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There are little data on the epidemiological and clinical features of adult patients with ulcerative colitis (UC) in the different Italian regions, mainly derived from the absence of a national registry. This prevents correct interpretation of the disease burden.To assess the main clinical and epidemiological features of adult patients diagnosed with UC in Sardinia, Italy.We performed a multicenter, observational, cross-sectional study that included adult patients with UC enrolled in seven gastroenterology unit centers in Sardinia. Data were obtained from the patients' medical records and from a questionnaire administered at the inclusion visit.Four hundred and forty-two patients with UC were included. The median age at diagnosis was 39 years (interquartile range 28-48). After a median disease duration of 10 years, 53 patients experienced proximal extension of proctitis or left-sided colitis. Seventy-five patients developed extraintestinal manifestations. Nineteen patients (4.3%) developed cancer: two with colorectal cancer and seventeen with extracolonic cancers. Mesalazine (5-ASA) remains the mainstay of treatment for UC. Overall, 95 patients (21.5%) were treated with one or more biologic agents, whereas 15 patients (3.4%) underwent surgery, mostly colectomy.Our results provide important insights into the clinical and epidemiological features of patients with UC, and while waiting for a national Italian registry, present eligible data on the UC population in Sardinia.

Background & Aims Malnutrition with the accumulation of fat tissue and nonalcoholic fatty liver disease (NAFLD) are conditions associated with inflammatory bowel disease (IBD). Visceral fat and NAFLD-related liver dysfunction can both worsen intestinal inflammation. Because the Mediterranean diet (Md) has been shown to ameliorate both obesity and NAFLD, the aim of this study was to analyze the impact of Md on the nutritional state, liver steatosis, clinical disease activity, and quality of life (QoL) in IBD patients. Methods Patients with IBD, both Crohn’s disease (CD) and ulcerative colitis (UC), followed Md for 6 months. Their body mass index (BMI), body tissue composition, liver steatosis and function, serum lipid profile, clinical disease activity, and inflammatory biomarkers (C-reactive protein and fecal calprotectin) were collected at baseline (T0) and compared with those obtained after 6 months (T180) to evaluate the impact of Md. Results One hundred forty-two IBD patients, 84 UC and 58 CD, followed Md for 6 months. At T180, diet-adherent CD and UC improved BMI (UC −0.42, P = 0.002; CD −0.48, P = 0.032) and waist circumference (UC −1.25 cm, P = 0.037; CD −1.37 cm, P = 0.041). Additionally, the number of patients affected by liver steatosis of any grade was significantly reduced in both groups (UC T0 31 of 84 [36.9%] vs T180 18 of 84 [21.4%], P = 0.0016; CD T0 27 of 58 [46.6%] vs T180 18 of 58 [31.0%], P < 0.001) after dietary intervention. Finally, after 6 months of the diet, fewer UC and CD patients with stable therapy had active disease (UC T0 14 of 59 [23.7%] vs T180 4 of 59 [6.8%], P = 0.004; CD T0 9 of 51 [17.6%] vs T180 2 of 51 [3.0%], P = 0.011) and elevated inflammatory biomarkers. Mediterranean diet improved QoL in both UC and CD, but neither serum lipid profile nor liver function were modified by the diet. Conclusions A significant reduction of malnutrition-related parameters and liver steatosis was observed in both CD and UC patients after short-term dietary intervention based on the adoption of Md, and this was associated with a spontaneous improvement of disease activity and inflammatory markers., In this prospective study, 6 months of Mediterranean diet in IBD patients was associated with improvement of several metabolic syndrome–associated parameters and response to therapies. The Mediterranean diet might be considered a “background therapy” in the therapeutic algorithm of IBD.

Smell strongly contributes to food choice and intake, influencing energy balance and body weight, its reduction or loss has been related to malnutrition problems. Some patients with inflammatory bowel disease (IBD), mainly Crohn’s disease (CD) and ulcerative colitis (UC), are underweight, while others are overweight. Some studies suggest that changes in eating habits could be linked to specific disorders of the olfactory functions. We assessed the olfactory performance in 199 subjects (healthy control (HC) n = 99, IBD n = 100), based on the olfactory Threshold, Discrimination and Identification score (TDI score), measured with the “Sniffin’ Sticks” test. Subjects were genotyped for the rs2590498 polymorphism of the OBPIIa gene. IBD patients showed both a slightly, but significantly, lower olfactory function and a higher BMI compared to HC subjects. Threshold (in both population) and Discrimination (in IBD patients) olfactory score were affected by the OBPIIa genotype. BMI was influenced by both health status and OBPIIa genotype. A lower olfactory function may delay the satiety sensation and thus increase meal duration and body weight in IBD patients. However, the AA genotype of the OBPIIa seems to “protect” IBD patients from more severe olfactory dysfunction.

