Training-to-Beat bioreactor for investigating Engineered Cardiac Tissues: design, development & validation

In last the decades, advances relevant to the generation of 3D Engineered Cardiac Tissues (ECTs) have been made. In reason of this, ECTs are now considered a great promise for in vitro studies of cardiac development, disease and, eventually, for strategies for the repair of the structure and function of the injured myocardium. Among the several physical stimuli which have been exploited to improve the functionality and maturation of ECTs, a preeminent role has been ascribed to mechanical stimulation. Appropriate mechanical stimulation can be recreated and maintained within bioreactors, which are devices/platforms devoted to mimic the physiological milieu in a monitored/controlled culture environment, where the engineered constructs can be properly stimulated. One main limitation of the bioreactor-based strategy for cardiac tissue engineering applications is that the devices which are currently used are meant to passively apply to ECTs a stimulus predefined by the user, regardless of their level of maturation along the duration of the in vitro culture. In this scenario, and trying to overcome current limitations, a novel bioreactor design has been conceived for the investigation of 3D ECTs with a biomimetic approach. Technically, the here proposed bioreactor is capable (1) to apply native-like or pathologic mechanical stimuli (cyclic strain) by means of a reliable linear actuator operating in a wide range of strains and frequencies, and (2) to monitor in real-time both chemo-physical parameters (e.g. oxygen tension, pH) of the milieu and the mechanical stiffness of ECTs by means of dedicated sensors, eventually adapting the stimulation to the actual stage of maturation of the constructs. As a proof of concept, a first experimental campaign has been carried out with a double aim: (1) to verify the bioreactor feasibility in delivering mechanical cyclical stimulation to 3D fibrin-based, ring shaped Engineered Cardiac Tissues (ECTs); (2) to assess the effect of cyclic strain on tissue maturation, contractility and modification on its mechanical properties. In detail, the bioreactor platform has been preliminarily tested to verify protocols for hold on, sterilization, and control of the delivered mechanical stimuli. Firstly, the suitability of the bioreactor platform in culturing ad-hoc designed constructs, in terms of ease of use and capability in setting the stimulation parameters, has been tested. Then, the observed maturation of ring shaped ECTs subject to sinusoidal cyclic strain within the bioreactor has confirmed the potency of the proposed approach and the instrumental role of mechanical stimulation in ECTs maturation and in the development of an adult-like cardiac phenotype responsive to electrical excitation. Even if further validation steps are required before the implementation of culture strategy fully adaptive in terms of mechanical stimuli applied to the engineered cardiac constructs, the developed bioreactor represents a valuable proof of concept for, in its most advanced operational mode, biomimetic culturing of engineered cardiac constructs

Immunology of biodegradable nanoparticles: a brief overview on a wide growing field

Immunity is continuously evolving by evolutionary mechanisms shaped by pathogenic stimuli of different kinds. Man-made nanomaterials (NMs) have been developed in the last decades and represent a novel challenge for our immune system, especially when applied to medical science. Toxicological studies of such nanoparticles (NPs) revealed that size, shape, and surface chemistry are key parameters to understand their noxious effects on cellular mechanisms. Less is known on the immune reactions to NMs since prolonged exposure data are not so detailed as the results for acute administration. The importance of immunity to biocompatible NPs is underlined by their increasing use as drug or gene delivery carriers in common pharmaceutical preparations and vaccines. In the latter case, the immunomodulatory properties of NMs allow their use also as efficient adjuvants to enhance the innate immune response. In the current manuscript, the authors discuss the main concepts in this fast-growing field by restricting our view to NMs with consolidated application in biomedicine

The Role of Quantic Molecular Resonance (QMR) in the Treatment of Inferior Turbinate Hypertrophy (ITH): Our Experience With Long-Term Follow-Up in Allergic and Nonallergic Rhinitis Refractory to Medical Therapy. Preliminary Results.

Objective: The aim of this study was to assess the long-term effectiveness of quantic molecular resonance (QMR) in the treatment of inferior turbinate hypertrophy (ITH) in allergic and nonallergic rhinitis refractory to medical therapy. Methods: This study enrolled 281 patients, 160 males (56.9%) and 121 females (43.1%), mean age 37.8 ± 4.1 years, range 18 to 71. Fifty-four patients have been lost to follow up and have been therefore excluded from the final analysis. Based on skin prick test results, 69 patients were considered allergic (group A) and 158 nonallergic (group B). All subjects underwent before surgery (T0) and 3 (T1), 12 (T2), 24 (T3), and 36 months (T4) after QMR treatment to: 4-phase rhinomanometric examination, nasal endoscopy evaluation, and visual analogue scale to quantify the subjective feelings about nasal obstruction. Results: Subjective and objective parameters showed statistically significant improvement in both groups. Group B parameters not changed during follow-up, while group A showed significant worsening between T1 and subsequent assessments. T4 outcome indicates a better result in nonallergic patients. Conclusions: In accordance with the literature, our preliminary data validate QMR treatment as a successful therapeutic option for nasal obstruction due to ITH. Nonallergic patients had a very good T4 outcome. Allergic patients showed a worsening trend after 1 year probably due to other causes

Diagnostic Value of Choline PET in the Preoperative Localization of Hyperfunctioning Parathyroid Gland(s): A Comprehensive Overview

