Parameterization of a coarse-grained model of cholesterol with point-dipole electrostatics.

We present a new coarse-grained (CG) model of cholesterol (CHOL) for the electrostatic-based ELBA force field. A distinguishing feature of our CHOL model is that the electrostatics is modeled by an explicit point dipole which interacts through an ideal vacuum permittivity. The CHOL model parameters were optimized in a systematic fashion, reproducing the electrostatic and nonpolar partitioning free energies of CHOL in lipid/water mixtures predicted by full-detailed atomistic molecular dynamics simulations. The CHOL model has been validated by comparison to structural, dynamic and thermodynamic properties with experimental and atomistic simulation reference data. The simulation of binary DPPC/cholesterol mixtures covering the relevant biological content of CHOL in mammalian membranes is shown to correctly predict the main lipid behavior as observed experimentally.

An overview of molecular dynamics simulations of oxidized lipid systems, with a comparison of ELBA and MARTINI force fields for coarse grained lipid simulations.

Biological membranes and model lipid systems containing high amounts of unsaturated lipids and sterols are subject to chemical and/or photo-induced lipid oxidation, which leads to the creation of exotic oxidized lipid products (OxPLs). OxPLs are known to have significant physiological impact in cellular systems and also affect physical properties of both biological and model lipid bilayers. In this paper we (i) provide a perspective on the existing literature on simulations of lipid bilayer systems containing oxidized lipid species as well as the main related experimental results, (ii) describe our new data of all-atom and coarse-grained simulations of hydroperoxidized lipid monolayer and bilayer systems and (iii) provide a comparison of the MARTINI and ELBA coarse grained force fields for lipid bilayer systems. We show that the better electrostatic treatment of interactions in ELBA is able to resolve previous conflicts between experiments and simulations. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.

Humanization of care in pediatric wards: differences between perceptions of users and staff according to department type.

BACKGROUND: As the quality and quantity of patient-centered care may be perceived differently by recipients and independent observers, assessment of humanization of pediatric care remains an elusive issue. Herein we aim to analyze differences between the degrees of verified existing vs. perceived humanization issues of a pediatric ward. Furthermore, we examine whether there is concurrence between the degrees of humanization perceived by users (parents/visitors) vs. staff members. METHODS: The study was conducted in the pediatric wards of seven medical centers of the Campania region (Italy) categorized as general (n = 4), children's (n = 1), and university (n = 2) hospitals. The degree of existing humanization was assessed by a multidisciplinary focus group for each hospital through a pediatric care-oriented checklist specifically developed to individuate the most critical areas (i.e., those with scores < 2.5). The degree of perceived humanization was assessed through four indicators: well-being, social aspects, safety and security, and health promotion. RESULTS: The focus groups showed that critical areas common to all centers were mainly concerned with welfare, mediation, translation, and interpretation services. Specific critical issues were care and organizational processes oriented to the respect and specificity of the person and care of the relationship with the patient. Perceived humanization questionnaires revealed a lack of recreational facilities and mediation and translation services. As for specific features investigated by both tools, it was found that mediation and interpretation services were lacking in all facilities while patient perceptions and observer ratings for space, comfort, and orientation concurred only in the general hospital evaluations. CONCLUSIONS: Future humanization interventions to ensure child- and family-friendly hospital care call for careful preliminary assessments, tailored to each pediatric ward category, which should consider possible differences between perceived and verified characteristics.

Methylene Blue Location in (Hydroperoxized) Cardiolipin Monolayer: Implication in Membrane Photodegradation.

