6 mice were randomly assigned to: Exercise 0 mg/Kg IND (Ex-0), Sedentary 0 mg/Kg IND (Sed-0), Exercise 2.5 mg/Kg IND (Ex-2.5), or Sedentary 2.5 mg/Kg IND (Sed-2.5) (n=8-11/group). Mice were given IND (gavage) 1 h before exercise (treadmill run at 25 m/min, 8% grade for 90 min) or rest for 5 consecutive days. Run times and body weight were recorded daily. Muscle and brain were examined for gene expression of inflammatory mediators after 5 days of treatment. While IND and exercise alone had little effect on inflammation, the combination treatment produced substantial increases in the muscle (IL-1ß, MCP-1 & TNF-α) and brain (IL-1ß & MCP-1) (P<0.05). Hematocrit and hemoglobin were decreased along with body weight (days 3-5), and run time to fatigue (days 3-5) (P<0.05) and in general, these were correlated with the increased expression of muscle and brain inflammatory mediators. The combination of IND and exercise can lead to inflammation in both the muscle and brain that is associated with serious side effects and impaired performance in mice.

Influence of chronic moderate sleep restriction and exercise training on anxiety, spatial memory, and associated neurobiological measures in mice.

Sleep deprivation can have deleterious effects on cognitive function and mental health. Moderate exercise training has myriad beneficial effects on cognition and mental health. However, physiological and behavioral effects of chronic moderate sleep restriction and its interaction with common activities, such as moderate exercise training, have received little investigation. The aims of this study were to examine the effects of chronic moderate sleep restriction and moderate exercise training on anxiety-related behavior, spatial memory, and neurobiological correlates in mice. Male mice were randomized to one of four 11-week treatments in a 2 [sleep restriction (∼4h loss/day) vs. ad libitum sleep] × 2 [exercise (1h/day/6 d/wk) vs. sedentary activity] experimental design. Anxiety-related behavior was assessed with the elevated-plus maze, and spatial learning and memory were assessed with the Morris water maze. Chronic moderate sleep restriction did not alter anxiety-related behavior, but exercise training significantly attenuated anxiety-related behavior. Spatial learning and recall, hippocampal cell activity (i.e., number of c-Fos positive cells), and brain derived neurotrophic factor were significantly lower after chronic moderate sleep restriction, but higher after exercise training. Further, the benefit of exercise training for some memory variables was evident under normal sleep, but not chronic moderate sleep restriction conditions. These data indicate clear detrimental effects of chronic moderate sleep restriction on spatial memory and that the benefits of exercise training were impaired after chronic moderate sleep restriction.

Blunted heart rate recovery is improved following exercise training in overweight adults with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) predisposes individuals to cardiovascular morbidity, and cardiopulmonary exercise test (CPET) markers prognostic for cardiovascular disease have been found to be abnormal in adults with OSA. Due to the persistence of OSA and its cardiovascular consequences, whether the cardiovascular adaptations normally conferred by exercise are blunted in adults not utilizing established OSA treatment is unknown. The aims of this study were to document whether OSA participants have abnormal CPET responses and determine whether exercise modifies these CPET markers in individuals with OSA. METHODS: The CPET responses of 43 sedentary, overweight adults (body mass index [BMI]>25) with untreated OSA (apnea-hypopnea index [AHI]≥ 15) were compared against matched non-OSA controls (n=9). OSA participants were then randomized to a 12-week exercise training (n=27) or stretching control treatment (n=16), followed by a post-intervention CPET. Measures of resting, exercise, and post-exercise recovery heart rate (HRR), blood pressure, and ventilation, as well as peak oxygen consumption (VO(2peak)), were obtained. RESULTS: OSA participants had blunted HRR compared to non-OSA controls at 1 (P=.03), 3 (P=.02), and 5-min post-exercise (P=.03). For OSA participants, exercise training improved VO2 peak (P=.04) and HRR at 1 (P=.03), 3 (P<.01), and 5-min post-exercise (P<.001) compared to control. AHI change was associated with change in HRR at 5-min post-exercise (r=-.30, P<.05), but no other CPET markers. CONCLUSIONS: These results suggest that individuals with OSA have autonomic dysfunction, and that exercise training, by increasing HRR and VO2 peak, may attenuate autonomic imbalance and improve functional capacity independent of OSA severity reduction.