Assessing the delivering of iMAgery-focused therapy for PSychosis (iMAPS) via telehealth.

OBJECTIVES: To examine the feasibility and acceptability of a novel telehealth (video-conferencing software and telephone calls) imagery-based therapeutic intervention for people experiencing persecutory delusions. Utilising a multiple baseline case series design and exploring imagery-focused therapy for psychosis (iMAPS). DESIGN: A non-concurrent A-B multiple baseline design was used. METHODS: Participants experiencing persecutory delusions and self-reporting a psychosis or schizophrenia-spectrum diagnosis were recruited through online adverts. On completion of assessments, participants were randomly assigned to multiple baseline assessments, of between three and five sessions. Six therapy sessions followed, consisting of imagery formulation, safe-place imagery creation, compassionate imagery, imagery manipulation and rescripting. Participants completed pre- and post-measures and sessional measures via an online survey software or in semi-structured interviews. Two weeks post-intervention, a final measure was completed exploring any potential adverse effects of psychotherapy. RESULTS: Five female participants completed all baseline and therapeutic sessions, suggesting the therapy was and mode of delivery was feasible and acceptable. Results indicate strong effect sizes across PANSS positive subscale and mood, as well as participants reporting a clinically significant change in at least one measure, for example, PSYRATS. All participants reported a reduction in the realness and compelling nature of distressing imagery. CONCLUSIONS: Results suggest delivering a telehealth imagery-focused therapy is acceptable and feasibly delivered via telehealth. A control group and blinding of assessments would strengthen the methodological limitations present.

The Mental Imagery for Suicidality in Students Trial (MISST): study protocol for a feasibility randomised controlled trial of broad-minded affective coping (BMAC) plus risk assessment and signposting versus risk assessment and signposting alone.

BACKGROUND: Going to university is an important milestone in many people's lives. It can also be a time of significant challenge and stress. There are growing concerns about mental health amongst student populations including suicide risk. Student mental health and counselling services have the potential to prevent suicide, but evidence-based therapies are required that fit these service contexts. The Broad-Minded Affective Coping intervention (BMAC) is a brief (6 sessions), positive imagery-based intervention that aims to enhance students access to past positive experiences and associated emotions and cognitions. Pilot data provides preliminary support for the BMAC for students struggling with suicidal thoughts and behaviours, but this intervention has not yet been evaluated in the context of a randomised controlled trial (RCT). The Mental Imagery for Suicidality in Students Trial (MISST) is a feasibility RCT that aims to determine the acceptability and feasibility of evaluating the BMAC as an intervention for university students at risk of suicide within a larger efficacy trial. Key feasibility uncertainties have been identified relating to recruitment, retention, and missing data. Intervention acceptability and safety will also be evaluated. METHOD: MISST is a feasibility randomised controlled trial design, with 1:1 allocation to risk assessment and signposting plus BMAC or risk assessment and signposting alone. Participants will be university students who self-report experiences of suicidal ideation or behaviour in the past 3 months. Assessments take place at baseline, 8, 16, and 24 weeks. The target sample size is 66 participants. A subset of up to 20 participants will be invited to take part in semi-structured qualitative interviews to obtain further data concerning the acceptability of the intervention. DISCUSSION: The BMAC intervention may provide an effective, brief talking therapy to help university students struggling with suicidal thoughts that could be readily implemented into university student counselling services. Depending on the results of MISST, the next step would be to undertake a larger-scale efficacy trial. TRIAL REGISTRATION: The trial was preregistered (17 December 2021) on ISRCTN (ISRCTN13621293) and ClinicalTrials.gov (NCT05296538).

iMAgery focused psychological therapy for persecutory delusions in PSychosis (iMAPS): a multiple baseline experimental case series.

BACKGROUND: Many people with psychosis experience persecutory delusions and report negative schematic beliefs and intrusive mental images which may be maintaining factors for psychotic symptoms. AIMS: This study examined the feasibility and acceptability of a new psychological therapy targeting schemas and images (iMAPS therapy). METHOD: The study used a randomised multiple baseline design. Participants with first episode psychosis were randomised using a multiple baseline design with 2-5 assessments. Six sessions of therapy, consisting of a combination of imagery techniques and imagery rescripting techniques, was used. In each session, participants completed a Mental Imagery in Psychosis Questionnaire (MIPQ) and imagery interview. Mood and delusional beliefs (PSYRATS) were also measured at each session. RESULTS: Five participants with first episode psychosis completed the baseline visits and attended all therapy sessions. One participant declined the final assessment. Results demonstrated significant reductions in negative schematic beliefs, delusions, imagery distress and other measures of schema (YSQ, SMI). Although multiple baseline randomisation strengthens the study, it lacked a control arm and blind assessments. CONCLUSIONS: iMAPS appears a feasible and acceptable treatment for psychosis, and further evaluation is indicated.

