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

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

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

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

Inverse psoriasis in patient treated with atezolizumab

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Breed and Feeding System Impact the Bioactive Anti-Inflammatory Properties of Bovine Milk

In the present study, we aimed at assessing the influence of breed and feeding system on the bovine milk profile of betaines and carnitines and milk capacity in counteracting the inflammatory endothelial cell (EC) damage induced by interleukin (IL)-6. In the first experimental design, two breeds were chosen (Holstein vs. Modicana) to investigate the biomolecule content and antioxidant capacity in milk and dairy products. In the second experimental design, two feeding systems (pasture vs. total mixed ratio) were tested only in Holstein to evaluate the possible effect on the functional profile of milk and dairy products. Finally, the bulk milk from the two experimental designs was used to evaluate the efficacy of preventing IL-6-induced endothelial inflammatory damage. Results showed that Modicana milk and whey had higher biomolecule content and antioxidant activity compared to Holstein milk (p < 0.01). Milk from Holstein fed TMR showed higher concentration of γ-butyrobetaine, δ-valerobetaine (p < 0.01), and l-carnitine (p < 0.05). Similarly, whey from Holstein fed TMR also showed higher content of δ-valerobetaine, glycine betaine, l-carnitine, and acetyl-l-carnitine (p < 0.01) compared to the Holstein fed pasture. Conversely, the antioxidant activity of milk and dairy products was not affected by the feeding system. In ECs, all milk samples reduced the IL-6-induced cytokine release, as well as the accumulation of reactive oxygen species (ROS) and the induction of cell death, with the most robust effect elicited by Modicana milk (p < 0.01). Overall, Modicana milk showed a higher content of biomolecules and antioxidant activity compared to Holstein, suggesting that the breed, more than the feeding system, can positively affect the health-promoting profile of dairy cattle milk

IL-6 Levels Influence 3-Month All-Cause Mortality in Frail Hospitalized Older Patients

The multidimensional prognostic index (MPI) is a sensitive and specific prognosis estimation tool that accurately predicts all-cause mortality in frail older patients. It has been validated to assess the risk of 1-month to 2-year mortality in frail older patients during hospitalization and after hospital discharge. However, whether the MPI is a valid prognostic tool for follow-up periods of different lengths remains to be validated. To this end, we followed up 80 hospitalized patients (female=37, male 43) at least 75 years of age (mean age=82.6±4.4, range=75-94 years) to assess the 3-month all-cause mortality (mean follow-up=61.0 ± 31.7 months [range 4-90 days]). Accordingly, patients were subdivided into low (MPI-1, score 0-0.33), moderate (MPI-2, score 0.34-0.66) and high (MPI-3, score 0.67-1) mortality risk classes. Moreover, baseline biochemical, inflammatory and metabolic parameters, as well as anamnestic and clinical characteristics, were obtained. Although the MPI-3 score was significantly associated with 3-month all-cause mortality in univariate analysis (HR=5.79, 95%CI=1.77-18.92, p=0.004), a multivariate model indicated that only low albumin (HR=0.33, 95%CI=0.16-0.68, p=0.003) and high IL6 (HR=1.01, 95%CI=1.00-1.02, p=0.010) levels were significantly associated with 3-month all-cause mortality. In conclusion, we suggest that measurement of IL6 as well as albumin, rather than the MPI score, may help in providing tailored therapeutic interventions to decrease short term mortality in older hospitalized individuals

Plasma fatty acid profile in Italian Holstein-Friesian dairy cows supplemented with natural polyphenols from the olive plant Olea Europaea L

This study evaluated the effects of supplementing with natural functional feed on the plasma fatty acid profile of lactating Italian Holstein-Friesian dairy cows. Thirty cows in mid-lactation received the natural olive extract PHENOFEED DRY (500 mg/cow/day) which mainly comprises hydroxytyrosol, tyrosol and verbascoside. The total content of polyphenols and the antioxidant power of standard feed, enriched feed and pure extract was evaluated respectively by Folin-Ciocalteu and DPPH assay, and a characterization in HPLC-UV (High-Perfor mance Liquid Chromatography-Ultraviolet) of bioactive molecules present in the extract PHENOFEED DRY was performed. PHENOFEED DRY was provided for 60 days, and the plasma profile of fatty acids was determined by Gas Chromatography. The administration of enriched feed resulted in an increase in the ratio of Omega-6 to Omega-3 polyunsaturated fatty acids from 3:1 to 4:1 (p<0.001). This was not influenced by the calving order. The addition of polyphenols helped to keep monounsaturated (MUFA) and saturated (SFA) levels constant and results in a significant increase in polyunsaturated (PUFA) fatty acid after 15 days of administration. The Omega 6/Omega-3 ratio was in the optimal range. The findings show that inclusion of natural functional food such as plant polyphenols helps to maintain a healthy blood fatty acid profile in lactating dairy cow

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN.</p