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Purpose: Wheelchair users and people with disabilities have limited access to physical exercise due to various factors, including medical follow-up and training facilities. Although tele-exercise guided by experts has become a viable option, there is limited knowledge about the acute performance decrement (APD) resulting from remote training methods. The current cross-sectional study aimed to: (1) assess the APD of muscle resistance strength after three synchronous tele-exercise training methods in wheelchair users and (2) compare the training loads associated with each training method., Materials and Methods: Eighteen male and female wheelchair users who participated in tele-exercise strength practices were recruited. The participants performed a maximum resistance strength test by synchronous tele-assessment (push-up test, PUT) at baseline and immediately after three training methods: high-intensity interval training (HIIT), moderate-intensity continuous training (MICT) and sprint interval training (SIT). The primary outcome was the APD, which was measured by the percentage decrease in the number of repetitions of the PUT immediately after the training methods., Results: APD was observed for all three training methods, with no significant differences between them (-34.8%, -29.9% and -38.0% for MICT, SIT and HII, respectively), and presented a non-significant correlation with the training loads. HIIT had a significantly higher training load than MICT and SIT., Conclusions: APD occurred in all training sessions, but did not correlate with training load, indicating that it is not an appropriate metric for comparison. Findings provide insight into APD response and highlight the need to consider multiple metrics when comparing training protocols.

Objective: The first objective is to examine the age-related trajectory of competitive performance and the age at peak competitive performance in wheelchair rugby players at the Paralympic Games. Another objective is to verify age correlations with performance over the years for each class., Design: This is a retrospective cohort study., Results: Data were collected from the official results books of the Paralympic games. The mean age (SD) of the 267 players and 448 analyzed data from all Paralympic games (from Sidney 2004 to Tokyo 2020) across all classes was 32.8 (6.4) yrs, and the age at peak competitive performance was 30.6 (7.4) yrs. Each class had no statistical difference in age at peak competitive performance. In addition, there was no significant correlation between age and performance within classes or across all Paralympic games., Conclusions: The findings indicate that wheelchair rugby players' age at peak competitive performance is 30.6 yrs, which remains consistent across all classes. There is no statistical correlation between age and performance in wheelchair rugby. These findings significantly affect effective talent identification and athlete development programs. This impact ensures that athletes receive the necessary support to reach their maximum potential while avoiding the pitfalls of underestimating or overestimating their stages of development., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Improvements in race times for male and female Para canoe athletes across different sports classes have led to a reduction in relative differences between classes over time. However, there is a lack of research examining the comparative developmental trajectories between high-performance Paralympic (PCS) and Olympic (OCS) canoe sprint. In this study, we compared the developmental trajectories of 200-meter kayak performances among PCS and OCS athletes. In total, we analyzed 628 race results obtained from public online databases, for nine competitions between 2015 and 2023. Race times were reduced over the years except in specific sports classes (KL3-M, K1-M, and K1-F; KL: Kayak Level, M: male, F: female), with a poor positive correlation (r = 0.17 to 0.33) between time and the years. For the remaining sports classes, these correlations ranged from poor to fair (r = -0.58 to -0.13). OCS K1 athletes outperformed their Paralympic counterparts. Among Paralympic classes, KL1 had slower times than KL2 and KL3 ( p ≤ .05), with KL2 times significantly lower than KL3 in the female category. OCS athletes exhibited less variability in race times compared to PCS athletes. In the male category, there were no significant differences in the coefficients of variation (CV) and amplitude of race times between sport classes, except for KL1-M, which had a larger CV than K1 ( p ≤ .05). In the female category, the CV and amplitude of race times were significantly higher in KL1-F compared to KL3-F and K1-F. OCS times remained stable from 2015, with KL3-M following a similar trend. PCS displayed greater race time variability, particularly in higher impairment classes, notably KL1. This underscores the existence of distinct developmental stages within the canoe sprint modality, particularly emphasizing the early developmental phase of KL1. It also provides valuable insights for coaches and sports selection, especially concerning athletes with more severe impairments, including those in Rehabilitation Centers and during athlete recruitment., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

Objective: The aim of the study is to verify the performance trajectory related to age, classification (KL: kayak level; M: male; F: female), and sex of elite kayak Para canoe athletes., Design: This is a retrospective cohort study., Results: Race results and athletes' data were retrieved from publicly available online databases for 17 competitions and 102 finals between 2015 and 2022. Race time reduced over the years except for KL3-M class. There was a reduction in the relative difference between KL2-M and KL3-M over the years ( r = -0.83, 95% confidence interval = -0.34 to -0.97, P ≤ 0.05). In addition, no significant differences were found in race times relative differences between KL2-F and KL3-F over the years. Although the correlation between age and performance was only found to be statistically significant in the KL3-F class, the ages of all classes (35.2, 32.6, 29.5, 34.6, 37.6, and 30.6 yrs for males and females KL1, KL2, and KL3, respectively) were higher than those in Olympic canoeing (27.8 yrs)., Conclusions: Race times have improved overall since 2015, but not for the KL3-M class. Nevertheless, because of the stochastic ages of the finalist athletes, it was not possible to determine the age at which peak performance is achieved in all classes. Kayak Para canoe classes should be monitored in the coming years to determine whether interventions are necessary to improve differentiation., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Mean propulsive velocity (MPV) has been associated with neuromuscular fatigue; however, its suitability for strength training in Paralympic powerlifting (PP) remains uncertain. The objective of this work was to evaluate the MPV in two training methods (traditional-TRAD and eccentric-ECC). Eleven PP athletes were evaluated pre, during the intervention and post intervention at a load of 80% of the 1RM for TRAD and 110%-80% of 1 RM for ECC. The results demonstrated that there was no significant neuromuscular fatigue for the TRAD (~5% performance loss), as well as no significant decline in MPV during the intervention. For the ECC, there is a significant reduction in MPV before and after training (~12% loss of performance). A difference between TRAD and ECC after the intervention was also identified (0.87 m/s±0.22, 95% CI 0.72-1.02 vs. 0.72±0.20, 95% CI 0.59-0.86 p=0.042, F(3.30)=10.190, η2p=0.505 - very high effect). During the intervention for ECC, no significant decline in MPV was observed. The results of this study suggest that the mechanical indices of MPV do not seem to be effective indicators of neuromuscular fatigue in the sample studied or in the context of this specific training regime, being more indicated as a control of training volume., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Two valid tests have been used in patients with post-COVID-19 syndrome (coronavirus disease 2019) due to their fast application, feasibility, and accessible procedures, facilitating data collection in large groups: the 1-minute sit-to-stand test (STS) and handgrip strength (HGS) dynamometry. The present study aimed to: i) assess the STS and HGS in men and women with post-COVID-19 syndrome who did not require invasive ventilator support; ii) correlate STS repetitions and HGS with time since the COVID-19 diagnosis. Six hundred and twenty-two men and women with post-COVID-19 syndrome who did not require invasive ventilatory support performed the STS and HGS tests at the beginning of the rehabilitation process at a Reference Hospital Centre. Women over 55 years presented significantly lower results compared to participants under 55 years. For the HGS, the median ranged from 42 to 48 kg and 70 to 81 kg for the female and male groups, respectively. The correlations of time since COVID-19 diagnosis with STS and HGS ranged from -0.16 to 0.02 (p>0.05) for women and men, respectively.The test results could be used for the initial analysis of normality ranges and comparisons with other populations. Although STS repetitions and HGS presented low and non-significant correlations with time since the COVID-19 diagnosis, some COVID-19 sequelae were not measured, so these data should be interpreted with caution.

