Cow\u27s Milk Protein-Induced Villous Atrophy and Elevated Celiac Autoimmunity in Children with Celiac Disease on a Glutten-Free Diet: A Report of Three Cases

Objective: To describe the serologic and histologic response of three patients with celiac disease who had persistent autoimmunity and villous atrophy despite a strict gluten-free diet, to the elimination of cow\u27s milk protein

Cyclic vomiting syndrome in children: a nationwide survey of current practice on behalf of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP)

Background: Cyclic Vomiting Syndrome (CVS) is a rare functional gastrointestinal disorder, which has a considerable burden on quality of life of both children and their family. Aim of the study was to evaluate the diagnostic modalities and therapeutic approach to CVS among Italian tertiary care centers and the differences according to subspecialties, as well as to explore whether potential predictive factors associated with either a poor outcome or a response to a specific treatment. Methods: Cross-sectional multicenter web-based survey involving members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP). Results: A total of 67 responses were received and analyzed. Most of the respondent units cared for less than 20 patients. More than half of the patients were referred after 3 to 5 episodes, and a quarter after 5 attacks. We report different diagnostic approaches among Italian clinicians, which was particularly evident when comparing gastroenterologists and neurologists. Moreover, our survey demonstrated a predilection of certain drugs during emetic phase according to specific clinic, which reflects the cultural background of physicians. Conclusion: In conclusion, our survey highlights poor consensus amongst clinicians in our country in the diagnosis and the management of children with CVS, raising the need for a national consensus guideline in order to standardize the practice

Molecular Simulations Study of Silver Precipitation from Aqueous Solution and on Silica Substrate. Control of Shape and Charge via Redox Condition

In the last decades, nanoparticles became a material of great interest, due to their ap- plications and properties. One of the possible applications for nanoparticles is for the creation of self-assembled materials. Nanoparticles can be self-assembled through chemical reactions. However, in recent years, anisotropic particles have been also used to produce self-assembled materials. Anisotropic particles are usually made of two or more materials, those materials differ from each other in physical or mechanical prop- erties. An example of anisotropic particles is silica nanoparticles covered with a noble metal (i.e. silver). These silica nanoparticles covered with a metal patch use the metal cover as a ”glue” to assemble the nanoparticles in complex structures. In this thesis, the main focus was on the creation of silver patches on silica nanoparticles. To have a complete understanding of the precipitation process, a smaller study is also presented on the precipitation in aqueous solution without any substrate. The formation of silver patches on silica nanoparticles is performed in aqueous solution through a chemical reaction, which uses a salt (silver nitrate) as a silver source. The silver is reduced using a reducing agent such as formaldehyde. The understanding of the precipitation/crystallization process for the formation of the silver patches is crucial to make the production reliable. This thesis is focused on the understanding of the silver patch growth process under the effect of different redox potential. The chemical reaction that is performed to create silver patches contains ammonia. Am- monia has two roles, to control the pH of the solution and to form silver-ammonia clusters. The variation of pH in the solutions affects the silver growth. The silver patches have a cup-like shape (i.e. uniform cover of the silica surface) when the pH of the solution is around 11. Reducing the pH, until 9.5, the patches gradually grow more in a dendritic way. In the molecular dynamics simulations it is not possible to reproduce directly all the effects of the pH variation. To simulate the pH effect on silver patch grow the redox potential was used. Previous theoretical studies regarding those types of systems are limited and none of them addressed the formation of patches using atomistic methods. Therefore, this work focused on the understanding of which factors influence the patch shape and in which proportion. Classical molecular dynamics methods can’t predict the shape of a metal cluster under the effect of different redox potentials. In previous studies by Milek et al. it was proven that the use of the charge equilibrium method (QEq) and the embedded atom method (EAM) can simulate both the variation of shape in the metal cluster due to charge variation and the associated redox potential. The very same approach was used in the simulations performed in this work. In the experimental set up, there are several species. All the species have a concentration in the order of 1-10 mM. The above-described condition can’t be simulated with molecu- lar dynamics methods. The problem was approached using limiting cases and increasing the level of complexity. In the heterogeneous crystallization processes the surface plays a major role, it is, thus, extremely important to have a model that describes the silica substrate accurately. The first part of this work was dedicated to the development of the silica surface. Particular attention was given in the modeling of the pH effect on the silica. The model and the parameters created to describe the silica surface work in a pH range between 5 and 12. Another aspect of high importance in the heterogeneous crystallization is the contribu- tion of the diffusion of the ions on the surface. The parameters created to simulate the silica surface proved to represent the diffusivity of both ions and small clusters on the silica substrate. The 2-D diffusivity of the ions and clusters on the surface was calculated using an algorithm that was developed to calculate the diffusivity on the surface. The results are divided into three chapters. The first chapter describes the development and test of the model and the force field parameters for the surface and the silver ions. In the second chapter, the methods were tested on silver precipitates in aqueous solutionsVI without substrate. In the last chapter, all the work previously done was combined and used to investigate the patch formation. The whole work confirmed that redox potential is the major factor influencing the shape of the patch but not the only one. The presence of the cations over the surface was proven to have a strong impact on the patch shape. The model for the silica surface was used to study the solvation layers over the silica surface and the diffusivity of the cations and solvent molecules in each solvation layer. The silica substrate was also used to analyze the diffusivity on the surface of a silver cluster with different oxidation states. In the third chapter, a study on silver particles in aqueous solution was performed. The study confirmed the relation between the redox potential and the silver particle shape. Using the combination of the QEq and the EAM, the effect of the surface charge on the calculation of the diffusivity using the Dynamic Light Scattering (DLS) were analyzed. In this chapter, also a method to calculate the solvation free energy (∆G) was developed. The method was used to analyze the affinity the silver particles have for different solu- tions (i.e. pure water or water-ammonia solutions). The study of the patch formation was made with all the methods previously adopted or developed, including the Kawzka-Zahn Method (KZM). The results of this chapter confirmed that the redox potential plays a major role in the growth of silver patches. The cations deposited on the surface act as obstacles for the silver patch growth. The simulation also highlighted how the polarity of the solution has a strong effect on the final patch shape. Changing the ammonia in solution with other amines (Methylamine, Dimethylamine) causes the silver patch to rearrange in a completely different way. The silver patch in contact with a solution with ammonia showed a more dendritic behavior, while with other amines the behavior was completely different. Finally, the simulations showed how the formaldehyde changes the solubility of the ammonia in solution. The ammonia present in solution together with formaldehyde shows a strong tendency to deposit over the silver patche

