In addition, our results showed an impact of the slope gradient on kvert (i.e., kvert increased with a positive increase in the slope), despite the lack of change in kleg with slope. Similar to experiments involving barefoot Alectinib purchase running,7, 8 and 9kleg was greater in MS than TS. These findings are consistent with the inverse relationship reported by Aerts and De Clercq 32 between heel-pad compression and midsole hardness determined from a series of pendulum impact tests at the heel. These authors showed that

heel-pad stiffness increased with the rate of loading, which was coupled with the amount of midsole hardness. Their results demonstrate, in theory, foot adaptations to footwear that assist in explaining the increase in kleg values observed herein in MS versus TS footwear. Various other arguments can be advanced to explain the observed differences in kleg between footwear, which are addressed below. In the current research, our subjects demonstrated a significant decrease in ΔL and increase in Fmax when running in MS on level compared to TS, which necessarily resulted in higher kleg conforming to equation (4). This decrease in ΔL could be caused by the reduced time during which the foot was in contact with the ground and received ground reaction forces; as suggests the lower tc and, indirectly, higher f observed in MS ( Tables 1 and 2). In fact, decreases in tc and increases in f have

been associated with increases in kleg previously, 33 and 34 with the change in tc suggested to explain up to Alpelisib clinical trial 90% of the change in kleg. 34 Regarding the effect of footwear on Fmax during running, there is conflicting evidence with studies reporting no differences between TS, MS, and barefoot conditions; 3, 5 and 7 lower impact forces in barefoot and MS than TS; 35 and, comparable to our findings, higher Fmax in barefoot and MS than TS. 36 Two plausible explanations for these variable findings are the between-study differences in the

methods employed to collect and compute Fmax and the degree Non-specific serine/threonine protein kinase of habituation of runners to the experimental footwear conditions. In our study, tc and tf were decisive parameters in the estimation of Fmax (c.f., equation (2)), with the significantly greater tf in MS compared to TS at −8%, 0%, and +2% explaining the significantly greater Fmax in MS at these slope gradients. These heightened Fmax are of concern taking into account that high impact forces are proposed to increase the risk of overuse and/or impact related running injuries. 37 This is of particular relevance to runners transitioning from TS to MS considering that foot bone marrow edema (a swelling/inflammation of the bone marrow with excess fluid in reaction to stress) can increase significantly during this time due to added stress, which might ultimately result in stress fractures with improper conditioning and/or habituation.