Comparison of walking energy cost between an anterior and a posterior ankle-foot orthosis in people with foot drop.

To compare walking energy cost between an anterior and a posterior ankle-foot orthosis in people with foot drop.Within-group comparisons.Twenty-three adults (14 women, 9 men; mean age 56.8 years (standard deviation 15.4)) with foot drop.PARTICIPANTS were asked to walk for 5 min at their self-selected walking speed under 3 conditions: (i) with shoes only; (ii) with a posterior ankle-foot orthosis; (iii) with an anterior ankle-foot orthosis. Spatio-temporal gait para-meters (speed, step length and step frequency) and walking energy cost per unit of distance were assessed for each walking condition. A visual analogue scale was used to quantify participants' level of perceived comfort for the 2 orthosis.Gait spatio-temporal parameters were higher with anterior ankle-foot orthoses than with posterior ankle-foot orthoses or shoes only. Walking energy cost per unit of distance was lower with anterior than posterior ankle-foot orthosis or shoes only ((mean ± standard error) 3.53 ± 1.00 vs 3.94 ± 1.27 and 3.98 ± 1.53 J·kg-1·m-1 respectively; p  0.05) and level of perceived comfort was higher with anterior ((mean ± standard error) 8.00 ± 1.32) than with posterior ankle-foot orthosis ((mean ± standard error) 4.52 ± 2.57; p  0.05).In people with foot drop the use of anterior ankle-foot orthoses resulted in lower energy costs of walking and higher levels of perceived comfort compared with posterior ankle-foot orthoses. Anterior ankle-foot orthoses may enable people with foot drop to walk further with less physical effort than posterior ankle-foot orthoses

Asymmetrical lower extremity loading early after ACL reconstruction is a significant predictor of asymmetrical loading at the time of return to sport

OBJECTIVES: The aim of this study was to examine whether asymmetrical lower limb loading early after anterior cruciate ligament reconstruction (1 mo) can predict asymmetrical lower limb loading at the time of return to sport (6 mos) and whether other early predictors as knee joint range of motion or maximal isometric strength affect this relationship. DESIGN: Ground reaction forces were measured during a sit-to-stand task 1 mo after anterior cruciate ligament reconstruction and a vertical countermovement jump 6 mos after anterior cruciate ligament reconstruction in 58 athletes. Other early postoperative measurements were knee joint range of motion (2 wks, 1 mo, and 2 mos after surgery) and maximal isometric strength of the knee extensor and flexor muscles (2 mos after surgery). Linear regression models were developed using side-to-side limb symmetry index (LSI) of countermovement jump as the dependent variable. RESULTS: LSI of sit-to-stand task 1 mo after surgery was a significant independent predictor of LSI of countermovement jump 6 mos after surgery. After accounting for deficits in knee joint range of motion and LSI of maximal isometric strength (ΔR² = 0.35, P < 0.01), LSI of sit-to-stand task predicted LSI of countermovement jump (ΔR² = 0.14 P < 0.01). CONCLUSIONS: Asymmetrical lower extremity loading 1 mo after anterior cruciate ligament reconstruction is an early predictor of asymmetrical lower extremity loading 6 mos after surgery

Chronic administration of saturated fats and fructose differently affect SREBP activity resulting in different modulation of Nrf2 and Nlrp3 inflammasome pathways in mice liver

