Targeted nanoparticles for the delivery of novel bioactive molecules to pancreatic cancer cells

Pancreatic cancer (PaCa) is a multifaceted disorder with an extremely poor prognosis. There is an urgent need to identify new and safe drugs as well as to develop novel tumor-targeted controlled release systems for effective treatment of late stage and resistant PaCa. Active targeting via the inclusion of specific ligands on the nanoparticles (NPs) is envisioned to provide a powerful therapeutic strategy. Herein, we present a study on the design and the development of novel DFCencapsulated biocompatible polymeric NPs, functionalized with peptides to selectively bind to Plec-1 (PTP), or densely decorated by low molecular weight organic molecules as alternative targeting ligands (2-ABA), and evaluated a) the impact on ligand binding and b) the in vitro antiproliferative efficacy against a panel of PaCa cells

Bio-inspired control concepts for elastic rotatory joint drives

Annunziata S. Bio-inspired control concepts for elastic rotatory joint drives. Bielefeld: Universität Bielefeld; 2014.Recent research in robotics focuses the attention on the control of compliant actuators to improve safety and to make the interaction with humans more natural. Lightweight construction, real elasticity directly integrated into the joint and control of joint compliance seem to play the most important role for improving safety in human-machine interaction. Humans are intrinsically elastic and the Central Nervous System (CNS) takes advantage of the nonlinear muscle properties to modulate joint stiffness through co-contraction of antagonistic muscles. If alterable compliance in robotic systems is desirable, its introduction can be achieved in two fundamentally different ways. The first way is a technical approach based on the idea of impedance control as formulated by Hogan (1985). The second approach is bioinspired and introduces physiological control mechanisms, muscle models and virtual antagonistic actuation into the control system of a robotics joint drive. Recently, biological models for the control of muscles in vertebrates have been developed (Franklin et al., 2008; Yang et al., 2011). Still, the question remains, how a control algorithm, acting on two or even more muscles, can be implemented in a technical joint. With the objective to implement bio-inspired control strategies on a robotic joint drive, in this thesis, musculoskeletal models, biological parameters and bio-inspired control laws are analyzed and tested. A simplified model of the human elbow joint is used to analyze muscle-like actuation and stiffness properties at the joint. Based on recent results related to how the CNS controls antagonistic muscles, a biological control pattern based on reciprocal activation and co-activation is tested for the control of torque and stiffness at the joint. However, a closer analysis of the musculoskeletal parameters reveals that, despite antagonistic co-activation, domains in the joint range of motion might occur for which stiffness variation is limited (low stiffness variability) or even impossible (stiffness nodes). The first part of this thesis presents novel strategies for simultaneous control of torque and stiffness in a hinge joint actuated by two antagonistic muscle pairs. One strategy handles stiffness nodes by shifting them away from the current joint position and thus regaining stiffness controllability. To prevent domains of low stiffness variation, an optimal biomechanical setup is sought and finally defined which allows for a maximal stiffness variation across a wide angular joint range. Based on this optimal setup, four additional control approaches are designed and tested in simulation which deliver stiffnesses and torques comparable to those obtained in the optimal case. The control approaches combine biologically justified aspects, like reciprocal activation and co-activation, with novel ideas like inverse dynamics model and activation overflow. The second part of the thesis focuses on the design, test and validation of a bio-inspired position and stiffness control strategy for a lightweight, intrinsically elastic, robotics joint drive. Reciprocal activation and co-activation are used here as a starting point to concurrently control stiffness and position (instead of torque). A stability analysis, performed on the human elbow joint model, confirms that the co-activation level (and, as a consequence, the stiffness level) affects the reaction of the joint to external perturbations in terms of oscillations and settling time. To account for the stability aspects and implement further mechanisms found in the CNS of vertebrates, models of the muscle spindles, Golgi tendon organs, alpha-motor neurons and Renshaw cells, are added to the control algorithm. Nevertheless, while in many biological systems, antagonistic muscles generate the movement of the joint, in simple robotic systems, the movement is generated by only one actuator. Therefore, in order to transmit the desired bio-inspired movement to the technical elbow, the sum of all muscle-torques acting on the joint (i.e. the net-torque at the joint), has to be transmitted to the lightweight, inherently elastic, joint drive and controlled. A speed-torque control cascade is designed, implemented and tested on the robotics joint drive. The impedance range of the human elbow joint is evaluated in simulation and compared to the range obtained when the technical joint drive is acting instead of its biological counterpart. The bio-inspired controlled joint drive is able to reach the desired position and modulate joint compliance according to the disturbance like humans do, both in static cases and during movements, while keeping stability

