Search

Kawasaki disease (KD)is an idiopathic acute febrile illness that primarily occurs in children <5 years of age and can lead to artery lesions if not promptly treated. Recent studies have shown possible correlations between KD onset and currents and air pollutants.The present study describes results on the correlation between environmental conditions, frequency, and variability ofKD onset in children under five years of age in Emilia-Romagna, a region of Northern Italy, over the period from 2000 to 2017. Since there are substantial climatic differences between the western-central (Emilia) and the eastern area (Romagna) of the region, the data for these areas are analyzed separately. The environmental factors considered are observed local surface daily temperature, daily precipitation, upper air wind regimes, and local air pollution. The results indicate that in Emilia-Romagna, KD onset occurs mainly during late autumn and early spring, which is in agreement with the literature. The frequency of KD onset in Emilia is significantly higher in months characterized by a high frequency of southerly flow, which is associated with milder than average night-time temperature, and in years with a prevailing south-westerly mean flow. These results are consistent with other studies, suggesting that certain wind conditions are more favorable for disease onset, which are possibly associated with one or more airborne agents., Competing Interests: The authors declare no conflict of interest.

Aim: A gluten-free diet (GFD) can expose children to excessive calories and fat intake. The study is intended to verify whether and how food intake, laboratory parameters, and growth are modified by a year of GFD., Methods: In 79 CD (coeliac disease) children (mean age 7.9 ± 3.8 years, 52 females, 27 males) diagnosed over 24 months, 24-h food diaries, food-frequency patterns, anthropometric and laboratory parameters (mainly blood sugar, insulin, lipid profile, and homocysteine) were prospectively collected before and during the first year of GFD. Nutrient intakes were compared over time and with recommendations. They were also used as regressors to explain the levels and changes of metabolic and growth variables. p -values < 0.05 were considered statistically significant., Results: Average macronutrient intake did not change during the year. Caloric intake remained below 90% ( p ≤ 0.0001) and protein intake above 200% ( p ≤ 0.0001) of recommendations. Lipid intake was stable at 34% of overall energy intake. Unsaturated fats increased (less omega-6 and more omega-3 with a ratio improvement from 13.3 ± 5.5 to 8.8 ± 3.1) and so did fibers, while folate decreased. The children who experienced a containment in their caloric intake during the year, presented a slower catch-up growth. Some differences were found across gender and age groups. In particular, adolescents consumed less calories, and females more omega-3. Fiber and simple sugar intakes emerged as implicated in lipid profile shift: fibers negatively with triglycerides (TG) ( p = 0.033), simple sugars negatively with high-density lipoprotein (HDL) ( p = 0.056) and positively with TG ( p = 0.004). Waist-to-height ratio was positively associated with homocysteine ( p = 0.018) and Homeostasis Model Assessment ( p = 0.001), negatively with fibers ( p = 0.004)., Conclusion: In the short run, GFD is nutritionally very similar to any diet with gluten, with some improvements in unsaturated fats and fiber intake. Along with simple sugars containment, this may offer CD patients the opportunity for a fresh start. Caloric intakes may shift and should be monitored, especially in adolescents.

Since resistance to intravenous immunoglobulin (IVIG) is associated with coronary lesions (CALs) in Kawasaki disease (KD), it is crucial to identify patients at risk to protect them from coronary involvement. The available risk scores to predict IVIG resistance were developed in Asian populations in whom their effectiveness has been proven, but data on non-Asian children are limited. The aim of this study is to evaluate the ability of the Kobayashi, Egami, and Formosa risk scores to predict IVIG resistance and CALs in Italian patients with KD. A multicenter retrospective analysis involving children with KD diagnosed between 2000 and 2015 was carried out: 257 patients were enrolled (57.9% boys, 89.9% Caucasian); 43 patients were IVIG resistant (16.7%). The scores have low sensitivity and specificity in predicting IVIG resistance: respectively, KS 64% and 62.5%, ES 41.4% and 77.4%, and FS 70.8% and 44.9%. The predictive value of the 3 scores for predicting CALs was also poor.Conclusion: Kobayashi, Egami, and Formosa Scores are ineffective in predicting IVIG resistance and coronary involvement in a predominantly Caucasian cohort. A specific score system for mostly Caucasian children with KD is needed enable the early identification of those at risk for CALs who could benefit from intensified treatment. What is Known: • There are several risk scores developed in the Asian population to early identify patients with KD at risk for immunoglobulin-resistance and thus for coronary lesions. • Data are scarce on their effectiveness in non-Asian children. What is New: • We present a comprehensive analysis of the ability of 3 Asian risk scores in a cohort of mostly Caucasian children to predict immunoglobulin resistance and coronary involvement. • Low sensitivity and specificity of the Asian scores for immunoglobulin-resistance and coronary lesions suggest the need for criteria specific for different ethnicities.