The overconsumption of both saturated fats and fructose in the modern society has been related to the development of nonalcoholic fatty liver disease (NAFLD). However, the specific contribution of individual dietary components on the progression of NAFLD to nonalcoholic steatohepatitis (NASH) has been poorly investigated.Therefore, the aim of our study was to investigate the dissimilar effects of these two dietary components on selected proinflammatory and antioxidant pathways in the liver of C57BL/6 mice fed a standard (SD), a 45% saturated fat (HFAT) or a 60% fructose (HFRT) diet for 12 weeks. HFAT diet evoked systemic metabolic alterations and overweight, not observed in HFRT mice. However, HFRT mice had a greater hepatic triglyceride deposition with increased ratio of triacylglycerols containing the palmitic acid compared to HFAT, as assessed by liquid chromatography-mass spectrometry analysis. This effect is due to the higher activation of the SCAP/SREBP1c lipogenic pathway by HFRT feeding. In addition, we found inhibition of Keap1/Nrf2 antioxidant signaling and more robust stimulation of the Nlrp3 inflammasome pathway in the livers of HFRT-fed mice when compared with HFAT-fed mice, which is consistent with the recent finding that palmitate and SREBP1c are implicated in hepatic oxidative stress and inflammation. These effects were associated with increased hepatic inflammation, as confirmed by high expression of markers of leukocyte infiltration in the HFRT group. Thus, we hypothesize an amplifying loop among lipogenesis, palmitate, Nrf2 and Nlrp3 that leads to a higher risk of NAFLD progression to NASH in a high-fructose diet compared to a high-saturated fat intake. (C) 2017 Elsevier Inc. All rights reserved

Whole body vibration of different frequencies inhibits H-reflex but does not affect voluntary activation

This study aimed to investigate the effects of whole-body vibration (WBV) at a frequency spectrum from 20 to 50 Hz on the Hoffmann (H) reflex and the voluntary motor output of ankle plantar-flexor muscles. A single-group (n: 8), repeated measures design was adopted with four conditions: standing (no vibration), 20, 35 and 50 Hz, each lasting one minute. H-reflex of the soleus muscle, maximal voluntary contraction (MVC) and central activation ratio (CAR) of the plantar-flexors were evaluated before, 1 and 5 min after each frequency condition. H-reflex decreased by 36.7% at 20 Hz, by 28% at 35 Hz, and by 34.8% at 50 Hz after one minute from WBV compared to baseline. Neither MVC nor CAR changed after WBV at all frequency conditions. The short-term, acute inhibition of the H-reflex after WBV at 20, 35 and 50 Hz suggested that decreased excitability of spinal motoneurons is not frequency dependent. On the other hand, the lack of vibration induced effects on MVC and CAR indicated that a 1-min WBV stimulus is not sufficient to affect the voluntary motor output

Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors

Non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine kinase inhibitors (TKIs), but is successful for only a limited amount of time; most cases relapse due to the development of drug resistance. Here we show that a vaccine against ALK induced a strong and specific immune response that both prophylactically and therapeutically impaired the growth of ALK-positive lung tumors in mouse models. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. We found that lung tumors containing ALK rearrangements induced an immunosuppressive microenvironment, regulating the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy, which could be restored by administration of anti-PD-1 immunotherapy. Thus, combinations of ALK vaccine with TKIs and immune checkpoint blockade therapies might represent a powerful strategy for the treatment of ALK-driven NSCLC

Preclinical toxicology and safety pharmacology of the first-in-class GADD45β/MKK7 inhibitor and clinical candidate, DTP3

Aberrant NF-κB activity drives oncogenesis and cell survival in multiple myeloma (MM) and many other cancers. However, despite an aggressive effort by the pharmaceutical industry over the past 30 years, no specific IκBα kinase (IKK)β/NF-κB inhibitor has been clinically approved, due to the multiple dose-limiting toxicities of conventional NF-κB-targeting drugs. To overcome this barrier to therapeutic NF-κB inhibition, we developed the first-in-class growth arrest and DNA-damage-inducible (GADD45)β/mitogen-activated protein kinase kinase (MKK)7 inhibitor, DTP3, which targets an essential, cancer-selective cell-survival module downstream of the NF-κB pathway. As a result, DTP3 specifically kills MM cells, ex vivo and in vivo, ablating MM xenografts in mice, with no apparent adverse effects, nor evident toxicity to healthy cells. Here, we report the results from the preclinical regulatory pharmacodynamic (PD), safety pharmacology, pharmacokinetic (PK), and toxicology programmes of DTP3, leading to the approval for clinical trials in oncology. These results demonstrate that DTP3 combines on-target-selective pharmacology, therapeutic anticancer efficacy, favourable drug-like properties, long plasma half-life and good bioavailability, with no target-organs of toxicity and no adverse effects preclusive of its clinical development in oncology, upon daily repeat-dose administration in both rodent and non-rodent species. Our study underscores the clinical potential of DTP3 as a conceptually novel candidate therapeutic selectively blocking NF-κB survival signalling in MM and potentially other NF-κB-driven cancers

