Blade loss transient dynamics analysis, volume 2. Task 2: Theoretical and analytical development. Task 3: Experimental verification

The component element method was used to develop a transient dynamic analysis computer program which is essentially based on modal synthesis combined with a central, finite difference, numerical integration scheme. The methodology leads to a modular or building-block technique that is amenable to computer programming. To verify the analytical method, turbine engine transient response analysis (TETRA), was applied to two blade-out test vehicles that had been previously instrumented and tested. Comparison of the time dependent test data with those predicted by TETRA led to recommendations for refinement or extension of the analytical method to improve its accuracy and overcome its shortcomings. The development of working equations, their discretization, numerical solution scheme, the modular concept of engine modelling, the program logical structure and some illustrated results are discussed. The blade-loss test vehicles (rig full engine), the type of measured data, and the engine structural model are described

mTOR-Inhibition and COVID-19 in Kidney Transplant Recipients: Focus on Pulmonary Fibrosis

Kidney transplant recipients are at high risk of developing severe COVID-19 due to the coexistence of several transplant-related comorbidities (e.g., cardiovascular disease, diabetes) and chronic immunosuppression. As a consequence, a large part of SARS-CoV-2 infected patients have been managed with a reduction of immunosuppression. The mTOR-I, together with antimetabolites, have been often discontinued in order to minimize the risk of pulmonary toxicity and to antagonize pharmacological interaction with antiviral/anti-inflammatory drugs. However, at our opinion, this therapeutic strategy, although justified in kidney transplant recipients with severe COVID-19, should be carefully evaluated in asymptomatic/paucisymptomatic patients in order to avoid the onset of acute allograft rejections, to potentially exploit the mTOR-I antiviral properties, to reduce proliferation of conventional T lymphocytes (which could mitigate the cytokine storm) and to preserve Treg growth/activity which could reduce the risk of progression to severe disease. In this review, we discuss the current literature regarding the therapeutic potential of mTOR-Is in kidney transplant recipients with COVID-19 with a focus on pulmonary fibrosis

Good subjective outcomes, stable knee and high return to sport after tibial eminence avulsion fracture in children

Avulsion fracture of the tibial spine (TSA) is uncommon in children, although its incidence is increasing with the earlier practice of competitive sport activities. This study aims to report mid to long term outcomes in children who sustained a TSA, with a special focus on a return to sport activities. Skeletally immature patients with a TSA, treated in two orthopedic hospitals, were evaluated for range of motion and knee laxity using KT1000, KiRA and Rolimeter. The pediatric International Knee Documentation Committee score (Pedi-IKDC) and the Hospital for Special Surgery pediatric Functional Activity Brief Scale (Pedi-FABS) questionnaires were recorded during the latest visit. Forty-two children were included. Twenty-six were treated nonoperatively and 16 underwent surgery. At a mean follow-up of 6.9 ± 3.6 years, 36 patients completed the questionnaires and 23 patients were tested with arthrometers. Among them, 96% had normal knee laxity. The Pedi-IKDC score averaged 96.4 ± 5.7 points, while the mean Pedi-FABS was 22.2 ± 5.9 points, without statistically significant differences between groups. Twenty-eight patients (78%) returned to their previous level of sport activity (eight amateur, 13 competitive, seven elite athletes). Eight patients (22%) quit sport, mostly because of re-injury fear. If properly treated, pediatric TSAs achieve a high rate of successful healing, with complete restoration of knee stability and an early return to sport activities

Cementless ceramic-on-ceramic total hip replacement in children and adolescents

Background: total hip replacement (THR) is a rare surgical option in children and adolescents with disabling hip diseases. The aim of this study is to report results from a retrospective cohort of patients aged 18 years or less who underwent cementless Ceramic-on-Ceramic (CoC) THR at a single institution, investigating clinical and radiographic outcomes, survival rates, and reasons for revision of the implants. Materials and methods: we queried the Registry of Prosthetic Orthopedic Implants (RIPO) to identify all children and adolescents undergoing THR between 2000 and 2019 at a single Institution. Inclusion criteria were patients undergoing cementless CoC THR, aged less than 18 years at surgery, followed for at least 2 years. Sixty-eight patients (74 hips) matched all the inclusion criteria and were enrolled in the study. We assessed the clinical and radiographic outcomes, the rate of complications, the survival rate, and reasons for revision of the implants. Results: The mean follow-up was 6.6 ± 4.4 years (range 2–20). The most frequent reason for THR was post-traumatic or chemotherapy-induced avascular necrosis (38%). The overall survival rate of the cohort was 97.6% (95% CI: 84.9–99.7%) at 5 years of follow-up, 94.4% (95% CI: 79.8–98.6%) at 10 years and 15 years of follow-up. Two THR in two patients (2.7%) required revision. With the numbers available, Cox regression analysis could not detect any significant interaction between preoperative or intraoperative variables and implant survivorship (p-value 0.242 to 0.989).” The average HOOS was 85 ± 14.3 (range 30.6–100). Overall, 23 patients (48%) reported excellent HOOS scores (>90 points), 21 patients (44%) reported acceptable HOOS scores (60–90 points) while 4 patients (8%) reported poor outcomes (<60 points). Twenty-one patients (43%) were regularly involved into moderate-to high-intensity sport activities (UCLA ≥ 6). Conclusions: Cementless CoC THR is a successful procedure in children and teenagers, having demonstrated high implant survivorship and low rates of complications and failure. A meticulous preoperative planning and implant selection is mandatory, to avoid implant malposition, which is the main reason of failure and revision in these cases. Further studies are needed to assess the impact of the THR on the psychosocial wellbeing of teenagers, as well as risks and benefits and cost-effectiveness in comparison to the hip preserving surgical procedures

