Do poles really "save the legs" during uphill pole walking at different intensities?

PURPOSE: In sky- and trail-running competitions, many athletes use poles. The aims of this study were to investigate whether the use of poles affects the force exerted on the ground at the feet (Ffoot), cardiorespiratory variables and maximal performance during uphill walking. METHODS: Fifteen male trail runners completed four testing sessions on different days. On the first two days, they performed two incremental uphill treadmill walking tests to exhaustion with (PWincr) and without poles (Wincr). On the following days, they performed submaximal and maximal tests with (PW80 and PWmax) and without (W80 and Wmax) poles on an outdoor trail course. We measured cardiorespiratory parameters, the rating of perceived exertion, the axial poling force and Ffoot. RESULTS: When walking on the treadmill, we found that poles reduced maximum Ffoot (- 2.8 ± 6.4%, p = 0.03) and average Ffoot (- 2.4 ± 3.3%, p = 0.0089). However, when outdoors, we found pole effect only for average Ffoot (p = 0.0051), which was lower when walking with poles (- 2.6 ± 3.9%, p = 0.0306 during submaximal trial and - 5.21 ± 5.51%, p = 0.0096 during maximal trial). We found no effects of poles on cardiorespiratory parameters across all tested conditions. Performance was faster in PWmax than in Wmax (+ 2.5 ± 3.4%, p = 0.025). CONCLUSION: The use of poles reduces the foot force both on the treadmill and outdoors at submaximal and maximal intensities. It is, therefore, reasonable to conclude that the use of poles "saves the legs" during uphill without affecting the metabolic cost.

Rational Design of Nucleoside-Bile Acid Conjugates Incorporating a Triazole Moiety for Anticancer Evaluation and SAR Exploration.

Herein we report a study on the synthesis and biological evaluation of a library of nucleoside-bile acid conjugates prepared by combining 2'-deoxyadenosine, 2'-deoxyguanosine, 2'-deoxyuridine as well as adenosine and guanosine derivatives with cheno-, urso-, nor-cheno-, nor-urso- and taurourso-desoxycholic acid derivatives by means of the click reaction. The new nucleoside-bile acid conjugates incorporating a triazole moiety were tested in vitro against leukemic K562 and HCT116 colon carcinoma, as well as on normal fibroblast cells. Six compounds displayed interesting anti-proliferative activity against the selected cancer lines and no cytotoxic effects against normal fibroblasts. A possible structure activity relationship was also investigated.

Energetics and Mechanics of Steep Treadmill Versus Overground Pole Walking: A Pilot Study.

PURPOSE: To compare energetics and spatiotemporal parameters of steep uphill pole walking on a treadmill and overground. METHODS: First, the authors evaluated 6 male trail runners during an incremental graded test on a treadmill. Then, they performed a maximal overground test with poles and an overground test at 80% (OG80) of vertical velocity of maximal overground test with poles on an uphill mountain path (length = 1.3 km, elevation gain = 433 m). Finally, they covered the same elevation gain using poles on a customized treadmill at the average vertical velocity of the OG80. During all the tests, the authors measured oxygen uptake, carbon dioxide production, heart rate, blood lactate concentration, and rate of perceived exertion. RESULTS: Treadmills required lower metabolic power (15.3 [1.9] vs 16.6 [2.0] W/kg, P = .002) and vertical cost of transport (49.6 [2.7] vs 53.7 [2.1] J/kg·m, P < .001) compared with OG80. Also, oxygen uptake was lower on a treadmill (41.7 [5.0] vs 46.2 [5.0] mL/kg·min, P = .001). Conversely, respiratory quotient was higher on TR80 compared with OG80 (0.98 [0.02] vs 0.89 [0.04], P = .032). In addition, rate of perceived exertion was higher on a treadmill and increased with elevation (P < .001). The authors did not detect any differences in other physiological measurements or in spatiotemporal parameters. CONCLUSIONS: Researchers, coaches, and athletes should be aware that steep treadmill pole walking requires lower energy consumption but same heart rate and rate of perceived exertion than overground pole walking at the same average intensity.

Pole Walking Is Faster but Not Cheaper During Steep Uphill Walking.

PURPOSE: The aim of this study was to compare pole walking (PW) and walking without poles (W) on a steep uphill mountain path (1.3 km, 433 m of elevation gain) at 2 different intensities: a maximal effort that would simulate a vertical kilometer intensity and a lower intensity (80% of maximal) simulating an ultratrail race. METHODS: On the first day, we tested the participants in the laboratory to determine their maximal physiological parameters, respiratory compensation point, and gas exchange threshold. Then, they completed 4 uphill tests along a mountain path on 4 separate days, 2 at their maximum effort (PWmax and Wmax, randomized order) and 2 at 80% of the mean vertical velocity maintained during the first 2 trials (PW80 and W80, randomized order). We collected metabolic data, heart rate, blood lactate concentration, and rating of perceived exertion at the end of each trial. We also collected rating of perceived exertion at every 100 m of elevation gain during PW80 and W80. RESULTS: Participants completed the maximal effort faster with poles versus without poles (18:51 [03:12] vs 19:19 [03:01] in min:s, P = .013, d = 0.08, small). Twelve of the 15 participants (80%) improved their performance when they used poles. During PW80 and W80, none of the physiological or biomechanical parameters were different. CONCLUSION: In the examined condition, athletes should use poles during steep uphill maximal efforts to obtain the best performance. Conversely, during submaximal effort, the use of poles does not provide advantages in uphill PW.