Efficacy of an Interdisciplinary Intensive Outpatient Program in Treating Combat-Related Traumatic Brain Injury and Psychological Health Conditions.

Background: Since 2000, over 413,000 US service members (SM) experienced at least one traumatic brain injury (TBI), and 40% of those with in-theater TBIs later screened positive for comorbid psychological health (PH) conditions, including post-traumatic stress disorder (PTSD), depression, and anxiety. Many SMs with these persistent symptoms fail to achieve a recovery that results in a desirable quality of life or return to full duty. Limited information exists though to guide treatment for SMs with a history of mild TBI (mTBI) and comorbid PH conditions. This report presents the methods and outcomes of an interdisciplinary intensive outpatient program (IOP) in the treatment of SMs with combat-related mTBI and PH comorbidities. The IOP combines conventional rehabilitation therapies and integrative medicine techniques with the goal of reducing morbidity in multiple neurological and behavioral health domains and enhancing military readiness. Methods: SMs (n = 1,456) with residual symptoms from mTBI and comorbid PH conditions were treated in a 4-week IOP at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center (WRNMMC). The IOP uses an interdisciplinary, holistic, and patient-centric rehabilitative care model. Interdisciplinary teams provide a diagnostic workup of neurological, psychiatric, and existential injuries, and from these assessments, individualized care plans are developed. Treatment response was assessed using the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Military Version (PCL-M), Satisfaction With Life Scale (SWLS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Epworth Sleepiness Scale (ESS), and Headache Impact Test-6 (HIT-6) and administered at admission, discharge, and at 1, 3, and 6 months post-discharge. Findings: Following treatment in the IOP, the symptomatic patients had statistically significant and clinically meaningful improvements across all outcome measures. The largest effect size was seen with GAD-7 (r = 0.59), followed by PHQ-8 (r = 0.56), NSI (r = 0.55), PCL-M (r = 0.52), ESS (r = 0.50), SWLS (r = 0.49), and HIT-6 (r = 0.42). In cross-sectional follow ups, the significant improvements were sustained at 1, 3, and 6 months post-discharge. Interpretation: This report demonstrates that an interdisciplinary IOP achieves significant and sustainable symptom recovery in SMs with combat-related mTBI and comorbid PH conditions and supports the further study of this model of care in complex medical conditions.

Pediatric Emergency Medicine Point-of-Care Ultrasound for the Diagnosis of Intussusception.

BACKGROUND: Delayed diagnosis of intussusception can lead to air enema failure and increased morbidity. There are limited studies reporting the accuracy of pediatric emergency medicine (PEM) physician point-of-care ultrasound (POCUS) in diagnosing intussusception. OBJECTIVES: The primary objective was to evaluate the accuracy of PEM POCUS in identifying ileocolic intussusception. The secondary objective was to identify factors associated with air enema failure. METHODS: This was a retrospective study of children who underwent POCUS for suspected intussusception in a pediatric emergency department between January 2001 and December 2015. Patients were included if a pediatric radiologist confirmed the POCUS examination interpretation by image review, radiology department ultrasound, or air enema. Age, symptom duration, recurrent intussusception, and location of intussusception were examined as factors for air enema failure. RESULTS: One hundred and two POCUS examinations were completed on 101 patients who met the inclusion criteria. The mean age of patients was 22 months. Of 75 patients with intussusception, 72 were detected with POCUS. PEM POCUS had a sensitivity of 96.0% (95% confidence interval [CI] 91.6-100.0%), specificity of 92.6% (95% CI 82.7-100.0%), positive predictive value of 97.3% (95% CI 93.6-100.0%), and negative predictive value of 89.3% (95% CI 77.8-100.0%). Air enema failure was associated with intussusception distal to the splenic flexure (odds ratio = 10.00 [95% CI 2.81-35.61]; p < 0.01) and age <6 months (OR = 6.83 [95% CI 1.94-24.09]; p < 0.01). CONCLUSION: PEM POCUS identifies intussusception with high sensitivity and specificity. Patients <6 months old or with intussusception distal to the splenic flexure had a higher risk of air enema failure.

Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans.