Introduction: Tele-exercise, defined as an intervention that offers physical training provided remotely, represents an alternative for remote care during social isolation and the absence of in-person interventions, considering the difficulties of regular exercise engagement in tetraplegia. The current study aimed to examine whether tele-exercise training in individuals with tetraplegia meets the recommendations proposed by the spinal cord injury (SCI)-specific guidelines, and the adherence., Methods: Twenty SCI tetraplegia performed tele-exercise training. The weekly training load of the tele-exercise training during the 27 weeks was compared to the estimated training load of SCI-specific guidelines: TW vigorous guideline: vigorous intensity of guideline proposed for Tweedy et al.; MG vigorous guideline: vigorous intensity of guideline proposed for Martin Ginis et al.; MG moderate guideline: moderate intensity of guideline proposed for Martin Ginis et al. Adherence was obtained weekly during 27 weeks., Results: The tele-exercise training load was 22.0% higher than the MG moderate guideline and 21.6% and 47.7% lower than the MG vigorous and TW vigorous guidelines, respectively. The tele-exercise training loads for men and women were, respectively, 2.3% and 35.0% higher than the MG moderate guideline; 34.0% and 13.2% lower than the MG vigorous guideline; and 56.1% and 42.1% lower than the TW vigorous guideline. Adherence was 45.1%., Conclusion: The tele-exercise training in men and women with tetraplegia for 7 months met the moderate intensity of recommendation proposed by one SCI exercise guideline. The adherence was 45.1%, with higher values for men compared to women. This finding shows that tele-exercise training may be an alternative exercise training intervention for tetraplegia and prompts reflexion on the inclusion of tele-exercise training in SCI exercise guidelines.

Context: One of the primary training variables, although often overlooked, is recovery level achieved before starting subsequent training sessions. To find a more practical measurement that is consonant with the daily training routine, the Perceived Recovery Status (PRS) scale is proposed. In this perspective, the present study aimed to translate and culturally adapt the PRS scale into Brazilian Portuguese., Design: This was a clinical measurement., Methods: The cross-cultural translation was performed according to guidelines. Linguistic validation consisted of 5 stages: forward translation, translation synthesis, back translation, analysis of inconsistencies, and cognitive debriefing., Results: During forward translation, different interpretations were obtained from the 2 translators (versions V1 and V2). Supported by an expert committee, a combined version (V3) was obtained from V1 and V2. During back translation, different interpretations were obtained from the 2 translators (versions V4 and V5). Discrepancies, applicability, and cultural equivalence were documented and analyzed by the expert committee participating in the cross-cultural translation procedure. During the cognitive debriefing, a group of 5 Brazilian people from the general population were asked to participate in a cognitive debriefing to assess the comprehensibility of the translated items., Conclusions: The PRS was translated and culturally adapted to Brazilian Portuguese (PRS-Brasil).

Abstract: Neto, FR, Dorneles, JR, Luna, RM, Spina, MA, Gonçalves, CW, and Gomes Costa, RR. Performance differences between the arched and flat bench press in beginner and experienced Paralympic powerlifters. J Strength Cond Res 36(7): 1936-1943, 2022-The present study aimed to verify the differences of the total load, trajectory of the barbell in the sagittal plane, and mean velocity of the barbell between the arched and flat techniques of the bench press in beginner (BG) and experienced (EG) Paralympic powerlifters. Twenty beginners (age: 34.4 years; experience: 3.3 months) and 23 experienced (age: 35.5 years; experience: 9.8 months) Paralympic powerlifters were selected from a Rehabilitation Hospital Network and a Paralympic sports center. Subjects were assessed in the one-maximum repetition test of the bench press exercise using the flat and arched bench press techniques (48-72-hour interval between sessions). Maximum strength, trajectory of the barbell in the sagittal plane, and mean velocity of the barbell were measured to compare the techniques and the groups. The total load corrected with the Haleczko formula was significantly higher in EG compared with BG (∆ = 21.1%; effect sizes [ES] = 0.39, p ≤ 0.05). There were no significant differences for all analyzed outcomes comparing the arched and flat techniques. During the eccentric phase of the bench press, all assessed differences ranged from -16.6 to 23.1% and presented ES of trivial to moderate. On the concentric phase, the assessed differences ranged from -20.7 to 13.9% and presented ES of trivial to moderate. The total load, trajectory of the barbell in the sagittal plane, and mean velocity of the barbell were not significantly different between the arched and flat techniques for experienced and beginner powerlifting athletes during both the eccentric and concentric phase of the movement. However, further analyses are essential to determine the best technique for athletes., (Copyright © 2020 National Strength and Conditioning Association.)

