Dual endothelin receptor antagonism increases resting energy expenditure in people with increased adiposity.

Increased adiposity is associated with dysregulation of the endothelin system, both of which increase the risk of cardiovascular disease (CVD). Preclinical data indicate that endothelin dysregulation also reduces resting energy expenditure (REE). The objective was to test the hypothesis that endothelin receptor antagonism will increase REE in people with obesity compared with healthy weight individuals. Using a double blind, placebo-controlled, crossover design, 32 participants [healthy weight (HW): n = 16, BMI: 21.3 ± 2.8 kg/m2, age: 26 ± 7 yr and overweight/obese (OB): n = 16, BMI: 33.5 ± 9.5 kg/m2, age: 31 ± 6 yr] were randomized to receive either 125 mg of bosentan (ETA/B antagonism) or placebo twice per day for 3 days. Breath-by-breath gas exchange data were collected and REE was assessed by indirect calorimetry. Venous blood samples were analyzed for concentrations of endothelin-1 (ET-1). Treatment with bosentan increased plasma ET-1 in both OB and HW groups. Within the OB group, the changes in absolute REE (PLA: -77.6 ± 127.6 vs. BOS: 72.2 ± 146.6 kcal/day; P = 0.046). The change in REE was not different following either treatment in the HW group. Overall, absolute plasma concentrations of ET-1 following treatment with bosentan were significantly associated with kcal/day of fat (r = 0.488, P = 0.005), percentage of fat utilization (r = 0.415, P = 0.020), and inversely associated with the percentage of carbohydrates (r = -0.419, P = 0.019), and respiratory exchange ratio (r = -0.407, P = 0.023). Taken together, these results suggest that modulation of the endothelin system may represent a novel therapeutic approach to increase both resting metabolism and caloric expenditure, and reduce CVD risk in people with increased adiposity.NEW & NOTEWORTHY Findings from our current translational investigation demonstrate that dual endothelin A/B receptor antagonism increases total REE in overweight/obese individuals. These results suggest that modulation of the endothelin system may represent a novel therapeutic target to increase both resting metabolism and caloric expenditure, enhance weight loss, and reduce CVD risk in seemingly healthy individuals with elevated adiposity.

Endothelin receptor blockade blunts the pressor response to acute stress in men and women with obesity.

Obesity is associated with dysregulation of the endothelin system. In individuals with obesity, an exaggerated pressor response to acute stress is accompanied by increased circulating endothelin-1 (ET-1). The impact of combined endothelin A/B receptor (ETA/B) antagonism on the stress-induced pressor response in overweight/obese (OB) individuals is unknown. The objective of this study is to test the hypothesis that treatment with an ETA/B antagonist (bosentan) would reduce the stress-induced pressor response and arterial stiffness in overweight/obese compared with normal weight (NW) individuals. Forty participants [normal weight (NW): n = 20, body mass index (BMI): 21.7 ± 2.4 kg/m2 and overweight/obese (OB): n = 20, BMI: 33.8 ± 8.2 kg/m2] were randomized to placebo or 125 mg of bosentan twice a day (250 mg total) for 3 days. Hemodynamics were assessed before, during, and after a cold pressor test (CPT). Endothelin-1 was assessed at baseline and immediately after CPT. Following a washout period, the same protocol was repeated with the opposite treatment. The change from baseline in mean arterial pressure (MAP) during CPT following bosentan was significantly lower (P = 0.039) in the OB group than in the NW group (OB: 28 ± 12 vs. NW: 34 ± 15 mmHg). These results suggest that ETA/B antagonism favorably blunts the pressor response to acute stress in overweight/obese individuals.NEW & NOTEWORTHY Findings from our current translational investigation demonstrate that dual endothelin A/B receptor antagonism blunts the pressor response to acute stress in overweight/obese individuals. These results suggest that modulation of the endothelin system may represent a novel therapeutic target to reduce cardiovascular disease (CVD) risk by blunting the stress response in overweight/obese individuals.