The properties of most systems composed of many interacting elements are neither determined by the topology of the interaction network alone, nor by the dynamical laws in isolation. Rather, they are the outcome of the interplay between topology and dynamics. In this paper, we consider four different types of systems with critical dynamic regime and with increasingly complex dynamical organization (loosely defined as the emergent property of the interactions between topology and dynamics) and analyze them from a structural and dynamic point of view. A first noteworthy result, previously hypothesized but never quantified so far, is that the topology per se induces a notable increase in dynamic organization. A second observation is that evolution does not change dramatically the size distribution of the present dynamic groups, so it seems that it keeps track of the already present organization induced by the topology. Finally, and similarly to what happens in other applications of evolutionary algorithms, the types of dynamic changes strongly depend upon the used fitness function.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract resulting from interactions among various factors with diet being one of the most significant. IBD-related dietary behaviors are not clearly related to taste dysfunctions. We analyzed body mass index (BMI) and perception of six taste qualities and assessed effects of specific taste genes in IBD patients and healthy subjects (HC). BMI in IBD patients was higher than in HC subjects. Taste sensitivity to taste qualities was reduced in IBD patients, except for sour taste, which was higher than in HC subjects. Genetic variations were related to some taste responses in HC subjects, but not in IBD patients. Frequencies of genotype AA and allele A in CD36 polymorphism (rs1761667) were significantly higher in IBD patients than in HC subjects. The taste changes observed could be explained by the oral pathologies and microbiome variations known for IBD patients and can justify their typical dietary behaviors. The lack of genetic effects on taste in IBD patients indicates that IBD might compromise taste so severely that gene effects cannot be observed. However, the high frequency of the non-tasting form of CD36 substantiates the fact that IBD-associated fat taste impairment may represent a risk factor for IBD.

Random Boolean networks are a widely acknowledged model for cell dynamics. Previous studies have shown the possibility of achieving Boolean Networks (BN) with given characteristics by means of evolutionary techniques. In this work we show that it is possible to evolve BNs exhibiting more positive than negative reactions to knock-out stresses. It is also interesting to observe that in the observed runs (i) the evolutionary processes can guide the BNs toward different dynamic regimes, depending on their internal structure and that (ii) the BNs forced to evolve by maintaining a critical dynamical regime achieve better results than those that do not have this characteristic; this observation supports the idea that criticality may be beneficial to an evolving population of dynamical systems.

Living beings share several common features at the molecular level, but there are very few large-scale &ldquo, operating principles&rdquo, which hold for all (or almost all) organisms. However, biology is subject to a deluge of data, and as such, general concepts such as this would be extremely valuable. One interesting candidate is the &ldquo, criticality&rdquo, principle, which claims that biological evolution favors those dynamical regimes that are intermediaries between ordered and disordered states (i.e., &ldquo, at the edge of chaos&rdquo, ). The reasons why this should be the case and experimental evidence are briefly discussed, observing that gene regulatory networks are indeed often found on, or close to, the critical boundaries. Therefore, assuming that criticality provides an edge, it is important to ascertain whether systems that are critical can further evolve while remaining critical. In order to explore the possibility of achieving such &ldquo, always-critical&rdquo, evolution, we resort to simulated evolution, by suitably modifying a genetic algorithm in such a way that the newly-generated individuals are constrained to be critical. It is then shown that these modified genetic algorithms can actually develop critical gene regulatory networks with two interesting (and quite different) features of biological significance, involving, in one case, the average gene activation values and, in the other case, the response to perturbations. These two cases suggest that it is often possible to evolve networks with interesting properties without losing the advantages of criticality. The evolved networks also show some interesting features which are discussed.

