Systemic immunosuppression depletes peripheral blood regulatory B cells in patients with immune thrombocytopenia.

Regulatory B (Breg) cells are potentially implicated in the pathogenesis of immune thrombocytopenia (ITP). We analysed a prospective cohort of newly diagnosed steroid naïve ITP patients enrolled in the multicentre FLIGHT trial and found that the numbers of Bregs in their peripheral blood were similar to healthy controls. In contrast, Breg numbers were significantly reduced in ITP patients treated with systemic immunosuppression (glucocorticoids or mycophenolate mofetil). We also demonstrate that glucocorticoid treatment impairs Breg interleukin-10 production via an indirect T-cell-mediated mechanism.

The effectiveness of heat preparation and alleviation strategies for cognitive performance: A systematic review.

A range of occupational and performance contexts (e.g. military personnel operations, emergency services, sport) require the critical maintenance of cognitive performance in environmentally challenging environments. Several reviews exist which evaluate the effectiveness of heat preparation strategies to facilitate physical performance. To date, no review has explored the usefulness of heat preparation strategies for cognitive performance. Therefore, this systematic review aimed to evaluate a range of interventions for the maintenance of cognitive performance, during or following active or passive heat exposure. Studies to be included were assessed by two authors reviewing title, abstract, and full-text. Forty articles were identified which met the inclusion criteria. Interventions were categorised into chronic (i.e. acclimation/acclimatisation) and acute strategies (i.e. hydration, cooling, supplementation, psychological). The results indicate that medium-term consecutive heat acclimation may mitigate some cognitive deficits under heat stress, although heat acclimation effectiveness could be influenced by age. Further, pre-cooling appears the most effective cooling method for maintaining cognitive performance under heat stress, although results were somewhat ambiguous. The hydration literature showed that the most effective hydration strategies were those which individualised electrolyte fortified fluid volumes to match for sweat loss. Limited research exploring psychological interventions indicates that motivational self-talk could be facilitative for maintaining cognitive skills following exercise in hot conditions. These findings can be used to help inform strategies for maintaining critical cognitive and decision-making skills in hot environments.

Temporal dynamics of normalization reweighting.

For decades, neural suppression in early visual cortex has been thought to be fixed. But recent work has challenged this assumption by showing that suppression can be reweighted based on recent history; when pairs of stimuli are repeatedly presented together, suppression between them strengthens. Here we investigate the temporal dynamics of this process using a steady-state visual evoked potential (SSVEP) paradigm that provides a time-resolved, direct index of suppression between pairs of stimuli flickering at different frequencies (5 and 7 Hz). Our initial analysis of an existing electroencephalography (EEG) dataset (N = 100) indicated that suppression increases substantially during the first 2-5 seconds of stimulus presentation (with some variation across stimulation frequency). We then collected new EEG data (N = 100) replicating this finding for both monocular and dichoptic mask arrangements in a preregistered study designed to measure reweighting. A third experiment (N = 20) used source-localized magnetoencephalography and found that these effects are apparent in primary visual cortex (V1), consistent with results from neurophysiological work. Because long-standing theories propose inhibition/excitation differences in autism, we also compared reweighting between individuals with high versus low autistic traits, and with and without an autism diagnosis, across our three datasets (total N = 220). We find no compelling differences in reweighting that are associated with autism. Our results support the normalization reweighting model and indicate that for prolonged stimulation, increases in suppression occur on the order of 2-5 seconds after stimulus onset.

The effect of exercise-induced fatigue and heat exposure on soccer-specific decision-making during high-intensity intermittent exercise.

Global warming and the globalisation of sport has increased the prevalence of sports competitions being held in hot environments. However, there is currently limited research investigating the impact of the heat on soccer-specific decision-making skills during exercise reflective of the physical demands of match-play. Therefore, the effects of heat exposure on physical and soccer-specific decision-making performance, biological markers (i.e., metanephrines), appraisal (i.e., challenge vs. threat) and affective states, during prolonged high-intensity intermittent exercise were investigated. Nine well-trained male soccer players completed a 92-min cycling intermittent sprint protocol (CISP), whilst simultaneously responding to a series of soccer-specific decision-making trials at various time points, in two temperature conditions: hot (32°C, 50%rh) and temperate (18°C, 50%rh). Results showed that decision-making score (p = .030) was impaired in the hot compared to the temperate condition. There was a reduced workload in the second half during the hot condition (p = .016), which coincided with a heightened threat state (p = .007) and more unpleasant feelings (p = .008) experienced in the hot, compared to temperate, condition. Furthermore, plasma normetanephrine (NMET) was higher at half-time (p = .012) and post-CISP (p ≤ .001). Also, plasma metanephrine (MET) was higher post-CISP (p = .009) in the hot compared to temperate condition, reflecting a heightened stress response. Our findings highlight the need for practitioners to consider the detrimental effects heat exposure can have on both physical and decision-making performance when looking to facilitate performance in hot conditions.