Smoking cessation reduces systemic inflammation and circulating endothelin-1.

Smoking increases systemic inflammation and circulating endothelin-1 (ET-1), both of which contribute to an elevated risk of cardiovascular disease (CVD). The present study sought to test the hypothesis that a 12-week smoking cessation intervention would contribute to a long-term reduction in circulating ET-1, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). 30 individuals participated in a 12-week evidence-based smoking cessation program at Augusta University. Serum cotinine, plasma inflammatory cytokines, and plasma ET-1 were determined at baseline, immediately after the 12-week cessation program (end of treatment, EOT), and 12-months (12M) following the cessation program. Serum cotinine was significantly reduced (p < 0.001) at EOT and 12M following the smoking cessation program. Compared to BL (7.0 ± 1.6 pg/mL), TNF-α was significantly reduced at EOT (6.3 ± 1.5 pg/mL, p = 0.001) and 12M (5.2 ± 2.7 pg/mL, p < 0.001). ET-1 was significantly lower at EOT (1.9 ± 0.6 pg/mL, p = 0.013) and at 12M (2.0 ± 0.8 pg/mL, p = 0.091) following smoking cessation compared with BL (2.3 ± 0.6 pg/mL). BL concentrations of cotinine were significantly associated with basal ET-1 (r = 0.449, p = 0.013) and the change in cotinine at 12M following smoking cessation was significantly associated with the change in plasma ET-1 at 12M (r = 0.457, p = 0.011). Findings from the present pilot investigation demonstrate that a 12-week smoking cessation program reduces circulating concentrations of ET-1 and TNF-α for at least a year. The reduction in serum cotinine was associated with the decrease in circulating ET-1. The attenuation in ET-1 and inflammation may in part, contribute to the lower risk of CVD that is observed with smoking cessation.

Comparing the Effects of Sleep and Rest on Memory Consolidation.

INTRODUCTION: There is ample evidence that overnight sleep and daytime naps benefit memory retention, compared to comparable amounts of active wakefulness. Yet recent evidence also suggests that a period of post-training rest (eg, quiet wakefulness with eyes closed) provides a similar memory benefit compared to wake. However, the relative benefits of sleep vs quiet waking rest on memory remain poorly understood. Here, we assessed the extent to which sleep provides a unique memory benefit, above and beyond that conferred by quiet waking rest. METHODS: In a sample of healthy undergraduate students (N=83), we tested the effect of 30 mins of post-learning sleep, rest, or active wake on concept learning (dot pattern classification) and declarative memory (word pair associates) across a 4-hr daytime training-retest interval. RESULTS AND CONCLUSIONS: Contrary to our hypotheses, we found no differences in performance between the three conditions for either task. The findings are interpreted with reference to methodological considerations including the length of the experimental interval, the nature of the tasks used, and challenges inherent in creating experimental conditions that can be executed by participants.

Does sleep protect memories against interference? A failure to replicate.

Across a broad spectrum of memory tasks, retention is superior following a night of sleep compared to a day of wake. However, this result alone does not clarify whether sleep merely slows the forgetting that would otherwise occur as a result of information processing during wakefulness, or whether sleep actually consolidates memories, protecting them from subsequent retroactive interference. Two influential studies suggested that sleep protects memories against the subsequent retroactive interference that occurs when participants learn new yet overlapping information (interference learning). In these studies, interference learning was much less detrimental to memory following a night of sleep compared to a day of wakefulness, an indication that sleep supports this important aspect of memory consolidation. In the current replication study, we repeated the protocol of and, additionally, we examined the impact of intrinsic motivation on performance in sleep and wake participants. We were unable to replicate the finding that sleep protects memories against retroactive interference, with the detrimental effects of interference learning being essentially the same in wake and sleep participants. We also found that while intrinsic motivation benefitted task acquisition it was not a modulator of sleep-wake differences in memory processing. Although we cannot accept the null hypothesis that sleep has no role to play in reducing the negative impact of interference, the findings draw into question prior evidence for sleep's role in protecting memories against interference. Moreover, the current study highlights the importance of replicating key findings in the study of sleep's impact on memory processing before drawing strong conclusions that set the direction of future research.