Context: Paracanoeing is one of the adapted sports eligible for different motor impairments. The acute:chronic workload ratio (ACWR) is an index between acute and chronic training workload. However, no studies have analyzed this variable in paracanoeing, relating it with training recovery markers., Objective: This study aimed to quantify the internal (session rating of perceived exertion) and external (distance traveled and total training time) training workloads in 4 experienced paracanoe athletes over 9 months and 5 canoeing events., Design: Cross-sectional study., Setting: Rehabilitation Hospital Network, Paralympic Program., Participants: Four experienced paracanoe athletes participated in 36 weeks of training for 5 events., Main Outcomes Measures: The daily and weekly training workload, monotony, ACWR, distance, and total training time were described for all the training phases. The perceived recovery status scale (PRS) and medicine ball throw (MBT) were used to quantify recovery., Results: The average daily and weekly training workload varied from 213.1 to 239.3 and 767.3 to 1036.8 arbitrary units, respectively. Average ACWR results ranged from 0.96 to 1.10 in the 4 athletes, findings that were outside the safety zone in 38% of the training weeks. All the correlations between MBT and PRS were classified as weak (ρ between .20 and .39, P > .05). ACWR showed a very weak correlation with MBT and moderately and highly significant correlations with PRS in 2 athletes, respectively., Conclusions: The training workloads of 4 paracanoe athletes may serve as a comparison with other periodization models. Pretraining recovery assessments (MBT and PRS) exhibited a low, nonsignificant correlation. However, ACWR correlated significantly with PRS in 2 athletes and might be a suitable tool for daily training adjustments.

Context: A detailed analysis of wheelchair basketball skills in beginner wheelchair basketball players (WBP) can provide practitioners with important indications regarding the selection and prospective development of potential sports talents. A comprehensive WBP evaluation can be very time consuming, mainly during the initial phases of the training processes, which could be a barrier in clinical and practical settings. Moreover, the large number and the turnover of beginner WBP attending rehabilitation centers make the applicability of field and strength tests unfeasible., Objective: To verify the relationships between the medicine ball throw (MBT) and wheelchair basketball mobility performance field tests and the shoulder and trunk peak torque in male and female beginner WBP., Design: Cross-sectional study., Setting: Rehabilitation Hospital Network, Paralympic Program., Participants: Thirty-seven female and male beginner WBP., Main Outcomes Measures: Participants performed wheelchair basketball field tests (speed, agility, strength, and power tests) and the maximum strength test in the isokinetic dynamometer. The outcomes were correlated with the MBT results., Results: The MBT presented significantly very high and perfect correlations with all wheelchair basketball field tests assessed (5-m sprint, 20-m sprint, and zig-zag agility test with and without a ball), and peak torque (R2 ranging from .810 to .995; P ≤ .05) for male and female athletes., Conclusions: The MBT, a simple and feasible test, can be used for estimating and determining the wheelchair mobility performance of female and male beginner WBP. It is suggested to measure the distance of a 5-kg medicine ball thrown by athletes during training and testing routines to follow the players' progression.

Background: Adequate muscle strength is essential for walking performance in individuals with stroke., Objective: To investigate the accuracy of different forms of muscle knee extension strength analysis to identify high or low walking performance in individuals with chronic stroke., Methods: Twenty-eight participants with a chronic stroke for more than six months participated. Independence for walking was judged by measurement of walking performance assessed for comfortable walking speed (CWS), maximum walking speed (MWS), and the Six Minute Walk Test (6MWT). Peak knee extension torque of the paretic side, non-paretic side, sum of the sides (SS), and difference in the sides (DS) was assessed during concentric movements using an isokinetic dynamometer., Results: The equation with greatest predictive capacity for CWS and MWS included the DS as the main predictor (R 2 of 0.65 and 0.71, respectively, p < 0.05). The variable with the greatest predictive capacity for 6MWT was time since injury (R 2 of 0.68, p < 0.05). The highest percentile for CWS in the receiver operating characteristic curve of DS was 25 Nm/kg (cut-off: -12.75 for CWS of 0.498 m/s). The 75th percentile of the 6MWT (324.3 m) was used as the cut-off for the SS (2.1 Nm/kg). The area under the curve for CWS was 0.76 (p < 0.05) on the DS and 0.75 (p < 0.05) for 6MWT on the SS., Conclusion: The models of muscle knee extension strength analysis using the SS and DS presented moderate accuracy to identify walking performance in individuals with chronic stroke., (Copyright © 2021 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: In Paralympic powerlifting (PP), athletes with and without spinal cord injury (SCI) compete in the same category. Athletes with SCI may be at a disadvantage in relation to the production of muscle strength and the execution of motor techniques., Objective: To analyze the indicators force, dynamic and static, at different intensities, on performance in athletes with and without SCI., Methods: The sample was composed of two groups of PP athletes: SCI (30.57 ± 4.20 years) and other deficiencies (OD; 25.67 ± 4.52 years). Athletes performed a test of maximum isometric force (MIF), time to MIF (Time), rate of force development (RFD), impulse, variability and fatigue index (FI), dynamic tests Mean Propulsive Velocity (MPV), Maximum Velocity (Vmax) and Power., Results: There were differences in the SCI in relation to OD, 50% 1RM ( p < 0.05), in relation to MPV and Vmax. There were no differences in the static force indicators. Regarding EMG, there were differences between the SCI triceps in relation to the previous deltoid ( p = 0.012)., Conclusion: We concluded that the static and dynamic strength indicators are similar in Paralympic powerlifting athletes with spinal cord injury and other disabilities.