Imbalances in the oral microbial community have been associated with reduced cardiovascular and metabolic health. A possible mechanism linking the oral microbiota to health is the nitrate (NO3-)-nitrite (NO2-)-nitric oxide (NO) pathway, which relies on oral bacteria to reduce NO3- to NO2-. NO (generated from both NO2- and L-arginine) regulates vascular endothelial function and therefore blood pressure (BP). By sequencing bacterial 16S rRNA genes we examined the relationships between the oral microbiome and physiological indices of NO bioavailability and possible changes in these variables following 10 days of NO3- (12 mmol/d) and placebo supplementation in young (18-22 yrs) and old (70-79 yrs) normotensive humans (n = 18). NO3- supplementation altered the salivary microbiome compared to placebo by increasing the relative abundance of Proteobacteria (+225%) and decreasing the relative abundance of Bacteroidetes (-46%; P < 0.05). After NO3-supplementation the relative abundances of Rothia (+127%) and Neisseria (+351%) were greater, and Prevotella (-60%) and Veillonella (-65%) were lower than in the placebo condition (all P < 0.05). NO3- supplementation increased plasma concentration of NO2- and reduced systemic blood pressure in old (70-79 yrs), but not young (18-22 yrs), participants. High abundances of Rothia and Neisseria and low abundances of Prevotella and Veillonella were correlated with greater increases in plasma [NO2-] in response to NO3- supplementation. The current findings indicate that the oral microbiome is malleable to change with increased dietary intake of inorganic NO3-, and that diet-induced changes in the oral microbial community are related to indices of NO homeostasis and vascular health in vivo.

The Content Validity of a Chemotherapy-Induced Peripheral Neuropathy Patient-Reported Outcome Measure.

PURPOSE/OBJECTIVES: To test the content validity of a 16-item version of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (QLQ-CIPN20). 
. RESEARCH APPROACH: Cross-sectional, prospective, qualitative design. 
. SETTING: Six outpatient oncology clinics within the University of Michigan Health System's comprehensive cancer center in Ann Arbor. 
. PARTICIPANTS: 25 adults with multiple myeloma or breast, gynecologic, gastrointestinal, or head and neck malignancies experiencing peripheral neuropathy caused by neurotoxic chemotherapy. 
. METHODOLOGIC APPROACH: Cognitive interviewing methodology was used to evaluate the content validity of a 16-item version of the QLQ-CIPN20 instrument.
. FINDINGS: Minor changes were made to three questions to enhance readability. Twelve questions were revised to define unfamiliar terminology, clarify the location of neuropathy, and emphasize important aspects. One question was deleted because of clinical and conceptual redundancy with other items, as well as concerns regarding generalizability and social desirability. 
. INTERPRETATION: Cognitive interviewing methodology revealed inconsistencies between patients' understanding and researchers' intent, along with points that required clarification to avoid misunderstanding. 
. IMPLICATIONS FOR NURSING: Patients' interpretations of the instrument's items were inconsistent with the intended meanings of the questions. One item was dropped and others were revised, resulting in greater consistency in how patients, clinicians, and researchers interpreted the items' meanings and improving the instrument's content validity. Following additional revision and psychometric testing, the QLQ-CIPN20 could evolve into a gold-standard CIPN patient-reported outcome measure.

Emotional response to a therapeutic technique: The social Broad Minded Affective Coping.

OBJECTIVES: It has been suggested that savouring positive memories can generate positive emotions. Increasing positive emotion can have a range of benefits including reducing attention to and experiences of threat. This study investigated individuals' emotional reactions to a guided mental imagery task focussing on positive social memory called the 'social Broad Minded Affective Coping (BMAC)' technique. The study examined possible predictors of individuals' responses to this intervention. METHOD: An internet-based, within-group, repeated-measures design was used. One hundred and twenty-three participants completed self-report measures of self-attacking and social safeness/pleasure. They were then guided through the social BMAC. Participants completed state measures of positive and negative affect and social safeness/pleasure before and after the intervention. Forty-nine participants took part in a 2-week follow-up. RESULTS: It was found that safe/warm positive affect, relaxed positive affect and feelings of social safeness increased following the social BMAC, whilst negative affect decreased. In addition, it was found that people scoring higher on inadequate self-attacking benefited most from this intervention. Changes in affect were not maintained at the 2-week follow-up. CONCLUSION: The results provide preliminary support for the efficacy of the social BMAC in activating specific types of mood (those associated with safeness rather than drive/reward). This task has potential as part of therapeutic interventions directed at clinical groups, but further evaluation is needed. PRACTITIONER POINTS: The social Broad Minded Affective Coping (BMAC) was related to improvements in forms of positive affect linked to the affiliative system. This task may be helpful in inducing these positive mood states within therapy. Further evaluation comparing the BMAC to a control task is needed. Individuals with a greater fear of compassion or more hated-self-criticism may gain less from the task, although effects were small.