Attraction Effects for Verbal Gender and Number Are Similar but Not Identical: Self-Paced Reading Evidence From Modern Standard Arabic.

Previous work on the comprehension of agreement has shown that incorrectly inflected verbs do not trigger responses typically seen with fully ungrammatical verbs when the preceding sentential context furnishes a possibly matching distractor noun (i.e., agreement attraction). We report eight studies, three being direct replications, designed to assess the degree of similarity of these errors in the comprehension of subject-verb agreement along the dimensions of grammatical gender and number in Modern Standard Arabic. A meta-analysis of the results demonstrate the presence of agreement attraction effects in reading comprehension for gender and number on verbs. Moreover, the meta-analysis demonstrates that these two features do not behave identically: gender effects are larger and occur later relative to number attraction effects. These results challenge models of agreement that predict agreement features to be equipotent and show that real-time models of agreement require modifications in the form of cue-weighting in order to account for these differential results.

Adequacy of Daily Fluid Intake Volume Can Be Identified From Urinary Frequency and Perceived Thirst in Healthy Adults.

Objective: Achieving and maintaining an optimal level of hydration has significant implications for both acute and chronic health, yet many hydration assessments are not feasible for the general public. Urinary frequency (UF) is a reliable method to self-assess hydration status in healthy individuals, and thirst can provide additional sensory information on adequacy of daily fluid intake volume (DFI). However, threshold values for these indices to detect optimal hydration have not been determined. In this study, we sought to determine threshold values for 24-hour UF and perceived thirst that could accurately distinguish between optimal and suboptimal hydration states.Methods: Thirty-two healthy adults (age 22 ± 3 years, body mass index 24.9 ± 4.1 kg/m2) collected urine over 24 hours on four separate occasions, where UF was recorded as well as thirst at each void using a numbered perceptual scale. Using urine osmolality as the criterion standard, all samples were either classified as representing an optimal (≤500 mOsm·kg-1) or suboptimal hydration status (>500 mOsm·kg-1).Results: A 24-hour UF ≤6 was able to detect suboptimal hydration with good accuracy (area under the curve [AUC] 0.815) and a 24-hour average perceived thirst rating > 3 ("a little thirsty") could detect it with reasonable accuracy (AUC 0.725). In addition, a UF ≤4 had a considerably higher positive likelihood ratio to detect suboptimal hydration versus a UF ≤6 (9.03 versus 2.18, respectively).Conclusions: These analyses suggest that individuals with a 24-hour UF ≤6 or perceiving themselves to be, on average, "a little thirsty" throughout the day are likely to be suboptimally hydrated and thus underconsuming an adequate DFI.

Whole body vibration elicits differential immune and metabolic responses in obese and normal weight individuals.