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a frequently reported condition in patients with inflammatory bowel disease (IBD). Both intestinal inflammation and metabolic factors are believed to contribute to the pathogenesis of IBD-associated NAFLD. AIM To evaluate the prevalence of steatosis and liver fibrosis (LF) in a cohort of IBD patients and the identification of metabolic- and IBD-related risk factors for NAFLD and LF. METHODS IBD patients were consecutively enrolled from December 2016 to January 2018. Demographic, anthropometric and biochemical data were collected so as eating habits. Abdominal ultrasound and transient elastography were performed to evaluate the presence of NAFLD and LF respectively. RESULTS A total of 178 consecutive patients were enrolled and included in the analysis (95 Ulcerative colitis, 83 Crohn’s disease). NAFLD was detected by imaging in 72 (40.4%) patients. Comparison between patients with and without NAFLD showed no significant differences in terms of IBD severity, disease duration, location/extension, use of IBD-related medications (i.e., steroids, anti-TNFs, and immunomodulators) and surgery. NAFLD was significantly associated with the presence of metabolic syndrome [MetS; odds ratio (OR): 4.13, P = 0.001] and obesity defined by body mass index (OR: 9.21, P = 0.0002). IBD patients with NAFLD showed higher caloric intake and lipid consumption than those without NAFLD, regardless disease activity. At the multivariate analysis, male sex, advanced age and high lipid consumption were independent risk factors for the development of NAFLD. An increased liver stiffness was detected in 21 patients (16%) and the presence of MetS was the only relevant factor associated to LF (OR: 3.40, P = 0.01). CONCLUSION In this study, we demonstrate that risk factors for NAFLD and LF in the IBD population do not differ from those in the general population.

Olfactory function varies by several orders of magnitude among healthy individuals, who may exhibit a reduced sensitivity (hyposmia), a high sensitivity (hyperosmia), or an olfactory blindness (anosmia). Environmental and genetic factors seem to account for this variability. Most of odorant molecules are hydrophobic and it has been suggested that odorants are transported to the olfactory receptors by means of odorant binding proteins (OBPs). Aim of this study was to evaluate the presence of a relationship between the olfactory performance of healthy subjects and the polymorphism in the odor binding-protein (OBPIIa) gene, the only OBP found in the olfactory epithelium of humans. Using the "Sniffin' Sticks" Extended Test we assessed the olfactory performance in 69 subjects, who were genotyped for the rs2590498 polymorphism of the OBPIIa gene, whose major allele A has been associated with a higher retronasal perception as compared to the minor allele G. We found that subjects homozygous for the A-allele exhibited threshold scores higher than subjects homozous for the G-allele or heterozygous. In addition, subjects classified as normosmic and hyposmic differed on the basis of genotype distribution and allelic frequencies. In fact, a normosmic condition was associated with genotype AA and allele A and a hyposmic condition was associated with genotype GG and allele G. In conclusion, our results show that a relationship exists between the physiological variations of olfactory performance and the OBPIIa gene polymorphism.

Random Boolean networks are a widely acknowledged model for cell dynamics. Previous studies have shown the possibility of achieving Boolean networks with given characteristics by means of evolutionary techniques. In this work we make a further step towards more biologically plausible models by aiming at evolving networks with a given fraction of active nodes along the attractors, while constraining the evolutionary process to move across critical networks. Results show that this path along criticality does not impede to climb the mount of improbable, yet biologically realistic requirements.

Background: Recently, several studies have shown that heparin possesses various anti-inflammatory and antiallergic properties. It has been proposed that heparin might play an important role in limiting the inflammatory events associated with asthma and allergic rhinitis by neutralizing inflammatory mediators, such as eosinophil cationic protein and major basic protein, and by limiting eosinophil recruitment. Objective: To test the hypothesis that heparin can limit the extent and magnitude of eosinophilic inflammation, we examined the effect of inhaled intranasal heparin on nasal response to allergen challenge in 10 patients with allergic rhinitis. Methods: The capacity of heparin to reduce nasal response was studied by evaluating symptom score, eosinophil cationic protein concentration, and eosinophil counts in nasal lavage fluids 10, 60, and 360 minutes after allergen challenge. Results: Pretreatment with intranasal heparin produced a significant reduction in symptom score 10 minutes after allergen challenge and reduced the eosinophil influx at each time point after antigen challenge, statistical significance being reached 60 and 360 minutes after allergen challenge. Similarly, the amount of eosinophil cationic protein in the nasal wash was reduced at each time point; this reached statistical significance 360 minutes after allergic challenge. Conclusion: Heparin was shown to provide protection with respect to nasal allergen challenge. The mechanism by which heparin produces its protective activity seems to be related to the neutralization of eosinophil cationic protein as well as to the reduction of eosinophil recruitment. (J Allergy Clin Immunol 2001;108:703-8.)