Hyperparathyroidism is a metabolic disorder characterized by the excessive production of the parathyroid hormone. The diagnosis is based on clinical and laboratory data. In most cases the only treatment is surgery and a correct preoperatory localization of the hyperfunctioning parathyroid gland(s) is essential. Currently, ultrasonography combined with [Tc-99m]Tc-MIBI parathyroid scintigraphy, optionally associated with single photon emission computed tomography/computed tomography (SPECT/CT), represent the standard preoperative imaging. In recent years, a number of studies have evaluated the potential role of choline positron emission tomography (PET) in hyperparathyroidism with promising results. Most of the recent evidence underlined its higher sensitivity and diagnostic accuracy in the localization of hyperfunctioning parathyroid glands. Choline PET has a higher spatial resolution that is useful for the detection of smaller parathyroid glands and it also has shorter examination times and favorable radiation exposure. These are just a few of the aspects that support it to overcome traditional imaging. Moreover, from the preliminary data, the choline uptake mechanism seems to also have an impact on its better performance. For these reasons, if first used as second level imaging in patients with negative or inconclusive traditional imaging results, several authors have supported its use as a first line investigation. This comprehensive overview aims to provide an accurate description of the preliminary results available in the literature about the use of choline PET/CT in hyperparathyroidism and to compare these results with the performance of traditional imaging methods

An electro-mechanical bioreactor providing physiological cardiac stimuli

In cardiac tissue engineering it has been widely demonstrated the fundamental role of physical stimuli in improving structural and functional properties of the engineered cardiac constructs. An electro-mechanical bioreactor has been designed and developed to provide physiological uniaxial stretching and electrical stimuli for inducing functional differentiation and promoting morphological and structural maturation of cultured cardiac constructs obtained from stem cell-seeded scaffolds. The bioreactor is composed of: a transparent and sterilizable culture chamber for housing four cell-seeded scaffolds and the culture medium (working volume = 70 ml); a mechanical stimulation system, with a dedicated grasping system, to provide cyclic stretching (strain up to 20%, cycling frequency up to 2 Hz); an electrical stimulation system to provide electrical monophasic square pulses (1-6 V/cm, 0.25-10 ms, 1-5 Hz); a recirculation system for the automated medium change; a control system for data acquisition and mechanical stimulation. Preliminary in-house tests confirmed the suitability and the performances of the bioreactor as regards fittingness of chamber isolation, grasping system, and physical stimulation systems. Cell culture tests are in progress for investigating the influence of stretching and electrical stimuli on development of engineered cardiac constructs. Due to its high versatility, this bioreactor is a multipurpose adaptable system for dynamic culture of cell-seeded scaffolds for tissue engineering research and application

An uncommon etiology of pancreatitis after endoscopic ultrasound-guided fine needle aspiration

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18F-FDGPET/CT: diabetes and hyperglycaemia

BACKGROUND: Some patients who undergo 18F-FDG PET/CT for neoplastic or benign disease are also affected by diabetes or hyperglycaemia. We propose different preparation procedures in patients (pts) with hyperglycaemia (acute, temporary or chronic) or diabetes (type 1 or 2) at the time of the 18F-FDG injection, in order to improve the diagnostic scheduling of 18F-FDG PET/CT. MATERIAL AND METHODS: We evaluated a sample of 13,063 pts, examined in two different PET/CT centres, one with a stationary scanner (94.4%) and the other with a mobile device (5.6%). High blood sugar was present in 1,698 patients (13%) at the time of the 18F-FDG injection (hyperglycaemia was defined as fasting blood glucose > 11.1 mmol/l). We considered all 18F-FDG PET/CT tests performed over a period of 4 years (2006-2009). In the first 2 years (6,236 tests), scheduling was done directly by the administrative secretary. In the next two years, 6,827 pts underwent a preliminary visit to assess the test indications, medical history, and therapy as well as pre-test preparation. We evaluated different preparation protocols for hyperglycaemic or diabetic pts, especially those recommended in the guidelines of the European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine (SNM). RESULTS: In the four-year period, 713/13,063 patients (5.45%) were rescheduled; of these, 78.8% were rescheduled in the two years before the implementation of our preparation protocols and 21.2% in the next two years. Before the implementation of our preparation protocols, 562 patients (9%) presented occasional, acute or chronic hyperglycaemia (56.7%), or diabetes (43.3%), requiring postponement of the test to a later date. The test was not performed in 17 of 6,236 pts (0.27%) because of blood glucose levels above 11.1 mmol/l for several days, while in 16/6236 pts (0.26%) the 18F-FDG injection was performed despite high blood glucose levels, in view of the clinical urgency. After the implementation of the preparation protocols, 2.2% of pts were rescheduled because of occasional, acute or chronic hyperglycaemia (79%), or diabetes (21%); 0.1% of pts did not undergo the test because of chronic high blood glucose levels. Although the administration of insulin is recommended in the EANM and SNM guidelines, in our new preparation procedures experience it was not necessary, because we reduced the numbers of hyperglycaemic pts thanks to screening at the preliminary visit and a subsequent good preparation of the patient before scheduling. CONCLUSIONS: The application of our preparation protocols improves the on-time performance and diagnostic accuracy, and increases patients' compliance. Copyright © 2013 Via Medica

Monitoring Etna volcanic plumes using a scanning LiDAR

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Dal fondovalle al crinale: ripensare il sistema insediativo a partire dalla matrice storico-paesaggistica

The project propose a new access to the medieval town of Vinci through the ancient crest-path. This will assure a higher landscape quality in comparison to the main roads of the adjoining valleys. The project also propose an ecological land settlement criterion for the surrounding rural areas. The ecological value should descend from the following aspects: hills areas are not menaced by the flood as river-side areas are; new settlements must grant highs energy-saving performances, reusable building materials and a very low visual impact, in order to respect the characteristics of the rural landscape. A competition procedure could be used to assign construction rights in order to select the plans that better respond to the ecological characteristics previously listed