We present molecular dynamics simulations of cardiolipin (CL) and CL monohydroperoxized derivative (CLOOH) monolayers to investigate the initial steps of phospholipid oxidation induced by methylene blue (MB) photoexcitation under continuous illumination. We considered different MB atomic charge distributions to simulate the MB electronic distribution in the singlet ground and triplet excited states. Simulation results allied to experimental data revealed that initial CL photooxidation probably occurs via a type II mechanism, to produce lipid hydroperoxide by singlet oxygen attack to the alkyl chain unsaturations. The resulting hydroperoxide group prefers to reside near the aqueous interface, to increase the membrane surface area and to decrease lipid packing. Interestingly, MB orientation changes from nearly parallel to the water-monolayer interface in the ground state to normal to the interface in its triplet excited state. The latter orientation favors oxidative chain reaction continuity via a type I mechanism, during which the hydrogen atom must be transferred from the hydroperoxide group to triplet MB. Taken together, the present results can be extrapolated to improve our understanding of how oxidation progresses in lipidic biomembrane, which will lead to the formation of oxidized species with shortened chains and will cause severe photodamage to self-organized systems.

Randomised clinical trial: a Lactobacillus GG and micronutrient-containing mixture is effective in reducing nosocomial infections in children, vs. placebo.

BACKGROUND: Nosocomial infections are a major public health issue and preventative strategies using probiotics and micronutrients are being evaluated. AIM: To investigate the efficacy of a mixture of Lactobacillus GG and micronutrients in preventing nosocomial infections in children. METHODS: A randomised, double-blind, placebo-controlled trial was conducted in hospitalised children. Children (6 months to 5 years of age) received Lactobacillus GG (6 × 10(9) CFU/day) together with vitamins B and C and zinc or placebo, for 15 days, starting on the first day of hospitalisation. The incidence of gastrointestinal and respiratory nosocomial infections after discharge was determined by follow-up telephone call at 7 days. After 3 months, another telephone call estimated the incidence of further infections during follow-up. RESULTS: Ninety children completed the follow-up. Of 19/90 children with a nosocomial infection (20%), 4/45 children (9%) were in the treatment group and 15/45 (33%) in the placebo group (P = 0.016). Specifically, 2/45 (4%) children in the treatment group vs. 11/45 (24%) children in the placebo group (P = 0.007) presented with diarrhoea. The duration of hospitalisation was significantly shorter in the treatment group (3.9 days ± 1.7 vs. 4.9 ± 1.2; P = 0.003). At the follow-up, a total of 11/45 (24.4%) children in the treatment group had at least one episode of infection compared to 22/45 (48.9%) in the placebo group (P = 0.016). CONCLUSION: A mixture containing Lactobacillus GG and micronutrients may reduce the incidence of nosocomial infections, supporting the hypothesis that this may represent a valid strategy to prevent nosocomial infections.

[Case report of asymptomatic toxocariasis. A 24-month follow up]. / Descrizione di un caso asintomatico di toxocariasi. Follow-up a 24 mesi.

An asympthomatic case of toxocariasis is described in a 9 years boy, who had been under follow-up observation for 24 months. He showed only a marked eosinophilia (42%) without any clinical alterations. The IgG antitoxocara dosage, performed by immunoenzymatic method, allowed to formulate the diagnosis. The oculistic checks, together with EEG carried out the time of diagnosis as well as at the end of follow-up did not show any alterations. No therapy was practised and the number of eosinophilis in to circulation went progressively down. At the end of follow-up the percentage of eosinophilis is 7%.

[The natural history of allergy to eggs in atopic dermatitis]. / La storia naturale dell'allergia all'uovo nella dermatite atopica.

The outcome of atopic dermatitis and the incidence [correction of prevalence] of asthma was ascertained in a four-year follow-up in 47 children with eczema due to egg allergy. At the end of the study, skin lesions had cleared in 32 (68%) children. Of these, 18 (38.2%) developed tolerance to egg about two years after diagnosis, while 14 (29.7%) continued an elimination diet. Fifteen children (31.9%) are still affected by eczema due to discontinuation of the egg-free diet. At the end of follow-up, 23 children had presented at least three asthma episodes. Therefore, the incidence [correction of prevalence] of asthma in children with atopic dermatitis appears to be significantly higher when egg allergy is present. Egg allergy could be a marker of an atopic condition and therefore be an unfavourable prognostic signal as to the outcome of the disease and the appearance of respiratory allergy.