Context: Monitoring training loads and consequent fatigue responses are usually a result of personal trainers' experiences and an adaptation of methods used in sports for people without disabilities. Currently, there is little scientific evidence on the relationship between training load and fatigue resulting from training sessions in wheelchair sports. Analogous to the vertical jump, which has been associated with competitive performance and used to assess fatigue in Olympic sports, the medicine ball throw (MBT) is a fast, feasible, and accessible test that might be used to measure performance outcomes in Paralympic athletes., Objective: To test the MBT responsiveness to detect meaningful changes after training sessions in beginner wheelchair basketball players (WBP)., Design: Cross-sectional study., Setting: Rehabilitation Hospital Network, Paralympic Program., Participants: Twelve male WBP., Main Outcomes Measures: The participants performed 3 consecutive days of training sessions involving exercises of wheelchair basketball skills, strength, and power. The MBT test was performed pre and post training sessions., Results: The smallest worthwhile change for MBT was 0.10 cm, and the lower and upper limits were 3.54 and 3.75 m, respectively. On the first day, the MBT started below the smallest worthwhile change lower limit and increased above the upper limit (3.53 and 3.78 m, respectively). On the second day, the MBT pretraining and posttraining session results were near the sample mean (3.62 and 3.59 m, respectively). On the third day, the WBP started the MBT test training higher than the upper limit (3.78 m) and decreased to near the mean (3.58 m)., Conclusions: During 3 consecutive days of training sessions, the magnitude-based inference model presented meaningful changes in MBT test performance. The accurate association of the magnitude-based inference model with the MBT allows coaches and sports team staff to interpret the correct magnitude of change in WBP performance.

Purpose : To determine whether the inclusion of three additional items improved the discriminative capacity of the Adapted Manual Wheelchair Circuit (AMWC). Design : Cross-sectional study. Methods : A total of 126 men (median age 28.9 years [percentiles 25 and 75: 23.7; 38.5 years]) with spinal cord injury were consecutively enrolled and divided into three subgroups: high paraplegia (HP), medium paraplegia (MP), and low paraplegia (LP). The participants performed the AMWC with three additional items. Ability score and total time of AMWC (AMWC AS and AMWC TT ) and AMWC plus the three additional items (AMWC+3 AS and AMWC+3 TT ), 3 min of overground wheeling test and performance score were evaluated. Results : AMWC was not able to discriminate HP from MP and LP (Wilks' lambda = 0.93; P = 0.07). In contrast, AMWC+3 was able to discriminate between the three subgroups (Wilks' lambda = 0.86; P ≤ 0.05). AMWC+3 AS presented a better sensitivity compared to AMWC AS (lower success rate for all subgroups, 38.5% vs. 82.1% for HP; 49.0% vs. 75.5% for MP; 78.9% vs. 94.7% for LP). The LP group presented a significant higher AMWC+3 AS compared to MP and HP (17.0 vs. 16.5 and 16.5, respectively, P ≤ 0.05). AMWC+3 TT was significantly lower in LP compared to MP and HP (139.85 s vs. 242.52 s and 326.21 s, respectively, P ≤ 0.05). Conclusion : The AMWC+3 outcomes were able to discriminate between HP, MP, and LP subgroups, and the addition of the three items enhanced the sensitivity of the wheelchair circuit. The performance of LP was more evident with significant differences compared to HP and MP for all AMWC+3 outcomes.

Objectives: The study aimed to test the cross-validation of a specific one maximum repetition (1RM) predictive equation based on the 4- to 12-maximum repetition test (4-12RM) for men with spinal cord injury (SCI). Study design: Cross-sectional study. Setting: Rehabilitation Hospital Network. Participants: Fifty-eight men aged 31.9 (20.0-38.0) years (median and quartile) with SCI were enrolled in the study. Interventions: None. Outcomes measures: Volunteers were tested in 1RM test or 4-12RM of the bench press exercise with 2-3 interval days in a random order. The intraclass correlation coefficient (ICC) with Bland Altman plot was used to compare a specific predictive equation (SPE) and six current predictive equations (CPE) based on the 4- to 12-maximum repetition with the 1RM test. Results: The SPE showed the highest intraclass correlation coefficient (ICC = 0.91; 95%CI 0.85-0.95), the smallest range of the interval around the differences (Δ = 36.6) and the second lowest mean difference between 1RM test and 1RM predictive equation (-2.4 kg). The CPE3 presented the lowest mean difference (-1.6 kg). All intraclass correlations' predictive equations were classified as excellent. Conclusion: The SPE presented a suitable and satisfactory validity to assess men with SCI at the bench press exercise. Thus, the equation is an accurate method to predict 1RM in SCI.

Objective: Determine trunk and shoulder muscle strength cutoff points for functional independence and wheelchair skills, and verify the predictive capacity of relative and absolute peak torque in men with spinal cord injury (SCI)., Design: Cross-sectional study., Setting: Rehabilitation hospital setting., Participants: Men (N=54) with SCI were recruited and stratified into high and low paraplegia groups., Interventions: All participants performed maximum strength tests for shoulder abduction or adduction (isokinetic) and trunk flexion or extension (isometric) to determine relative and absolute peak torque cutoff points for the Spinal Cord Independence Measure version III (SCIM-III) and Adapted Manual Wheelchair Circuit (AMWC)., Main Outcome Measures: The primary outcome measures were SCIM-III, AMWC-Brazil test, and strength variables (peak torques). Demographic characteristics obtained from participants' electronic medical records were the secondary outcomes used as predictor variables of functional independence., Results: The best predictive model for SCIM-III (R=0.78, P≤.05) used the sum of trunk flexion and extension relative peak torque values to determine the cutoff points (1.42 N·m/kg for a score of 70). Relative shoulder abduction peak torque was used in the predictive models for AMWC outcomes: performance score (R=0.77, P≤.05, cutoff points of 0.97 N·m/kg for 300.0m) and 3-minute overground wheeling (R=0.72, P≤.05, cutoff points of 0.96 N·m/kg for 18.5s)., Conclusions: Relative peak torque showed better predictive capacity compared to absolute peak torque. Cutoff points were established for relative muscle strength and could help health professionals set appropriate goals for individuals with SCI to achieve high functional independence and wheelchair ability., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Context: There seems to be no consensus on which aspects better distinguish the different levels of spinal cord injury regarding body composition, strength, and functional independence., Objective: The study aimed to determine which variables better differentiate tetraplegia (TP) from paraplegia and high paraplegia (HP) from low paraplegia (LP)., Design: Cross-sectional study., Setting: Rehabilitation hospital network., Patients: Forty-five men with spinal cord injury, n = 15 for each level (TP, HP, and LP) causing complete motor impairment (American Spinal Injury Association Impairment Scale: A or B) were enrolled in the study., Main Outcome Measures: The 1-maximum repetition test, functional independence measure, spinal cord independence measure, and body composition (skinfold sum, body fat percentage, and body mass index) were assessed. Discriminant analysis was carried out using the Wilks lambda method to identify which strength and functional variables can significantly discriminate subjects for injury classification (TP, HP, and LP)., Results: The discriminant variable for TP versus HP was body mass index and for TP versus LP was 1-maximum repetition (P ≤ .05). There were no variables that discriminated HP versus LP., Conclusions: The discriminant variables for TP versus HP and TP versus LP were body mass index and 1-maximum repetition, respectively. The results showed that HP and LP are similar for strength and functional variables.

