Mapping expectancy-based appetitive placebo effects onto the brain in women.

Suggestions about hunger can generate placebo effects on hunger experiences. But, the underlying neurocognitive mechanisms are unknown. Here, we show in 255 women that hunger expectancies, induced by suggestion-based placebo interventions, determine hunger sensations and economic food choices. Functional magnetic resonance imaging in a subgroup (n = 57/255) provides evidence that the strength of expecting the placebo to decrease hunger moderates medial prefrontal cortex activation at the time of food choice and attenuates ventromedial prefrontal cortex (vmPFC) responses to food value. Dorsolateral prefrontal cortex activation linked to interference resolution formally mediates the suggestion-based placebo effects on hunger. A drift-diffusion model characterizes this effect by showing that the hunger suggestions bias participants' food choices and how much they weigh tastiness against the healthiness of food, which further moderates vmPFC-dlPFC psychophysiological interactions when participants expect decreased hunger. Thus, suggestion-induced beliefs about hunger shape hunger addressing economic choices through cognitive regulation of value computation within the prefrontal cortex.

Sex differences in hemodynamic response to high-intensity interval exercise.

Sex differences in the cardiorespiratory and hemodynamic response to exercise exist due to differences in heart size, blood volume, and hemoglobin mass, eliciting higher maximal oxygen uptake (VO2max ) in men versus women. Data are equivocal whether sex differences in training responsiveness occur. This study investigated potential sex differences in the hemodynamic response (stroke volume (SV) and cardiac output (CO)) to high-intensity interval exercise (HIIE). Habitually active men (n = 15) and women (n = 13) underwent VO2max testing, followed by three HIIE sessions consisting of the 4 × 4, 10 × 1, and reduced exertion high-intensity training (REHIT), whose order was randomized. During exercise, oxygen uptake (VO2 ) and hemodynamic responses were determined. Results showed no sex difference in peak relative VO2 (p = 0.263), CO (p = 0.277), or SV (p = 0.116), although absolute values were higher in men (p < 0.05). Peak absolute (127.3 ± 20.6 vs. 115.2 ± 16.6 mL/beat, p = 0.004, d = 0.66) and relative SV (111.0 ± 15.5 vs. 100.7 ± 11.1% max, p = 0.005, d = 0.78) were higher with REHIT versus 4 × 4. No sex differences in mean relative VO2 , CO, or SV occurred (p > 0.05). Data showed lower mean VO2 during REHIT versus 4 × 4 (59.3 ± 6.8 vs. 65.8 ± 5.8 %VO2max , p < 0.001, d = 1.05) and 10 × 1 (59.3 ± 6.8 vs. 69.1 ± 7.4 %VO2max , p < 0.001, d = 1.4). Mean CO was lower in REHIT than 10 × 1 (79.8 ± 8.6 vs. 84.0 ± 7.4% max, p = 0.012, d = 0.53). Previously reported differences in VO2max response to HIIE may not be due to unique hemodynamic responses.

Effect of Resistance Training With Total and Partial Blood Flow Restriction on Biomarkers of Oxidative Stress and Apoptosis in Untrained Men.

Introduction: The characterization of immune and oxidative stress responses to acute and chronic exercise training is important because it may aid in the safety and dose-response prescription of resistance training (RT) in many populations. Purpose: The present study compared changes in acute oxidative stress and markers of apoptosis in immune cells before and after 8 weeks of low-load RT with total or partial blood flow restriction (BFR) versus high-load traditional RT. Methods: Twenty-seven untrained men were randomly divided into three groups: traditional RT [75% one-repetition maximum (1-RM)], RT with partial (20% 1-RM), and total BFR (20% 1-RM). Over an 8-week period, participants performed six sets of arm curls until failure with 90 seconds of recovery for 3 days/week. Blood samples were obtained before and after the first and last training sessions. Results: Data indicated that all training groups showed similar increases in muscular strength (p < 0.001), reduction in mitochondrial membrane potential (MMP) after exercise in neutrophils (p < 0.001), and increase in caspase-3 activity after exercise (p < 0.001). Traditional RT and total BFR showed increased plasma lipid peroxidation (p < 0.001) and protein carbonyls (p < 0.001) and lower levels of reduced glutathione (GSH) (p < 0.001) after exercise. No change was observed in oxidative stress biomarkers in response to partial BFR (p > 0.05). Conclusion: Data show that RT with partial BFR can increase muscular strength but still does not augment biomarkers of oxidative stress in untrained men. In addition, RT with total BFR promoted similar responses of oxidative stress and markers of immune cell apoptosis versus traditional RT.