Cyclophosphamide depletes tumor infiltrating T regulatory cells and combined with anti-PD-1 therapy improves survival in murine neuroblastoma.

The outcome for children with high-risk neuroblastoma is poor despite intensive multi-modal treatment protocols. Toxicity from current treatments is significant, and novel approaches are needed to improve outcome. Cyclophosphamide (CPM) is a key component of current chemotherapy regimens and is known to have immunomodulatory effects. However, this has not been investigated in the context of tumor infiltrating lymphocytes in neuroblastoma. Using murine models of neuroblastoma, the immunomodulatory effects of low-dose CPM were investigated using detailed immunophenotyping. We demonstrated that CPM resulted in a specific depletion of intratumoral T regulatory cells by apoptosis, and when combined with anti-PD-1 antibody therapy, this resulted in improved therapeutic efficacy. CPM combined with anti-PD-1 therapy was demonstrated to be an effective combinational therapy, with metronomic CPM found to be more effective than single dosing in more resistant tumor models. Overall, this pre-clinical data strongly support clinical evaluation of such combination strategies in neuroblastoma.

Fc-null anti-PD-1 monoclonal antibodies deliver optimal checkpoint blockade in diverse immune environments.

BACKGROUND: Despite extensive clinical use, the mechanisms that lead to therapeutic resistance to anti-programmed cell-death (PD)-1 monoclonal antibodies (mAbs) remain elusive. Here, we sought to determine how interactions between the Fc region of anti-PD-1 mAbs and Fcγ receptors (FcγRs) affect therapeutic activity and how these are impacted by the immune environment. METHODS: Mouse and human anti-PD-1 mAbs with different Fc binding profiles were generated and characterized in vitro. The ability of these mAbs to elicit T-cell responses in vivo was first assessed in a vaccination setting using the model antigen ovalbumin. The antitumor activity of anti-PD-1 mAbs was investigated in the context of immune 'hot' MC38 versus 'cold' neuroblastoma tumor models, and flow cytometry performed to assess immune infiltration. RESULTS: Engagement of activating FcγRs by anti-PD-1 mAbs led to depletion of activated CD8 T cells in vitro and in vivo, abrogating therapeutic activity. Importantly, the extent of this Fc-mediated modulation was determined by the surrounding immune environment. Low FcγR-engaging mouse anti-PD-1 isotypes, which are frequently used as surrogates for human mAbs, were unable to expand ovalbumin-reactive CD8 T cells, in contrast to Fc-null mAbs. These results were recapitulated in mice expressing human FcγRs, in which clinically relevant hIgG4 anti-PD-1 led to reduced endogenous expansion of CD8 T cells compared with its engineered Fc-null counterpart. In the context of an immunologically 'hot' tumor however, both low-engaging and Fc-null mAbs induced long-term antitumor immunity in MC38-bearing mice. Finally, a similar anti-PD-1 isotype hierarchy was demonstrated in the less responsive 'cold' 9464D neuroblastoma model, where the most effective mAbs were able to delay tumor growth but could not induce long-term protection. CONCLUSIONS: Our data collectively support a critical role for Fc:FcγR interactions in inhibiting immune responses to both mouse and human anti-PD-1 mAbs, and highlight the context-dependent effect that anti-PD-1 mAb isotypes can have on T-cell responses. We propose that engineering of Fc-null anti-PD-1 mAbs would prevent FcγR-mediated resistance in vivo and allow maximal T-cell stimulation independent of the immunological environment.

Glucocorticoid treatment in patients with newly diagnosed immune thrombocytopenia switches CD14++ CD16+ intermediate monocytes from a pro-inflammatory to an anti-inflammatory phenotype.