[Children at social risk and the utilization of health services]. / I bambini a rischio sociale e l'utilizzazione dei servizi sanitari.

To investigate the association between social risk factors and access to emergency health services, 333 children, with a medium age of 39.1 months, have been recruited. 31.2% of these children had at least one social risk factor. After 12 months through a phone call we evidentiated that children with social risk showed an access to emergency services about double (relative risk factor more than double) in respect to children with no social risk factors.

[The prevention of allergic diseases with a hypoallergenic formula: a follow-up at 24 months. The preliminary results]. / La prevenzione delle malattie allergiche con formula H.A.: follow-up a 24 mesi. Primi risultati.

One hundred-eight infants from atopic families were admitted to the study. Each had at least one first-degree relative affected by asthma or rhinitis, conjunctivitis, eczema, cow's milk protein intolerance. All infants not breast fed were hypoallergenic formula. 46 infants were breast fed, 39 were bottle fed by the ordinary formula and 23 received the hypoallergenic one. No other food was introduced up to 6 months. Cow's milk proteins, egg, poultry and fish were introduced after 6 months. All infants were followed up to 24 months. Incidence of allergic diseases up to 24 months was not significantly different among the 3 groups.

[Correlation of prick tests, RAST and food challenge tests in atopic dermatitis]. / Correlazione tra prick tests, rast e diete di scatenamento nella dermatite atopica.

Prick skin allergometry is actually accepted as the best test for the diagnosis of allergic disease, being reliable and not invasive. Nevertheless questions about it use in children have been put forward. The aim of this study is to evaluate the usefulness and the reliability of prick and Rast tests for the diagnosis of atopic dermatitis due to food allergy. The correlations between Prick and Rast have been studied as well as their relation to the food challenge test. Prick and Rast tests results overlay in almost all cases, while in only 25% of cases there has been copositivity between Prick & Rast and the food challenge. This finding confirms that the pathogenetic mechanism involved in A.D. due to food allergy is not only IgE mediated, but it may also require alternative immunoreactions. Although the prick test is a simple, cheap and reliable method, the diagnosis of food allergy cannot rely solely on it. The diagnostic and therapeutic approach to food allergy borne A.D. is based upon elimination diet and food challenges.

[Parasitic arthritis: a case report]. / Le artriti parassitarie: descrizione di un caso clinico.

In Protozoan-type infections muscular and/or articular manifestations are not unusual. They are directly correlated to the presence of the parasite in the organism. In such cases a good diagnostic support can be given by the demonstration of the parasitic infection, the inefficacy of the classical therapy with FANS or steroids, and the good results obtained with a specific antiparasitic therapy. The most significant data that emerge from this description regard the possibility that when an arthritis or an arthralgia cannot be defined a parasitic infection has also to be excluded.

[Growth deficiency and renal tubular acidosis. The possible etiopathogenic mechanisms]. / Deficit di crescita ed acidosi tubulare renale. Possibili meccanismi etiopatogenetici.

The authors have studied two cases of renal tubular acidosis in 2 children underlining that a possible defective mechanism of growth is based on alteration of the receptors of somatomedine C to level of cartilage. The deficit of receptors could be the consequence of the alterations of the acidosis on cartilage.

[The attitude and vaccination practice of a sample of Campania pediatricians]. / Orientamento e pratica vaccinale di un campione di pediatri campani.

One hundred-twenty-six pediatricians were questioned about their attitudes concerning the practice of immunization, their feelings about the new vaccines (measles, mumps, german measles, hepatitis b) and about the pertussis vaccine. 80% of them reported that indications and contraindications were still unclear: Down's syndrome and atopic eczema are still thought to be real contraindications--despite the mass of papers suggesting that they are not so--, moreover 95% of the participants persists into the unnecessary evaluation of the antibody title following hepatitis b immunization. We conclude that it would be wise to periodically diffuse to pediatricians update recommendations about the extended immunization program, especially in our region, were still an high number of children are not properly immunized.