Pharmacy students as educators: An interprofessional approach to insulin management education.

INTRODUCTION: Student pharmacists may increase the knowledge and comfort level of student nurses and student physicians through peer-assisted teaching (PAT) on insulin management for patients with type 2 diabetes mellitus. METHODS: Fourth-year student pharmacists completing their primary care rotation provided instruction to third-year student nurses and third-year student physicians on the selection, dosing, administration, and counseling of insulin products in type 2 diabetes. Learners were asked to complete a pre- and post-survey to determine comfort level and knowledge before and after the educational experience. RESULTS: A total of 200 student nurses and student physicians were included in the analysis. All but two questions from the pre- to post-survey resulted in a statistically significant increase in the number of respondents who agreed or strongly agreed with the statements. In both the pre- and post-survey, >90% of participants agreed or strongly agreed that pharmacists add value to the medical team. An overwhelming majority of students indicated that this learning experience would assist them with making clinical decisions regarding insulin therapy for patients with type 2 diabetes during clinical rotations. CONCLUSION: The education provided by student pharmacists improved knowledge and confidence in selecting, dosing, administering, and counseling on insulin products, but not with adjusting therapy. Although the student nurses and student physicians valued pharmacy prior to the study, their willingness to reach out to pharmacists increased. This study demonstrates the usefulness of PAT for collaboration between healthcare professional students for improved knowledge and confidence to ultimately enhance patient-centered care.

Morphine Use in Renal Failure: A Case Report of Single-Dose Morphine Toxicity in a Patient Requiring Peritoneal Dialysis.

OBJECTIVE: We describe a case of morphine toxicity presumably caused by accumulation of its active metabolite morphine-6-glucuronide (M6G) secondary to reduced clearance by peritoneal dialysis. METHODS: We present the relevant history and laboratory data and review pertinent literature regarding the use of opioids in renal failure. RESULTS: A 76-year-old African-American female received one dose of morphine sulfate and developed signs and symptoms of morphine toxicity for 2 days, even after multiple peritoneal dialysis sessions. CONCLUSION: Because of reduced renal clearance of morphine and its metabolites in patients requiring peritoneal dialysis, morphine should be avoided as an analgesic option in this population due to increased risk of morphine toxicity.

Comparison of perceptual responses between different upper-body sprint interval exercise protocols.

This study examined the perceptual responses to various upper-body sprint interval exercise (SIE) protocols matched for total work and work/rest ratio. Fourteen active men (24 ±â€¯4 years, BMI = 26.2 ±â€¯2.7 kg/m2, body fat = 11.5 ±â€¯4.4%) participated in 3 all-out SIE protocols consisting of battling rope exercise: P10:30 (12 × 10-s bouts with 30-s recovery); P15:45 (8 × 15-s bouts with 45 s recovery); and P30:90 (4 × 30-s bouts with 90-s recovery). During exercise, affective valence (FS +5 to -5), arousal (FAS 1-6), rating of perceived exertion (RPE 6-20), and heart rate (HR) were assessed. Post-exercise, enjoyment, self-efficacy, and intentions were measured. Results revealed a significant decline in FS (p = .02; partial eta squared [η2p] = 0.27) and a progressive increase in FAS (p = .001; η2p = 0.86), RPE (p = .001; η2p = 0.88), and HR (p = .001; η2p = 0.94), but no protocol X time interaction. Affective valence reached a nadir at values equal to -0.36 ±â€¯3.41 (Cohen's d = -0.49), -0.43 ±â€¯3.75 (Cohen's d = -0.44), and - 0.93 ±â€¯3.49 (Cohen's d = -0.56) in response to P10:30, P15:45, and P30:90, respectively. There were no differences between protocols for enjoyment, intention, or self-efficacy. A negative relationship exhibited between FS and RPE was moderated by participants' tolerance of exercise intensity (ß = 1.84, p < .05). Further, the association between FS and future intention was mediated by self-efficacy. Overall, upper-body SIE protocols exhibit similar perceptual responses when volume and work to rest ratio (1:3) are matched. Tolerance of exercise intensity may be used to predict changes in FS during SIE.

Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease.

Importance: Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM). Objective: To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD). Design, Setting, and Participants: Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015. Genome-wide association studies (GWAS) and exome-wide association studies (EWAS) were conducted in patients of European ancestry. The replication cohort comprised 73 patients affected by TIM and 840 thiopurine-tolerant unaffected patients. Exposures: Genetic variants associated with TIM. Main Outcomes and Measures: Thiopurine-induced myelosuppression, defined as a decline in absolute white blood cell count to 2.5 × 109/L or less or a decline in absolute neutrophil cell count to 1.0 × 109/L or less leading to a dose reduction or drug withdrawal. Results: Among 1077 patients (398 affected and 679 unaffected; median age at IBD diagnosis, 31.0 years [interquartile range, 21.2 to 44.1 years]; 540 [50%] women; 602 [56%] diagnosed as having Crohn disease), 919 (311 affected and 608 unaffected) were included in the GWAS analysis and 961 (328 affected and 633 unaffected) in the EWAS analysis. The GWAS analysis confirmed association of TPMT (chromosome 6, rs11969064) with TIM (30.5% [95/311] affected vs 16.4% [100/608] unaffected patients; odds ratio [OR], 2.3 [95% CI, 1.7 to 3.1], P = 5.2 × 10-9). The EWAS analysis demonstrated an association with an in-frame deletion in NUDT15 (chromosome 13, rs746071566) and TIM (5.8% [19/328] affected vs 0.2% [1/633] unaffected patients; OR, 38.2 [95% CI, 5.1 to 286.1], P = 1.3 × 10-8), which was replicated in a different cohort (2.7% [2/73] affected vs 0.2% [2/840] unaffected patients; OR, 11.8 [95% CI, 1.6 to 85.0], P = .03). Carriage of any of 3 coding NUDT15 variants was associated with an increased risk (OR, 27.3 [95% CI, 9.3 to 116.7], P = 1.1 × 10-7) of TIM, independent of TPMT genotype and thiopurine dose. Conclusions and Relevance: Among patients of European ancestry with IBD, variants in NUDT15 were associated with increased risk of TIM. These findings suggest that NUDT15 genotyping may be considered prior to initiation of thiopurine therapy; however, further study including additional validation in independent cohorts is required.

Within-session responses to high-intensity interval training in spinal cord injury.

AIM: Completion of high-intensity interval training (HIIT) increases maximal oxygen uptake and health status, yet its feasibility in persons with spinal cord injury is unknown. PURPOSE: To compare changes in cardiorespiratory and metabolic variables between two interval training regimes and moderate intensity exercise. METHOD: Nine adults with spinal cord injury (duration = 6.8 ± 6.2 year) initially underwent determination of peak oxygen uptake. During subsequent sessions, they completed moderate intensity exercise, HIIT, or sprint interval training. Oxygen uptake, heart rate, and blood lactate concentration were measured. RESULTS: Oxygen uptake and heart rate increased (p < 0.05) during both interval training sessions and were similar (p > 0.05) to moderate intensity exercise. Peak oxygen uptake and heart rate were higher (p < 0.05) with HIIT (90% peak oxygen uptake and 99% peak heart rate) and sprint interval training (80% peak oxygen uptake and 96% peak heart rate) versus moderate intensity exercise. CONCLUSIONS: Despite a higher intensity and peak cardiorespiratory strain, all participants preferred interval training versus moderate exercise. Examining long-term efficacy and feasibility of interval training in this population is merited, considering that exercise intensity is recognized as the most important variable factor of exercise programming to optimize maximal oxygen uptake. Implications for Rehabilitation Spinal cord injury (SCI) reduces locomotion which impairs voluntary physical activity, typically resulting in a reduction in peak oxygen uptake and enhanced chronic disease risk. In various able-bodied populations, completion of high-intensity interval training (HIIT) has been consistently reported to improve cardiorespiratory fitness and other health-related outcomes, although its efficacy in persons with SCI is poorly understood. Data from this study in 9 men and women with SCI show similar changes in oxygen uptake and heart in response to HIIT compared to a prolonged bout of aerobic exercise, although peak values were higher in response to HIIT. Due to the higher peak metabolic strain induced by HIIT as well as universal preference for this modality versus aerobic exercise as reported in this study, further work testing utility of HIIT in this population is merited.