Immune thrombocytopenia (ITP) is thought to result from an aberrant adaptive autoimmune response, involving autoantibodies, B and T lymphocytes, directed at platelets and megakaryocytes. Previous reports have demonstrated skewed CD4+ T-helper subset distribution and enhanced production of pro-inflammatory cytokines such as interleukin 17A and interferon gamma. The role of monocytes (MCs) in ITP is less widely described, but innate immune cells have a role in shaping CD4+ T-cell phenotypes. Glucocorticoids (GCs) are commonly used for first-line ITP treatment and modulate a broad range of immune cells including T cells and MCs. Using multiparameter flow cytometry analysis, we demonstrate the expansion of intermediate MCs (CD14++ CD16+ ) in untreated patients with newly diagnosed ITP, with these cells displaying a pro-inflammatory phenotype, characterised by enhanced expression of CD64 and CD80. After 2 weeks of prednisolone treatment (1 mg/kg daily), the proportion of intermediate MCs reduced, with enhanced expression of the anti-inflammatory markers CD206 and CD163. Healthy control MCs were distinctly different than MCs from patients with ITP before and after GC treatment. Furthermore, the GC-induced phenotype was not observed in patients with chronic ITP receiving thrombopoietin receptor agonists. These data suggest a role of MCs in ITP pathogenesis and clinical response to GC therapy.

The Effects of Heat Exposure During Intermittent Exercise on Physical and Cognitive Performance Among Team Sport Athletes.

This study investigated the effects of heat exposure on physical and cognitive performance during an intermittent exercise protocol so as to reflect the incremental fatigue experienced during team sports. Twelve well-trained male team sport players completed an 80-minute cycling intermittent sprint protocol (CISP), alongside computerized vigilance and congruent (i.e., simple) and incongruent (i.e., complex) Stroop tasks of cognitive functioning, in two counterbalanced temperature conditions; hot (32°C[50%rh]) and control (18°C[50%rh]). Incongruent Stroop accuracy declined over time (p = .002), specifically in the second (Mdiff = -3.75, SD = 0.90%, p = .009) and third (Mdiff = -4.58, SD = 1.22%, p = .019) quarters compared to the first quarter of the CISP; but there were no differences between temperature conditions. Congruent Stroop reaction time (RT) was quicker in the second quarter of exercise in the hot condition (M = 561.99, SD = 112.93 ms) compared to the control condition (M=617.80, SD = 139.71 ms; p = .022), but no differences were found for congruent Stroop accuracy nor vigilance measures. Additionally, peak power output was lower during the third quarter of the CISP in the hot condition (M = 861.31, SD = 105.20 W) compared to the control condition (M = 900.68, SD = 114.84 W; p < .001). Plasma normetanephrine and metanephrine concentrations increased from pre- to post-CISP (Mdiff = +616.90, SD = 306.99, p < .001; and Mdiff = +151.23, SD = 130.32, p = .002, respectively), with a marginal interaction suggesting a higher normetanephrine increase from pre- to post-CISP in the hot versus the control condition (p = .070). Our findings suggest that accuracy for more complex decisions suffered during prolonged high-intensity intermittent exercise, perhaps due to exercise-induced catecholamine increases. Athletes may have also reduced physical effort under increased heat exposure, indicating how cognitive performance may be sustained in physically demanding environments.

Successful Pacing Profiles of Olympic Men and Women 3,000 m Steeplechasers.

The presence of barriers in the steeplechase increases energy cost and makes successful pacing more difficult. This was the first study to analyze pacing profiles of successful (qualifiers for the final/Top 8 finalists) and unsuccessful (non-qualifiers/non-Top 8 finalists) Olympic steeplechasers across heats and finals, and to analyze differences between race sections (e.g., water jump vs. home straight). Finishing and section splits were collected for 77 men and 84 women competing at the 2008 and 2016 Olympic Games. Competitors were divided into groups based on finishing position (in both rounds analyzed). After a quick opening 228 m (no barriers), men who qualified for the final or finished in the Top 8 in the final had even paces for the first half with successive increases in speed in the last three laps; unsuccessful pacing profiles were more even. Successful women had mostly even paces for the whole race, and less successful athletes slowed after Lap 2. Women started the race relatively quicker than men, resulting in slower second half speeds. The best men completed most race sections at the same speed, but less successful men were slower during the water jump section, suggesting less technically proficiency. Similarly, women were slower during this section, possibly because its landing dimensions are the same as for men and have a greater effect on running speed. Coaches should note the different pacing profiles adopted by successful men and women steeplechasers, and the importance of technical hurdling skills at the water jump.