Cationic PMMA nanoparticles bind and deliver antisense oligoribonucleotides allowing restoration of dystrophin expression in the mdx mouse.

For subsets of Duchenne muscular dystrophy (DMD) mutations, antisense oligoribonucleotide (AON)-mediated exon skipping has proven to be efficacious in restoring the expression of dystrophin protein. In the mdx murine model systemic delivery of AON, recognizing the splice donor of dystrophin exon 23, has shown proof of concept. Here, we show that using cationic polymethylmethacrylate (PMMA) (marked as T1) nanoparticles loaded with a low dose of 2'-O-methyl-phosphorothioate (2'OMePS) AON delivered by weekly intraperitoneal (IP) injection (0.9 mg/kg/week), could restore dystrophin expression in body-wide striated muscles. Delivery of an identical dose of naked AON did not result in detectable dystrophin expression. Transcription, western, and immunohistochemical analysis showed increased levels of dystrophin transcript and protein, and correct localization at the sarcolemma. This study shows that T1 nanoparticles have the capacity to bind and convoy AONs in body-wide muscle tissues and to reduce the dose required for dystrophin rescue. By immunofluorescence and electron microscopy studies, we highlighted the diffusion pathways of this compound. This nonviral approach may valuably improve the therapeutic usage of AONs in DMD as well as the delivery of RNA molecules with many implications in both basic research and medicine.

Exon skipping-mediated dystrophin reading frame restoration for small mutations.

Exon skipping using antisense oligonucleotides (AONs) has successfully been used to reframe the mRNA in various Duchenne muscular dystrophy patients carrying deletions in the DMD gene. In this study we tested the feasibility of the exon skipping approach for patients with small mutations in in-frame exons. We first identified 54 disease-causing point mutations. We selected five patients with nonsense or frameshifting mutations in exons 10, 16, 26, 33, and 34. Wild-type and mutation specific 2'OMePS AONs were tested in cell-free splicing assays and in cultured cells derived from the selected patients. The obtained results confirm cell-free splicing assay as an alternative system to test exon skipping propensity when patients' cells are unavailable. In myogenic cells, similar levels of exon skipping were observed for wild-type and mutation specific AONs for exons 16, 26, and 33, whereas for exon 10 and exon 34 the efficacy of the AONs was significantly different. Interestingly, in some cases skipping efficiencies for mutated exons were quite dissimilar when compared with previous reports on the respective wild-type exons. This behavior may be related to the effect of the mutations on exon skipping propensity, and highlights the complexity of identifying optimal AONs for skipping exons with small mutations.

Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid.

CONTEXT: Zidovudine (AZT) is employed against AIDS and hepatitis; its use is limited by active efflux transporters (AETs) that induce multidrug resistance for intracellular therapies and hamper AZT to reach the brain. Ursodeoxycholic acid (UDCA) conjugation with AZT (prodrug UDCA-AZT) allows to elude the AET systems. OBJECTIVE: To investigate the effect of the Pluronic F68 coating on the loading, release and stability of poly(D,L lactide-co-glicolide) nanoparticles (NPs) embedded with UDCA-AZT. MATERIALS AND METHODS: The mean diameter of the NP prepared by nanoprecipitation or emulsion/solvent evaporation methods was determined using both photon correlation spectroscopy and sedimentation field-flow fractionation; particle morphology was detected by scanning electron microscope. The stability of the free and encapsulated UDCA-AZT was evaluated in rat liver homogenates by high-performance liquid chromatography analysis. RESULTS AND DISCUSSION: The mean diameter of the NPs was found to be ∼ 600 nm with a relatively high polydispersity. The NPs obtained by emulsion/solvent evaporation were not able to control the prodrug release, differently from NPs obtained by nanoprecipitation. The presence of the Pluronic coating did not substantially modify the kinetics of the drug release, or the extent of the burst effect that were instead only influenced by the preparation parameters. UDCA-AZT incorporated in the NPs was more stable in the rat liver homogenates than the free prodrug and no influence of the Pluronic coating was observed. CONCLUSIONS: Considering the different potential applications of nanoparticles coated and uncoated with Pluronic (brain and macrophage targeting, respectively), both of these nanoparticle systems could be useful in the therapies against HIV.