Changes in fat oxidation in response to various regimes of high intensity interval training (HIIT).

Increased whole-body fat oxidation (FOx) has been consistently demonstrated in response to moderate intensity continuous exercise training. Completion of high intensity interval training (HIIT) and its more intense form, sprint interval training (SIT), has also been reported to increase FOx in different populations. An explanation for this increase in FOx is primarily peripheral adaptations via improvements in mitochondrial content and function. However, studies examining changes in FOx are less common in response to HIIT or SIT than those determining increases in maximal oxygen uptake which is concerning, considering that FOx has been identified as a predictor of weight gain and glycemic control. In this review, we explored physiological and methodological issues underpinning existing literature concerning changes in FOx in response to HIIT and SIT. Our results show that completion of interval training increases FOx in approximately 50% of studies, with the frequency of increased FOx higher in response to studies using HIIT compared to SIT. Significant increases in ß-HAD, citrate synthase, fatty acid binding protein, or FAT/CD36 are likely responsible for the greater FOx seen in these studies. We encourage scientists to adopt strict methodological procedures to attenuate day-to-day variability in FOx, which is dramatic, and develop standardized procedures for assessing FOx, which may improve detection of changes in FOx in response to HIIT.

Increased cardiac output elicits higher V̇O2max in response to self-paced exercise.

Recently, a self-paced protocol demonstrated higher maximal oxygen uptake versus the traditional ramp protocol. The primary aim of the current study was to further explore potential differences in maximal oxygen uptake between the ramp and self-paced protocols using simultaneous measurement of cardiac output. Active men and women of various fitness levels (N = 30, mean age = 26.0 ± 5.0 years) completed 3 graded exercise tests separated by a minimum of 48 h. Participants initially completed progressive ramp exercise to exhaustion to determine maximal oxygen uptake followed by a verification test to confirm maximal oxygen uptake attainment. Over the next 2 sessions, they performed a self-paced and an additional ramp protocol. During exercise, gas exchange data were obtained using indirect calorimetry, and thoracic impedance was utilized to estimate hemodynamic function (stroke volume and cardiac output). One-way ANOVA with repeated measures was used to determine differences in maximal oxygen uptake and cardiac output between ramp and self-paced testing. Results demonstrated lower (p < 0.001) maximal oxygen uptake via the ramp (47.2 ± 10.2 mL·kg(-1)·min(-1)) versus the self-paced (50.2 ± 9.6 mL·kg(-1)·min(-1)) protocol, with no interaction (p = 0.06) seen for fitness level. Maximal heart rate and cardiac output (p = 0.02) were higher in the self-paced protocol versus ramp exercise. In conclusion, data show that the traditional ramp protocol may underestimate maximal oxygen uptake compared with a newly developed self-paced protocol, with a greater cardiac output potentially responsible for this outcome.

Effect of chronic activity-based therapy on bone mineral density and bone turnover in persons with spinal cord injury.