Aggiornamenti epidemiologici sull’echinococcosi animale in Italia

Cystic Echinococcosis (CE) is one of the most widespread parasitoses in the Mediterranean Region (MR). This is due to various factors, the most important being the close association between man, sheep and dogs in areas where open farming is practised. Although this disease has been known for several years and many studies have been carried out, nowadays in Italy there are no complete epidemiological data on its diffusion and distribution. The available data show that CE is mainly diffused in those districts where the sheep-dog cycle can be perpetuated, such as central and southern Italy, and the islands. Furthermore, no data are available on biomolecular characterisation of the strains of Echinococcus granulosus in Italy, apart form those in Sardinia, where the G1 (sheep-dog) and G7 (pig-dog) strains were recently isolated. One of the reasons why CE is a problem with no easy solution is undoubtedly the difficulty of making a certain diagnosis in the dog, the principal definitive host of E. granulosus

The Role of 18

Purpose. To provide a first evidence-based review of the literature on the role of fluorine-18-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography (FDG-PET and PET/CT) in patients with colorectal liver metastases (CRLM) undergoing selective internal radiation therapy (SIRT) with yttrium-90 (90Y) microspheres. Methods. A comprehensive computer literature search was conducted to find relevant published articles on whole-body FDG-PET or PET/CT in patients with CRLM undergoing SIRT. Results. We identified 19 studies including 833 patients with CRLM undergoing SIRT. The role of FDG-PET or PET/CT was analysed in treatment planning, treatment response evaluation, and as prognostic tool. Conclusion. FDG-PET and PET/CT provide additional information in treatment evaluation of CRLM patients treated with SIRT and may have a role in treatment planning and patient selection. FDG-PET/CT is emerging as good prognostic tool in these patients

Escenarios regionalizados de cambio climático sobre España

Seminario del Departamento de Desarrollo y Aplicaciones impartido en la sede central de AEMET el 20 de marzo de 201

High expression of glycolytic genes in Cirrhosis correlates with the risk of developing liver cancer

© 2018 Lee, Carella, Papa and Bubici. A marked increase in the rate of glycolysis is a key event in the pathogenesis of hepatocellular carcinoma (HCC), the main type of primary liver cancer. Liver cirrhosis is considered to be a key player in HCC pathogenesis as it precedes HCC in up to 90% of patients. Intriguingly, the biochemical events that underlie the progression of cirrhosis to HCC are not well understood. In this study, we examined the expression profile of metabolic gene transcripts in liver samples from patients with HCC and patients with cirrhosis. We found that gene expression of glycolytic enzymes is up-regulated in precancerous cirrhotic livers and significantly associated with an elevated risk for developing HCC. Surprisingly, expression levels of genes involved in mitochondrial oxidative metabolism are markedly increased in HCC compared to normal livers but remain unchanged in cirrhosis. Our findings suggest that key glycolytic enzymes such as hexokinase 2 (HK2), aldolase A (ALDOA), and pyruvate kinase M2 (PKM2) may represent potential markers and molecular targets for early detection and chemoprevention of HCC

Giant endobronchial hamartoma resected by fiberoptic bronchoscopy electrosurgical snaring

Less than 1% of lung neoplasms are represented by benign tumors. Among these, hamartomas are the most common with an incidence between 0.025% and 0.32%. In relation to the localization, hamartomas are divided into intraparenchymal and endobronchial