The Role of Fructose as a Cardiovascular Risk Factor: An Update

There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their prevention should be assessed and managed comprehensively and not by the evaluation of individual risk factor components. Lifestyle risk factors for CVD include low degree of physical activity, high body mass index, alcohol consumption, smoking, and nutritional factors. Indeed, nutritional risk factors for CVD include unhealthy dietary behaviors, such as high intake of refined foods, unhealthy fats, added sugars, and sodium and a low intake of fruits, vegetables, whole grains, fiber, fish, and nuts. Even though there is no definitive association between CVD incidence and high consumption of total sugar, such as sucrose and fructose, there is, however, evidence that total sugars, added sugars, and fructose are harmfully associated with CVD mortality. Since high fructose intake is associated with elevated plasma triglyceride levels, as well as insulin resistance, diabetes hyperuricemia, and non-alcoholic fatty liver disease, further longitudinal studies should be conducted to fully elucidate the potential association between certain sugars and CVD

Rapamycin promotes autophagy cell death of Kaposi’s sarcoma cells through P75NTR activation

The mammalian target of rapamycin inhibitor (mTOR-I) Rapamycin, a drug widely used in kidney transplantation, exerts important anti-cancer effects, particularly in Kaposi's Sarcoma (KS), through several biological interactions. In this in vivo and in vitro study, we explored whether the activation of the autophagic pathway through the low-affinity receptor for nerve growth factor, p75NTR, may have a pivotal role in the anti-cancer effect exerted by Rapamycin in S. Our Kimmunohistochemistry results revealed a significant hyper-activation of the autophagic pathway in KS lesions. In vitro experiments on KS cell lines showed that Rapamycin exposure reduced cell viability by increasing the autophagic process, in the absence of apoptosis, through the transcriptional activation of p75NTR via EGR1. Interestingly, p75NTR gene silencing prevented the increase of the autophagic process and the reduction of cell viability. Moreover, p75NTR activation promoted the upregulation of phosphatase and tensin homolog (PTEN), a tumour suppressor that modulates the PI3K/Akt/mTOR pathway. In conclusion, our in vitro data demonstrated, for the first time, that in Kaposi's sarcoma, autophagy triggered by Rapamycin through p75NTR represented a major mechanism by which mTOR inhibitors may induce tumour regression. Additionally, it suggested that p75NTR protein analysis could be proposed as a new potential biomarker to predict response to Rapamycin in kidney transplant recipients affected by Kaposi's sarcoma

CD40 cross-linking induces migration of renal tumor cell through nuclear factor of activated T cells (NFAT) activation

CD40 crosslinking plays an important role in regulating cell migration, adhesion and proliferation in renal cell carcinoma (RCC). CD40/CD40L interaction on RCC cells activates different intracellular pathways but the molecular mechanisms leading to cell scattering are not yet clearly defined. Aim of our study was to investigate the main intracellular pathways activated by CD40 ligation and their specific involvement in RCC cell migration. CD40 ligation increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH (2)-terminal kinase (JNK) and p38 MAPK. Furthermore, CD40 crosslinking activated different transcriptional factors on RCC cell lines: AP-1, NFkB and some members of the Nuclear Factor of Activated T cells (NFAT) family. Interestingly, the specific inhibition of NFAT factors by cyclosporine A, completely blocked RCC cell motility induced by CD40 ligation. In tumor tissue, we observed a higher expression of NFAT factors and in particular an increased activation and nuclear migration of NFATc4 on RCC tumor tissues belonging to patients that developed metastases when compared to those who did not. Moreover, CD40-CD40L interaction induced a cytoskeleton reorganization and increased the expression of integrin β1 on RCC cell lines, and this effect was reversed by cyclosporine A and NFAT inhibition. These data suggest that CD40 ligation induces the activation of different intracellular signaling pathways, in particular the NFATs factors, that could represent a potential therapeutic target in the setting of patients with metastatic RCC