Purpose : To translate, culturally adapt and validate the Adapted Manual Wheelchair Circuit (AMWC) into Brazilian-Portuguese. Design : Cross-sectional study. Methods : Sixty-six men (median age of 30.5 years [percentiles 25 and 75: 24.0; 38.3 years]) with traumatic spinal cord injury were consecutively enrolled and divided into two groups: tetraplegia (TP) and paraplegia (PP). The participants performed the AMWC-Brazil and were evaluated by the Spinal Cord Injury Measure version III (SCIM-III). Translation, translation synthesis, back-translation, committee review and construct validity were adopted for the cross-cultural adaptation. Construct validity was performed by testing whether the test scores were significantly correlated (Spearman's correlation coefficient) to the subjects' injury level, age, time since injury, body mass index (BMI) and SCIM-III scale. Results : All the AMWC-Brazil's outcomes were significantly correlated with SCIM-III total score and subscales (P ≤ 0.01). However, when the analyses were stratified over injury level, only the TP showed a high correlation between the AMWC-Brazil's outcomes and the SCIM-III. For construct validity, 4 of 5 hypotheses were confirmed. Only BMI was not a significant predictor of the AMWC-Brazil outcomes. Conclusion : The AMWC was successfully translated to the Brazilian-Portuguese (AMWC-Brazil) and presented high and satisfactory construct validity.

Context: Strength training is one of the most common interventions employed to increase functional independence during rehabilitation of individuals with spinal cord injury (SCI). However, in the literature, different results have been reported in terms of strength modifications after a SCI compared with a control group (CG)., Objective: This study aimed to verify whether discriminant analysis using relative and absolute strength is able to discriminate individuals with different levels of SCI from a CG and to compare strength values of men with different levels of SCI with a CG., Design: Cross-sectional study., Setting: Rehabilitation hospital setting., Participants: A total of 36 individuals with SCI stratified in tetraplegia (TP; C6-C8), high paraplegia (HP; T1-T6), and low paraplegia (LP; T7-L2), and 12 matched control subjects were enrolled in the study., Main Outcome Measures: The subjects performed a maximum strength test of elbow extension/flexion and also shoulder abduction/adduction and flexion/extension in an isokinetic dynamometer. Discriminant analysis was carried out to identify which strength variables would be able to discriminate the TP, HP, or LP groups from the CG. A 1-way analysis of variance was performed to compare peak torque and agonist/antagonist ratio means., Results: Shoulder adduction, followed by elbow extension peak torque, was the best variable for discriminating the TP group from the CG (function coefficients: -0.056 and 0.051, respectively, Wilks Λ = 0.41, P ≤ .05). There were no significant differences between the HP group, LP group, and CG., Conclusions: The strength similarity of the paraplegic groups and the CG should not be extrapolated for activities of daily living or sports. The TP group demonstrated lower peak torque for all movements than the CG.

Objective: To investigate the influence of strength values and fat mass on functional independence of men with different spinal cord injury (SCI) levels., Design: Cross-sectional study., Setting: Hospital network., Participants: Men with SCI (N=45)., Interventions: Subjects were assessed in functional independence scales, a 1 repetition maximum (1RM) test, and body composition to detect absolute and relative strength: 1RM divided by body mass (BM) and lean body mass (LBM), respectively., Main Outcome Measures: Stepwise multiple regression analysis was used to verify the influence of predictors on functional independence (FIM and Spinal Cord Independence Measure [SCIM] scale and subscales). Receiver operating characteristic curves were created to identify cutoff points of strength for functional independence., Results: The best models for FIM total, FIM mobility, and SCIM total used 1RM as the best predictor (adjusted R 2 =.75, .67, and .65, respectively; P<.05). Relative strength (1RM/LBM) was the best predictor for SCIM mobility (adjusted R 2 =.62, P<.05). A FIM score of 69 has a 1RM cutoff point of 50.1kg, and a FIM score of 76 has cutoff points of .73 for 1RM/BM and .91 for 1RM/LBM. A SCIM score of 68 has cutoff points for 1RM, 1RM/BM, and 1RM/LBM of 50.1kg, .77, and .92, respectively., Conclusions: Cutoff points of relative strength should be used as determinant variables for independence, health, or sports performance. This study may contribute to more adequate guidance of physical activity during a rehabilitation program and after discharge., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