IL-10 and IL-17 expression by CD4+ T cells is altered in corticosteroid refractory immune thrombocytopenia (ITP).

BACKGROUND: Corticosteroids remain the first-line treatment for patients with immune thrombocytopenia (ITP). However, 20% to 30% of patients do not respond to treatment at tolerable doses. This variation in corticosteroid efficacy is replicated in other autoimmune diseases and may have an adaptive immune basis. OBJECTIVE: To test the hypothesis that CD4+ T-cell responses to corticosteroids are different in patients with clinically defined corticosteroid refractory ITP. METHODS: In this prospective cohort study, CD4+ T cells from patients with ITP were cultured in the presence or absence of dexamethasone (Dex). Intracellular cytokine expression was then quantified by flow cytometry and compared with patients' clinical response to corticosteroid treatment. A control cohort of patients with autoimmune uveitis was also studied to evaluate whether our findings were limited to ITP or are potentially generalizable across autoimmune diseases. RESULTS: The ratio of interleukin (IL)-10 to IL-17 expression following CD4+ T cell culture with Dex was able to discriminate between ITP patients with a clinically defined complete (n = 33), partial (n = 12) or nonresponse (n = 11) to corticosteroid treatment (P = .002). These findings were replicated in patients with autoimmune uveitis (complete response n = 14, nonresponse n = 22; P = .01). CONCLUSIONS: There is a relative abrogation of IL-10 and persistence of IL-17 expression in the CD4+ T cells of patients who clinically fail corticosteroid therapy. This observation has potential to inform both our mechanistic understanding of the action of corticosteroids in the treatment of ITP, and as a biomarker for steroid refractory disease, with potential application across a range of hematological and nonhematological conditions.

Intravenous indocyanine green dye is insufficient for robust immune cell labelling in the human retina.

It is not currently possible to reliably visualise and track immune cells in the human central nervous system or eye. Previous work demonstrated that indocyanine green (ICG) dye could label immune cells and be imaged after a delay during disease in the mouse retina. We report a pilot study investigating if ICG can similarly label immune cells within the human retina. Twelve adult participants receiving ICG angiography as part of routine standard of care were recruited. Baseline retinal images were obtained prior to ICG administration then repeated over a period ranging from 2 hours to 9 days. Matched peripheral blood samples were obtained to examine systemic immune cell labelling and activation from ICG by flow cytometry with human macrophage cultures as positive controls. Differences between the delayed near infrared ICG imaging and 488 nm autofluorescence was observed across pathologies, likely arising from the retinal pigment epithelium (RPE). Only one subject demonstrated ICG signal on peripheral blood myeloid cells and only three distinct cell-sized signals appeared over time within the retina of three participants. No significant increase in immune cell activation markers were detected after ICG administration. ICG accumulated in the endosomes of macrophage cultures and was detectable above a minimum concentration, suggesting cell labelling is possible. ICG can label RPE and may be used as an additional biomarker for RPE health across a range of retinal disorders. Standard clinical doses of intravenous ICG do not lead to robust immune cell labelling in human blood or retina and further optimisation in dose and route are required.

Intermediate Monocytes in Acute Alcoholic Hepatitis Are Functionally Activated and Induce IL-17 Expression in CD4+ T Cells.

In humans, the three main circulating monocyte subsets are defined by their relative cell surface expression of CD14 and CD16. They are all challenging to study because their characteristics are strongly context specific, and this has led to a range of conflicting reports about their function, which is especially so for CD14++CD16+ (intermediate) monocytes. Ex vivo cultures are also often confounded by the concomitant use of immunosuppressive drugs. We therefore sought to characterize the phenotype and function of intermediate monocytes in the setting of acute inflammation prior to treatment in a cohort of 41 patients with acute alcoholic hepatitis (AH). Circulating intermediate monocytes were enriched in patients with AH and had an activated phenotype with enhanced expression of CCR2 and CD206 compared with healthy controls. Proinflammatory cytokine expression, including IL-1ß and IL-23, was also higher than in healthy controls, but both classical (CD14++CD16-) and intermediate monocytes in AH were refractory to TLR stimulation. Compared with healthy controls, both AH monocyte subsets had greater phagocytic capacity, enhanced ability to drive memory T cell proliferation in coculture, and skewed CD4+ T cells to express an increased ratio of IL-17/IFN-γ. Furthermore, liver tissue from AH patients demonstrated an enrichment of monocytes including the intermediate subset compared with controls. These data demonstrate that intermediate monocytes are expanded, functionally activated, induce CD4+ T cell IL-17 expression, and are enriched in the liver of patients with AH.