Background and Aim of the Work: The possibility of an allergic reaction or an intolerance to additives is frequently suspected by parents, especially for chronic illness with frequent exacerbations such as atopic dermatitis or chronic urticaria. For more than 50 years, potential adverse reactions to additives have been suggested, but to date data are conflicting. The purpose of this article is to provide the clinicians with general information about additives and adverse reactions to them and to suggest a practical approach to children suspected to have reactions to food additives., Methods: We performed an extensive research on all English-language Medline articles, case reports and reviews published online until December 2018. Used search terms were: food additives, food dye, adverse reactions, food allergy, food hypersensitivity, intolerance, drugs, children., Results: There are only few case reports of adverse reactions in childhood with a clear involvement of additives. In this review article we reported the associations between additives and adverse reactions described in literature, in order to inform the pediatrician about the potential clinical manifestations., Conclusions: Prior to suspect an adverse reaction to additives, it is important to rule out other possible causes: the diagnostic process is complicated and rarely conclusive. The gold standard is the double-blind placebo controlled oral challenge after an exclusion diet.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome is a mysterious disorder characterized by periodically recurrent fevers, oropharyngeal inflammation, and adenitis, which mainly affects children, though in very recent times, it has been also recognized in adulthood. We enrolled 115 unrelated pediatric and adult patients with history of periodic fevers who fulfilled the current diagnostic criteria for PFAPA syndrome in three Italian referral centers and highlighted differences between children and adults. Eighty-five children and 30 adults were evaluated: the frequency of flares was significantly higher in pediatric cases, while febrile attack duration was significantly longer in adults. Clockwork periodicity of fever and recurrent pharyngitis were more frequently observed in childhood, but no differences were identified for aphthosis and cervical adenopathy. Conversely, joint symptoms, myalgia, headache, fatigue, ocular signs, and rashes were more common in adults. The simultaneous occurrence of two or three cardinal PFAPA signs did not show any statistical difference between the groups, while the occurrence of only one cardinal manifestation was more frequent in adults. Corticosteroids were effective in 98.82 % of children and 88.2 % of adults. Tonsillectomy was rarely performed, resulting effective in only two patients. Our data illustrate the clinical overlap between pediatric and adult cases of PFAPA syndrome. Adults are characterized by a wider repertoire of inflammatory signs, suggesting that onset in adulthood might leave the disease misdiagnosed. Clinicians, not only pediatricians, should take into account this clinical entity in every patient of whatever age suffering from recurrent fevers of unknown origin.

Short-lived systemic inflammatory reactions arising from disrupted rules in the innate immune system are the operating platforms of hereditary autoinflammatory disorders (HAIDs). Multiple organs may be involved and aseptic inflammation leading to disease-specific phenotypes defines most HAIDs. Lungs are infrequently involved in children with HAIDs: the most common pulmonary manifestation is pleuritis in familial Mediterranean fever (FMF) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), respectively caused by mutations in the MEFV and TNFRSF1A genes, while interstitial lung disease can be observed in STING-associated vasculopathy with onset in infancy (SAVI), caused by mutations in the TMEM173 gene. The specific pleuropulmonary diseases may range from sub-clinical abnormalities during inflammatory flares of FMF and TRAPS to a severe life-threatening disorder in children with SAVI., Competing Interests: The authors declare no conflict of interest.

