A telerehabilitation platform for cognitive, physical and behavioural rehabilitation in elderly patients affected by dementia

Dementia is one of the main causes of disability in elderly people and its treatment becomes, year after year, an increasingly compelling priority for the public health system. In the last years, home assistance and telemedicine have paved the way to decrease the treatments’ costs and to improve the patients and caregivers quality of life quality. In this framework, the aim of ABILITY project is to design, develop and validate an integrated platform of services aimed at supporting and enhancing the rehabilitation process for patients with dementia at their homes. ABILITY platform allows the clinician to assign rehabilitation plans with a strong compliance monitoring, enabled by the technological solutions integrated, and the holistic approach to rehabilitation, as the plan includes physical, cognitive and behavioral therapies/exercises. The ABILITY platform will be assessed through a set of validation activities, involving a small group of pilot patients, and a Randomized Control Trial. In conclusion, the ABILITY project generates a series of assistive services inside a modular and flexible platform, adaptable to the single patient and his/her needs, increasing the treatment efficiency and efficacy with respect to the state of the art

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

ANALYSIS OF THE PASSIVE MECHANICAL BEHAVIOR OF TAENIAE COLI: EXPERIMENTAL AND NUMERICAL APPROACH

The constitutive analysis of gastrointestinal tissues represents a fundamental aspect for the biomechanical investigation of gastrointestinal structures and organs by using computational methods. This approach makes it possible to obtain an accurate and extensive set of results, also offering the possibility to evaluate the interaction with surgical devices. The constitutive analysis of taeniae coli tissue is performed by a multi-disciplinary approach that requires the cooperation between medical, experimental and computational competences, as common practice in biological tissues mechanics. The analysis of taeniae coli histology suggests the assumption of a transversally isotropic scheme, because of the orientation of muscular fibres along a preferential direction. Mechanical tests are designed and planned in consideration of the mentioned structural conformation, considering tensile tests imposed according to different loading directions. The results from histological and experimental investigations lead to the definition of a constitutive model in the framework of fibre-reinforced hyperelastic materials. The constitutive parameters are evaluated by the comparative analysis between experimental and numerical results by means of a minimization of their discrepancy. The reliability of the constitutive formulation and parameters is assessed by the analysis of additional experimental data and the evaluation of satisfaction of thermo-mechanics requirements about material stability

A COUPLED EXPERIMENTAL AND NUMERICAL APPROACH TO CHARACTERIZE THE ANISOTROPIC MECHANICAL BEHAVIOR OF AORTIC TISSUES

Nowadays, the investigation of aortic wall biomechanics is a fundamental tool in clinicalresearch and vascular prosthesis design. This study aims at analyzing the biomechanicalbehavior of aortic tissues using a coupled experimental and computational approach. Con-sidering the typical fiber-reinforced configuration of aortic tissues, uni-axial tensile tests alongsix different loading directions were performed on specimens from pig aorta. Starting from theobtained experimental data, a suitable constitutive framework was defined and a methodologyfor the identification of the constitutive parameters was developed using the inverse analysis ofmechanical tests. Transversal stretch versus loading stretch and nominal stress versus loadingstretch curves were evaluated, showing the anisotropic and nonlinear mechanical behaviordetermined by tissue conformation with fibers distributed along preferential directions. Indetail, experimental data showed different mechanical responses between longitudinal andcircumferential directions, with a greater tissue stiffness along the longitudinal one. The reli-ability of the developed constitutive framework was evaluated by the comparison betweenexperimental data and model results. The mentioned analysis can be considered as a useful toolfor the development of reliable computational models, which allow a better understanding ofthe pathophysiology of cardiovascular diseases and can be applied for a proper planning ofsurgical procedures

Characterization of the anisotropic mechanical behaviour of colon tissues: experimental activities and constitutive formulation.

New Findings: What is the central question of this study? The wall of the colon shows an anisotropic and non-linear mechanical response, because of the distribution and mechanical properties of sub-components. This study aimed to provide, by a coupled experimental and computational approach, a constitutive framework to interpret the mechanics of colonic tissues. What is the main finding and its importance? Tensile tests on tissue samples from pig colon were developed. The experimental data were processed to define proper constitutive formulations. Constitutive parameters were identified by the inverse analysis of experimental tests. The reliability of parameters was assessed by agreement between the experimental and model results and the satisfaction of material thermomechanics principles. The developed constitutive framework is capable of interpreting the general anisotropic and non-linear mechanical behaviour of colonic tissues. The aim was to investigate the biomechanical behaviour of colonic tissues by a coupled experimental and numerical approach. The wall of the colon is composed of different tissue layers. Within each layer, different fibre families are distributed according to specific spatial orientations, which lead to a strongly anisotropic configuration. Accounting for the complex histology of the tissues, mechanical tests must be planned and designed to evaluate the behaviour of the colonic wall in different directions. Uni-axial tensile tests were performed on tissue specimens from 15 fresh pig colons, accounting for six different loading directions (five specimens for each loading direction). The next step of the investigation was to define an appropriate constitutive framework and develop a procedure for identification of the constitutive parameters. A specific hyperelastic formulation was developed that accounted for the multilayered conformation of the colonic wall and the fibre-reinforced configuration of the tissues. The parameters were identified by inverse analyses of the mechanical tests. The comparison of model results with experimental data, together with the evaluation of satisfaction of material thermomechanics principles, confirmed the reliability of the analysis developed. This work forms the basis for more comprehensive activities that aim to provide computational tools for the interpretation of surgical procedures that involve the gastrointestinal tract, considering the specific biomedical devices adopted