Influence of dietary nitrate supplementation on physiological and muscle metabolic adaptations to sprint interval training.

We hypothesized that 4 wk of dietary nitrate supplementation would enhance exercise performance and muscle metabolic adaptations to sprint interval training (SIT). Thirty-six recreationally active subjects, matched on key variables at baseline, completed a series of exercise tests before and following a 4-wk period in which they were allocated to one of the following groups: 1) SIT and [Formula: see text]-depleted beetroot juice as a placebo (SIT+PL); 2) SIT and [Formula: see text]-rich beetroot juice (~13 mmol [Formula: see text]/day; SIT+BR); or 3) no training and [Formula: see text]-rich beetroot juice (NT+BR). During moderate-intensity exercise, pulmonary oxygen uptake was reduced by 4% following 4 wk of SIT+BR and NT+BR (P < 0.05) but not SIT+PL. The peak work rate attained during incremental exercise increased more in SIT+BR than in SIT+PL (P < 0.05) or NT+BR (P < 0.001). The reduction in muscle and blood [lactate] and the increase in muscle pH from preintervention to postintervention were greater at 3 min of severe-intensity exercise in SIT+BR compared with SIT+PL and NT+BR (P < 0.05). However, the change in severe-intensity exercise performance was not different between SIT+BR and SIT+PL (P > 0.05). The relative proportion of type IIx muscle fibers in the vastus lateralis muscle was reduced in SIT+BR only (P < 0.05). These findings suggest that BR supplementation may enhance some aspects of the physiological adaptations to SIT.NEW & NOTEWORTHY We investigated the influence of nitrate-rich and nitrate-depleted beetroot juice on the muscle metabolic and physiological adaptations to 4 wk of sprint interval training. Compared with placebo, dietary nitrate supplementation reduced the O2 cost of submaximal exercise, resulted in greater improvement in incremental (but not severe-intensity) exercise performance, and augmented some muscle metabolic adaptations to training. Nitrate supplementation may facilitate some of the physiological responses to sprint interval training.

Influence of beetroot juice supplementation on intermittent exercise performance.

PURPOSE: This study tested the hypothesis that nitrate (NO3-) supplementation would improve performance during high-intensity intermittent exercise featuring different work and recovery intervals. METHOD: Ten male team-sport players completed high-intensity intermittent cycling tests during separate 5-day supplementation periods with NO3 (-)-rich beetroot juice (BR; 8.2 mmol NO3- day(-1)) and NO3 (-)-depleted beetroot juice (PL; 0.08 mmol NO3- day(-1)). Subjects completed: twenty-four 6-s all-out sprints interspersed with 24 s of recovery (24 × 6-s); seven 30-s all-out sprints interspersed with 240 s of recovery (7 × 30-s); and six 60-s self-paced maximal efforts interspersed with 60 s of recovery (6 × 60-s); on days 3, 4, and 5 of supplementation, respectively. RESULT: Plasma [NO2-] was 237% greater in the BR trials. Mean power output was significantly greater with BR relative to PL in the 24 × 6-s protocol (568 ± 136 vs. 539 ± 136 W; P < 0.05), but not during the 7 × 30-s (558 ± 95 vs. 562 ± 94 W) or 6 × 60-s (374 ± 57 vs. 375 ± 59 W) protocols (P > 0.05). The increase in blood [lactate] across the 24 × 6-s and 7 × 30-s protocols was greater with BR (P < 0.05), but was not different in the 6 × 60-s protocol (P > 0.05). CONCLUSION: BR might be ergogenic during repeated bouts of short-duration maximal-intensity exercise interspersed with short recovery periods, but not necessarily during longer duration intervals or when a longer recovery duration is applied. These findings suggest that BR might have implications for performance enhancement during some types of intermittent exercise.

Dietary nitrate improves sprint performance and cognitive function during prolonged intermittent exercise.