PURPOSE: Osteoporosis is a severe complication of spinal cord injury (SCI). Many exercise modalities are used to slow bone loss, yet their efficacy is equivocal. This study examined the effect of activity-based therapy (ABT) targeting the lower extremities on bone health in individuals with SCI. METHODS: Thirteen men and women with SCI (age and injury duration = 29.7 ± 7.8 and 1.9 ± 2.7 years) underwent 6 months of ABT. At baseline and after 3 and 6 months of training, blood samples were obtained to assess bone formation (serum procollagen type 1 N propeptide (PINP) and bone resorption (serum C-terminal telopeptide of type I collagen (CTX), and participants underwent dual-energy X-ray absorptiometry scans to obtain total body and regional estimates of bone mineral density (BMD). RESULTS: Results demonstrated significant increases (p < 0.05) in spine BMD (+4.8 %; 1.27 ± 0.22-1.33 ± 0.24 g/cm(2)) and decreases (p < 0.01) in total hip BMD (-6.1 %; 0.98 ± 0.18-0.91 ± 0.16 g/cm(2)) from 0 to 6 months of training. BMD at the bilateral distal femur (-7.5 to -11.0 %) and proximal tibia (- 8.0 to -11.2 %) declined but was not different (p > 0.05) versus baseline. Neither PINP nor CTX was altered (p > 0.05) with training. CONCLUSIONS: Chronic activity-based therapy did not reverse bone loss typically observed soon after injury, yet reductions in BMD were less than the expected magnitude of decline in lower extremity BMD in persons with recent SCI.

The effects of caffeinated "energy shots" on time trial performance.

An emerging trend in sports nutrition is the consumption of energy drinks and "energy shots". Energy shots may prove to be a viable pre-competition supplement for runners. Six male runners (mean ± SD age and VO2max: 22.5 ± 1.8 years and 69.1 ± 5.7 mL·kg-1·min-1) completed three trials [placebo (PLA; 0 mg caffeine), Guayakí Yerba Maté Organic Energy Shot™ (YM; 140 mg caffeine), or Red Bull Energy Shot™ (RB; 80 mg caffeine)]. Treatments were ingested following a randomized, placebo-controlled crossover design. Participants ran a five kilometer time trial on a treadmill. No differences (p > 0.05) in performance were detected with RB (17.55 ± 1.01 min) or YM ingestion (17.86 ± 1.59 min) compared to placebo (17.44 ± 1.25 min). Overall, energy shot ingestion did not improve time-trial running performance in trained runners.

Caffeine ingestion and intense resistance training minimize postexercise hypotension in normotensive and prehypertensive men.

The primary aim of the study was to compare changes in blood pressure (BP) in normotensive and prehypertensive men completing resistance exercise following caffeine ingestion. Normotensive (n = 7) and hypertensive men (n = 7) ingested caffeine (6 mg x kg(-1)) or placebo 1 h preexercise, then completed four sets of bench press, leg press, lat pull-down, and shoulder press at 70%-80% one repetition maximum (1-RM). Heart rate (HR) and BP were measured preexercise, during exercise, and for 75 min postexercise. Caffeine increased (p < 0.05) resting, exercise, and recovery systolic BP, yet had no effect on HR (p = 0.16) or diastolic BP (p = 0.10). HR and BP were significantly higher (p < 0.05) in prehypertensive men versus normotensives. Postexercise hypotension did not occur in either treatment, suggesting that intense resistance training with or without caffeine intake may mitigate the BP-lowering effect of resistance exercise.

Attenuated RPE and leg pain in response to short-term high-intensity interval training.

This study examined the effect of 6 days of high intensity interval training (HIT) on rating of perceived exertion (RPE) and leg pain. Eleven men (age and VO(2)max=25.3±5.5 year and 45.6± mL/kg/min) and 9 women (age and VO(2)max=25.2±3.1 year and 41.1±6.1 mL/kg/min) with similar activity level and VO(2)max underwent HIT consisting of repeated Wingate tests separated by 5 min recovery over a 2-3 week period. Five men and four women served as controls and did not perform HIT. Four minutes after each bout across all days of training, RPE and leg pain were recorded using categorical scales. Repeated measure ANOVA was used to assess differences in RPE and leg pain in response to acute bouts and days of HIT. Data revealed that RPE and pain increased (p<0.05) after bout 1 to after bout 4. Compared to day 1 (6.3±1.9), RPE after bout 4 (5.0±1.4) decreased (p=0.001) in response to 6d of HIT. Training significantly reduced (p<0.05) leg pain, as pain declined from day 1 (6.20±2.29) of HIT versus day 6 (5.20±2.04). Data show that RPE and leg pain are significantly attenuated by 6 d of HIT, which is likely due to the physiological adaptations accrued in response to this modality of training.

