No abstract

The present study was carried out in order to quantify the athlete's endurance impairment after two out of three sequential events of Olympic Triathlon (OT). Furthermore the significance of ventilatory threshold (Tvent) and peak of oxygen uptake (VO2peak) as triathlete's performance predictors was assessed. Tvent and VO2peak were measured in six male triathletes performing an incremental treadmill test a week before an ad hoc triathlon event. The same test was applied immediately after the first two segments of the triathlon (1.5 km swim, 32 km bike). VO2peak and Tvent measured during the latter test were reduced compared to the first test. VO2peak decreased from 69 to 64 ml.kg-1.min-1 and Tvent from 58 to 51 ml.kg-1.min-1 p < 0.01), respectively. VO2peak and Tvent measured in the first test were well correlated (P < 0.05) to both running and cycling times. The Tvent measured during the second test was related to the running time but with a higher significance (p < 0.01) than in the first test. The impairment in the endurance performance induced by the first two segments of OT is an important aspect to consider both in training and in race strategy. These results also provide evidence that VO2peak and Tvent are good predictors of triathlon performance at least in cycling and running events.

A reciprocating gait orthosis (ROO) is, among others, the most widely adopted device to restore the standing and walking capability of paraplegic patients. The aim of the present s�udy was the evaluation of the energy demand (V02), and cardiopulmonary load (HR and VE) imposed on the subject by different working tasks while sitting in a wheelchair or standing using a ROO. In addition, a comparison with the performance of normal subjects was also attempted. The ROO use allowed a dramatic improvement of patients mobility and reach space in the workplace. A further advantage provided by the use of the ROO was represented by the increased mobility of the subjects with respect to the wheelchair confined situation. The energy demand and the cardiorespiratory load imposed on the subjects by the use of the ROO were not different from those observed both in the same subjects sitting in a wheelchair and in the controls. The energy demand slightly exceeded the values typical of light work and was, thus, compatible with the normal duration of a working day. On the other hand, the cardiac load corresponded to that typical of moderate activity, thus limiting the duration of the working task to 5-8 h. Based on the ergometry test, all of the working activities considered can be classified as aerobic activities, energy demand being under the ventilatory threshold.

Natural Killer (NK) cells act as important regulators in the development and progression of hematological malignancies and their suppressor activity against Multiple Myeloma (MM) cells has been confirmed in many studies. Significant changes in the distribution of NK cell subsets and dysfunctions of NK cell effector activities were described in MM patients and correlated with disease staging. Thus, restoring or enhancing the functionality of these effectors for the treatment of MM represents a critical need. Neddylation is a post-translational modification that adds a ubiquitin-like molecule, NEDD8, to the substrate protein. One of the outcomes is the activation of the Cullin Ring Ligases (CRLs), a class of ubiquitin-ligases that controls the degradation of about 20% of proteasome-regulated proteins. Overactivation of CRLs has been described in cancer and can lead to tumor growth and progression. Thus, targeting neddylation represents an attractive approach for cancer treatment. Our group has recently described how pharmacologic inhibition of neddylation increases the expression of the NKG2D activating receptor ligands, MICA and MICB, in MM cells, making these cells more susceptible to NK cell degranulation and killing. Here, we extended our investigation to the direct role of neddylation on NK cell effector functions exerted against MM. We observed that inhibition of neddylation enhanced NK cell-mediated degranulation and killing against MM cells and improved Daratumumab/Elotuzumab-mediated response. Mechanistically, inhibition of neddylation increased the expression of Rac1 and RhoA GTPases in NK cells, critical mediators for an efficient degranulation at the immunological synapse of cytotoxic lymphocytes, and augmented the levels of F-actin and perforin polarization in NK cells contacting target cells. Moreover, inhibition of neddylation partially abrogated TGFβ-mediated repression of NK cell effector activity. This study describes the role of neddylation on NK cell effector functions and highlights the positive immunomodulatory effects achieved by the inhibition of this pathway in MM.