Kawasaki syndrome (KS) is the most relevant cause of heart disease in children living in developed countries. Intravenous immunoglobulin (IVIG) has a preventive function in the formation of coronary artery abnormalities and a poor strictly-curative action in established coronary damage. More than two decades ago, the Harada score was set to assess which children with KS should be subject to administration of IVIG, evaluating retrospectively a large cohort of patients with regard to age, sex and laboratory data. Nowadays, high dose IVIG is administered to all children with a confirmed diagnosis of KS, but a tool for predicting non-responsiveness to the initial infusion of IVIG has not been found. The prediction of IVIG resistance is a crucial issue, as recognising these high-risk patients should consent the administration of an intensified initial treatment in combination with IVIG in order to prevent coronary injuries. Few reports have focused on factors, referring to both clinical parameters and laboratory data at the onset of KS, in order to predict which patients might be IVIG non-responsive. We have analysed three different risk scores which were formulated to predict IVIG resistance in Japanese children with typical KS, but their application in non-Japanese patients or in those with incomplete and atypical patterns of the disease has been studied in a fragmentary way. Overall, our analysis showed that early and definite ascertainment of likely IVIG non-responders who require additional therapies reducing the development of coronary artery involvement in children with KS is still a challenge.

Group A Streptococcus (GAS) strains are lately classified on the basis of sequence variations in the emm gene encoding the M protein, but despite the high number of distinct emm genotypes, the spectrum of phenotypes varying from invasive suppurative to non-suppurative GAS-related disorders has still to be defined. The relationship of GAS types with the uprising of acute rheumatic fever (ARF), a multisystemic disease caused by misdirected anti-GAS response in predisposed people, is also obscure. Studies published over the last 15 years were retrieved from PubMed using the keywords: "Streptococcus pyogenes" or "group A Streptococcus" and "acute rheumatic fever": the prevalence of peculiar emm types across different countries of the world is highly variable, depending on research designs, year of observation, country involved, patients' age, and gender. Most studies revealed that a relatively small number of specific emm/M protein types can be considered "rheumatogenic", as potentially characterized by the possibility of inducing ARF, with remarkable differences between developing and developed countries. The association between emm types and post-streptococcal manifestations is challenging, however surveillance of disease-causing variants in a specific community with high rate of ARF should be reinforced with the final goal of developing a potential primary prophylaxis against GAS infections., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A complex web of dynamic relationships between innate and adaptive immunity is now evident for many autoinflammatory and autoimmune disorders, the first deriving from abnormal activation of innate immune system without any conventional danger triggers and the latter from self-/non-self-discrimination loss of tolerance, and systemic inflammation. Due to clinical and pathophysiologic similarities giving a crucial role to the multifunctional cytokine interleukin-1, the concept of autoinflammation has been expanded to include nonhereditary collagen-like diseases, idiopathic inflammatory diseases, and metabolic diseases. As more patients are reported to have clinical features of autoinflammation and autoimmunity, the boundary between these two pathologic ends is becoming blurred. An overview of monogenic autoinflammatory disorders, PFAPA syndrome, rheumatoid arthritis, type 2 diabetes mellitus, uveitis, pericarditis, Behçet's disease, gout, Sjögren's syndrome, interstitial lung diseases, and Still's disease is presented to highlight the fundamental points that interleukin-1 displays in the cryptic interplay between innate and adaptive immune systems.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), formerly known as familial Hibernian fever, is the most common autosomal dominant autoinflammatory disease, resulting from mutations in the TNFRSF1A gene, encoding the 55-kD tumor necrosis factor receptor. The pathophysiologic mechanism of TRAPS remains ambiguous and only partially explained. The onset age of the syndrome is variable and the clinical scenery is characterized by recurrent episodes of high-grade fever that typically lasts 1-3 weeks, associated with migrating myalgia, pseudocellulitis, diffuse abdominal pain, appendicitis-like findings, ocular inflammatory signs, and risk of long-term amyloidosis. Fever episodes are responsive to high-dose corticosteroids, but different classes of drugs have been reported to be ineffective. The use of etanercept is unable to control systemic inflammation, while interleukin-1 blockade has been shown as effective in the control of disease activity in many patients reported so far.