Insulin resistance and impaired glucose tolerance in obese children and adolescents from Southern Italy.

BACKGROUND AND AIM: Obesity in children may lead to insulin resistance and impaired glucose regulation over time. The aim of this study was to investigate the insulin resistance status and the frequency of impaired glucose regulation in obese children and adolescents from the Campania region (Southern Italy), where the prevalence of obesity is among the highest in Europe. METHODS AND RESULTS: We studied 100 (62 male) Italian obese children and adolescents (mean age 10.1+/-2.7 years) and 50 (27 male) normal weight healthy subjects (mean age 10.2+/-2.7 years). Anthropometric measures and biochemical tests were performed in all subjects. In obese patients an oral glucose tolerance test was also performed. The estimate of insulin resistance was calculated by a homeostasis model assessment (HOMA) index. A cut-off HOMA level of >2.5 in children and >4.0 in adolescents was used to identify an insulin-resistance status. Insulin resistance was found in 40.8% of obese children and 41.2% of obese adolescents, whereas it was found in 3.0% of normal children and none of the 17 normal adolescents (p<0.0001 and p<0.002, respectively). None of the subjects had impaired fasting glucose or diabetes, while 4 obese patients had impaired glucose tolerance (4%). CONCLUSIONS: Impaired glucose tolerance is still rare whereas insulin-resistance is already detectable in more than 40% of obese children and adolescents in Southern Italy. Our observations confirm that metabolic risk factors can be found at a very early age and strengthen the case for implementing programmes for prevention and treatment of childhood obesity.

[Juvenile xanthogranuloma. Description of a case with liver involvement]. / Xantogranuloma giovanile. Descrizione di un caso con interessamento epatico.

Juvenile Xanthogranuloma. Report of a case with hepatic involvement. The Authors present a case of Juvenile Xanthogranuloma (JX) in a 3 months female child with cutaneous and hepatic nodules associated to dyspnea attributable to obstructive bronchopneumopathy. Histologically the lesions are xanthomatous with proliferation of fat-laden histiocytes. The hepatic involvement is characterized by hepatomegaly and yellow nodules on liver surface as seen at laparoscopy. On liver biopsy there is remarkable expansion of portal triad caused by aggregates of large foamy mono-polynuclear histiocytes with Touton giant cells. The cutaneous nodule biopsy shows histiocytic infiltrate in inter-adnexal dermal space with many giant cells holding great lipidic vacuoles. The patient's follow-up is characterized by slow and progressive clinical improvement with resolution of cutaneous, hepatic and pulmonary pathology. The Authors emphasize the differential diagnosis between this systemic form of JX and Langerhans cell Histiocytosis (Histiocytosis X) with multiorgan involvement. This diagnosis is necessary in order to establish therapy and prognosis.

Atopy and coeliac disease: bias or true relation?

Several reports have suggested a relationship between atopy and coeliac disease and atopy has also been linked to the pathogenesis of the mucosal damage. Conclusive epidemiological evidence of the relationship has not been satisfactorily established. The case-control study reported here was undertaken to test the hypothesis that coeliac disease is linked to atopy. Eighty-two coeliac disease cases and a group of 180 age matched controls and all their first degree relatives were investigated for atopy. Siblings of cases reported an increased prevalence of food intolerance, compared to siblings of controls. No increase in asthma, eczema, rhinitis, conjunctivitis, cow's milk protein allergy (CMPA) were detected in relatives of cases, compared to those of controls. When each index case and each control were investigated no increased prevalence of atopic conditions was found. Skin prick testing to major allergens was positive in a similar proportion of cases and controls. Serum total IgE of a random sample of cases and controls showed no difference in mean values. This study supports the null hypothesis: there is no difference in the prevalence of atopy in cases affected by coeliac disease and their relatives, compared to controls and their relatives. The sources of possible bias in previous reports are discussed.