Effects of Functional Electrical Stimulation Cycling of Different Duration on Viscoelastic and Electromyographic Properties of the Knee in Patients with Spinal Cord Injury

The benefits of functional electrical stimulation during cycling (FES-cycling) have been ascertained following spinal cord injury. The instrumented pendulum test was applied to chronic paraplegic patients to investigate the effects of FES-cycling of different duration (20-min vs. 40-min) on biomechanical and electromyographic characterization of knee mobility. Seven adults with post-traumatic paraplegia attended two FES-cycling sessions, a 20-min and a 40-min one, in a random order. Knee angular excursion, stiffness and viscosity were measured using the pendulum test before and after each session. Surface electromyographic activity was recorded from the rectus femoris (RF) and biceps femoris (BF) muscles. FES-cycling led to reduced excursion (p < 0.001) and increased stiffness (p = 0.005) of the knee, which was more evident after the 20-min than 40-min session. Noteworthy, biomechanical changes were associated with an increase of muscle activity and changes in latency of muscle activity only for 20-min, with anticipated response times for RF (p < 0.001) and delayed responses for BF (p = 0.033). These results indicate that significant functional changes in knee mobility can be achieved by FES-cycling for 20 min, as evaluated by the pendulum test in patients with chronic paraplegia. The observed muscle behaviour suggests modulatory effects of exercise on spinal network aimed to partially restore automatic neuronal processes

LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity

Immunosuppressive regulatory T cells (Tregs) have been hypothesized to exert a protective role in animal models of spontaneous (Buffalo/Mna) and/or drug induced (Adriamycin) nephrotic syndrome. In this study, we thought to define whether Tregs can modify the outcome of LPS nephropathy utilizing IL-2 as inducer of tissue and circulating Tregs. LPS (12 mg/Kg) was given as single shot in C57BL/6, p2rx7−/− and Foxp3EGFP; free IL-2 (18.000 U) or, in alternative, IL-2 coupled with JES6-1 mAb (IL-2/anti-IL-2) were injected before LPS. Peripheral and tissue Tregs/total CD4+ cell ratio, urinary parameters and renal histology were evaluated for 15 days. IL-2 administration to wild type mice had no effect on peripheral Tregs number, whereas a significant increase was induced by the IL-2/anti-IL-2 immunocomplex after 5 days. Spleen and lymph nodes Tregs were comparably increased. In p2rx7−/− mice, IL-2/anti-IL-2 treatment resulted in increase of peripheral Tregs but did not modify the spleen and lymph nodes quota. LPS induced comparable and transient proteinuria in both wild type and p2rx7−/− mice. Proteinuria was inhibited by co-infusion of human IL-2, with reduction at each phase of the disease (24 −48 and 72 hours) whereas IL-2/anti-IL-2 produced weaker effects. In all mice (wild type and p2rx7−/−) and irrespective of treatment (IL-2, IL-2/anti-IL-2), LPS was associated with progressive signs of renal pathologic involvement resulting in glomerulosclerosis. In conclusion, IL-2 plays a transient protective effect on proteinuria induced by LPS independent of circulating or tissue Tregs but does not modify the outcome of renal degenerative renal lesions

LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity.

Immunosuppressive regulatory T cells (Tregs) have been hypothesized to exert a protective role in animal models of spontaneous (Buffalo/Mna) and/or drug induced (Adriamycin) nephrotic syndrome. In this study, we thought to define whether Tregs can modify the outcome of LPS nephropathy utilizing IL-2 as inducer of tissue and circulating Tregs. LPS (12 mg/Kg) was given as single shot in C57BL/6, p2rx7⁻/⁻ and Foxp3EGFP; free IL-2 (18.000 U) or, in alternative, IL-2 coupled with JES6-1 mAb (IL-2/anti-IL-2) were injected before LPS. Peripheral and tissue Tregs/total CD4+ cell ratio, urinary parameters and renal histology were evaluated for 15 days. IL-2 administration to wild type mice had no effect on peripheral Tregs number, whereas a significant increase was induced by the IL-2/anti-IL-2 immunocomplex after 5 days. Spleen and lymph nodes Tregs were comparably increased. In p2rx7⁻/⁻ mice, IL-2/anti-IL-2 treatment resulted in increase of peripheral Tregs but did not modify the spleen and lymph nodes quota. LPS induced comparable and transient proteinuria in both wild type and p2rx7⁻/⁻ mice. Proteinuria was inhibited by co-infusion of human IL-2, with reduction at each phase of the disease (24 -48 and 72 hours) whereas IL-2/anti-IL-2 produced weaker effects. In all mice (wild type and p2rx7⁻/⁻) and irrespective of treatment (IL-2, IL-2/anti-IL-2), LPS was associated with progressive signs of renal pathologic involvement resulting in glomerulosclerosis. In conclusion, IL-2 plays a transient protective effect on proteinuria induced by LPS independent of circulating or tissue Tregs but does not modify the outcome of renal degenerative renal lesions

