On the Expressive Power of Multiple Heads in CHR

Constraint Handling Rules (CHR) is a committed-choice declarative language which has been originally designed for writing constraint solvers and which is nowadays a general purpose language. CHR programs consist of multi-headed guarded rules which allow to rewrite constraints into simpler ones until a solved form is reached. Many empirical evidences suggest that multiple heads augment the expressive power of the language, however no formal result in this direction has been proved, so far. In the first part of this paper we analyze the Turing completeness of CHR with respect to the underneath constraint theory. We prove that if the constraint theory is powerful enough then restricting to single head rules does not affect the Turing completeness of the language. On the other hand, differently from the case of the multi-headed language, the single head CHR language is not Turing powerful when the underlying signature (for the constraint theory) does not contain function symbols. In the second part we prove that, no matter which constraint theory is considered, under some reasonable assumptions it is not possible to encode the CHR language (with multi-headed rules) into a single headed language while preserving the semantics of the programs. We also show that, under some stronger assumptions, considering an increasing number of atoms in the head of a rule augments the expressive power of the language. These results provide a formal proof for the claim that multiple heads augment the expressive power of the CHR language.Comment: v.6 Minor changes, new formulation of definitions, changed some details in the proof

Polysaccharide-based self-assembling nanohydrogels: An overview on 25-years research on pullulan

The aim of this overview is to review the evolution of the studies carried out, during more than 25 years, on nanohydrogels obtained by self-assembling of pullulan (PUL) using several hydrophobization strategies. After the first publications, mainly devoted to the preparation and characterization of PUL nanogels, a remarkable number of studies demonstrated how wide can be the field of applications within the main topic of biopharmaceutics. Numerous hydrophilic and lipophilic drugs were entrapped in the nanogel networks, consequently PUL nanogels have been proposed as delivery systems for single drugs and for combination therapies which allowed improvements of pharmacological activities and patient compliance. Furthermore, the large amount of water content allowed loading also proteins which could maintain their native structure and properties. Stimuli-sensitive and stealth PUL nanogel formulations allowed improving the performances of antitumor drugs. These nanohydrogels have also been studied for imaging techniques and for vaccines to be administered by injection and by mucosal application. The studies on PUL nanogels are still in progress and the perspectives for future researches are also addressed

Does the use of dietary supplements enhance athletes’ sport performances? A systematic review and a meta-analysis

Background: The consumption of dietary supplements has increased in recent years. Despite their widespread use, there is confusion about effects on sport performances. The aim of this study was to investigate association between use of supplements and enhance of athletes’ sports performance. Methods: A review and a meta-analysis of studies conducted on Dietary Supplements and Sports between 2003 and 2013 were performed. Enhancement on sport performances was considered as outcome. The following aspects related to enhancement were considered: ergogenic effect (EE), time to exhaustion (TTE), muscular endurance (ME), post-exercise recovery (PER) and body mass (BM). With respect to meta-analysis, data on level of post Exercise Glucose (GpE [mg/dL]) and level of post exercise Lactate (LpE [mmol/L]) were considered as  indicators of TTE, PER and EE. Similarly, Change in Body Mass (CBM) [kg] was used as indicator of BM. Results: The most investigated dietary supplements were: Creatine, Carbohydrates, Beta-alanine, Proteins. The qualitative analysis evaluating the effect of supplements on sports listed by the International Olympic Committee has achieved interesting results: supplements didn’t show statistically significant effects when compared to placebo in more than 48% of papers. For the quantitative analysis, 15 studies were considered. The meta-analysis showed that there was no significant effect of Beta-alanine, Creatine and Carbohydrates on LpE and GpE. Furthermore, a non-significant increase in BM was observed in athletes undergoing Creatine compared to placebo. Conclusion: Considering the increasing attention to this topic, it would be interesting to investigate the existing awareness about effectiveness and possible risks of supplements

Design of hybrid gels based on gellan-cholesterol derivative and P90G liposomes for drug depot applications

Gels are extensively studied in the drug delivery field because of their potential benefits in therapeutics. Depot gel systems fall in this area, and the interest in their development has been focused on long-lasting, biocompatible, and resorbable delivery devices. The present work describes a new class of hybrid gels that stem from the interaction between liposomes based on P90G phospholipid and the cholesterol derivative of the polysaccharide gellan. The mechanical properties of these gels and the delivery profiles of the anti-inflammatory model drug diclofenac embedded in such systems confirmed the suitability of these hybrid gels as a good candidate for drug depot applications

Decidability properties for fragments of CHR

We study the decidability of termination for two CHR dialects which, similarly to the Datalog like languages, are defined by using a signature which does not allow function symbols (of arity >0). Both languages allow the use of the = built-in in the body of rules, thus are built on a host language that supports unification. However each imposes one further restriction. The first CHR dialect allows only range-restricted rules, that is, it does not allow the use of variables in the body or in the guard of a rule if they do not appear in the head. We show that the existence of an infinite computation is decidable for this dialect. The second dialect instead limits the number of atoms in the head of rules to one. We prove that in this case, the existence of a terminating computation is decidable. These results show that both dialects are strictly less expressive than Turing Machines. It is worth noting that the language (without function symbols) without these restrictions is as expressive as Turing Machines

Hyaluronan and Derivatives: An In Vitro Multilevel Assessment of Their Potential in Viscosupplementation