Presence of Spotters Improves Bench Press Performance: A Deception Study.

Sheridan, A, Marchant, DC, Williams, EL, Jones, HS, Hewitt, PA, and Sparks, SA. Presence of spotters improves bench press performance: a deception study. J Strength Cond Res 33(7): 1755-1761, 2019-Resistance exercise is a widely used method of physical training in both recreational exercise and athletic populations. The use of training partners and spotters during resistance exercise is widespread, but little is known about the effect of the presence of these individuals on exercise performance. The purpose of the current study was to investigate the effect of spotter presence on bench press performance. Twelve recreationally trained participants (age, 21.3 ± 0.8 years, height, 1.82 ± 0.1 m, and mass, 84.8 ± 11.1 kg) performed 2 trials of 3 sets to failure at 60% of 1 repetition maximum on separate occasions. The 2 trials consisted of spotters being explicitly present or hidden from view (deception). During the trials, total repetitions (reps), total weight lifted, ratings of perceived exertion (RPE), and self-efficacy were measured. Total reps and weight lifted were significantly greater with spotters (difference = 4.5 reps, t = 5.68, p < 0.001 and difference = 209.6 kg, t = 5.65, p < 0.001, respectively). Although RPE and local RPE were significantly elevated in the deception trials (difference = 0.78, f = 6.16, p = 0.030 and difference = 0.81, f = 5.89, p = 0.034, respectively), self-efficacy was significantly reduced (difference = 1.58, f = 26.90, p < 0.001). This study demonstrates that resistance exercise is improved by the presence of spotters, which is facilitated by reduced RPE and increased self-efficacy. This has important implications for athletes and clients, who should perform resistance exercise in the proximity of others, to maximize total work performed.

Antibodies to Costimulatory Receptor 4-1BB Enhance Anti-tumor Immunity via T Regulatory Cell Depletion and Promotion of CD8 T Cell Effector Function.

The costimulatory receptor 4-1BB is expressed on activated immune cells, including activated T cells. Antibodies targeting 4-1BB enhance the proliferation and survival of antigen-stimulated T cells in vitro and promote CD8 T cell-dependent anti-tumor immunity in pre-clinical cancer models. We found that T regulatory (Treg) cells infiltrating human or murine tumors expressed high amounts of 4-1BB. Intra-tumoral Treg cells were preferentially depleted by anti-4-1BB mAbs in vivo. Anti-4-1BB mAbs also promoted effector T cell agonism to promote tumor rejection. These distinct mechanisms were competitive and dependent on antibody isotype and FcγR availability. Administration of anti-4-1BB IgG2a, which preferentially depletes Treg cells, followed by either agonistic anti-4-1BB IgG1 or anti-PD-1 mAb augmented anti-tumor responses in multiple solid tumor models. An antibody engineered to optimize both FcγR-dependent Treg cell depleting capacity and FcγR-independent agonism delivered enhanced anti-tumor therapy. These insights into the effector mechanisms of anti-4-1BB mAbs lay the groundwork for translation into the clinic.

Effects of Dietary Nitrate Supplementation on Physiological Responses, Cognitive Function, and Exercise Performance at Moderate and Very-High Simulated Altitude.