Differential Dynamics of SARS-CoV-2 Binding and Functional Antibodies upon BNT162b2 Vaccine: A 6-Month Follow-Up

To investigate the dynamic association among binding and functional antibodies in health-care-workers receiving two doses of BNT162b2 mRNA COVID-19-vaccine, SARS-CoV-2 anti-RBD IgG, anti-Trimeric-S IgG, and neutralizing antibodies (Nabs) were measured in serum samples collected at 2 weeks, 3 months, and 6 months from full vaccination. Despite the high correlation, results for anti-RBD and anti-Trimeric S IgG were numerically different even after recalculation to BAU/mL following WHO standards indications. Moreover, after a peak response at 2 weeks, anti-RBD IgG levels showed a 4.5 and 13 fold decrease at 3 and 6 months, respectively, while the anti-Trimeric S IgG presented a less pronounced decay of 2.8 and 4.7 fold. Further different dynamics were observed for Nabs titers, resulting comparable at 3 and 6 months from vaccination. We also demonstrated that at NAbs titers ≥40, the area under the receiver operating characteristic curve and the optimal cutoff point decreased with time from vaccination for both anti-RBD and anti-Trimeric S IgG. The mutating relation among the anti-RBD IgG, anti-Trimeric S IgG, and neutralizing antibodies are indicative of antibody maturation upon vaccination. The lack of standardized laboratory procedures is one factor interfering with the definition of a correlate of protection from COVID-19

Retention of Neutralizing Response against SARS-CoV-2 Omicron Variant in Sputnik V-Vaccinated Individuals

The new Omicron variant of SARS-CoV-2, first identified in November 2021, is rapidly spreading all around the world. Omicron has become the dominant variant of SARS-CoV-2. There are many ongoing studies evaluating the effectiveness of existing vaccines. Studies on the neutralizing activity of vaccinated sera against the Omicron variant are currently being carried out in many laboratories. In this study, we have shown the neutralizing activity of sera against the SARS-CoV-2 Omicron variant compared to the reference Wuhan D614G variant in individuals vaccinated with two doses of Sputnik V up to 6 months after vaccination and in individuals who experienced SARS-CoV-2 infection either before or after vaccination. As a control to our study we also measured neutralizing antibody titers in individuals vaccinated with two doses of BNT162b2. The decrease in NtAb titers to the Omicron variant was 8.1-fold for the group of Sputnik V-vaccinated individuals. When the samples were stratified for the time period after vaccination, a 7.6-fold or 8.8-fold decrease in NtAb titers was noticed after up to 3 and 3-to-6 months after vaccination. We observed a 6.7- and 5-fold decrease in Sputnik V-vaccinated individuals experiencing asymptomatic or symptomatic infection, respectively. These results highlight the observation that the decrease in NtAb to the SARS-CoV-2 Omicron variant compared to the Wuhan variant occurs for different COVID-19 vaccines in use, with some showing no neutralization at all, confirming the necessity of a third booster vaccination

Safety and immune response kinetics of GRAd-COV2 vaccine: phase 1 clinical trial results

Despite the successful deployment of efficacious vaccines and therapeutics, the development of novel vaccines for SARS-CoV-2 remains a major goal to increase vaccine doses availability and accessibility for lower income setting. We report here on the kinetics of Spike-specific humoral and T-cell response in young and old volunteers over 6 months follow-up after a single intramuscular administration of GRAd-COV2, a gorilla adenoviral vector-based vaccine candidate currently in phase-2 of clinical development. At all three tested vaccine dosages, Spike binding and neutralizing antibodies were induced and substantially maintained up to 3 months, to then contract at 6 months. Potent T-cell responses were readily induced and sustained throughout the study period, with only minor decline. No major differences in immune response to GRAd-COV2 vaccination were observed in the two age cohorts. In light of its favorable safety and immunogenicity, GRAd-COV2 is a valuable candidate for further clinical development and potential addition to the COVID-19 vaccine toolbox to help fighting SARS-CoV-2 pandemic