Defect-driven water migration in MgCl2 tetra- and hexahydrates

This molecular dynamics simulations study elucidates how water diffusion in MgCl2·nH2O (n=4 and 6) is facilitated by defects and dopants. Both the impact of a single vacancy (one water molecule was removed) and an interstitial (one water molecule was added) on long range water motion has been investigated. Spontaneous vacancy-interstitial pair defect formation was not observed, which is in line with the predicted high energy costs for defect formation: 150 and 200 kJ/mol for the tetrahydrate and hexahydrate, respectively. The vacancy defects did not show long range mobility, which we relate to the strong bonding of water in the coordination shell of the Mg-ion that prevents water molecules from shifting to neighbouring magnesium ions. On the contrary, the addition of an extra water molecule, facilitates long range motion, which was found as a sequence of hopping events. The interstitial motion is anisotropic in both tetrahydrate and hexahydrate crystals, as interstitials preferentially reside at locations of unfavourable Cl-Cl interactions. Strikingly, Mg ↔ Ca substitutional defects neither increase the mobility of vacancies nor facilitates interstitial motion in the MgCl2 lattice. While Ca dopants slightly facilitate vacancy formation, it also stabilizes interstitial water molecules by incorporating these molecules in its coordination shell. As a consequence, the interstitial becomes trapped and loses its mobility. Therefore, Ca dopants will not increase the hydration/dehydration kinetics of MgCl2 hydrates and cannot be used to boost the power output of MgCl2-based heat storage devices

Defect-driven water migration in MgCl\u3csub\u3e2\u3c/sub\u3e tetra- and hexahydrates

\u3cp\u3eThis molecular dynamics simulations study elucidates how water diffusion in MgCl\u3csub\u3e2\u3c/sub\u3e·nH\u3csub\u3e2\u3c/sub\u3eO (n=4 and 6) is facilitated by defects and dopants. Both the impact of a single vacancy (one water molecule was removed) and an interstitial (one water molecule was added) on long range water motion has been investigated. Spontaneous vacancy-interstitial pair defect formation was not observed, which is in line with the predicted high energy costs for defect formation: 150 and 200 kJ/mol for the tetrahydrate and hexahydrate, respectively. The vacancy defects did not show long range mobility, which we relate to the strong bonding of water in the coordination shell of the Mg-ion that prevents water molecules from shifting to neighbouring magnesium ions. On the contrary, the addition of an extra water molecule, facilitates long range motion, which was found as a sequence of hopping events. The interstitial motion is anisotropic in both tetrahydrate and hexahydrate crystals, as interstitials preferentially reside at locations of unfavourable Cl-Cl interactions. Strikingly, Mg ↔ Ca substitutional defects neither increase the mobility of vacancies nor facilitates interstitial motion in the MgCl\u3csub\u3e2\u3c/sub\u3e lattice. While Ca dopants slightly facilitate vacancy formation, it also stabilizes interstitial water molecules by incorporating these molecules in its coordination shell. As a consequence, the interstitial becomes trapped and loses its mobility. Therefore, Ca dopants will not increase the hydration/dehydration kinetics of MgCl\u3csub\u3e2\u3c/sub\u3e hydrates and cannot be used to boost the power output of MgCl\u3csub\u3e2\u3c/sub\u3e-based heat storage devices.\u3c/p\u3

Abdominal Pain-Associated Functional Gastrointestinal Disorder Prevalence in Children and Adolescents with Celiac Disease on Gluten-Free Diet: A Multinational Study