Purpose: Nitric oxide (NO) bioavailability is reduced during acute altitude exposure, contributing toward the decline in physiological and cognitive function in this environment. This study evaluated the effects of nitrate ([Formula: see text]) supplementation on NO bioavailability, physiological and cognitive function, and exercise performance at moderate and very-high simulated altitude. Methods:Ten males (mean (SD): [Formula: see text]: 60.9 (10.1) ml·kg-1·min-1) rested and performed exercise twice at moderate (~14.0% O2; ~3,000 m) and twice at very-high (~11.7% O2; ~4,300 m) simulated altitude. Participants ingested either 140 ml concentrated [Formula: see text]-rich (BRJ; ~12.5 mmol [Formula: see text]) or [Formula: see text]-deplete (PLA; 0.01 mmol [Formula: see text]) beetroot juice 2 h before each trial. Participants rested for 45 min in normobaric hypoxia prior to completing an exercise task. Exercise comprised a 45 min walk at 30% [Formula: see text] and a 3 km time-trial (TT), both conducted on a treadmill at a 10% gradient whilst carrying a 10 kg backpack to simulate altitude hiking. Plasma nitrite concentration ([[Formula: see text]]), peripheral oxygen saturation (SpO2), pulmonary oxygen uptake ([Formula: see text]), muscle and cerebral oxygenation, and cognitive function were measured throughout. Results: Pre-exercise plasma [[Formula: see text]] was significantly elevated in BRJ compared with PLA (p = 0.001). Pulmonary [Formula: see text] was reduced (p = 0.020), and SpO2 was elevated (p = 0.005) during steady-state exercise in BRJ compared with PLA, with similar effects at both altitudes. BRJ supplementation enhanced 3 km TT performance relative to PLA by 3.8% [1,653.9 (261.3) vs. 1718.7 (213.0) s] and 4.2% [1,809.8 (262.0) vs. 1,889.1 (203.9) s] at 3,000 and 4,300 m, respectively (p = 0.019). Oxygenation of the gastrocnemius was elevated during the TT consequent to BRJ (p = 0.011). The number of false alarms during the Rapid Visual Information Processing Task tended to be lower with BRJ compared with PLA prior to altitude exposure (p = 0.056). Performance in all other cognitive tasks did not differ significantly between BRJ and PLA at any measurement point (p ≥ 0.141). Conclusion: This study suggests that BRJ improves physiological function and exercise performance, but not cognitive function, at simulated moderate and very-high altitude.

Development and validation of a novel bioassay to determine glucocorticoid sensitivity.

BACKGROUND: Glucocorticoids (GCs) remain the first line treatment for almost all non-infectious inflammatory diseases, ranging from acute asthma to rheumatoid arthritis. However, across all conditions, patients have a variable response to GCs with approximately 30% being non-responders. This group of GC resistant patients is typically exposed to high-dose GCs and their side-effects before more appropriate immunotherapy is instituted. Hence, there is a pressing clinical need for a predictive biomarker of GC responsiveness. The availability of such a tool would also enable patient stratification for the conduct of smart clinical trials in GC resistance. Lymphocyte GC sensitivity has been shown to be closely associated with clinical GC sensitivity in a number of inflammatory diseases. However, the method for determining in vitro GC response is not standardized and requires the use of specialist equipment, including a radioisotope to quantify cellular proliferation, making it challenging to translate into clinical practice. RESULTS: Here we describe the optimization and validation of a novel non-radioactive in vitro bioassay based on measuring cellular proliferation by incorporation of bromodeoxyuridine (BrdU), termed the BrdU incorporation in lymphocyte steroid sensitivity assay (BLISS). In comparison to the current gold standard lymphocyte GC sensitivity assay in 101 healthy control samples, BLISS has an area under receiver operating characteristic of 0.82 and a sensitivity of 83% for correctly identifying GC resistant subjects. CONCLUSIONS: The performance of the novel BLISS bioassay makes it a strong candidate biomarker for clinical application. It now requires validation in a prospective patient cohort.

Deceptive Manipulation of Competitive Starting Strategies Influences Subsequent Pacing, Physiological Status, and Perceptual Responses during Cycling Time Trials.

