Fasting Neurotensin Levels in Pediatric Celiac Disease Compared with a Control Cohort

Background and Aims. Neurotensin (NT) is a gut hormone secreted by specific endocrine cells scattered throughout the epithelial layer of the small intestine, which has been identified as an important mediator in several gastrointestinal functions and disease conditions. Its potential involvement in celiac disease (CD) has been investigated, but there are conflicting findings. The aim of this study was to evaluate serum NT levels in children with CD at diagnosis, compared to a control group, and to investigate whether NT correlated in CD patients with symptoms, antibody response, and intestinal mucosal damage. Materials and Methods. Children (1-16 years old) undergoing gastrointestinal endoscopy for CD or for other clinical reasons were included in this study. Patients with CD diagnosed according to the 2012 European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines without biopsy were also recruited. Fasting serum samples were analyzed for NT levels using ELISA. Logistic regression, Wilcoxon rank sum, and Spearman's rank tests were used for statistical analysis. Results. Thirty children (18 females, 2.2-15.9 years old) were enrolled. Of 25 patients who underwent endoscopy, 9 were CD patients, 13 were controls, and 3 were excluded due to nonspecific inflammation at duodenal biopsy. CD was diagnosed in 5 patients without biopsy. NT median was higher in CD patients compared to controls (13.25 (IQR 9.4-17.5) pg/ml vs. 7.8 (IQR 7.6-10) pg/ml; p=0.02). No statistically significant association between NT and clinical, serological, or histological data of CD was observed in this CD cohort. Conclusions. To our knowledge, this is the first study that evaluates NT in CD children from Italy. Results show that NT is higher in the serum of CD children at diagnosis compared to controls. However, larger-scale studies are required to validate these findings. Whether serum NT levels can be an adjunctive marker for pediatric CD remains currently elusive

Relating seismic velocities, thermal cracking and permeability in Mt. Etna and Iceland basalts

We report simultaneous laboratory measurements of seismic velocities and fluid permeability on lava flow basalt from Etna (Italy) and columnar basalt from Seljadur (Iceland). Measurements were made in a servo-controlled steady-state-flow permeameter at effective pressures from 5–80 MPa, during both increasing and decreasing pressure cycles. Selected samples were thermally stressed at temperatures up to 900 °C to induce thermal crack damage. Acoustic emission output was recorded throughout each thermal stressing experiment. At low pressure (0–10 MPa), the P-wave velocity of the columnar Seljadur basalt was 5.4 km/s, while for the Etnean lava flow basalt it was only 3.0–3.5 km/s. On increasing the pressure to 80 MPa, the velocity of Etnean basalt increased by 45%–60%, whereas that of Seljadur basalt increased by less than 2%. Furthermore, the velocity of Seljadur basalt thermally stressed to 900 °C fell by about 2.0 km/s, whereas the decrease for Etnean basalt was negligible. A similar pattern was observed in the permeability data. Permeability of Etnean basalt fell from about 7.5×10−16 m2 to about 1.5×10−16 m2 over the pressure range 5–80 MPa, while that for Seljadur basalt varied little from its initial low value of 9×10−21 m2. Again, thermal stressing significantly increased the permeability of Seljadur basalt, whilst having a negligible effect on the Etnean basalt. These results clearly indicate that the Etnean basalt contains a much higher level of crack damage than the Seljadur basalt, and hence can explain the low velocities (3–4 km/s) generally inferred from seismic tomography for the Mt. Etna volcanic edifice

The challenge of treatment in potential celiac disease

Potential celiac disease (PCD) is defined by the presence of positive serum antibodies, HLA-DQ2/DQ8 haplotypes, and a normal small intestinal mucosa (Marsh grade 0-1). This condition occurs in one-fifth of celiac disease (CD) patients and usually represents a clinical challenge. We reviewed genetic, histologic, and clinical features of this specific condition by performing a systematic search on MEDLINE, Embase, and Scholar database. Accordingly, we identified different genetic features in patients with PCD compared to the classical forms. Frequently, signs of inflammation (deposits of immunoglobulin A (IgA) and/or increased number of intraepithelial lymphocytes) can be clearly identify in the mucosa of PCD patients after an accurate histological assessment. Finally, the main challenge is represented by the treatment: the gluten-free diet should be considered only in the presence of gluten-dependent symptoms in both children and adults. What is known: (i) potential celiac disease (PCD) occurs in one-fifth of all celiac diseases (CD), and (ii) despite the absence of classical lesions, clear signs of inflammation are often detectable. What is new: (i) patients with PCD show different genetic features, and (ii) the presence of gluten-dependent symptoms is the main determinant to initiate the gluten-free diet, after a complete diagnostic work-up

Type 1 diabetes, thyroid, gastric and adrenal humoral autoantibodies are present altogether in almost one third of adult celiac patients at diagnosis, with a higher frequency than children and adolescent celiac patients

