Blade loss transient dynamics analysis, volume 1. Task 1: Survey and perspective

An analytical technique was developed to predict the behavior of a rotor system subjected to sudden unbalance. The technique is implemented in the Turbine Engine Transient Rotor Analysis (TETRA) computer program using the component element method. The analysis was particularly aimed toward blade-loss phenomena in gas turbine engines. A dual-rotor, casing, and pylon structure can be modeled by the computer program. Blade tip rubs, Coriolis forces, and mechanical clearances are included. The analytical system was verified by modeling and simulating actual test conditions for a rig test as well as a full-engine, blade-release demonstration

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

The Role of Natural Killer Cells in the Immune Response in Kidney Transplantation

Natural killer cells (NK) represent a population of lymphocytes involved in innate immune response. In addition to their role in anti-viral and anti-tumor defense, they also regulate several aspects of the allo-immune response in kidney transplant recipients. Growing evidence suggests a key role of NK cells in the pathogenesis of immune-mediated graft damage in kidney transplantation. Specific NK cell subsets are associated with operational tolerance in kidney transplant patients. On the other side, allo-reactive NK cells are associated with chronic antibody-mediated rejection and graft loss. Moreover, NK cells can prime the adaptive immune system and promote the migration of other immune cells, such as dendritic cells, into the graft leading to an increased allo-immune response and, eventually, to chronic graft rejection. Finally, activated NK cells can infiltrate the transplanted kidney and cause a direct graft damage. Interestingly, immunosuppression can influence NK cell numbers and function, thus causing an increased risk of post-transplant neoplasia or infection. In this review, we will describe how these cells can influence the innate and the adaptive immune response in kidney transplantation and how immunosuppression can modulate NK behavior

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

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

mTOR inhibitors effects on regulatory T cells and on dendritic cells.

The mammalian target of rapamycin (mTOR), a cytoplasmic serine/threonine kinase, represents a key biologic "switch" modulating cell metabolisms in response to environmental signals and is now recognized as a central regulator of the immune system. There is an increasing body of evidence supporting the hypothesis that mTOR inhibitors exhibit several biological properties in addition to immunosuppression, including anti-neoplastic effects, cardio-protective activities, and an array of immunomodulatory actions facilitating the development of an operational graft tolerance. The biological mechanisms explaining how mTOR inhibition can enable a tolerogenic state are still largely unclear. The induction of transplant tolerance might at the same time decrease rejection rate and minimize immunosuppression-related side effects, leading to an improvement in long-term graft outcome. In this scenario, T cell immunoregulation has been defined as the hallmark of peripheral tolerance. Two main immunologic cell populations have been reported to play a central role in this setting: regulatory T cells (Tregs) and dendritic cells (DCs). In this review we focus on mTOR inhibitors effects on Treg and DCs differentiation, activation, and function in the transplantation setting

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

Age-Related Central Auditory Processing Disorder, MCI, and Dementia in an Older Population of Southern Italy

Objective: We explored the associations of age-related central auditory processing disorder (CAPD) with mild cognitive impairment (MCI) and dementia in an older population-based cohort in Apulia, Southern Italy (GreatAGE Study). / Study Design: Cross-sectional data from a population-based study. / Setting: Castellana Grotte, Bari, Italy. / Subjects and Methods: Between 2013 and 2018, MCI, dementia, age-related CAPD (no disabling hearing loss and 65 years. / Results: The prevalences of age-related CAPD, MCI, and dementia were 14.15%, 15.79%, and 3.58%, respectively. Among the subjects with MCI and dementia, 19.61% and 42.37% had age-related CAPD. In the regressive models, age-related CAPD was associated with MCI (odds ratio, 1.50; 95% CI, 1.01-2.21) and dementia (odds ratio, 2.23; 95% CI, 1.12-4.42). Global cognition scores were positively associated with increasing SSI-ICM scores in linear models. All models were adjusted for demographics and metabolic serum biomarkers. / Conclusion: The tight association of age-related CAPD with MCI and dementia suggests the involvement of central auditory pathways in neurodegeneration, but it is not clear which is the real direction of this association. However, CAPD is a possible diagnostic marker of cognitive dysfunction in older patients