It is widely accepted that a temperature region exists above the glass transition temperature, playing a fundamental role in the physics of polymers and glass formers. In this region, several dynamic crossovers have been experimentally and numerically revealed in the past years and the onset of glassy behavior is generally located, because of cooperative and heterogeneous features exhibited by the dynamics. In this Article, the rotational dynamics of two different stiff molecular spin probes dissolved in poly(propylene glycol) has been investigated by electron spin resonance spectroscopy in a wide temperature range. Decoupling phenomena between macroscopic and microscopic transport properties have been observed in the crossover region. A comparison with previous studies carried out with the same tracers dissolved in different polymers and glass formers strongly supports the idea that the observed crossover signals the onset of spatial correlations of dynamics on the length scale probed by the tracers.

The enthalpy relaxation mechanism of a low molecular weight synthesis of polymethylmethacrylate was investigated by means of calorimetric experiments. The data were analyzed in terms of a kinetic approach treating nonlinearity in a different manner with respect to the Tool-Narayanaswamy-Moynihan model. The relaxation isotherms recorded at four different temperatures were well reproduced by this approach that, however, failed in describing the relaxation asymmetry towards the equilibrium after opposite temperature jumps. A modification of the model was proposed with an additional free parameter accounting for the stretching of the relaxation function. In this way all the experimental data were reproduced fairly well.

The rotational dynamics of the spin probe cholestane dissolved in a narrow distribution poly(n-butyl acrylate) sample has been investigated via electron spin resonance (ESR) spectroscopy. The measurements were carried out in a wide temperature range: different dynamic regions have been recognized, and the coupling of the probe dynamics to the α and secondary relaxations has been revealed. In particular, the coupling with the structural relaxation is ruled by two fractionary Vogel-Fulcher laws (VF). The crossover from one VF region to the other occurs at the temperature T(C) = 1.17T(g), signalling the onset of the cooperativity in the dynamics and confirming a behaviour previously observed in ESR studies carried out on polymeric glass-formers. Furthermore, in this work we discuss the activated regime at the highest temperatures and show that the activation energy does not depend on the length of the polymer main- and side-chains, while its onset temperature linearly depends on the chain length.

Low-temperature plasma was used to activate mercerized cotton fabrics, to be followed by grafting with various methacrylates. Careful analysis of the experimental electron spin resonance (ESR) lineshapes of cotton samples treated at different RF powers made it possible to recognize and quantify four different species of free radicals still persistent 30 h after irradiation in the samples maintained under inert atmosphere. The decay rate of these species at room temperature was also evaluated with the analysis of the time evolution of the ESR spectra. The nature of the free radical species actually involved in the monomer grafting reaction has been discussed for cotton fabrics prepared under different plasma treatment conditions by analyzing the ESR lineshapes.

Objectives: To determine (1) patterns of secure vs insecure attachment relationships in infants of adolescent and nonadolescent mothers and (2) if these patterns are mediated by parenting characteristics, including depression, self-esteem, parenting stress, child abuse potential, psychological distress, rating of infant temperament, and the caregiving environment., Participants: Fifty-one adolescent mothers and their 18-month-old infants were compared with 76 nonadolescent mothers and their 18-month-old infants., Main Outcome Measures: Infant attachment classifications were assessed via the Ainsworth Strange Situation. Maternal and infant characteristics were obtained through self-report measures., Results: There were no differences in attachment classification between infants of adolescent mothers and nonadolescent mothers. Secure attachment classification was found in 67% of the infants of adolescent mothers and 62% of the infants of nonadolescent mothers. There were significant differences in the self-reported maternal characteristics. Adolescent mothers reported lower self-esteem (P<.05), more parenting stress (P<.05), more child abuse potential (P<.05), and provided a lower quality of home environment (P<.05) than nonadolescent mothers. Adolescent mothers also rated their infants as having a higher activity level (P<.05) than infants born to nonadolescent mothers. In multivariate analysis, none of these variables or social classes were found to affect attachment classification., Conclusions: Infants of adolescent and nonadolescent mothers show similar patterns of attachment. Adolescent and nonadolescent mothers show substantial differences in parenting characteristics and in how they rate their infants' temperaments. However, these differences do not seem to impair the infant-mother attachment relationship.