Background: No data are available on the frequency of organ-specific humoral autoimmunity at diagnosis of adult celiac disease (CD). Aim: To evaluate the humoral immunoreactivities specific of type 1 diabetes (T1D), thyroid (THD), atrophic-gastritis (AG) and Addison’s (AD) diseases in 92 adult CD patients at diagnosis and 237 adult healthy subjects (CTRL). Methods: T1D, THD and AD specific autoantibodies were analyzed by radioimmunoprecipitation assays. AG autoantibodies were detected by enzyme-linked immunosorbent assay. Results: Of 92 CD patients, 31.5% were positive for at least one of the organ-specific autoantibodies investigated (p <.0001 vs CTRL). Thyroid, diabetes, gastric and adrenal-autoantibodies, that increase with age at diagnosis, were detected in 12.0%, 10.9%, 10.9%, 2.2% of CD patients, respectively. Gastric- and diabetes- rather than thyroid- and adrenal-autoimmunity seem to be specifically related to presence of CD. Conclusions: One third of adult CD patients at diagnosis is target of at least one organ-specific autoantibody. A systematic organ-specific autoantibody screening in these patients might be of value to promptly identify, prevent or treat the relative diseases

Association between elevated TGA-IgA titers and older age at diagnosis with absence of HBV seroconversion in celiac children

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, "responders" and "non-responders" were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of "non-responders", aiming to organize surveillance and eventual revaccination strategy

A numerical approach to copolymers at selective interfaces

We consider a model of a random copolymer at a selective interface which undergoes a localization/delocalization transition. In spite of the several rigorous results available for this model, the theoretical characterization of the phase transition has remained elusive and there is still no agreement about several important issues, for example the behavior of the polymer near the phase transition line. From a rigorous viewpoint non coinciding upper and lower bounds on the critical line are known. In this paper we combine numerical computations with rigorous arguments to get to a better understanding of the phase diagram. Our main results include: - Various numerical observations that suggest that the critical line lies strictly in between the two bounds. - A rigorous statistical test based on concentration inequalities and super-additivity, for determining whether a given point of the phase diagram is in the localized phase. This is applied in particular to show that, with a very low level of error, the lower bound does not coincide with the critical line. - An analysis of the precise asymptotic behavior of the partition function in the delocalized phase, with particular attention to the effect of rare atypical stretches in the disorder sequence and on whether or not in the delocalized regime the polymer path has a Brownian scaling. - A new proof of the lower bound on the critical line. This proof relies on a characterization of the localized regime which is more appealing for interpreting the numerical data.Comment: accepted for publication on J. Stat. Phy

Adsorption-like Collapse of Diblock Copolymers

A linear copolymer made of two reciprocally attracting N-monomer blocks collapses to a compact phase through a novel transition, whose exponents are determined with extensive MC simulations in two and three dimensions. In the former case, an identification with the statistical geometry of suitable percolation paths allows to predict that the number of contacts between the blocks grows like $N^{9/16}$. In the compact phase the blocks are mixed and, in two dimensions, also zipped, in such a way to form a spiral, double chain structure.Comment: 4 pages, 5 Postscript figure

A Variant in TBCD Associated with Motoneuronopathy and Corpus Callosum Hypoplasia: A Case Report

Mutations in the tubulin-specific chaperon D (TBCD) gene, involved in the assembly and disassembly of the α/β-tubulin heterodimers, have been reported in early-onset progressive neurodevelopment regression, with epilepsy and mental retardation. We describe a rare homozygous variant in TBCD, namely c.881G>A/p.Arg294Gln, in a young woman with a phenotype dominated by distal motorneuronopathy and mild mental retardation, with neuroimaging evidence of corpus callosum hypoplasia. The peculiar phenotype is discussed in light of the molecular interpretation, enriching the literature data on tubulinopathies generated from TBCD mutations

Effects of oral citicoline in perimetric glaucoma defects

Abstract: Purpose: to study the neuroprotective effect of oral citicoline (CT) in patients with primary open-angle glaucoma (POAG). Methods: this study recruits 110 patients with stage IV POAG and well-controlled intraocular pressure (IOP). Enrollees were randomly allocated in two groups: therapy group (TG) or control group (CG). Subjects in TG were treated with citicoline 500 mg / die for 4 months. The treatment period was followed by a wash-out phase of 2 months. At the end of the washout phase, subjects in TG resumed CT in the same fashion. Both groups were treated with pressurelowering medications. Each subject was evaluated with standard automated perimetry (SAP) at baseline, and then again 12, 24, and 36 months after enrollment. Results: TG showed a statistically significant improvement in MD values at 12 months (∆ = 21%) and T24 (∆ = 35%), and gradual improvements of the stage, up to the 3rd stage with localized defects after 36 months of therapy. Conversely, in CG, both the MD and PSD indices continued to deteriorate throughout the duration of the study. Conclusion: long-term daily treatment with citicoline might have a neuroprotective effect. Patients treated with oral citicoline showed an improvement in perimetric indices. Additional studies with larger samples and longer follow-ups are needed to confirm these results