Traditional aerobic exercise reduces the risk of developing chronic diseases by inducing immune, metabolic, and myokine responses. Following traditional exercise, both the magnitude and time-course of these beneficial responses are different between obese compared to normal weight individuals. Although obesity may affect the ability to engage in traditional exercise, whole body vibration (WBV) has emerged as a more tolerable form of exercise . The impact of WBV on immune, metabolic, and myokine responses as well as differences between normal weight and obese individuals, however, is unknown. Purpose: To determine if WBV elicits differential magnitudes and time-courses of immune, metabolic, and myokine responses between obese and normal weight individuals. Methods: 21 participants [Obese (OB): n = 11, Age: 33 ±â€¯4 y, percent body fat (%BF): 39.1 ±â€¯2.4% & Normal weight (NW) n = 10, Age: 28 ±â€¯8 y, %BF: 17.4 ±â€¯2.1%] engaged in 10 cycles of WBV exercise [1 cycle = 1 min of vibration followed by 30 s of rest]. Blood samples were collected pre-WBV (PRE), immediately (POST), 3 h (3H), and 24 h (24H) post-WBV and analyzed for leukocytes, insulin, glucose, and myokines (IL-6, decorin, myostatin). Results: The peak (3H) percent change in neutrophil counts (OB: 13.9 ±â€¯17.4 vs. NW: 47.2 ±â€¯6.2%Δ; p = 0.007) was different between groups. The percent change in neutrophil percentages was increased in NW (POST: -1.6 ±â€¯2.0 vs. 3H: 13.0 ±â€¯7.2%Δ, p = 0.019) but not OB (p > 0.05). HOMA ß-cell function was increased at 24H (PRE: 83.4 ±â€¯5.4 vs. 24H: 131.0 ±â€¯14.1%; p = 0.013) in NW and was not altered in OB (p > 0.05). PRE IL-6 was greater in OB compared to NW (OB: 2.7 ±â€¯0.6 vs. NW: 0.6 ±â€¯0.1 pg/mL; p = 0.011); however, the percent change from PRE to peak (3H) was greater in NW (OB: 148.1 ±â€¯47.9 vs. NW: 1277.9 ±â€¯597.6 %Δ; p = 0.035). Creatine kinase, decorin, and myostatin were not significantly altered in either group (p > 0.05). Conclusion: Taken together, these data suggest that acute whole body vibration elicits favorable immune, metabolic, and myokine responses and that these responses differ between obese and normal weight individuals.

Resting States and Memory Consolidation: A Preregistered Replication and Meta-Analysis.

While several recent studies have found that a post-encoding period of quiet, eyes-closed waking rest benefits memory consolidation, others have reported null effects. To more precisely estimate this effect, we conducted a quasi-exact behavioural replication of a recent study from our lab, which found that post-training eyes-closed waking rest improved declarative memory relative to a distractor task. Contrary to our hypothesis, the observed effect was not significant; however, it did fall within the 95% confidence interval of our previous finding. Furthermore, a meta-analytic effect summarizing n = 10 similar studies indicates a moderately sized and significant benefit of waking rest for verbal memory (d = 0.38, p < 0.001). We argue that the apparently conflicting results in this literature are most parsimoniously explained by variability due to sampling and/or measurement error, in a group of studies often underpowered to detect a smaller-than-expected effect of rest. Additionally, exploratory analyses revealed that increased trait daydreaming frequency negatively correlated with memory retention during eyes-closed rest. Together with our replication and meta-analysis, these studies suggest that waking rest confers a small but significant benefit on memory consolidation, and that this benefit requires the mind to be free from attention to either external tasks or spontaneous thought.

Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress.

Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. Purpose. To determine if ingestion of a single antioxidant cocktail (AOC) improves vascular endothelial function in patients with CF. Methods. In 18 patients with CF (age 8-39 y), brachial artery flow-mediated dilation (FMD) was assessed using a Doppler ultrasound prior to and two hours following either an AOC (n = 18; 1,000 mg vitamin C, 600 IU vitamin E, and 600 mg α-lipoic acid) or a placebo (n = 9). In a subgroup of patients (n = 9), changes in serum concentrations of α-tocopherol and lipid hydroperoxide (LOOH) were assessed following AOC and placebo. Results. A significant (p = 0.032) increase in FMD was observed following AOC (Δ1.9 ± 3.3%), compared to no change following placebo (Δ - 0.8 ± 1.9%). Moreover, compared with placebo, AOC prevented the decrease in α-tocopherol (Δ0.48 ± 2.91 vs. -1.98 ± 2.32 µM, p = 0.024) and tended to decrease LOOH (Δ - 0.2 ± 0.1 vs. 0.1 ± 0.1 µM, p = 0.063). Conclusions. These data demonstrate that ingestion of an antioxidant cocktail can improve vascular endothelial function and improve oxidative stress in patients with CF, providing evidence that oxidative stress is a key contributor to vascular endothelial dysfunction in CF.