'Compositional chromosomal mapping', namely the assessment of the GC level of chromosomal bands, led to the identification, in the human chromosomes, of the GC-richest H3+ bands and of the GC-poorest L1+ bands, which were so called on the basis of the isochore family predominantly present in the bands. The isochore organization of the avian genome is very similar to those of most mammals, the only difference being the presence of an additional, GC-richest, H4 isochore family. In contrast, the avian karyotypes are very different from those of mammals, being characterized, in most species, by few macrochromosomes and by a large number of microchromosomes. The 'compositional mapping' of chicken mitotic and meiotic chromosomes by in-situ hybridization of isochore families showed that the chicken GC-richest isochores are localized not only on a large number of microchromosomes but also on almost all telomeric bands of macrochromosomes. On the other hand, the GC-poorest isochores are generally localized on the internal regions of macrochromosomes and are almost absent in microchromosomes. Thus, the distinct localization of the GC-richest and the GC-poorest bands observed on human chromosomes appears to be a general feature of chromosomes from warm-blooded vertebrates.

We have hybridized the vertebrate telomeric sequence (TTAGGG)n on DNA compositional fractions from 13 mammalian species and 3 avian species, representing 9 and 3 orders, respectively. Our results indicate that the 50- to 100-kb fragments derived from telomeric regions are composed of GC-rich and GC-richest isochores. Previous works from our laboratory demonstrated that single-copy sequences from the human H3 isochore family (the GC-richest and gene-richest isochore in the human genome) share homology with compositionally correlated compartments of warm-blooded vertebrates. This correlation suggested that the GC-richest isochores are, as in the human genome, the gene-richest regions of warm-blooded vertebrates' genome. Moreover, this evidence suggests that telomeric regions are the most gene-dense region of all warm-blooded vertebrates. The implications of these findings are discussed.

In the last few decades quite a few articles have been published concerning Volterra's contributions to biomathematics. These articles are usually focused on the works of Volterra published after 1926, while they overlook Volterra's intense activity as scientific organizer in the field of oceanographic studies in the years that span from 1910 - the year of his celebrated dissertation about the applications of mathematics to social and biological sciences - to 1925, when he met his prospective son-in-law Umberto D'Ancona. In this article I shall try to fill this gap by telling the history of Volterra's scientific collaboration with Italian biologists (such as Giovan Battista Grassi, Luigi de Marchi and Gustavo Brunelli) in the decades before his meeting with Umberto D'Ancona. This story is worth telling because it helps to explain the stronger emphasis Volterra placed in his first biomathematical papers on the importance of the applications of mathematics to biology for practical matters (such as the prevention of epidemics and the enhancement of the fishing industry) rather than on more theoretical issues, which he tackled only in the last years of his life.

The human genome is formed by isochores belonging to five families, L1, L2, H1, H2 and H3, that are characterized by increasing GC levels and gene concentrations. In-situ hybridization of DNA from different isochore families provides, therefore, information not only on the correlation between isochores and chromosomal bands, but also on the distribution of genes in chromosomes. Three subsets of R(everse) bands were identified: H3+, H3* and H3-, that contain large, moderate, and no detectable amounts, respectively, of the gene-richest H2 and H3 isochores, and replicate very early and early, respectively, in S phase of the cell cycle. Here, we investigated the GC levels, replication timings and DNA compaction of G(iemsa) bands. We showed that G bands comprise two different subsets of bands, one of which is predominantly composed of L1 isochores, replicates at the end of the S phase, has a higher DNA compaction relative to H3+ bands and corresponds to the darkest G bands of Francke (1994). In contrast, the other subset is composed of L2 and H1 isochores, has less-extreme properties in replication and composition and corresponds to the less-dark G bands of Francke.

Phenolphthalein is a nonprescription laxative agent that has been widely used during this century. Recent studies in animal models have shown that phenolphthalein has carcinogenic activity. In order to assess cytogenetic effects on human cells in vitro, we tested phenolphthalein in a chromosome aberration assay in human embryo cells derived from amniotic fluid. Our results show that phenolphthalein induces a significant increase in the frequency of chromosome aberrations in human cells. The lowest dose level at which the clastogenic effect is evident is 23.2 microg/ml. Similar positive results were obtained in a Chinese hamster liver cell line, which is metabolically competent to activate different classes of promutagens and procarcinogens into biologically active metabolites. Instead, parallel experiments in Chinese hamster ovary cells did not show any clastogenic effect due to phenolphthalein. These latter data suggested that phenolphthalein acts as a promutagen and must be metabolically activated to exert its clastogenic effect. Teratogenesis Carcinog. Mutagen. 20:209-217, 2000., (Copyright 2000 Wiley-Liss, Inc.)