UNLABELLED: It is possible that dietary nitrate (NO3 (-)) supplementation may improve both physical and cognitive performance via its influence on blood flow and cellular energetics. PURPOSE: To investigate the effects of dietary NO3 (-) supplementation on exercise performance and cognitive function during a prolonged intermittent sprint test (IST) protocol, which was designed to reflect typical work patterns during team sports. METHODS: In a double-blind randomised crossover study, 16 male team-sport players received NO3 (-)-rich (BR; 140 mL day(-1); 12.8 mmol of NO3 (-)), and NO3 (-)-depleted (PL; 140 mL day(-1); 0.08 mmol NO3 (-)) beetroot juice for 7 days. On day 7 of supplementation, subjects completed the IST (two 40-min "halves" of repeated 2-min blocks consisting of a 6-s "all-out" sprint, 100-s active recovery and 20 s of rest), on a cycle ergometer during which cognitive tasks were simultaneously performed. RESULTS: Total work done during the sprints of the IST was greater in BR (123 ± 19 kJ) compared to PL (119 ± 17 kJ; P < 0.05). Reaction time of response to the cognitive tasks in the second half of the IST was improved in BR compared to PL (BR first half: 820 ± 96 vs. second half: 817 ± 86 ms; PL first half: 824 ± 114 vs. second half: 847 ± 118 ms; P < 0.05). There was no difference in response accuracy. CONCLUSIONS: These findings suggest that dietary NO3 (-) enhances repeated sprint performance and may attenuate the decline in cognitive function (and specifically reaction time) that may occur during prolonged intermittent exercise.

The effect of dietary nitrate supplementation on the oxygen cost of cycling, walking performance and resting blood pressure in individuals with chronic obstructive pulmonary disease: A double blind placebo controlled, randomised control trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) results in exercise intolerance. Dietary nitrate supplementation has been shown to lower blood pressure (BP), reduce the oxygen cost of exercise, and enhance exercise tolerance in healthy volunteers. This study assessed the effects of dietary nitrate on the oxygen cost of cycling, walking performance and BP in individuals with mild-moderate COPD. METHODS: Thirteen patients with mild-moderate COPD were recruited. Participants consumed 70 ml of either nitrate-rich (6.77 mmol nitrate; beetroot juice) or nitrate-depleted beetroot juice (0.002 mmol nitrate; placebo) twice a day for 2.5 days, with the final supplement ~3 hours before testing. BP was measured before completing two bouts of moderate-intensity cycling, where pulmonary gas exchange was measured throughout. The six-minute walk test (6 MWT) was completed 30 minutes subsequent to the second cycling bout. RESULTS: Plasma nitrate concentration was significantly elevated following beetroot juice vs. placebo (placebo; 48 ± 86 vs. beetroot juice; 215 ± 84 µM, P = 0.002). No significant differences were observed between placebo vs. beetroot juice for oxygen cost of exercise (933 ± 323 vs. 939 ± 302 ml: min(-1); P = 0.88), distance covered in the 6 MWT (456 ± 86 vs. 449 ± 79 m; P = 0.37), systolic BP (123 ± 14 vs. 123 ± 14 mmHg; P = 0.91), or diastolic BP (77 ± 9 vs. 79 ± 9 mmHg; P = 0.27). CONCLUSION: Despite a large rise in plasma nitrate concentration, two days of nitrate supplementation did not reduce the oxygen cost of moderate intensity cycling, increase distance covered in the 6 MWT, or lower BP.

Dietary nitrate supplementation: effects on plasma nitrite and pulmonary O2 uptake dynamics during exercise in hypoxia and normoxia.

We investigated the effects of dietary nitrate (NO3 (-)) supplementation on the concentration of plasma nitrite ([NO2 (-)]), oxygen uptake (V̇o2) kinetics, and exercise tolerance in normoxia (N) and hypoxia (H). In a double-blind, crossover study, 12 healthy subjects completed cycle exercise tests, twice in N (20.9% O2) and twice in H (13.1% O2). Subjects ingested either 140 ml/day of NO3 (-)-rich beetroot juice (8.4 mmol NO3; BR) or NO3 (-)-depleted beetroot juice (PL) for 3 days prior to moderate-intensity and severe-intensity exercise tests in H and N. Preexercise plasma [NO2 (-)] was significantly elevated in H-BR and N-BR compared with H-PL (P < 0.01) and N-PL (P < 0.01). The rate of decline in plasma [NO2 (-)] was greater during severe-intensity exercise in H-BR [-30 ± 22 nM/min, 95% confidence interval (CI); -44, -16] compared with H-PL (-7 ± 10 nM/min, 95% CI; -13, -1; P < 0.01) and in N-BR (-26 ± 19 nM/min, 95% CI; -38, -14) compared with N-PL (-1 ± 6 nM/min, 95% CI; -5, 2; P < 0.01). During moderate-intensity exercise, steady-state pulmonary V̇o2 was lower in H-BR (1.91 ± 0.28 l/min, 95% CI; 1.77, 2.13) compared with H-PL (2.05 ± 0.25 l/min, 95% CI; 1.93, 2.26; P = 0.02), and V̇o2 kinetics was faster in H-BR (τ: 24 ± 13 s, 95% CI; 15, 32) compared with H-PL (31 ± 11 s, 95% CI; 23, 38; P = 0.04). NO3 (-) supplementation had no significant effect on V̇o2 kinetics during severe-intensity exercise in hypoxia, or during moderate-intensity or severe-intensity exercise in normoxia. Tolerance to severe-intensity exercise was improved by NO3 (-) in hypoxia (H-PL: 197 ± 28; 95% CI; 173, 220 vs. H-BR: 214 ± 43 s, 95% CI; 177, 249; P = 0.04) but not normoxia. The metabolism of NO2 (-) during exercise is altered by NO3 (-) supplementation, exercise, and to a lesser extent, hypoxia. In hypoxia, NO3 (-) supplementation enhances V̇o2 kinetics during moderate-intensity exercise and improves severe-intensity exercise tolerance. These findings may have important implications for individuals exercising at altitude.