Assessment of endothelial function is reproducible in patients with cystic fibrosis.

BACKGROUND: New treatments have improved life-expectancy in patients with cystic fibrosis (CF); however, cardiovascular health remains an area of concern in this population. Flow-mediated dilation (FMD), a non-invasive assessment of vascular endothelial function that predicts future cardiovascular disease and events, is attenuated in patients with CF compared to controls. The reproducibility of FMD in CF; however, has yet to be evaluated. Thus, this study sought to examine the within-day, between-day, and between-month reproducibility of FMD in patients with CF. METHODS: Pulmonary function, baseline diameter (cm), peak diameter (cm), and FMD(%) were assessed 5 times (sessions A-E) over four visits in 13 patients with CF (six males, seven females, age range: 13-43 years old; mean forced expiratory volume in 1 s = 71% predicted). Sessions A and B (within-day), C (between-day), and D and E (between-month) were separated by 3 h, at least 10 days, and ~3 months, respectively. Reproducibility was assessed by: (1) paired t-tests, (2) coefficients of variation (CV), (3) CV prime, (4) Pearson's correlation (r), (5) intra-class correlation coefficient, and (6) Bland-Altman plots. Five acceptable parameters were required to determine reproducibility. RESULTS: Pulmonary function was stable throughout all visits. FMD(%) and baseline diameter (cm) satisfied all six reproducibility criteria for within-day, while peak diameter (cm) met five of six criteria. All six reproducibility criteria were met for all between-day and between-month assessments. CONCLUSION: The present study provides evidence that endothelial function assessed by FMD is reproducible in patients with CF not only within-day, but also between-day and between-month.

Tetrahydrobiopterin improves endothelial function in patients with cystic fibrosis.

Cystic fibrosis (CF) is a genetic disorder associated with vascular endothelial dysfunction. Nitric oxide (NO) plays a major role in maintaining vascular function, and tetrahydrobiopterin (BH4) is a critical determinant of NO bioavailability. Thus the purpose of this study was to investigate the effects of oral administration of BH4 on endothelial function in patients with CF. Twenty-nine patients with CF (18 ± 8 yr old) and 29 healthy matched controls were recruited. Patients with CF participated in a randomized trial where they received a 5 mg/kg dose of oral BH4 (BH4-5; n = 17) or a 20 mg/kg dose of oral BH4 (BH4-20; n = 12). On a separate visit, a subset of patients from each group was retested following a placebo (PLC; n = 9). Brachial artery flow-mediated dilation (FMD) was used to evaluate vascular endothelial function, and a plasma sample was obtained before and 3 h after treatment. Cultured endothelial cells were treated with plasma to assess NO bioavailability. Baseline FMD was lower in patients compared with controls (5.7 ± 3.4 vs. 8.4 ± 3.5%, respectively, P = 0.005). No change in FMD was observed following PLC or BH4-5 (∆FMD: -0.8 ± 1.9% and -0.5 ± 2.5%; P = 0.273 and 0.132, respectively). Treatment with BH4-20, however, resulted in significant improvements in FMD (∆FMD: 1.1 ± 1.4%) compared with BH4-5 ( P = 0.023) and PLC ( P = 0.017). Moreover, BH4-20 significantly decreased endothelial cell superoxide production and increased NO production. These data suggest that a single oral dose of BH4 at 20 mg/kg improves vascular endothelial function in patients with CF, likely via increased endothelial NO synthase coupling. These findings support the hypothesis that loss of BH4 bioactivity contributes, in part, to endothelial dysfunction in patients with CF. NEW & NOTEWORTHY For the first time, the present study documents that a single dose of oral BH4 can improve vascular endothelial function in patients with cystic fibrosis (CF), and our in vitro data suggest this is via decreasing uncoupled nitric oxide. These data provide insight into the important role of BH4 bioactivity in vascular dysfunction and provide the foundation for further investigation into the chronic effects of BH4 treatment in patients with CF.

