Systematic Review: Adipose-Derived Mesenchymal Stem Cells,Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects

The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors’ experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.     

The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets

Cannabidiol (CBD), the major nonpsychoactive Cannabis constituent, has been proposed for the treatment of a wide panel of neurological and neuropsychiatric disorders, including anxiety, schizophrenia, epilepsy and drug addiction due to the ability of its versatile scaffold to interact with diverse molecular targets that are not restricted to the endocannabinoid system. Albeit the molecular mechanisms responsible for the therapeutic effects of CBD have yet to be fully elucidated, many efforts have been devoted in the last decades to shed light on its complex pharmacological profile. In particular, an ever-increasing number of molecular targets linked to those disorders have been identified for this phytocannabinoid, along with the modulatory effects of CBD on their cascade signaling. In this view, here we will try to provide a comprehensive and up-to-date overview of the molecular basis underlying the therapeutic effects of CBD involved in the treatment of neurological and neuropsychiatric disorders.     

Milk from cows fed a diet with a high forage:concentrate ratio improves inflammatory state,oxidative stress,and mitochondrial function in rats

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage:concentrate ratio (high forage milk, HFM). In view of the low n-6:n-3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage:concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin:adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism.     

Tough salami-inspired Cf/ZrB2 UHTCMCs produced by electrophoretic deposition

One of the biggest challenges of the materials science is the mutual exclusion of strength and toughness. This issue was minimized by mimicking the natural structural materials. To date, few efforts were done regarding materials that should be used in harsh environments. In this work we present novel continuous carbon fiber reinforced ultra-high-temperature ceramic matrix composites (UHTCMCs) for aerospace featuring optimized fiber/matrix interfaces and fibers distribution. The microstructures – produced by electrophoretic deposition of ZrB₂ on unidirectional carbon fibers followed by ZrB₂ infiltration and hot pressing – show a maximum flexural strength and fracture toughness of 330 MPa and 14 MPa m^1/2, respectively. Fracture surfaces are investigated to understand the mechanisms that affect strength and toughness. The EPD technique allows the achievement of a peculiar salami-inspired architecture alternating strong and weak interfaces.     

Non-pinched, minimum energy distillation designs

Non-pinched, minimum energy solutions are important class of distillation designs that offer the potential advantage of a better trade-off between capital investment and operating costs. In this paper, two important tasks associated with non-pinched distillation designs are studied. Thus the novel contributions of this work to the literature are

(1) A comprehensive methodology for finding non-pinched minimum energy designs.

(2) Understanding of the reasons for the existence of non-pinched distillation designs.

It is shown that the recent shortest stripping line distance approach of Lucia et al. [Lucia, A., Amale, A. and Taylor, R., 2007, Distillation pinch points and more. Comput Chem Eng, available on-line] is capable of systematically and reliably finding non-pinched, minimum energy distillation designs. In addition, we provide an understanding of the reasons behind the existence of non-pinched designs, which include trajectories that follow unstable branches of a pinch point curve in azeotropic systems, the inherent looping structure of trajectories in hydrocarbon separations, and the presence of ancillary constraints in multi-unit processes like extraction/distillation. Several distillation examples are studied and many numerical results and geometric illustrations are presented that show the shortest stripping line distance methodology is indeed a powerful and systematic tool for computing non-pinched, minimum energy designs and that support the underlying reason we provide for the existence of non-pinched designs.     

A Neural Network Model of Caenorhabditis Elegans: The Circuit of Touch Sensitivity

The paper presents a neural network model of the touch sensitivity circuit of the nematode Caenorhabditis elegans. We describe a serie of simulations in which neural networks are trained, using a genetic algorithm, to reproduce the habituation of the nematode's touch sensitive behavior. A lesion study of the network allows to make a direct comparison between the fine functioning of the model and the data collected in real organisms. The model accords well with the known neurobiological data and it suggests some hypotheses about the functioning of the neural circuit and of single neurons.     

On the relationships among latent variables and residuals in PLS path modeling: The formative-reflective scheme

A new approach for the estimation and the validation of a structural equation model with a formative-reflective scheme is presented. The basis of the paper is a proposal for overcoming a potential deficiency of PLS path modeling. In the PLS approach the reflective scheme assumed for the endogenous latent variables (LVs) is inverted; moreover, the model errors are not explicitly taken into account for the estimation of the endogenous LVs. The proposed approach utilizes all the relevant information in the formative manifest variables (MVs) providing solutions which respect the causal structure of the model. The estimation procedure is based on the optimization of the redundancy criterion. The new approach, entitled redundancy analysis approach to path modeling (RA-PM) is compared with both traditional PLS Path Modeling and LISREL methodology, on the basis of real and simulated data.