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Rationale: Adipose-derived stem cells express multiple growth factors that inhibit endothelial cell apoptosis, and demonstrate substantial pulmonary trapping after intravascular delivery. Objectives: We hypothesized that adipose stem cells would ameliorate chronic lung injury associated with endothelial cell apoptosis, such as that occurring in emphysema. Methods: Therapeutic effects of systemically delivered human or mouse adult adipose stem cells were evaluated in murine models of emphysema induced by chronic exposure to cigarette smoke or by inhibition of vascular endothelial growth factor receptors. Measurements and Main Results: Adipose stem cells were detectable in the parenchyma and large airways of lungs up to 21 days after injection. Adipose stem cell treatment was associated with reduced inflammatory infiltration in response to cigarette smoke exposure, and markedly decreased lung cell death and airspace enlargement in both models of emphysema. Remarkably, therapeutic results of adipose stem cells extended beyond lung protection by rescuing the suppressive effects of cigarette smoke on bone marrow hematopoietic progenitor cell function, and by restoring weight loss sustained by mice during cigarette smoke exposure. Pulmonary vascular protective effects of adipose stem cells were recapitulated by application of cell-free conditioned medium, which improved lung endothelial cell repair and recovery in a wound injury repair model and antagonized effects of cigarette smoke in vitro. Conclusions: These results suggest a useful therapeutic effect of adipose stem cells on both lung and systemic injury induced by cigarette smoke, and implicate a lung vascular protective function of adipose stem cell derived paracrine factors.

The recent competitive successes of a bilateral, transtibial amputee sprint runner who races with modern running prostheses has triggered an international controversy regarding the relative function provided by his artificial limbs. Here, we conducted three tests of functional similarity between this amputee sprinter and competitive male runners with intact limbs: the metabolic cost of running, sprinting endurance, and running mechanics. Metabolic and mechanical data, respectively, were acquired via indirect calorimetry and ground reaction force measurements during constant-speed, level treadmill running. First, we found that the mean gross metabolic cost of transport of our amputee sprint subject (174.9 ml O2·kg−1·km−1; speeds: 2.5–4.1 m/s) was only 3.8% lower than mean values for intact-limb elite distance runners and 6.7% lower than for subelite distance runners but 17% lower than for intact-limb 400-m specialists [210.6 (SD 13.2) ml O2·kg−1·km−1]. Second, the speeds that our amputee sprinter maintained for six all-out, constant-speed trials to failure (speeds: 6.6–10.8 m/s; durations: 2–90 s) were within 2.2 (SD 0.6)% of those predicted for intact-limb sprinters. Third, at sprinting speeds of 8.0, 9.0, and 10.0 m/s, our amputee subject had longer foot-ground contact times [+14.7 (SD 4.2)%], shorter aerial [−26.4 (SD 9.9)%] and swing times [−15.2 (SD 6.9)%], and lower stance-averaged vertical forces [−19.3 (SD 3.1)%] than intact-limb sprinters [top speeds = 10.8 vs. 10.8 (SD 0.6) m/s]. We conclude that running on modern, lower-limb sprinting prostheses appears to be physiologically similar but mechanically different from running with intact limbs.

Improvements in prosthesis design have facilitated participation in competitive running for persons with lower limb loss (AMP).The purpose of this study was to examine the physiological responses of AMP using a run-specific prosthesis (RP) versus a traditional prosthesis (P) and cross-referenced with nonamputee controls (C) matched by training status, age, gender, and body composition during level treadmill running (TM).Twelve trained runners completed a multistage submaximal TM exercise during which HR and oxygen uptake (VO(2)) were obtained. Steady state measures at 134 m x min(-1) were compared between RP and P in AMP. AMP using RP (AMP-RP) and C also performed a continuous speed-incremented maximal TM test until volitional fatigue.RP elicited lower HR and VO(2) compared with P in AMP. Using RP, AMP achieved similar VO(2max) and peak TM speed compared with C but with higher HR(max). Relative HR (%HR(max)) and oxygen uptake (%VO(2max)), the regression intercept, slope, SEE, and Pearson's r correlation were not different between AMP-RP and C. %HR(max) calculated with the published equation, %HR(max) = 0.73(%VO(2max)) + 30, was not significantly different from actual %HR(max) for AMP-RP or C in any stage.RP permits AMP to attain peak TM speed and aerobic capacity similar to trained nonamputees and significantly attenuates HR and energy cost of submaximal running compared with a P. Use of RP confers no physiological advantage compared with nonamputee runners because energy cost at the set speed was not significantly different for AMP-RP. Current equations on the basis of the relative HR-VO(2) relationship seem appropriate to prescribe exercise intensity for persons with transtibial amputations using RP.