Exercise testing in patients with cystic fibrosis-importance of ventilatory parameters.

BACKGROUND: Ventilatory parameters obtained during exercise predict survival in several chronic diseases; however, long-term changes in exercise ventilatory parameters in patients with cystic fibrosis (CF) have yet to be examined and potential differences between sexes in CF are unknown. PURPOSE: We sought to examine the change in exercise ventilatory parameters over time in patients with CF and determine if the change is different between sexes. METHODS: Exercise capacity (VO2 peak) and exercise ventilatory parameters (VE/VO2 peak, VE/VCO2 peak, and VE/VCO2 slope) were determined from a maximal cardio-pulmonary test on a cycle ergometer on two visits separated by 39 ± 16 months in 20 patients with CF (10 female, 10 male). RESULTS: No differences between sexes were observed at visit 1 (all p > 0.05). Overall, exercise ventilatory parameters significantly (p < 0.05) deteriorated between visits, with no change (p > 0.05) in VO2 peak. Moreover, compared to males, female patients exhibited greater deteriorations in VE/VO2 peak (p = 0.001), VE/VCO2 peak (p = 0.002), and VE/VCO2 slope (p = 0.016) between visits. CONCLUSIONS: These data in patients with CF indicate that exercise ventilatory parameters decline over time despite no change in VO2 peak, and female patients exhibit a more rapid deterioration compared to males.

The effect of passive heat stress on distress andself-control in male smokers and non-smokers.

In the current study, we tested the effects of core body temperature increases (e.g. heat stress) on affect, self-reported physical discomfort, and subsequent self-control in male smokers and nonsmokers using a novel passive heat stress paradigm, within a distress tolerance framework. Twenty-eight men (14 smokers), completed both heat stress and control sessions in randomized order. Results revealed that increases in core body temperature were associated with increased anxiety, irritability, and body discomfort as well as decreased happiness, with stronger effects for smokers. Smokers and nonsmokers both evidenced less self-control during the heat session and did not differ on this measure, nor on a measure of interoceptive sensitivity. The current study indicates that heat stress is a viable method for studying distress tolerance in men, and suggests the value in examining dynamic changes in self-control as a function of distress. Implications will be discussed for distress tolerance in general and smokers in specific.

Sildenafil improves vascular endothelial function in patients with cystic fibrosis.

Cystic fibrosis (CF), characterized by defective CFTR function, is associated with multiple systemic complications, including vascular dysfunction. Sildenafil, a phosphodiesterase type 5 inhibitor, not only enhances nitric oxide (NO) metabolism but has been shown to improve CFTR functionality as well. Thus, sildenafil has been proposed as a therapy to improve vascular health in CF; however, its potential therapeutic role has yet to be determined. We sought to investigate the effect of sildenafil on endothelial function in patients with CF. Patients with CF completed a randomized, double-blind, placebo-controlled, crossover study with an acute dose of sildenafil (50 mg) or placebo followed by a 4-wk open-label extension with sildenafil (20 mg/day). Flow-mediated dilation (FMD) was used to evaluate endothelial function before and after treatments. In addition, phosphorylated endothelial NO synthase (pNOS3) and total NOS3 protein expression was determined from endothelial cells that were exposed to plasma from the patients before and after 4 wk of sildenafil treatment. No changes ( P ≥ 0.110) in endothelial function were observed after the acute dose of sildenafil. However, FMD significantly ( P = 0.029) increased after 4 wk of treatment (∆FMD: 1.5 ± 2.2%). Moreover, pNOS3 protein expression significantly ( P = 0.013) increased after 4 wk of treatment (∆pNOS3: 0.31 ± 0.39 arbitrary units) and was associated ( r = 0.593, P = 0.033) with the change in FMD. These data suggest that 4 wk of sildenafil treatment can improve vascular endothelial function in patients with CF, likely through an increase in NOS3 phosphorylation. NEW & NOTEWORTHY Findings from the present study demonstrate, for the first time, significant improvement of endothelial function in patients with cystic fibrosis treated with sildenafil that is associated with greater phosphorylation of endothelial nitric oxide synthase. These results support the use of sildenafil as a potential novel therapy for this patient population.