Adaptations to high-intensity training are independent of gender.

The purpose of this study was to identify potential gender discrepancies in adaptation to low-volume high-intensity interval training (HIT). Active, young men (n = 11, age = 25.3 ± 5.5 years) and women (n = 9, age = 25.2 ± 3.1 years) matched for age, physical activity, and VO(2max) completed six sessions of HIT separated by 48 h over a 2-3 week period. Subjects completed four Wingate tests on days 1 and 2, five on days 3 and 4, and six on days 5 and 6. A control group of five men and four women (age = 22.8 ± 2.8 years) completed all testing, but did not perform HIT. Changes in VO(2max), oxygen (O(2)) pulse, peak/mean power output, fatiguability, substrate oxidation, and voluntary force production of the knee flexors and extensors were examined pre- and post-training with repeated measures ANOVA, with gender and group as between-subjects variables. Results showed significant (p < 0.05) improvements in VCO(2max) and peak/mean power output in response to HIT, as well as reduced respiratory exchange ratio and heart rate during submaximal exercise. The magnitude of change in VO(2max) (5.9 vs. 6.8%), power output (10.4-14.9% vs. 9.1-10.9%), and substrate oxidation was similar (p > 0.05) between men and women. Data show that adaptations to 6 days of low-volume HIT are similar in men and women matched for VO(2max) and physical activity.

Substrate metabolism during exercise in the spinal cord injured.

The primary aim of the study was to examine substrate metabolism during combined passive and active exercise in individuals with spinal cord injury (SCI). Nine men and women with SCI (mean age 40.6 +/- 3.4 years) completed two trials of submaximal exercise 1 week apart. Two maintained a complete injury and seven had an incomplete injury. Level of injury ranged from thoracic (T4-T6 and T10) to cervical (four C5-C6 and three C6-C7 injuries). During two bouts separated by 1 week, subjects completed two 30 min sessions of active lower-body and passive upper-body exercise, during which heart rate (HR) and gas exchange data were continuously assessed. One-way analysis of variance with repeated measures was used to examine differences in all variables over time. Results demonstrated significant increases (P < 0.05) in HR and oxygen uptake (VO(2)) from rest to exercise. Respiratory exchange ratio (RER) significantly increased (P < 0.05) during exercise from 0.85 +/- 0.02 at rest to 0.95 +/- 0.01 at the highest cadence, reflecting increasing reliance on carbohydrate from 50.0 to 83.0% of energy metabolism. Data demonstrate a large reliance on carbohydrate utilization during 30 min of exercise in persons with SCI, with reduced contribution of lipid as exercise intensity was increased. Strategies to reduce carbohydrate utilization and increase lipid oxidation in this population should be addressed.

Intracranial dural sinus thrombosis: novel use of a mechanical thrombectomy catheter and review of management strategies.

Management of intracranial dural sinus thrombosis with involvement of multiple sinuses is complex, often involving not only the primary problem (thrombosis) but acute adverse events consequent to the disease. We highlight the novel use of an endovascular device (typically for suction thrombectomy in the peripheral vascular system) used in our patient with a life-threatening multi-sinus thrombosis. As there is no standard treatment yet for cranial sinus thrombosis, our review of the literature highlights some effective management strategies. A 35-year-old woman developed associated complications of cranial sinus thrombosis that included intracranial hypertension caused by an expanding intracranial hematoma, pulmonary embolism treated by placement of filters in superior and inferior vena cava to eliminate intra- and extracranial sources of emboli, and procedure-related retroperitoneal hematoma that necessitated peripheral vascular intervention. After failure of several common devices during mechanical thrombolysis, a thrombectomy catheter (typically for peripheral vascular intervention to aide in the clot removal) was used. Our case highlights the fine balance of anticoagulation and thrombolysis and the proactive, aggressive approach used by our multispecialty team to manage concurrent factors.