Objective To test the hypothesis that children with celiac disease (CD) on gluten-free diet are at increased risk of abdominal pain (AP) associated-functional gastrointestinal disorders (FGIDs).Study design This was a multinational cross-sectional study performed from 2014 to 2015. Patients 4-18 years of age with CD on gluten-free diet for longer than 6 months were recruited from pediatric CD clinics in US and Italy. Control groups included siblings of children with CD (with normal tissue transglutaminase levels) and unrelated controls. Subjects or parents completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III.Results Children (n = 289) were recruited (55% US, 45% Italy): 96 children with CD, 96 sibling controls, and 97 unrelated controls. Chronic AP was present in 30 (30.9%) subjects with CD, 22 (22.7%) sibling controls, and 21 (21.6%) unrelated controls (P =.26 patients with CD vs siblings; P =.18 patients with CD vs unrelated; P =.96 siblings vs unrelated). AP-FGIDs were present in 8 (8.2%) subjects with CD, 8 (8.2%) sibling controls, and 2 (2.1%) unrelated controls (P = 1.00 subjects with CD vs sibling controls; P =.06 subjects with CD vs unrelated controls; P =.06 sibling controls vs unrelated controls).Conclusion This multinational study evaluated the prevalence of chronic abdominal pain and AP-FGIDs in the pediatric population with CD. We found that subjects with CD and controls have a similar prevalence of chronic AP and AP-FGIDs. This suggests that not all types of gastrointestinal inflammation result in AP-FGIDs in children

The Gluten Free Diet's Impact on Growth in Children with Celiac Disease in Two Different Countries

The effects of gluten free diet (GFD) on body mass index (BMI) and growth parameters in pediatric patients with celiac disease (CD) and their dependence on different socio-cultural environments are poorly known. We conducted an international retrospective study on celiac patients diagnosed at the University of Verona, Italy, and at the University of Chicago, Chicago, IL, USA, as underweight. A total of 140 celiac children and 140 controls (mean age 8.4 years) were enrolled in Chicago; 125 celiac children and 125 controls (mean age 7.3 years, NS) in Verona. At time of diagnosis, Italian celiac children had a weight slightly lower (p= 0.060) and a BMI z-score significantly (p< 0.001) lower than their American counterparts. On GFD, Italian celiac children showed an increased prevalence of both underweight (19%) as well as overweight (9%), while American children showed a decrease prevalence of overweight/obese. We concluded that while the GFD had a similar impact on growth of celiac children in both countries, the BMI z-score rose more in American than in Italian celiac children. Additionally, in Italy, there was an alarming increase in the proportion of celiac children becoming underweight. We speculate that lifestyle and cultural differences may explain the observed variations

Breast Safety and Efficacy of Genistein Aglycone for Postmenopausal Bone Loss: A Follow-Up Study

Context: Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain. Objective: We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy. Design: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24-months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Patients and Interventions: Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67). Both treatment arms received calcium and vitamin D(3) in therapeutic doses. Main Outcomes: Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchange, and endometrial thickness were also evaluated. Lumbar spine and femoral neck bone mineral density were also assessed. Secondary outcomes were biochemical levels of bone markers. Results: After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved, whereas sister chromatid exchange was reduced compared with placebo. Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein also significantly reduced pyridinoline, as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappa B ligand while increasing bone-specific alkaline phosphatase, IGF-I, and osteoprotegerin levels. There were no differences in discomfort or adverse events between groups. Conclusions: After 3 yr of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women. (J Clin Endocrinol Metab 93: 4787-4796, 2008

Predictive factors for oropharyngeal mycosis during radiochemotherapy for head and neck carcinoma and consequences on treatment duration. Results of mycosis in radiotherapy (MIR): A prospective longitudinal study

Background and purpose Oropharyngeal mycosis (OPM) is a complication of radiotherapy (RT) treatments for head and neck (H&N) cancer, worsening mucositis and dysphagia, causing treatment interruptions and increasing overall treatment time. Prophylaxis with antifungals is expensive. Better patient selection through the analysis of prognostic factors should improve treatment efficacy and reduce costs. Materials and methods A multicentre, prospective, controlled longitudinal study, with ethics committee approval, examined H&N cancer patients who were candidates for curative treatments with radio-chemotherapy. Patients were divided in groups according to OPM appearance: before the starting of RT (cases), during RT (new cases) and never (no cases). Results Of 410 evaluable patients, 20 were existing cases, 201 new cases and 189 did not report OPM. In our study OPM appears in 42.4% of people >70 years and in 58.2% of younger individuals (p = 0.0042), and in 68.6% of women versus 50.8% of men (p = 0.0069). Mucositis and dysphagia were higher and salivation reduced among people with OPM (p 12 days) treatment interruptions (p = 0.0288). Conclusions Patients with OPM had higher toxicity and a greater number of long treatment interruptions. Analyses of prognostic factors can help clinicians understand OPM distribution and select patients with the highest probability of OPM for antifungal prophylaxis