Scopolamine does not impact declarative and motor memory consolidation across a night of sleep or a day of wakefulness.

It has been proposed that normal waking levels of acetylcholine (ACH) are important for initial memory acquisition, and that decreased ACH is critical for memory consolidation. Sleep is thought to benefit memory consolidation in part due to the predominance of low ACH levels observed during non-rapid eye movement sleep. Here we examined whether sleep and ACH suppression with the cholinergic antagonist scopolamine impact declarative and motor memory consolidation across a night of sleep or a day of wakefulness. Eighty-seven participants trained on a declarative and motor memory task in the morning or evening. Following training, participants were administered a scopolamine (0.4 mg) or placebo capsule. Participants were retested on the tasks 12 h later after a day of wake or a night of sleep. Reducing ACH levels with scopolamine provided no consolidation benefit for either task. Additionally, we found that sleep had a pronounced beneficial effect for declarative, but not motor memory consolidation. Lastly, in an exploratory analysis of the relationship between motivation and memory performance, we found that indices of intrinsic motivation were associated with improved memory acquisition and consolidation. Our findings show that reducing ACH levels after memory acquisition has no impact on the consolidation of declarative or motor memories. Additionally, sleep benefitted declarative memory but not motor memory consolidation, which highlights the interesting, though uncommon, finding that performance on some tasks might not benefit from sleep. Interestingly, the future study of intrinsic motivation may be warranted given its relationship to memory acquisition and consolidation. These findings add to our understanding of how sleep and acetylcholine impact memory consolidation, and may provide some insight about the role of ACH in memory disorders such as Alzheimer's disease.

Obesity, but not hypohydration, mediates changes in mental task load during passive heating in females.

BACKGROUND: The independent effects of hypohydration and hyperthermia on cognition and mood is unclear since the two stresses often confound each other. Further, it is unknown if obese individuals have the same impairments during hyperthermia and hypohydration that is often observed in non-obese individuals. METHODS: The current study was designed to assess the independent and combined effects of mild hypohydration and hyperthermia on cognition, mood, and mental task load in obese and non-obese females. Twenty-one healthy females participated in two passive heating trials, wherein they were either euhydrated or hypohydrated prior to and throughout passive heating. Cognition (ImPACT), mental task load (NASA-TLX), and mood (Brunel Mood Scale; BRUMS) were measured before and after a 1.0 °C increase in core temperature (TC). RESULTS: After a 1.0 °C TC elevation, hypohydration resulted in greater (p < 0.05) body mass loss (-1.14 ± 0.48 vs -0.58 ± 0.48 kg; hypohydrated and euhydrated, respectively) and elevation in serum osmolality (292 ± 4 vs 282 ± 3 mOsm; p < 0.05) versus euhydration. Hypohydration, independent of hyperthermia, did not affect mental task load or mood (p > 0.05). Hyperthermia, regardless of hydration status, impaired (∼5 A.U) measures of memory-based cognition (verbal and visual memory), and increased mental task load, while worsening mood (p < 0.05). Interestingly, obese individuals had increased mental task load while hyperthermic compared to the non-obese individuals (p < 0.05) even while euhydrated. Hypohydration did not exacerbate any heat-related effects on cognition between obese and non-obese females (p > 0.05). CONCLUSION: These data indicate that hyperthermia independently impairs memory-based aspects of cognitive performance, mental task load, and leads to a negative mood state. Mild hypohydration did not exacerbate the effects of hyperthermia. However, obese individuals had increased mental task load during hyperthermia.