Background: Recent studies have shown that inhaled heparin exerts a protective effect against various bronchoconstrictor stimuli in asthma, possible through an inhibition of mast cell activation. Objective: Because adenosine 5′-monophosphate (AMP) elicits bronchoconstriction by augmenting mast cell mediator release, we have investigated the effect of inhaled heparin (15,000 units USP/ml, 4 ml) on the bronchoconstrictor response to this agonist and to methacholine in a randomized, double-blind, placebo-controlled study of 10 subjects with asthma. We also carried out a separate randomized, double-blind study in seven additional volunteers with asthma to examine in more detail the time-course of change in bronchial reactivity to inhaled AMP after treatment with nebulized heparin. Results: Inhaled heparin significantly increased the provocative concentration of AMP causing a 20% decrease in forced expiratory volume in 1 second (PC 20 FEV 1 -AMP) from the postplacebo treatment value of 22.3 mg/ml (range, 5.7 to 68.9 mg/ml) to 48.1 mg/ml (range, 5.1 196.8 mg/ml) ( p < 0.01). When compared with placebo, inhaled heparin failed to alter the airway responsiveness to methacholine; the mean (range) PC 20 methacholine values were 1.00 mg/ml (0.44 to 4.76 mg/ml) and 1.08 mg/ml (0.46 to 5.08 mg/ml), respectively. After placebo administration, the PC 20 AMP values at 15, 60, and 180 minutes did not differ significantly from each other; their geometric mean (range) values were 26.1 mg/ml (5.9 to 85.8 mg/ml), 26.6 mg/ml (6.3 to 87.8 mg/ml), and 24.9 mg/ml (5.2 to 80.2 mg/ml), respectively. When compared with placebo, the PC 20 values for AMP after administration of inhaled heparin were significantly increased up to 57.3 mg/ml (14.7 to 176.0 mg/ml) and to 52.7 mg/ml (13.9 to 90.8 mg/ml) at 15 minutes and 60 minutes, respectively. At 180 minutes, inhaled heparin failed to affect AMP airway responsiveness; the PC 20 AMP was not significantly different from that of placebo, with a value of 30.6 mg/ml (4.8 to 93.3 mg/ml). Conclusion: Heparin administered by inhalation is effective in attenuating the airway response to AMP but not to methacholine. The time course of change in bronchial reactivity to AMP has a peak effect at 15 minutes and lasts up to 60 minutes. It is possible that the mechanism(s) underlying the protective effects of inhaled heparin in asthma may be related to an inhibitory modulation of mast cell activation. (J Allergy Clin Immunol 1997;99:338-44.)

The endogenous tachykinins exhibit a range of properties which may be relevant in the pathophysiology of asthma. Their effects on the airways seem to be modulated by a variety of lung peptidases, including neutral endopeptidase (NEP). In order to evaluate the potential role of endogenous NEP activity in modulating tachykinins-induced bronchoconstriction in man in vivo, six atopic asthmatic patients, with a mean FEV1 value of 3.38 +/- 0.76 l, and a histamine PD20 mean value of 0.024 mg, were studied. The influence of inhaled phosphoramidon (a potent NEP inhibitor) was examined against the NKA-induced bronchospasm in a double-blind, placebo-controlled randomized study. Changes in airway calibre were followed as FEV1 and agonists responsiveness expressed as PD20 and PD15 for histamine and NKA respectively. Patients received nebulized phosphoramidon sodium salt (10(-5) M) or a control solution 10 min prior to the bronchoprovocation test with NKA. No significant difference was noticed between any of the study days and after inhaled phosphoramidon on baseline FEV1 values (3.29 +/- 0.90 l) in comparison with the control solution (3.31 +/- 0.79 l). Inhaled NKA produced a dose-dependent fall in FEV1 values in all the subjects studied with a mean PD15 value of 20.91 x 10(-9) mol. Phosphoramidon administered by inhalation elicited a significant (P0.01 vs baseline and control solution) potentiation in the airway responsiveness to inhaled NKA, the NKA PD15 value decreasing to 9.45 x 10(-9) mol. The present study confirms that inhaled NKA induces a dose-related bronchoconstriction in asthmatic patients and demonstrates that inhaled phosphoramidon potentiates NKA-induced bronchoconstriction.