Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration

SmartBone^® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-β.     

A project scheduling approach to production planning with feeding precedence relations

In Manufacturing-to-Order or Engineering-to-Order systems producing complex and highly customised items, each item has its own characteristics that are often tailored for a specific customer. Project scheduling approaches are suitable for production planning in such environments. However, when we consider the production of complex items, the distinct production operations are often aggregated into activities representing whole production phases. In such cases, the planning and scheduling problem works on the aggregate activities, considering that, in most cases, such activities also have to be manually executed. Moreover, simple finish-to-start precedence relations no longer correctly represent the real production process, but overlapping among activities should be allowed. In this paper, a project scheduling approach is proposed for production planning in Manufacturing-to-Order systems. The Variable Intensity formulation is used to allow the effort committed to the execution of activities to vary over time. Feeding precedences are developed to model generalised precedence relations when the execution mode of activities is not known a priori. Two mathematical formulations of these precedence relations are proposed. The formulations are applied both to randomly generated instances and to an industrial system producing machining centres and are compared in terms of computational efficiency.     

Cognitive Abilities, Healthcare and Screening Tests

We relate indicators of cognitive abilities and health promotion to the propensity to screen for breast cancer, using microeconomic data available in a sample of women aged 50 or above in 11 European countries. Our findings suggest that health promotion activities attenuate the effect of human capital on the decision to undertake mammography, thus implying that disparities in education achievements and cognitive skills do not fully translate into differences in the propensity to do preventive screening.     

Characterization of pop-in phenomena and indentation modulus in a polycrystalline ZrB2 ceramic

Low-load nanoindentation tests were carried out on a polycrystalline ZrB₂-based ceramic. Pop-in phenomena were observed when indentation marks were placed in the interior of the ZrB₂ grains. Both pop-in loads and pop-in extents were statistically distributed with a mutual strong correlation. The critical shear stresses at pop-in were in good agreement with the theoretical shear strength of ZrB₂. The experimental pop-in extents were also compared to a simplified model developed for homogeneous dislocation nucleation. The influence of the grain orientation on the indentation modulus was derived from the model of Delafargue and Ulm (2004)⁵⁰ and compared to the experimental results. Some results were definitely influenced by the polycrystalline structure of the investigated ceramic.     

Sensitivity and devaney’s chaos in uniform spaces

We give sufficient conditions for sensitivity of continuous group actions on uniform spaces.     

On the effect of aortic root geometry on the coronary entry-flow after a bileaflet mechanical heart valve implant: a numerical study

The simultaneous replacement of a diseased aortic valve, aortic root and ascending aorta with a prosthesis is known as Bentall procedure (Bentall and De Bono in Thorax 23:338, 1968). This is a nowadays standard surgical approach in which the Valsalva sinuses of the aortic root are sacrificed and the coronary arteries are reconnected directly to the graft. The important function of the natural sinuses in the presence of the natural valve is well established; however, very little information is available about whether or not their presence can affect the functioning of a prosthetic bi-leaflet valve and the coronary flow. In the present work, we study the effect of the aortic root geometry on the blood flow through such devices, focusing the attention on the coronary entry-flow. Three root geometries have been considered, two mimicking the prostheses used in practice by surgeons (a straight tube, and the more recent tube with a circular pseudo-sinus), and a third maintaining the natural shape with three sinuses, obtained by Reul et?al. (J Biomech 23:181?C191, 1990) by averaging numerous angiographies of the aortic root in healthy patients. Direct numerical simulations of the flow inside the three prostheses, assumed as undeformable, under physiological pulsatile inflow conditions are presented. The dynamics of the valvular leaflets is obtained by a fully-coupled fluid?Cstructure-interaction approach and the coronary perfusion is reproduced by modulating in time an equivalent porosity, an thus the resistance, of the coronary channels. The results indicate that the sinuses do not significantly influence the coronary entry flow, in agreement with the in vivo observations of De Paulis et?al. (Eur J Cardio-thorac Surg 26:66?C72, 2004). Nevertheless, the peak pressure at the joints of the coronary arteries is smaller in the natural-like aortic root geometry. The latter also produces a further beneficial effect of a reduction in the leaflets?? angular velocity at the closure onto the valvular ring. These phenomena, if confirmed in more realistic clinical conditions, suggest that the use of a prothesis with physiologic sinuses would potentially reduce the local pressure peak, with the associated risk of post-operative bleeding and pseudo-aneurysm formation. It would also reduce the haemolysis effects caused by the red blood cells squashing between impacting solid artificial surfaces.     

Feasibility of a long-term low-sodium diet in mild hypertension

The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice. After screening and a run-in phase of 6-8 weeks, a total of 77 previously undiagnosed mildly hypertensive patients were identified. Half of them were randomized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage; the others were randomized to receive no advice. The patients were followed up for 12 months with quarterly visits. A total of 56 patients (72.7%) completed the study, 26 on a low-sodium diet (LD) and 30 on their usual diet (UD). At each visit in the diet phase, patients provided 24h urine, which was analysed for volume and sodium concentration in order to assess their sodium intake. Blood pressure, heart the rate and body weight were recorded. The mean urinary sodium excretion for all diet phase visits overlapped in the two groups (177.0 +/- 32.9 vs. 169.3 +/- 49.4 mEq/24h respectively in the LD and UD groups). Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group (144.2 +/- 11.1/91.6 +/- 6.4 and 148.0 +/- 13.7/95.6 +/- 4.7 mmHg respectively, P less than 0.01). Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions, the only ones suitable for widespread application in general practice.