Postsynaptic cutaneous vasodilation and sweating: influence of adiposity and hydration status.

INTRODUCTION: Obesity and hypohydration independently affect postsynaptic endothelial function, but it is unknown if hypohydration affects lean and obese individuals differently. PURPOSE: To examine the effect of hypohydration on postsynaptic cutaneous vasodilation and sweating in men with high and low adiposity (HI- and LO-BF, respectively). METHODS: Ten males with LO-BF and ten with HI-BF were instrumented for forearm microdialysis when euhydrated and hypohydrated. Changes in cutaneous vascular conductance (CVC) with intradermal infusion of sodium nitroprusside (SNP) and methacholine chloride (MCh) were assessed. Local sweat rate (LSR) was simultaneously assessed at the MCh site. At the end of the last dose, maximal CVC was elicited by delivering a maximal dose of SNP for 30 min to both sites with simultaneous local heating at the SNP site. The concentration of drug needed to elicit 50% of the maximal response (EC50) was compared between groups and hydration conditions. RESULTS: When euhydrated, EC50 of MCh-induced CVC was not different between LO- vs. HI-BF [- 3.04 ± 0.12 vs. - 2.98 ± 0.19 log (MCh) M, P = 0.841]. EC50 of SNP-induced CVC was higher in euhydrated HI- vs. LO-BF (- 1.74 ± 0.17 vs. - 2.13 ± 0.06 log (SNP) M, P = 0.034). Within each group, hydration status did not change MCh- or SNP-induced CVC (P > 0.05). LSR was not different between groups or hydration condition (P > 0.05). CONCLUSIONS: These data suggest reduced sensitivity of endothelium-independent vasodilation in individuals with high adiposity when euhydrated. However, hypohydration does not affect cutaneous vasodilation or local sweat rate differently between individuals with low or high adiposity.

Beneficial effects of a daytime nap on verbal memory in adolescents.

This study aimed to examine the sleep-dependent memory consolidation of verbal declarative memory in Chinese adolescents in a naturalistic experimental setting. Thirty-nine healthy boarding school students (ages 15-18, 70% female) were randomized to either a one-hour afternoon nap or wake group between the baseline and the retest sessions of three verbal declarative memory tasks: a Prose Stories Recall task, a Word Pair Associates task, and Rey Auditory Verbal Learning Test. Results showed that the nap group performed better than the no-nap group on both the Prose Stories Recall task and the Word Pair Associates task, but not on list learning. Our findings suggest that napping is beneficial to verbal declarative memory in adolescents, providing ecologically-valid empirical support for the sleep-dependent memory consolidation hypothesis using a napping paradigm in participants' naturalistic habitat. Our results demonstrate the potential importance of napping as a practical mnemonic intervention/compensatory strategy for student populations.

Oral NaHCO3 Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells.

We tested the hypothesis that oral NaHCO3 intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO3 loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and FOXP3+CD4+ T-lymphocytes increased in the spleen, blood, and kidneys of rats. Similar anti-inflammatory changes in macrophage polarization were observed in the blood of human subjects following NaHCO3 ingestion. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response in rats and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous connections lined by mesothelial cells were found to connect to the capsular mesothelium. Mesothelial cells in these connections stained positive for the pan-neuronal marker PGP9.5 and acetylcholine esterase and contained many ultrastructural elements, which visually resembled neuronal structures. Both disruption of the fragile mesothelial connections or transection of the vagal nerves resulted in the loss of capsular mesothelial acetylcholine esterase staining and reduced splenic mass. Our data indicate that oral NaHCO3 activates a splenic anti-inflammatory pathway and provides evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal-like function of mesothelial cells.