In this research work, viscosupplements based on linear, derivatized, crosslinked and complexed HA forms were extensively examined, providing data on the hydrodynamic parameters for the water-soluble-HA-fraction, rheology, sensitivity to enzymatic hydrolysis and capacity to modulate specific biomarkers’ expression in human pathological chondrocytes and synoviocytes. Soluble HA ranged from 0 to 32 mg/mL and from 150 to 1330 kDa MW. The rheological behavior spanned from purely elastic to viscoelastic, suggesting the diversity of the categories that are suitable for restoring specific/different features of the healthy synovial fluid. The rheological parameters were reduced in a diverse manner upon dilution and hyaluronidases action, indicating different durations of the viscosupplementation effect. Bioactivity was found for all the samples, increasing the expression of different matrix markers (e.g., hyaluronan-synthase); however, the hybrid cooperative complexes performed better in most of the experiments. Hybrid cooperative complexes improved COLII mRNA expression (~12-fold increase vs. CTR), proved the most effective at preserving cell phenotype. In addition, in these models, the HA samples reduced inflammation. IL-6 was down-regulated vs. CTR by linear and chemically modified HA, and especially by hybrid complexes. The results represent the first comprehensive panel of data directly comparing the diverse HA forms for intra-articular injections and provide valuable information for tailoring products’ clinical use as well as for designing new, highly performing HA-formulations that can address specific needs

Pursuing intracellular pathogens with hyaluronan. From a 'pro-infection' polymer to a biomaterial for 'trojan horse' systems

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Hyaluronan (HA) is among the most important bioactive polymers in mammals, playing a key role in a number of biological functions. In the last decades, it has been increasingly studied as a biomaterial for drug delivery systems, thanks to its physico-chemical features and ability to target and enter certain cells. The most important receptor of HA is 'Cluster of Differentiation 44' (CD44), a cell surface glycoprotein over-expressed by a number of cancers and heavily involved in HA endocytosis. Moreover, CD44 is highly expressed by keratinocytes, activated macrophages and fibroblasts, all of which can act as 'reservoirs' for intracellular pathogens. Interestingly, both CD44 and HA appear to play a key role for the invasion and persistence of such microorganisms within the cells. As such, HA is increasingly recognised as a potential target for nano-carriers development, to pursuit and target intracellular pathogens, acting as a 'Trojan Horse'. This review describes the biological relationship between HA, CD44 and the entry and survival of a number of pathogens within the cells and the subsequent development of HA-based nano-carriers for enhancing the intracellular activity of antimicrobials

Preparation of gellan-cholesterol nanohydrogels embedding baicalin and evaluation of their wound healing activity

[EN] In the present work, the preparation, characterization and therapeutic potential of baicalin-loaded nanohydrogels are reported. The nanohydrogels were prepared by sonicating (S nanohydrogel) or autoclaving (A nanohydrogel) a dispersion of cholesterol-derivatized gellan in phosphate buffer. The nanohydrogel obtained by autoclave treatment showed the most promising results: smaller particles ( similar to 362 nm vs. similar to 530 nm), higher homogeneity (polydispersity index = similar to 0.24 vs. similar to 0.47), and lower viscosity than those obtained by sonication. In vitro studies demonstrated the ability of the nanohydrogels to favour the deposition of baicalin in the epidermis. A high biocompatibility was found for baicalin-loaded nanohydrogels, along with a great ability to counteract the toxic effect induced by hydrogen peroxide in cells, as the nanohydrogels re-established the normal conditions (similar to 100% viability). Further, the potential of baicalin-loaded nanohydrogels in skin wound healing was demonstrated in vivo in mice by complete skin restoration and inhibition of specific inflammatory markers (i.e., myeloperoxidase, tumor necrosis factor-alpha, and oedema.Financial support from University "Sapienza" - Progetti di Ricerca: grant RP116154C2EF9AC8 and grant RM11715C1743EE89 are acknowledged.Manconi, M.; Manca, M.; Caddeo, C.; Cencetti, C.; Di Meo, C.; Zoratto, N.; Nácher Alonso, A.... (2018). Preparation of gellan-cholesterol nanohydrogels embedding baicalin and evaluation of their wound healing activity. European Journal of Pharmaceutics and Biopharmaceutics. 127:244-249. https://doi.org/10.1016/j.ejpb.2018.02.015S24424912

Breast Cancer-Related Neoplastic Alopecia: A Case Report and Review of the Literature

Neoplastic alopecia (NA) is defined as an organized hair loss in single or multiple areas of the scalp caused by a primary tumor that has metastasized to the skin of the scalp. Due to its localization and clinical appearance, NA should be placed in differential diagnosis with alopecia areata or other entities. To date, pathognomonic dermoscopic criteria of NA have not yet been described: the absence of classical criteria of other scalp diseases in addition to a major neovascularization with on-focus arborizing vessels and erosions or ulcerations may help the clinician to suspect a diagnosis of secondary alopecia. Dermatologists should pay more attention to these rare forms of secondarism because in exceptional cases, a simple alopecia of the scalp can hide a new, relapsing or metastatic neoplasia

Cardiac surgery in the elderly: What goals of care?

At present, the majority of cardiac surgery interventions have been performed in the elderly with successful short-term mortality and morbidity, however significant difficulties must to be underlined about our capacity to predict long-term outcomes such as disability, worsening quality of life and loss of functional capacity.The reason probably resides on inability to capture preoperative frailty phenotype with current cardiac surgery risk scores and consequently we are unable to outline the postoperative trajectory of an important patients' centered outcome such as disability free survival. In this perspective, more than one geriatric statements have stressed the systematic underuse of patient reported outcomes in cardiovascular trials even after taking account of their relevance to older feel and wishes. Thus, in the next future is mandatory for geriatric cardiology community closes this gap of evidences through planning of trials in which patients' centered outcomes are considered as primary goals of therapies as well as cardiovascular ones.</p