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In the sports domain, cannabis is prohibited by the World Anti-Doping Agency (WADA) across all sports in competition since 2004. The few studies on physical exercise and cannabis focused on the main compound i.e. Δ9-tetrahydrocannabinol. Cannabidiol (CBD) is another well-known phytocannabinoid present in dried or heated preparations of cannabis. Unlike Δ9-tetrahydrocannabinol, CBD is non-intoxicating but exhibits pharmacological properties that are interesting for medical use. The worldwide regulatory status of CBD is complex and this compound is still a controlled substance in many countries. Interestingly, however, the World Anti-Doping Agency removed CBD from the list of prohibited substances - in or out of competition - since 2018. This recent decision by the WADA leaves the door open for CBD use by athletes. In the present opinion article we wish to expose the different CBD properties discovered in preclinical studies that could be further tested in the sport domain to ascertain its utility. Preclinical studies suggest that CBD could be useful to athletes due to its anti-inflammatory, analgesic, anxiolytic, neuroprotective properties and its influence on the sleep-wake cycle. Unfortunately, almost no clinical data are available on CBD in the context of exercise, which makes its use in this context still premature., Competing Interests: Declaration of Competing Interest V. Di Marzo receives research grants from GW Pharmaceuticals, UK. The remaining authors have no conflicts of interests to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patients with typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history. The 2-year overall survival was 90%, but was 95% for those who were infection-free at HCT vs 81% for those with active infection ( P = .009). Other factors, including the diagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, use of preparative chemotherapy, or the type of donor used, did not impact survival. Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day +100 post-HCT revealed that CD3 < 300 cells/μL, CD8 < 50 cells/μL, CD45RA < 10%, or a restricted Vβ T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free. The trial was registered at www.clinicaltrials.gov as #NCT01186913.