Novel Approach for Evaluation of Bacteroides fragilis Protective Role against Bartonella henselae Liver Damage in Immunocompromised Murine Model

Bartonella henselae is a gram-negative facultative intracellular bacterium and is the causative agent of cat-scratch disease. Our previous data have established that Bacteroides fragilis colonization is able to prevent B. henselae damages through the polysaccharide A (PSA) in an experimental murine model. In order to determine whether the PSA is essential for the protection against pathogenic effects of B. henselae in immunocompromised hosts, SCID mice were co-infected with B. fragilis wild type or its mutant B. fragilis 1PSA and the effects of infection on murine tissues have been observed by High-Frequency Ultrasound (HFUS), histopathological examination, and Transmission Electron Microscopy (TEM). For the first time, echostructure, hepatic lobes length, vascular alterations, and indirect signs of hepatic dysfunctions, routinely used as signs of disease in humans, have been analyzed in an immunocompromised murine model. Our findings showed echostructural alterations in all infected mice compared with the Phosphate Buffer Solution (PBS) control group; further, those infected with B. henselae and co-infected with B. henselae/B. fragilis 1PSA presented the major echostructural alterations. Half of the mice infected with B. henselae and all those co-infected with B. henselae/B. fragilis 1PSA have showed an altered hepatic echogenicity compared with the renal cortex. The echogenicity score of co-infected mice with B. henselae/B. fragilis 1PSA differed significantly compared with the PBS control group (p < 0.05). Moreover the inflammation score of the histopathological evaluation was fairly concordant with ultrasound findings. Ultrastructural analysis performed by TEM revealed no significant alterations in liver samples of SCID mice infected with B. fragilis wild type while those infected with B. fragilis 1PSA showed the presence of collagen around the main vessels compared with the PBS control group. The liver samples of mice infected with B. henselae showed macro-areas rich in collagen, stellate cells, and histiocytic cells. Interestingly, our data demonstrated that immunocompromised SCID mice infected with B. henselaeand co-infected with B. henselae/B. fragilis ΔPSA showed the most severe morpho-structural liver damage. In addition, these results suggests that the HFUS together with histopathological evaluation could be considered good imaging approach to evaluate hepatic alterations

Seroprevalence of Bartonella henselae in patients awaiting heart transplant in Southern Italy

Background Bartonella henselae is the etiologic agent of cat-scratch disease. B. henselae infections are responsible for a widening spectrum of human diseases, although often symptomless, ranging from self-limited to life-threatening and show different courses and organ involvement due to the balance between host and pathogen. The role of the host immune response to B. henselae is critical in preventing progression to systemic disease. Indeed in immunocompromised patients, such as solid organ transplant patients, B. henselae results in severe disseminated disease and pathologic vasoproliferation. The purpose of this study was to determine the seroprevalence of B. henselae in patients awaiting heart transplant compared to healthy individuals enrolled in the Regional Reference Laboratory of Transplant Immunology of Second University of Naples. Methods Serum samples of 38 patients awaiting heart transplant in comparison to 50 healthy donors were examined using immunfluorescence assay. Results We found a B. henselae significant antibody positivity rate of 21% in patients awaiting heart transplant ( p = 0.002). There was a positive rate of 8% ( p > 0.05) for immunoglobulin (Ig)M and a significant value of 13% ( p = 0.02) for IgG, whereas controls were negative both for IgM and IgG antibodies against B. henselae . The differences in comorbidity between cases and controls were statistically different (1.41 ± 0.96 vs 0.42 ± 0.32; p = 0.001). Conclusions Although this study was conducted in a small number of patients, we suggest that the identification of these bacteria should be included as a routine screening analysis in pretransplant patients

Awareness of obesity among patients with psoriasis

Dear Editor, Chronic plaque psoriasis is frequently associated with metabolic comorbidities, including obesity that have an important impact on the disease