3D printing of composite calcium phosphate and collagen scaffolds for bone regeneration.

Low temperature 3D printing of calcium phosphate scaffolds holds great promise for fabricating synthetic bone graft substitutes with enhanced performance over traditional techniques. Many design parameters, such as the binder solution properties, have yet to be optimized to ensure maximal biocompatibility and osteoconductivity with sufficient mechanical properties. This study tailored the phosphoric acid-based binder solution concentration to 8.75 wt% to maximize cytocompatibility and mechanical strength, with a supplementation of Tween 80 to improve printing. To further enhance the formulation, collagen was dissolved into the binder solution to fabricate collagen-calcium phosphate composites. Reducing the viscosity and surface tension through a physiologic heat treatment and Tween 80, respectively, enabled reliable thermal inkjet printing of the collagen solutions. Supplementing the binder solution with 1-2 wt% collagen significantly improved maximum flexural strength and cell viability. To assess the bone healing performance, we implanted 3D printed scaffolds into a critically sized murine femoral defect for 9 weeks. The implants were confirmed to be osteoconductive, with new bone growth incorporating the degrading scaffold materials. In conclusion, this study demonstrates optimization of material parameters for 3D printed calcium phosphate scaffolds and enhancement of material properties by volumetric collagen incorporation via inkjet printing.

Beetroot juice and exercise: pharmacodynamic and dose-response relationships.

Dietary supplementation with beetroot juice (BR), containing approximately 5-8 mmol inorganic nitrate (NO3(-)), increases plasma nitrite concentration ([NO2(-)]), reduces blood pressure, and may positively influence the physiological responses to exercise. However, the dose-response relationship between the volume of BR ingested and the physiological effects invoked has not been investigated. In a balanced crossover design, 10 healthy men ingested 70, 140, or 280 ml concentrated BR (containing 4.2, 8.4, and 16.8 mmol NO3(-), respectively) or no supplement to establish the effects of BR on resting plasma [NO3(-)] and [NO2(-)] over 24 h. Subsequently, on six separate occasions, 10 subjects completed moderate-intensity and severe-intensity cycle exercise tests, 2.5 h postingestion of 70, 140, and 280 ml BR or NO3(-)-depleted BR as placebo (PL). Following acute BR ingestion, plasma [NO2(-)] increased in a dose-dependent manner, with the peak changes occurring at approximately 2-3 h. Compared with PL, 70 ml BR did not alter the physiological responses to exercise. However, 140 and 280 ml BR reduced the steady-state oxygen (O2) uptake during moderate-intensity exercise by 1.7% (P = 0.06) and 3.0% (P < 0.05), whereas time-to-task failure was extended by 14% and 12% (both P < 0.05), respectively, compared with PL. The results indicate that whereas plasma [NO2(-)] and the O2 cost of moderate-intensity exercise are altered dose dependently with NO3(-)-rich BR, there is no additional improvement in exercise tolerance after ingesting BR containing 16.8 compared with 8.4 mmol NO3(-). These findings have important implications for the use of BR to enhance cardiovascular health and exercise performance in young adults.

Effects of nitrate on the power-duration relationship for severe-intensity exercise.

