Altered erythroid-related miRNA levels as a possible novel biomarker for detection of autologous blood transfusion misuse in sport.

BACKGROUND: Autologous blood transfusion (ABT) is a performance-enhancing method prohibited in sport; its detection is a key issue in the field of anti-doping. Among novel markers enabling ABT detection, microRNAs (miRNAs) might be considered a promising analytical tool. STUDY DESIGN AND METHODS: We studied the changes of erythroid-related microRNAs following ABT, to identify novel biomarkers. Fifteen healthy trained males were studied from a population of 24 subjects, enrolled and randomized into a Transfusion (T) and a Control (C) group. Seriated blood samples were obtained in the T group before and after the two ABT procedures (withdrawal, with blood refrigerated or cryopreserved, and reinfusion), and in the C group at the same time points. Traditional hematological parameters were assessed. Samples were tested by microarray analysis of a pre-identified set of erythroid-related miRNAs. RESULTS: Hematological parameters showed moderate changes only in the T group, particularly following blood withdrawal. Among erythroid-related miRNAs tested, following ABT a pool of 7 miRNAs associated with fetal hemoglobin and regulating transcriptional repressors of gamma-globin gene was found stable in C and differently expressed in three out of six T subjects in the completed phase of ABT, independently from blood conservation. Particularly, two or more erythropoiesis-related miRNAs within the shortlist constituted of miR-126-3p, miR-144-3p, miR-191-3p, miR-197-3p, miR-486-3p, miR-486-5p, and miR-92a-3p were significantly upregulated in T subjects after reinfusion, with a person-to-person variability but with congruent changes. CONCLUSIONS: This study describes a signature of potential interest for ABT detection in sports, based on the analysis of miRNAs associated with erythroid features.

Changes in hemoglobin profile reflect autologous blood transfusion misuse in sports.

The changes in hemoglobin (Hb) profile following autologous blood transfusion (ABT) for the first time were studied for anti-doping purposes. Twenty-four healthy, trained male subjects (aged 18‒40) were enrolled and randomized into either the transfusion (T) or control (C) groups. Blood samples were taken from the T subjects at baseline, after withdrawal and reinfusion of 450 ml of refrigerated or cryopreserved blood, and from C subjects at the same time points. Hematological variables (Complete blood count, Reticulocytes, Immature Reticulocytes Fraction, Red-cell Distribution Width, OFF-hr score) were measured. The Hb types were analyzed by high-performance liquid chromatography and the Hemoglobin Profile Index (HbPI) arbitrarily calculated. Between-group differences were observed for red blood cells and reticulocytes. Unlike C, the T group, after withdrawal and reinfusion, showed a significant trend analysis for both hematological variables (Hemoglobin concentration, reticulocytes, OFF-hr score) and Hb types (glycated hemoglobin-HbA1c, HbPI). The control charts highlighted samples with abnormal values (> 3-SD above/below the population mean) after reinfusion for hematological variables in one subject versus five subjects for HbA1c and HbPI. A significant ROC-curve analysis (area = 0.649, p = 0.015) identified a HbA1c cut-off value ≤ 2.7% associated to 100% specificity of blood reinfusion (sensitivity 25%). Hemoglobin profile changed in trained subjects after ABT, with abnormal values of HbA1c and HbPI in 42% of subjects after reinfusion. Future studies will confirm the usefulness of these biomarkers in the anti-doping field.

Effects of low-intensity endurance and resistance training on mobility in chronic stroke survivors: a pilot randomized controlled study.