ZFP36L2 protein destabilizes AU-rich element-containing transcripts and has been implicated in female fertility. In the C57BL/6NTac mouse, a mutation in Zfp36l2 that results in the decreased expression of a form of ZFP36L2 in which the 29 N-terminal amino acid residues have been deleted, ΔN-ZFP36L2, leads to fertilized eggs that arrest at the two-cell stage. Interestingly, homozygous ΔN-Zfp36l2 females in the C57BL/6NTac strain release 40% fewer eggs than the WT littermates (Ramos et al., 2004), suggesting an additional defect in ovulation and/or oocyte maturation. Curiously, the same ΔN-Zfp36l2 mutation into the SV129 strain resulted in anovulation, prompting us to investigate a potential problem in ovulation and oocyte maturation. Remarkably, only 20% of ΔN-Zfp36l2 oocytes in the 129S6/SvEvTac strain matured ex vivo, suggesting a defect on the oocyte meiotic maturation process. Treatment of ΔN-Zfp36l2 oocytes with a PKA inhibitor partially rescued the meiotic arrested oocytes. Furthermore, cAMP levels were increased in ΔN-Zfp36l2 oocytes, linking the cAMP/PKA pathway and ΔN-Zfp36l2 with meiotic arrest. Since ovulation and oocyte maturation are both triggered by LHR signaling, the downstream pathway was investigated. Adenylyl cyclase activity was increased in ΔN-Zfp36l2 ovaries only upon LH stimulation. Moreover, we discovered that ZFP36L2 interacts with the 3'UTR of LHR mRNA and that decreased expression levels of Zfp36l2 correlates with higher levels of LHR mRNA in synchronized ovaries. Furthermore, overexpression of ZFP36L2 decreases the endogenous expression of LHR mRNA in a cell line. Therefore, we propose that lack of the physiological down regulation of LHR mRNA levels by ZFP36L2 in the ovaries is associated with anovulation and oocyte meiotic arrest.

Introduction: Hypertension is the most prevalent modifiable risk factor with a high prevalence among older adults. Exercise is a nonpharmacological treatment shown to benefit all patients with hypertension., Objective: This study examined the effects of a 14-week moderate intensity resistance training program (RT) on the maintenance of blood pressure and hand grip strength during an extended detraining period in elderly hypertensive women., Methods: Twelve hypertensive sedentary elderly women completed 14 weeks of whole body RT at a moderate perceived exertion following a detraining period of 14 weeks., Results: Following the training period, participants demonstrated an increase in absolute hand grip strength (P=0.001), relative hand grip strength (P=0.032) and a decrease of systolic (P=0.001), diastolic (P=0.008), and mean blood pressure (P=0.002) when compared to pre-exercise values. In addition, these effects were sustained after 14 weeks of detraining., Conclusion: Resistance training may be a valuable method to improve muscular strength and blood pressure in elderly people with benefits being maintained up to 14 weeks following training cessation.

cAMP is an ubiquitous second messenger. Localized areas with high cAMP concentration, i.e. cAMP microdomains, provide an elegant mechanism to generate signaling specificity and transduction efficiency. However, the mechanisms underlying cAMP effector targeting into these compartments is still unclear. Here we report the identification of radixin as a scaffolding unit for both cAMP effectors, Epac and PKA. This complex localizes in a submembrane compartment where cAMP synthesis occurs. Compartment disruption by shRNA and dominant negative approaches negatively affects cAMP action. Inhibition can be rescued by expression of Rap1b, a substrate for both Epac1 and PKA, but only in its GTP-bound and phosphorylated state. We propose that radixin scaffolds both cAMP effectors in a functional cAMP-sensing compartment for efficient signal transduction, using Rap1 as a downstream signal integrator.

Rap1b has been implicated in the transduction of the cAMP mitogenic response. Agonists that increase intracellular cAMP rapidly activate (i.e. GTP binding) and phosphorylate Rap1b on Ser(179) at its C terminus. cAMP-dependent protein kinase (PKA)-mediated phosphorylation of Rap1b is required for cAMP-dependent mitogenesis, tumorigenesis, and inhibition of AKT activity. However, the role of phosphorylation still remains unknown. In this study, we utilized amide hydrogen/deuterium exchange mass spectroscopy (DXMS) to assess potential conformational changes and/or mobility induced by phosphorylation. We report here DXMS data comparing exchange rates for PKA-phosphorylated (Rap1-P) and S179D phosphomimetic (Rap1-D) Rap1b proteins. Rap1-P and Rap1-D behaved exactly the same, revealing an increased exchange rate in discrete regions along the protein; these regions include a domain around the phosphorylation site and unexpectedly the two switch loops. Thus, local effects induced by Ser(179) phosphorylation communicate allosterically with distal domains involved in effector interaction. These results provide a mechanistic explanation for the differential effects of Rap1 phosphorylation by PKA on effector protein interaction.

Rap1b has been implicated in the transduction of the cAMP mitogenic signal. It is phosphorylated and activated by cAMP, and its expression in models where cAMP is mitogenic leads to proliferation and tumorigenesis. Akt is a likely downstream effector of cAMP-Rap1 action. cAMP elevation induced a rapid and transient Akt inhibition that required activated and phosphorylated Rap1b. However, the mechanism(s) by which cAMP-Rap regulates Akt remains unclear. Here we show that (i) upstream regulators, PIK and PDK1, are not the target(s) of the cAMP inhibitory action; (ii) constitutively active Akt and calyculin A-stimulated Akt are resistant to cAMP inhibition, suggesting the action of a phosphatase; (iii) cAMP increases the rate of Akt dephosphorylation, directly implicating an Akt-phosphatase; (iv) Epac- and protein kinase A (PKA)-specific analogs synergistically inhibit Akt, indicating the involvement of both cAMP-dependent effector pathways; (v) H89 and dominant negative Epac 279E block cAMP-inhibitory action; (vi) Epac associates in a complex with Akt and PP2A, and the associated-phosphatase activity is positively modulated by cAMP in a PKA- and Rap1-dependent manner; (vii) like its action on Akt inhibition, PKA- and Epac-specific analogs synergistically activate Epac-associated PP2A; and (viii) dominant negative PP2A blocks cAMP-inhibitory action. Thus, we uncovered a novel cAMP-Epac/PKA-Rap1b-PP2A signaling module involved in Akt regulation that may represent a physiological event in the process of cAMP stimulation of thyroid mitogenesis.