Little is currently known regarding competitor influence on pacing at the start of an event and in particular the subsequent effect on the remaining distance. The purpose of the present study was to investigate the influence of starting pace on the physiological and psychological responses during cycling time trials (TT) utilizing an innovative approach allowing pace to be accurately and dynamically replicated, as well as deceptively manipulated. Ten competitive male cyclists completed five 16.1 km TT, two baseline trials performed alone (BLs), and three with a simulated, dynamic avatar of which they were to match the pace of for the initial 4 km. The avatar represented either the cyclist's fastest BL performance (NORM), 105% (FAST), or 95% (SLOW), of fastest BL performance (FBL). Physiological and psychological responses were measured every quartile of the TT. Despite manipulating a starting speed of ± 5% of fastest previous performance, there was no effect on overall 16.1 km TT performance. Manipulated starting strategies did however evoke different physiological and perceptual responses. Whole trial differences found that SLOW produced lower HR, VO2, BLa and RPE than FBL (p ≤ 0.03) and higher SE than FAST (p ≤ 0.03). Additionally, FAST had greater internal attention than NORM (p < 0.04). Over time all psychological and physiological variables had a significant condition × quartile interaction in the initial or second quartile mediated by the prescribed starting strategies. Furthermore, RPE, affect, and internal attention remained elevated throughout FAST despite an attenuation in pace during self-selection of pace. There were no differences in performance time when manipulating a 16.1 km cycling TT starting strategy. A slow start, encouraged greater positive perceptions, and less negative physiological consequences than a faster start, and produces no impairment to performance time. It would therefore be considered an advantage in a non-drafting event, not to follow pace of fellow, superior competitors at the start of an event but perform a more negative pacing strategy, with the potential for a greater speed increase against opponents in the latter stages.

Improvements in Cycling Time Trial Performance Are Not Sustained Following the Acute Provision of Challenging and Deceptive Feedback.

The provision of performance-related feedback during exercise is acknowledged as an influential external cue used to inform pacing decisions. The provision of this feedback in a challenging or deceptive context allows research to explore how feedback can be used to improve performance and influence perceptual responses. However, the effects of deception on both acute and residual responses have yet to be explored, despite potential application for performance enhancement. Therefore, this study investigated the effects of challenging and deceptive feedback on perceptual responses and performance in self-paced cycling time trials (TT) and explored whether changes in performance are sustained in a subsequent TT following the disclosure of the deception. Seventeen trained male cyclists were assigned to either an accurate or deceptive feedback group and performed four 16.1 km cycling TTs; (1 and 2) ride-alone baseline TTs where a fastest baseline (FBL) performance was identified, (3) a TT against a virtual avatar representing 102% of their FBL performance (PACER), and (4) a subsequent ride-alone TT (SUB). The deception group, however, were initially informed that the avatar accurately represented their FBL, but prior to SUB were correctly informed of the nature of the avatar. Affect, self-efficacy and RPE were measured every quartile. Both groups performed PACER faster than FBL and SUB (p < 0.05) and experienced lower affect (p = 0.016), lower self-efficacy (p = 0.011), and higher RPE (p < 0.001) in PACER than FBL. No significant differences were found between FBL and SUB for any variable. The presence of the pacer rather than the manipulation of performance beliefs acutely facilitates TT performance and perceptual responses. Revealing that athletes' performance beliefs were falsely negative due to deceptive feedback provision has no effect on subsequent perceptions or performance. A single experiential exposure may not be sufficient to produce meaningful changes in the performance beliefs of trained individuals beyond the acute setting.

Ingestion of a Nitric Oxide Enhancing Supplement Improves Resistance Exercise Performance.

Mosher, SL, Sparks, SA, Williams, EL, Bentley, DJ, and Mc Naughton, LR. Ingestion of a nitric oxide enhancing supplement improves resistance exercise performance. J Strength Cond Res 30 (12): 3520-3524, 2016-Studies have established that supplementation of nitrate increases nitric oxide which in turn improves exercise performance. The current study aimed to investigate the effects of nitrate ingestion on performance of bench press resistance exercise until failure. Twelve recreationally active (age, 21 ± 2 years, height, 177.2 ± 4.0 cm, weight, 82.49 ± 9.78 kg) resistance-trained men participated in the study. The study used a double-blind, randomized cross-over design, where participants ingested either 70 ml of "BEET It Sport" nitrate shot containing 6.4 millimoles (mmol·L) or 400 mg of nitrate or a blackcurrant placebo drink. Participants completed a resistance exercise session, consisting of bench press exercise at an intensity of 60% of their established 1 repetition maximum (1RM), for 3 sets until failure with 2 minutes rest interval between sets. The repetitions completed, total weight lifted, local and general rate of perceived exertion (RPE), and blood lactate were all measured. The results showed a significant difference in repetitions to failure (p ≤ 0.001) and total weight lifted (p ≤ 0.001). However, there were no significant difference between blood lactate over the 2 trials (p = 0.238), and no difference in Local (p = 0.807) or general (p = 0.420) indicators of fatigue as measured by RPE. This study demonstrates that nitrate supplementation has the potential to improve resistance training performance and work output compared with a placebo.