The mouse genome is a mosaic of isochores, consisting of long (> 300 kb), compositionally homogeneous DNA segments that can be divided into two GC-poor families, L1 and L2, representing 56% of the genome, and two GC-rich families, H1 and H2, representing 26% and 7% of the genome, respectively, the remaining 11% being formed by satellite and ribosomal DNAs. (GC is the molar fraction of guanine + cytosine in DNA.) The mouse genome differs from the human genome (which is representative of most mammalian genomes) because it shows a narrower compositional spectrum of isochores and it has a karyotype formed exclusively by acrocentric chromosomes. The chromosomal distribution of the four isochore families, as investigated here by in situ hybridization of single-copy sequences from compositional DNA fractions, has shown that G(lemsa) bands are essentially composed of GC-poor isochores, whereas R(everse) bands comprise three subsets of bands: R' bands, containing GC-poor isochores and GC-rich isochores of the H1 family, and T and T' bands, containing all H2 isochores (in addition to other isochores), the former containing a higher proportion of H2 isochores than the latter. Mouse T and T' bands are generally syntenic with, and are compositionally related to, human T and T' bands and have the highest gene concentrations. These findings indicate that the distribution of isochore families and genes in chromosomal bands is basically similar in mouse and in human genomes, in spite of their remarkable differences and their extremely large phylogenetic distance.

Objective: To determine the degree to which knowing certain characteristics about young high-risk families can help distinguish those families most likely to maltreat their children from those families at lower risk of maltreating their children., Design: Observational cohort from which the following predictor variables were gathered when infants were 2 months old: maternal age, depressive symptoms, childrearing attitudes, social support, and living situation (with or apart from related adults). Families were followed up for 24 months to identify the occurrence of maltreatment., Setting: An urban, socioeconomically disadvantaged cohort of teenage mothers and their infants attending a hospital-based special primary care clinic for teen mothers and their infants., Participants: All full-term infants and mothers enrolled into the clinic in 1990 participated in the study. This included 47 mother-infant pairs enrolled when infants were 2 months of age. Forty-five of these pairs were available for follow-up when infants were 24 months of age., Main Outcome Measures: Maltreatment defined as any incident that prompted investigation by the state child protective agency and was found to be a substantiated case of maltreatment by that agency., Results: Maltreatment occurred in 15 of 45 families before the child's second birthday. Discriminate function analysis produced a model that correctly classified 13 of 15 maltreating mothers and misclassified one of 30 non-maltreating mothers. Stepwise analysis revealed that living situation was by far the strongest predictive variable (R2 = 7)., Conclusion: Maltreatment was a predictable outcome within this extremely high-risk cohort. Living apart from related adults was the strongest risk factor associated with maltreatment. This easily obtainable piece of information may be an important risk marker for practitioners, social service personnel, and others working with this very-high-risk population. It may allow early supportive interventions that might prevent maltreatment.

This is a case study of a 6-week-old infant referred for colic whose mother was using fluoxetine hydrochloride and breast feeding the infant. The mother switched to a commercial formula and reported a dramatic decrease in the infant's crying. We asked the mother to feed the infant breast milk from a bottle and she agreed. Throughout the study the mother kept a daily diary of her infant's crying, sleeping, stooling patterns, and feeding problems. Analysis of the mother's breast milk showed concentrations of 69 ng/mL for fluoxetine and 90 ng/mL for norfluoxetine. Infant blood serum/plasma level was analyzed for fluoxetine hydrochloride following return to breast milk. The concentrations were 340 ng/mL for fluoxetine and 208 ng/mL for norfluoxetine. The diary records showed increased crying, decreased sleep, increased vomiting, and watery stools when fluoxetine hydrochloride was transmitted through breast feeding or breast milk in bottle. These symptoms were reduced when the infant was formula fed. We suggest a possible relationship between colic and associated symptoms and fluoxetine hydrochloride in maternal breast milk.