PURPOSE: The power asymptote (critical power [CP]) and curvature constant (W') of the power-duration relationship dictate the tolerance to severe-intensity exercise. We tested the hypothesis that dietary nitrate supplementation would increase the CP and/or the W' during cycling exercise. METHODS: In a double-blind, randomized, crossover study, nine recreationally active male subjects supplemented their diet with either nitrate-rich concentrated beetroot juice (BR; 2 × 250 mL·d, ∼8.2 mmol·d nitrate) or a nitrate-depleted BR placebo (PL; 2 × 250 mL·d, ∼0.006 mmol·d nitrate). In each condition, the subjects completed four separate severe-intensity exercise bouts to exhaustion at 60% of the difference between the gas exchange threshold and the peak power attained during incremental exercise (60% Δ), 70% Δ, 80% Δ, and 100% peak power, and the results were used to establish CP and W'. RESULTS: Nitrate supplementation improved exercise tolerance during exercise at 60% Δ (BR, 696 ± 120 vs PL, 593 ± 68 s; P < 0.05), 70% Δ (BR, 452 ± 106 vs PL, 390 ± 86 s; P < 0.05), and 80% Δ (BR, 294 ± 50 vs PL, 263 ± 50 s; P < 0.05) but not 100% peak power (BR, 182 ± 37 vs PL, 166 ± 26 s; P = 0.10). Neither CP (BR, 221 ± 27 vs PL, 218 ± 26 W) nor W' (BR, 19.3 ± 4.6 vs PL, 17.8 ± 3 kJ) were significantly altered by BR. CONCLUSION: Dietary nitrate supplementation improved endurance during severe-intensity exercise in recreationally active subjects without significantly increasing either the CP or the W'.

Dietary nitrate supplementation improves team sport-specific intense intermittent exercise performance.

Recent studies have suggested that dietary inorganic nitrate (NO3(-)) supplementation may improve muscle efficiency and endurance exercise tolerance but possible effects during team sport-specific intense intermittent exercise have not been examined. We hypothesized that NO3(-) supplementation would enhance high-intensity intermittent exercise performance. Fourteen male recreational team-sport players were assigned in a double-blind, randomized, crossover design to consume 490 mL of concentrated, nitrate-rich beetroot juice (BR) and nitrate-depleted placebo juice (PL) over ~30 h preceding the completion of a Yo-Yo intermittent recovery level 1 test (Yo-Yo IR1). Resting plasma nitrite concentration ([NO2(-)]) was ~400% greater in BR compared to PL. Plasma [NO2(-)] declined by 20% in PL (P < 0.05) and by 54 % in BR (P < 0.05) from pre-exercise to end-exercise. Performance in the Yo-Yo IR1 was 4.2% greater (P < 0.05) with BR (1,704 ± 304 m) compared to PL (1,636 ± 288 m). Blood [lactate] was not different between BR and PL, but the mean blood [glucose] was lower (3.8 ± 0.8 vs. 4.2 ± 1.1 mM, P < 0.05) and the rise in plasma [K(+)] tended to be reduced in BR compared to PL (P = 0.08). These findings suggest that NO3(-) supplementation may promote NO production via the nitrate-nitrite-NO pathway and enhance Yo-Yo IR1 test performance, perhaps by facilitating greater muscle glucose uptake or by better maintaining muscle excitability. Dietary NO3(-) supplementation improves performance during intense intermittent exercise and may be a useful ergogenic aid for team sports players.

Effects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adults.

Dietary nitrate (NO(3)(-)) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults. We investigated whether these effects might also be evident in older adults. In a double-blind, randomized, crossover study, 12 healthy, older (60-70 yr) adults supplemented their diet for 3 days with either nitrate-rich concentrated beetroot juice (BR; 2 × 70 ml/day, ∼9.6 mmol/day NO(3)(-)) or a nitrate-depleted beetroot juice placebo (PL; 2 × 70 ml/day, ∼0.01 mmol/day NO(3)(-)). Before and after the intervention periods, resting blood pressure and plasma [nitrite] were measured, and subjects completed a battery of physiological and cognitive tests. Nitrate supplementation significantly increased plasma [nitrite] and reduced resting systolic (BR: 115 ± 9 vs. PL: 120 ± 6 mmHg; P < 0.05) and diastolic (BR: 70 ± 5 vs. PL: 73 ± 5 mmHg; P < 0.05) blood pressure. Nitrate supplementation resulted in a speeding of the Vo(2) mean response time (BR: 25 ± 7 vs. PL: 28 ± 7 s; P < 0.05) in the transition from standing rest to treadmill walking, although in contrast to our hypothesis, the O(2) cost of exercise remained unchanged. Functional capacity (6-min walk test), the muscle metabolic response to low-intensity exercise, brain metabolite concentrations, and cognitive function were also not altered. Dietary nitrate supplementation reduced resting blood pressure and improved Vo(2) kinetics during treadmill walking in healthy older adults but did not improve walking or cognitive performance. These results may have implications for the enhancement of cardiovascular health in older age.

Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats.

Defects in excitation-contraction coupling have been reported in failing hearts, but little is known about the relationship between these defects and the development of heart failure (HF). We compared the early changes in intracellular Ca(2+) cycling to those that underlie overt pump dysfunction and arrhythmogenesis found later in HF. Laser-scanning confocal microscopy was used to measure Ca(2+) transients in myocytes of intact hearts in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) at different ages. Early compensatory mechanisms include a positive inotropic effect in SHRs at 7.5-9 mo compared with 6 mo. Ca(2+) transient duration increased at 9 mo in SHRs, indicating changes in Ca(2+) reuptake during decompensation. Cell-to-cell variability in Ca(2+) transient duration increased at 7.5 mo, decreased at 9 mo, and increased again at 22 mo (overt HF), indicating extensive intercellular variability in Ca(2+) transient kinetics during disease progression. Vulnerability to intercellular concordant Ca(2+) alternans increased at 9-22 mo in SHRs and was mirrored by a slowing in Ca(2+) transient restitution, suggesting that repolarization alternans and the resulting repolarization gradients might promote reentrant arrhythmias early in disease development. Intercellular discordant and subcellular Ca(2+) alternans increased as early as 7.5 mo in SHRs and may also promote arrhythmias during the compensated phase. The incidence of spontaneous and triggered Ca(2+) waves was increased in SHRs at all ages, suggesting a higher likelihood of triggered arrhythmias in SHRs compared with WKY rats well before HF develops. Thus serious and progressive defects in Ca(2+) cycling develop in SHRs long before symptoms of HF occur. Defective Ca(2+) cycling develops early and affects a small number of myocytes, and this number grows with age and causes the transition from asymptomatic to overt HF. These defects may also underlie the progressive susceptibility to Ca(2+) alternans and Ca(2+) wave activity, thus increasing the propensity for arrhythmogenesis in HF.

Inspiratory muscle training enhances pulmonary O(2) uptake kinetics and high-intensity exercise tolerance in humans.

Fatigue of the respiratory muscles during intense exercise might compromise leg blood flow, thereby constraining oxygen uptake (Vo(2)) and limiting exercise tolerance. We tested the hypothesis that inspiratory muscle training (IMT) would reduce inspiratory muscle fatigue, speed Vo(2) kinetics and enhance exercise tolerance. Sixteen recreationally active subjects (mean + or - SD, age 22 + or - 4 yr) were randomly assigned to receive 4 wk of either pressure threshold IMT [30 breaths twice daily at approximately 50% of maximum inspiratory pressure (MIP)] or sham treatment (60 breaths once daily at approximately 15% of MIP). The subjects completed moderate-, severe- and maximal-intensity "step" exercise transitions on a cycle ergometer before (Pre) and after (Post) the 4-wk intervention period for determination of Vo(2) kinetics and exercise tolerance. There were no significant changes in the physiological variables of interest after Sham. After IMT, baseline MIP was significantly increased (Pre vs. Post: 155 + or - 22 vs. 181 + or - 21 cmH(2)O; P < 0.001), and the degree of inspiratory muscle fatigue was reduced after severe- and maximal-intensity exercise. During severe exercise, the Vo(2) slow component was reduced (Pre vs. Post: 0.60 + or - 0.20 vs. 0.53 + or - 0.24 l/min; P < 0.05) and exercise tolerance was enhanced (Pre vs. Post: 765 + or - 249 vs. 1,061 + or - 304 s; P < 0.01). Similarly, during maximal exercise, the Vo(2) slow component was reduced (Pre vs. Post: 0.28 + or - 0.14 vs. 0.18 + or - 0.07 l/min; P < 0.05) and exercise tolerance was enhanced (Pre vs. Post: 177 + or - 24 vs. 208 + or - 37 s; P < 0.01). Four weeks of IMT, which reduced inspiratory muscle fatigue, resulted in a reduced Vo(2) slow-component amplitude and an improved exercise tolerance during severe- and maximal-intensity exercise. The results indicate that the enhanced exercise tolerance observed after IMT might be related, at least in part, to improved Vo(2) dynamics, presumably as a consequence of increased blood flow to the exercising limbs.