cAMP stimulates proliferation in many cell types. For many years, cAMP-dependent protein kinase (PKA) represented the only known cAMP effector. PKA, however, does not fully mimic the action of cAMP, indicating the existence of a PKA-independent component. Since cAMP-mediated activation of the G-protein Rap1 and its phosphorylation by PKA are strictly required for the effects of cAMP on mitogenesis, we hypothesized that the Rap1 activator Epac might represent the PKA-independent factor. Here we report that Epac acts synergistically with PKA in cAMP-mediated mitogenesis. We have generated a new dominant negative Epac mutant that revealed that activation of Epac is required for thyroid-stimulating hormone or cAMP stimulation of DNA synthesis. We demonstrate that Epac's action on cAMP-mediated activation of Rap1 and cAMP-mediated mitogenesis depends on the subcellular localization of Epac via its DEP domain. Disruption of the DEP-dependent subcellular targeting of Epac abolished cAMP-Epac-mediated Rap1 activation and thyroid-stimulating hormone-mediated cell proliferation, indicating that an Epac-Rap-PKA signaling unit is critical for the mitogenic action of cAMP.

cAMP signaling leads to activation and phosphorylation of Rap1b. Using cellular models where cAMP stimulates cell proliferation, we have demonstrated that cAMP-mediated activation, as well as phosphorylation of Rap1b, is critical for cAMP stimulation of DNA synthesis. To determine whether Rap1b stimulates mitogenesis in vivo, we have constructed a transgenic mouse where a constitutively active G12V-Rap1b, flanked by Cre recombinase LoxP sites, is followed by the dominant negative S17N mutant. Employing this novel mouse model, we have switched, in a tissue-specific (thyroid) and temporally controlled manner, the expression of Rap1b from a stimulatory to an inhibitory form. These experiments provide conclusive evidence that Rap1b is oncogenic in the thyroid in ways linked to transduction of the cAMP mitogenic signal.

The CCCH tandem zinc finger protein, Zfp36l2, like its better-known relative tristetraprolin (TTP), can decrease the stability of AU-rich element-containing transcripts in cell transfection studies; however, its physiological importance is unknown. We disrupted Zfp36l2 in mice, resulting in decreased expression of a truncated protein in which the N-terminal 29 amino acids had been deleted (DeltaN-Zfp36l2). Mice derived from different clones of ES cells exhibited complete female infertility, despite evidence from embryo and ovary transplantation experiments that they could gestate and rear wild-type young. DeltaN-Zfp36l2 females apparently cycled and ovulated normally, and their ova could be fertilized; however, the embryos did not progress beyond the two-cell stage of development. These mice represent a specific model of disruption of the earliest stages of embryogenesis, implicating Zfp36l2, a probable mRNA-binding and destabilizing protein, in the physiological control of female fertility at the level of early embryonic development. This newly identified biological role for Zfp36l2 may have implications for maternal mRNA turnover in normal embryogenesis, and conceivably could be involved in some cases of unexplained human female infertility.

Guanine nucleotide exchange factors (GEFs) and their associated GTP-binding proteins (G-proteins) are key regulatory elements in the signal transduction machinery that relays information from the extracellular environment into specific intracellular responses. Among them, the MAPK cascades represent ubiquitous downstream effector pathways. We have previously described that, analogous to the Ras-dependent activation of the Erk-1/2 pathway, members of the Rho family of small G-proteins activate the JNK cascade when GTP is loaded by their corresponding GEFs. Searching for novel regulators of JNK activity we have identified Epac (exchange protein activated by cAMP) as a strong activator of JNK-1. Epac is a member of a growing family of GEFs that specifically display exchange activity on the Rap subfamily of Ras small G-proteins. We report here that while Epac activates the JNK severalfold, a constitutively active (G12V) mutant of Rap1b does not, suggesting that Rap-GTP is not sufficient to transduce Epac-dependent JNK activation. Moreover, Epac signaling to the JNKs was not blocked by inactivation of endogenous Rap, suggesting that Rap activation is not necessary for this response. Consistent with these observations, domain deletion mutant analysis shows that the catalytic GEF domain is dispensable for Epac-mediated activation of JNK. These studies identified a region overlapping the Ras exchange motif domain as critical for JNK activation. Consistent with this, an isolated Ras exchange motif domain from Epac is sufficient to activate JNK. We conclude that Epac signals to the JNK cascade through a new mechanism that does not involve its canonical catalytic action, i.e. Rap-specific GDP/GTP exchange. This represents not only a novel way to activate the JNKs but also a yet undescribed mechanism of downstream signaling by Epac.

Rap1b has been implicated in the transduction of the cAMP mitogenic signal. Rap1b is phosphorylated and activated by cAMP, and its expression in cells where cAMP is mitogenic leads to an increase in G(1)/S phase entry and tumor formation. The PCCL3 thyroid follicular cells represent a differentiated and physiologically relevant system that requires thyrotropin (TSH), acting via cAMP, for a full mitogenic response. In this model system, cAMP stimulation of DNA synthesis requires activation and phosphorylation of Rap1b by the cAMP-dependent protein kinase A (PKA). This scenario presents the challenge of identifying biochemical processes involved in the phosphorylation-dependent Rap1b mitogenic action. In thyroid cells, Akt has been implicated in the stimulation of cell proliferation by TSH and cAMP. However, the mechanism(s) by which cAMP regulates Akt activity remains unclear. In this study we show that in PCCL3 cells 1) TSH inhibits Akt activity via cAMP and PKA; 2) Rap1b is required for cAMP inhibition of Akt; and 3) transduction of the cAMP signal into Akt requires activation as well as phosphorylation of Rap1b by PKA.