Background: Recent randomized controlled trials have suggested that dietary nitrate (NO3(-)), found in beetroot and other vegetables, and inorganic NO3(-) salts decrease metabolic rate under resting and exercise conditions., Objective: Our aim was therefore to determine from a systematic review and meta-analysis whether dietary NO3(-) supplementation significantly reduces metabolic rate, expressed as oxygen uptake (VO2), under resting and exercise conditions in healthy humans and those with cardiorespiratory diseases., Design: A systematic article search was performed on electronic databases (PubMed, Scopus and Web of Science) from February to March 2015. The inclusion criteria included 1) randomized controlled trials; 2) studies reporting the effect of NO3(-) on VO2 under resting and/or exercise conditions; 3) comparison between dietary NO3(-) supplementation and placebo. Random-effects models were used to calculate the pooled effect size., Results: Twenty nine randomized placebo-controlled trials were included in the systematic review, and 26 of which were included in the meta-analysis. Dietary NO3(-) supplementation significantly decreases VO2 during submaximal intensity exercise [-0.26 (95% IC: -0.38, -0.15), p < 0.01], but not in the sub-analysis of subjects with chronic diseases [-0.09 (95% IC: -0.50, 0.32), p = 0.67]. When data were separately analyzed by submaximal intensity domains, NO3(-) supplementation reduces VO2 during moderate [-0.29 (95% IC: -0.48,-0.10), p < 0.01] and heavy [-0.33 (95% IC: -0.54,-0.12), p < 0.01] intensity exercise. When the studies with the largest effects were excluded from the meta-analysis, there is a trend for a VO2 decrease under resting condition in dietary NO3(-) supplementation [-0.28 (95% IC: -0.62, 0.05), p = 0.10]., Conclusion: Dietary NO3(-) supplementation decreases VO2 during exercise performed in the moderate and heavy intensity domains in healthy subjects. The present meta-analysis did not show any significant effect of dietary NO3(-) supplementation on metabolic rate in subjects with chronic diseases, despite enhanced exercise tolerance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Dietary nitrate (NO3(-)) supplementation has been shown to increase exercise tolerance and improve oxidative efficiency during aerobic exercise in healthy subjects. We tested the hypothesis that a 3-day supplementation in beetroot juice (BJ) rich in NO3(-) would improve the tolerance to supramaximal intensity intermittent exercise consisting of 15-s exercise periods at 170% of the maximal aerobic power interspersed with 30-s passive recovery periods. The number of repetitions completed before reaching volitional exhaustion was significantly higher in the BJ than in the placebo condition (26.1 ± 10.7 versus 21.8 ± 8.0 respectively, P < 0.05). In contrast to previous findings during exercise performed at intensity below the peak oxygen uptake (VO2peak), oxygen uptake (VO2) was unaffected (BJ: 2735 ± 345 mL kg(-1) min(-1) vs. placebo: 2787 ± 346 mL kg(-1) min(-1), NS). However, the Area Under the Curve for microvascular total hemoglobin (AUC-THb) in the vastus lateralis muscle assessed by near infrared spectroscopy during 3 time-matched repetitions was significantly increased with NO3(-) supplementation (BJ: 9662 ± 1228 a.u. vs. placebo:8178 ± 1589 a.u.; P < 0.05). Thus, increased NO3(-) (BJ: 421.5 ± 107.4 μM vs placebo:39.4 ± 18.0 μM) and NO2(-) (BJ: 441 ± 184 nM vs placebo: 212 ± 119 nM) plasma levels (P < 0.001 for both) are associated with improved muscle microvascular Red Blood Cell (RBC) concentration and O2 delivery during intense exercise, despite no effect on resting femoral artery blood flow, and vascular conductance. Maximal voluntary force during an isometric leg extensor exercise, and blood lactate levels were also unaffected by NO3(-) supplementation. To conclude, dietary NO3(-) supplementation enhances tolerance to exercise at supramaximal intensity, with increased microvascular total RBC concentration in the working muscle, in the absence of effect on contractile function and resting hemodynamic parameters., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Numerous chronic graft-versus-host disease (cGVHD) biomarkers have been identified in limited, single-institution studies without validation. We hypothesized that plasma-derived biomarkers could diagnose, classify, and evaluate response in children with cGVHD. We performed a concomitant analysis of a number of known and predicted peripheral blood cGVHD biomarkers from a Children's Oncology Group (COG) phase 3 cGVHD therapeutic trial. A total of 52 newly diagnosed patients with extensive cGVHD were compared for time of onset after blood and marrow transplantation (BMT) (early, 3-8 months; late, > or = 9 months) with 28 time-matched controls with no cGVHD (early, 6 months after BMT; late, 12 months after BMT). Soluble B-cell activation factor (sBAFF), anti-dsDNA antibody, soluble IL-2 receptor alpha (sIL-2Ralpha), and soluble CD13 (sCD13) were elevated in patients with early-onset cGVHD compared with controls. sBAFF and anti-dsDNA were elevated in patients with late-onset cGVHD. Some of the biomarkers correlated with specific organ involvement and with therapeutic response. These 4 biomarkers had high specificity with higher sensitivity in combination. Changes in biomarker concentrations with immune reconstitution after transplantation significantly affected interpretation of results. The identified biomarkers have the potential for improved classification, early response evaluation, and direction of cGVHD treatment, but require validation in larger studies. This study is registered at www.cancer.gov/clinicaltrials as no. COG-ASCT0031.

Porcine plasma is a by-product of the meat industry that can be used as a food ingredient. It is a protein mixture, hence its composition can be modified to meet specific functionality requirements. In the present paper, the gelation properties of plasma and its two major fractions (serum and albumin) have been studied at pH 4.5, 6.0 and 7.5. Polyacrylamide gel electrophoresis (SDS-PAGE) revealed that albumin was the constituent that remained soluble to a larger extent during heat-treatments, and that acidic coagulation occurred at pH 4.5, making weak interactions the predominating ones between protein aggregates. Differential scanning calorimetry (DSC) and rheological tests showed that both the thermal stability and the gelation point of protein solutions were lower as pH decreased. The textural properties and water-holding capacities of plasma and albumin gels were more pH-dependent than serum. Albumin gels were the weakest and those of plasma at pH 7.5, the strongest. It has been determined that interactions between protein fractions play a key role in the gelling properties due to synergistic effects. This knowledge should be useful in the engineering of a plasma derivative product designed for specific food requirements, by reformulating its natural composition and enhanced by controlling pH.

Gelatin gel properties have been studied using three techniques. Optical rotation measurements have shown that the lower the ageing temperature, the faster the helix content increases but the lower the helix stability. Rheological measurements show that a small increase in temperature leads to a melting of some junction zones followed by a build up of new ones. By ageing the gel at two successive temperatures one can show the existence of two populations of junction zones with different thermal stabilities. The same result is shown on melting thermograms obtained by differential scanning calorimetry. All these results are consistent with the hypothesis of the presence of junction zones of various lengths, the thermostability of which being proportional to their lengths.