Radiomics Applications in Spleen Imaging: A Systematic Review and Methodological Quality Assessment

The spleen, often referred to as the “forgotten organ”, plays numerous important roles in various diseases. Recently, there has been an increased interest in the application of radiomics in different areas of medical imaging. This systematic review aims to assess the current state of the art and evaluate the methodological quality of radiomics applications in spleen imaging. A systematic search was conducted on PubMed, Scopus, and Web of Science. All the studies were analyzed, and several characteristics, such as year of publication, research objectives, and number of patients, were collected. The methodological quality was evaluated using the radiomics quality score (RQS). Fourteen articles were ultimately included in this review. The majority of these articles were published in non-radiological journals (78%), utilized computed tomography (CT) for extracting radiomic features (71%), and involved not only the spleen but also other organs for feature extraction (71%). Overall, the included papers achieved an average RQS total score of 9.71 ± 6.37, corresponding to an RQS percentage of 27.77 ± 16.04. In conclusion, radiomics applications in spleen imaging demonstrate promising results in various clinical scenarios. However, despite all the included papers reporting positive outcomes, there is a lack of consistency in the methodological approaches employed

Treg level regulation by IL-2 and IL-2/anti-IL-2.

<p>Peripheral (A) and spleen/lymph nodes (B) Tregs levels were evaluated at several intervals after IL-2 and IL-2/anti-IL-2 treatment and after LPS in both WT and P2×7^−/− mice. In the case of IL-2, determination of circulating and tissue Tregs was done after 7 and 14 days from IL-2 that is the time potentially required to achieve a regulatory effect of the cytokine <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111285#pone.0111285-Boyman1" target="_blank">[21]</a>.; Tregs were also determined 3 days after LPS that means 17 days from IL-2 treatment. The time required for a regulatory effect of IL-2/anti-IL-2 is instead 5 days. Treg levels were accordingly determined at this time (i.e. 5 days after IL-2/anti-IL-2) and after 3 days from LPS corresponding to 8 days of treatment. * = p≤0.05, ** = p≤0.005, *** = p≤0.0005.</p

Proteinuria outcome in LPS mice.

<p>Urinary albumin levels were evaluated with immune-western after LPS (12 mg/Kg) treatment (24 hrs, 48 hrs and 72 hrs after treatment) in wild C57BL/6 and in P2×7^−/− mice. In some cases and in both experimental groups (WT and P2×7^−/−) IL-2 (18.000 U) and/or IL-2/anti-IL-2 were infused prior LPS to regulate circulating and tissue Tregs (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111285#pone-0111285-g003" target="_blank">Figure 3</a>). * = p≤0.05, ** = p≤0.005, *** = p≤0.0005.</p

Histology features.

<p>Classical histology (Ematoxylin Eosin, PAS) of kidney biopsies was evaluated after several times from LPS infusion (24hrs, 72 hrs and 7 days). Three main features were observed: 1-mesangial hypercellularity, 2-mesangial expansion and 3-focal segmental glomerulosclerosis that were determined in a semi-quantitative basis (score 0–3 for the former two parameters, score 0–0.3 for glomerulosclerosis). Relevant results observed after 7 days are presented in this figure (A). Specific patterns are shown in (B); stains are hematoxylin eosin for all with the exception of Masson Blue stain for LPS alone.</p