Muscle atrophy (sarcopenia) in the elderly is associated with a reduced rate of muscle protein synthesis. The purpose of this study was to determine if weight-lifting exercise increases the rate of muscle protein synthesis in physically frail 76- to 92-yr-old women and men. Eight women and 4 men with mild to moderate physical frailty were enrolled in a 3-mo physical therapy program that was followed by 3 mo of supervised weight-lifting exercise. Supervised weight-lifting exercise was performed 3 days/wk at 65–100% of initial 1-repetition maximum on five upper and three lower body exercises. Compared with before resistance training, the in vivo incorporation rate of [13C]leucine into vastus lateralis muscle protein was increased after resistance training in women and men ( P < 0.01), although it was unchanged in five 82 ± 2-yr-old control subjects studied two times in 3 mo. Maximum voluntary knee extensor muscle torque production increased in the supervised resistance exercise group. These findings suggest that muscle contractile protein synthetic pathways in physically frail 76- to 92-yr-old women and men respond and adapt to the increased contractile activity associated with progressive resistance exercise training.

to the editor: We thank the authors of the comments for their time and ideas. Drs. Buckley and Cavagna (see Ref. [3][1]) raise important points regarding how leg spring stiffness affects running speed. It is well established that biological leg stiffness remains nearly constant across slow to

feature-negative discrimination task based on colors or symbols and were then transferred to a feature-positive or feature-negative discrimination based on the other stimulus dimension (symbols-colors, colors-symbols). Initial task results yielded a substantial feature-positive effect and indicated that the color task was easier than the symbol task. Transfer task results indicated that the feature-positive effect was maintained and showed that consistent transfer (positive-positive, negative-negative) led to superior performance on the transfer task. These results were obtained when the correct solution to the initial task was provided to the subject prior to transfer (Experiment 1) and when it was not (Experiment 2.) These results systematically replicated the existence of the feature-positive effect in adult humans and showed that both feature-positive and feature-negative discrimination learning were facilitated by consistent examples of these problems. Jenkins and Sainsbury (1969, 1970) found that pigeons manifested a remarkable asymmetry in the learning of discriminations based on a distinguishing feature. In feature-positive (FP) discriminations, a distinctive feature (e.g., a dot) appeared on reinforced (S +) trials and was absent on nonreinforced (S -) trials. Pigeons exposed to FP problems learned rapidly to respond exclusively on S + trials. In feature-negative (FN) discriminations, the distinctive feature appeared on S - trials and was absent on S + trials. Pigeons exposed to FN problems showed poor discrimination performance, i.e., they persisted in responding on both S + and S - trials. Jenkins and Sainsbury labeled this superiority of FP discrimination learning the feature-positive effect (FPE). The FPE was initially thought of as an experimental curiosity, and accordingly, a number of studies explored its generality. Perhaps sur

In three experiments, adult humans were tested in a feature-positive or feature-negative simultaneous symbol task. In Experiment 1, some persons focused on the correct side of the stimulus cards, whereas other persons focused on the not-correct side of the stimulus cards. The feature-positive group learned faster than the feature-negative group did in the correct side condition; the feature-negative group learned faster than the feature-positive group did in the not-correct side condition. In Experiments 2 and 3, all persons focused on both the correct and not-correct sides of the stimulus cards. Under these circumstances, feature-positive and feature-negative performances were comparable. These results indicated that the usual superiority of feature-positive over feature-negative learning results from a tendency to attend to only a portion of the stimulus array.