Preface of the 31st Italian Symposium on Advanced Database Systems

This volume contains the proceedings of the 31st Italian Symposium on Advanced Database Systems (SEBD - Sistemi Evoluti per Basi di Dati), held in Galzinagno Terme (Padua, Italy) from 2 to 5 July 2023.</p

Preface of the 31st Italian Symposium on Advanced Database Systems

This volume contains the proceedings of the 31st Italian Symposium on Advanced Database Systems (SEBD - Sistemi Evoluti per Basi di Dati), held in Galzinagno Terme (Padua, Italy) from 2 to 5 July 2023.</p

The neurophysiology of central and peripheral fatigue during sub-maximal lower limb isometric contractions

Fatigue has been defined as an exercise-induced decline in force generation capacity because of changes at both the peripheral and central levels. Movement is preceded and accompanied by brain activities related to the preparation and execution of movement (movement related cortical potentials, MRCP), which have been correlated with the perception of effort (RPE). We combined force measurements, surface electromyography (sEMG), peripheral electrical stimulation (maximal twitch, MT) and MRCP analysis to further our understanding of the neural correlates of peripheral and central changes during a fatiguing task involving the lower limbs. Eighteen healthy volunteers performed 4 blocks of isometric knee extensions at 40% of the maximal voluntary contraction (MVC) for a total of 240 2-s contractions. At the baseline and after each block, we measured RPE, MT and MVC. We simultaneously recorded the force of the knee extensor muscles, root mean square (RMS) of the sEMG of the vastus lateralis muscle, and electroencephalography (EEG) from 64 channels. The MRCPs were extracted from the EEG recordings and averaged in the early (Block 1–2) and late (Block 3–4) blocks. Two cohorts were obtained by cluster analysis based on the RPE (i.e., perception of effort) and MT (i.e., peripheral fatigue). We observed a significant decline in both the MVC (−13%) and RMS (−25%) of the sEMG signal over the course of the task; thus, muscle fatigue had occurred in all of the participants regardless of the cohort. The MRCP amplitude was larger in the fatigued than the non-fatigued MT cohort in the supplementary and premotor areas, whereas the MRCP amplitude was larger in the fatigued than the non-fatigued RPE cohort in the aforementioned areas, and also in the primary motor and prefrontal cortices (PFC). The increase in the positive activity of the PFC, along with the perception of effort, represents a novel result, suggesting that it is modulated more by the perception of effort than peripheral fatigue

Effects of rhythmical and extra-rhythmical qualities of music on heart rate during stationary bike activities

Backgorund: The aim of this study was to evaluate the effects of rhythmical and extra-rhythmical qualities of music on the heart rate (hr) and rates of perceived exertion (rpe), during sub-maximal stationary bike activity. MeThodS: hr of 28 female adult participants was monitored during 3 session of physical activity, performed under 3 different conditions: hi-BpM (music with 150-170 BpM), rhyThM (rhythmical qualities only of hi-BpM condition) and control condition without music (conTROL). Four parameters were analyzed: the highest HR value (High-HR), High-HR minus starting HR (?HR), time to reach the 75% of Maximal HR (MHR) (TimeTo75%) and time over 75% MHR (TimeOver75%). HR trend analysis was performed to evaluate differences among the three conditions. oMni-cycle Scale was administered to evaluate rpe. RESULTS: MANOVA showed signifcant differences between the three conditions in TimeTo75%, δHR (P&lt;0.01) and TimeOver75% (P&lt;0.05). In RHYTHM and CONTROL conditions after reaching 75% MHR, the HR increase were signifcantly lower than Hi-BPM (P&lt;0.01). No signifcant differences were found in OMNI-Cycle Scale scores of Hi-BPM and RHYTHM whereas RPE was signifcantly higher in CONTROL condition (P&lt;0.05). concluSionS: hi-BpM and rhyThM music allowed a faster reaching of the aerobic training zone compared to conTrol conditions. Nevertheless, after 75% MHR, extra-rhythmical qualities are necessary to maintain or to increase the working HR levels