BACKGROUND: Chronic stroke survivors are exposed to long-term disability and physical deconditioning, effects that may impact their independence and quality of life. Community-based programs optimizing the dose of exercise therapy that are simultaneously low risk and able to achieve high adherence should be identified. AIM: We tested the hypothesis that an 8-week, community-based, progressive mixed endurance-resistance exercise program at lower cardiovascular and muscular load yielded more mobility benefits than a higher-intensity program in chronic stroke survivors. DESIGN: A two-arm, parallel-group, pilot randomized, controlled clinical trial. SETTING: Hospital (recruitment); community-based adapted physical activity center (training). POPULATION: Thirty-five chronic stroke patients (mean age: 68.4±10.4 years; 27 males). METHODS: Participants were randomized to a low-intensity experimental (LI-E; N.=18) or a high-intensity active control group (HI-C; N.=17). Patients in the LI-E group performed over-ground intermittent walking (weeks 1-8) and muscle power training with portable tools (weeks 5-8); patients in the HI-C group executed treadmill walking (weeks 1-8) and strength training with gym machines (weeks 5-8). Changes in mobility, assessed using the 6-Minute Walking Distance test, were the primary outcome. Secondary outcomes included quality of life (Short-Form-36 Questionnaire), gait speed (10-Meter Walking Test), balance (Berg Balance Scale) and muscle performance of the lower limbs (strength and power of the quadriceps and femoral biceps). RESULTS: After 8 weeks, the 6MWD revealed more improvement for the LI-E group than the HI-C group (P=0.009). The SF36 physical activity domain (P=0.012) and peak power of the femoral quadriceps and biceps were also significantly improved for the LI-E group (P=0.008 and P<0.001, respectively) compared with the HI-C. Gait speed, balance and lower-limb strength increased in both groups; no significant differences were noted. The muscle power of the affected limb was the muscle parameter most correlated with mobility in the entire population. CONCLUSIONS: A low-intensity exercise program exhibited better results in terms of mobility, quality of life and muscle power compared with a higher-intensity program. Data need to be confirmed in a larger trial. CLINICAL REHABILITATION IMPACT: The effectiveness, low-intensity and possible implementation in poorly equipped community-based settings make the LI-E program potentially suitable for stroke survivors and frail individuals.

Planning the International Competition Schedules for the Health of Elite Athletes: A 21-Year Retrospective Study Evaluating the Effectiveness and Economic Impact in an Olympic Sport.

BACKGROUND: The increased number of trips and competitions scheduled in the international agonistic calendars meets commercial demands while acting as a source of stress for the athletes. A model, developed in biathlons to monitor the so-called competition load, revealed an upward trend over time. The aim of this study was to evaluate, in a 21-year period, the effects of the International Biathlon Union's rescheduling of the competitive calendars to control the competition load, as well as its stability over time and the economic impact of this intervention. METHODS: For each season competition, the load factors from the international agonistic calendar (number of venues/events, competition days/distance) were considered, and the athletes' daily and maximal stress scores were calculated. The calendar rescheduling, which started in 2001, involved the length of competitions, number of resting days and frequency of travels. Data from the period pre (1994-2000) and post (2001-2007) the intervention, as well as follow-up (2008-2015), were compared and analyzed in relation to the federation's budget. RESULTS: The competition load and athletes' daily stress score progressively increased pre, plateaued post and remained stable in follow-up. Their annual variations within the final two periods were significantly lower than in the pre period, in spite of the higher average values. The maximal stress score decreased over time. The direct correlation between most of the competition load factors with the economic budget present in pre was lost in post and follow-up. Similarly, the athletes' daily stress score had a stable trend in post and follow-up, while budget continued to increase. CONCLUSIONS: The management of an athlete's potential source of stress by an international federation stabilized the competition load over time, but it did not affect the budget. Furthermore, it uncoupled the relationship between the athlete's effort and federation income.

Reliability of the vascular claudication reporting in diabetic patients with peripheral arterial disease: a study with near-infrared spectroscopy.

We evaluated whether altered reporting of ischemic symptoms occurs in diabetic patients with peripheral arterial disease (PAD) and stable claudication. Patients (n = 152) with claudication were enrolled (120 males; mean age: 71.0 ± 8.6 years): 74 with diabetes (DM-PAD) and 78 without (DMfree-PAD). The degree of muscle oxygenation at symptom onset and maximal speed (Smax) during an incremental treadmill test was recorded at the gastrocnemius by near-infrared spectroscopy (NIRS) and quantified by area under the curve of oxygenated hemoglobin (AUC-Hbo 2) and area under the curve of differential hemoglobin (AUC-dHb). The DM-PAD and DMfree-PAD showed similar exercise capacities inversely correlated with the degree of muscle oxygenation but significantly lower values of AUC-Hbo 2 and AUC-dHb for DM-PAD at symptom onset and Smax (-356 vs -122 and -1200 vs -359, P < .0001). During a NIRS-assisted test, the report of claudication in the presence of diabetes was delayed, occurring at a lower degree of oxygenation than in patients with PAD only, with potential implications for testing, functional staging, and balance disorders.