We have shown that the small GTPase Rap1b, a protein known to antagonize the mitogenic and transforming activity of Ras, is endowed with both mitogenic and tumorigenic properties. Rap1b can be activated by cAMP, an intracellular message known to either stimulate or inhibit cell proliferation. The oncogenic property of Rap1b was revealed in a model system in which cAMP stimulates cell proliferation and was linked to Rap's ability to promote S phase entry. We have now tested the significance of the mitogenic action of Rap1b in a physiologically relevant model, the differentiated thyroid follicular cells, a system that requires thyroid-stimulating hormone (TSH), acting via cAMP, to mediate a full mitogenic response. Here we report that cAMP-dependent hormonal stimulation of DNA synthesis requires Rap1b in a manner dependent on its phosphorylation by protein kinase A.

It has been widely reported that the small GTP-binding protein Rap1 has an anti-Ras and anti-mitogenic activity. Thus, it is generally accepted that a normal physiological role of Rap1 proteins is to antagonize Ras mitogenic signals, presumably by forming nonproductive complexes with proteins that are typically effectors or modulators of Ras. Rap1 is activated by signals that raise intracellular levels of cAMP, a molecule that has long been known to exert both inhibitory and stimulatory effects on cell growth. We have now tested the intriguing hypothesis that Rap1 could have mitogenic effects in systems in which cAMP stimulates cell proliferation. The result of experiments addressing this possibility revealed that Rap1 has full oncogenic potential. Expression of Rap1 in these cells results in a decreased doubling time, an increased saturation density, and an unusual anchorage-dependent morphological transformation. Most significantly, however, Rap1-expressing cells formed tumors when injected into nude mice. Thus, we propose that the view that holds Rap1 as an antimitogenic protein should be restricted and conclude that Rap1 is a conditional oncoprotein.

Water and electrolyte transport in turtle urinary bladder closely resembles that present in the mammalian collecting tubule. Although cAMP is known to participate in the control of mucosal transport processes, the GTP-binding inhibitory Gi and stimulatory Gs proteins which link receptors on the cell surface to the adenylate cyclase system remain to be identified in this urinary epithelium. To this end, individual cells harvested from the mucosal surface of the turtle bladder were isolated using a discontinuous density Ficoll gradient. Examination by electron microscopy of the material from the different layers of the Ficoll gradient confirmed that bands II and III contained carbonic anhydrase-rich cells and granular cells, respectively. Identification of Gi and Gs in carbonic anhydrase-rich and granular cells was accomplished using pertussis (PT) and cholera toxins to promote [32P] ADP ribosylation of the proteins. Separation of Gi and Gs from other cell proteins was accomplished using polyacrylamide gel electrophoresis and autoradiography. Pretreatment of cells with 0.2% triton X-100 substantially magnified the ADP-ribosylation of Gi by PT. A doublet form of Gi was present in the 40-kD region and indicated heterogeneity of the PT substrate in granular and carbonic anhydrase-rich cells. Gs was observed as a single polypeptide at the 42-kD region in both cell types. A distinct 45-kD peptide not present in mammalian collecting tubule was identified by both toxins in granular cells and by cholera toxin in carbonic anhydrase-rich cells. In summary, this investigation identified and characterized Gi and Gs proteins in carbonic anhydrase-rich and granular cells from the mucosa of turtle urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS)

ADP ribosylation of membranes by pertussis toxin (PT) and cholera toxin (CT) was studied as a function of addition of ATP, various guanine nucleotides, Mg2+, and inorganic phosphate (Pi). ADP ribosylation of a 40 kilodalton (kDa) band by PT is markedly enhanced by ATP and GTP and is strongly inhibited by Pi or Mg2+. GTP analogs (GTP gamma S and GMP-adenyl-5'-yl imidodiphosphate) were less effective. In contrast, ADP ribosylation of two substrates for CT (of 42 and 50 kDa) is stimulated by Pi, Mg2+, and GTP or GTP analogs such as GTP gamma S, but is unaffected by ATP. These stimulatory conditions correlate well with GTP-mediated activation of stimulated nucleotide-binding regulatory component of adenyl cyclase. Optimal conditions for ADP ribosylation by PT do not correlate simply with conditions thought to lead to stabilization of an inactive form of inhibitory nucleotide-binding regulatory component of adenyl cyclase (Gi) or Gi-like protein; rather, the data suggest the involvement of both a stimulatory nucleotide site on PT (positively affected by either ATP or GTP) and a stabilizing site on the PT substrate (affected by GDP, GDP beta S, or GTP). Treatment of membranes with Lubrol PX increased ADP ribosylation by PT by as much as 25- to 30-fold, but inhibited the action of CT. Using defined conditions for ADP ribosylation by PT and CT, distinct labeling patterns were observed in thyroid, brain, corpus luteum, liver, heart, and erythrocytes membranes. All membranes were more intensely labeled by PT rather than CT.

Pretreatment of bovine thyroid slices with TSH resulted in desensitization of TSH-sensitive adenylyl cyclase activity but no change in stimulatory nucleotide binding regulatory component of adenylyl cyclase (Gs) activity assessed by reconstitution of the Gs-defective cyc-S49 adenylyl cyclase system. Possible changes in substrates for pertussis toxin (PT)-induced ADP ribosylation due to TSH treatment and/or in endogenous ADP ribosylation of membrane proteins were explored. Using 10 microM [32P]NAD+ as substrate, endogenous ADP ribosylation was not observed in membranes from control or TSH-treated slices. ADP ribosylation of alpha-subunits of Gs by cholera toxin was also unaffected by incubation of thyroid slices with TSH. In contrast, ADP ribosylation of 40 kilodalton (kDa) substrates for PT was decreased between 40% and 60% by TSH treatment. This effect of TSH was dependent on its concentration and the time of incubation of the slices and was specific for labeling of the 40 kDa PT substrate. Prostaglandin E1 treatment of thyroid slices, which results in a much smaller homologous desensitizing effect, did not result in changes in ADP ribosylation by PT. The effect of incubation of slices with TSH was abolished by pretreatment of the membranes with 0.3-1.0% Lubrol PX, which increased the labeling of the 40 kDa polypeptides. The data suggests that TSH induces in thyroid tissue a redistribution of 40 kDa polypeptides changing their availability to PT.