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Background: There is controversy in the literature regarding the potential relationship between atopic predisposition (AP) and serum cholesterol levels. To this purpose, we reviewed human studies that investigated this possible link. Methods: Following PRISMA guidelines, a literature search of PubMed and Science Direct for peer-reviewed journal articles in English from January 2003, with updates through to August 2016, was conducted. Relevant publications were reviewed that included pediatric and adult populations. Information on the study design, sample, intervention, comparators, outcome, time frame, and risk of bias were abstracted for each article. Results: Of 601 reviewed reports, 18 were included in this systematic review. Fifteen studies assessed the relationship between AP and serum cholesterol levels. Due to the lack both of observational and cross-sectional studies from the literature search at this time (only 8 studies also analyzed confounding factors) there is a high possibility of confounding variables (familial and genetic predisposition, age, gender, BMI, comorbidity, and medication status) that could not be ruled out. Conclusion: Existing studies are heterogeneous, making it difficult to draw broad conclusions. Future studies and more detailed analyses, considering confounding variables and including a larger and homogeneous population, are needed to strengthen the argument for a link between lipid metabolism and atopy.

Oxidative stress is worldwide recognized as a fundamental component of the aging, a process that begins before birth. There is a critical balance between free radical generation and antioxidant defenses. Oxidative stress is caused by an imbalance between the production of free radicals and the ability of antioxidant system to detoxify them. Oxidative stress can occur early in pregnancy and continue in the postnatal period; this damage is implicated in the pathophysiology of pregnancy-related disorders, including recurrent pregnancy loss, preeclampsia and preterm premature rupture of membranes. Moreover, diseases of the neonatal period such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and periventricular leukomalacia are related to free radical damage. The specific contribution of oxidative stress to the pathogenesis and progression of these neonatal diseases is only partially understood. This review summarizes what is known about the role of oxidative stress in pregnancy and in the pathogenesis of common disorders of the newborn, as a component of the early aging process.

Fibrodysplasia ossificans progressiva is a rare genetic disease that manifests in early life with malformed big toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites. Mutation c.617G>A in the activin A receptor type I gene is reported in all patients with fibrodysplasia ossificans progressiva. No cases of cardiac involvement have been described in children. We report the case of a child with halluces valgi at birth, along with two tender, firm, immovable masses located on the right and left parietal-occipital region, a transitory subluxation of the right hip and an unusual ventricular septal hypertrophy. We hypothesize that the ventricular septal hypertrophy could be the result of a thickening of the fibrous portion of the septum, and a possible new element of the phenotype, probably resulting from the mechanical stimuli secondary to the significant hemodynamic changes occurring at birth.

To date studies on the relation between mode of delivery and atopic diseases in are controversial.The aim of the study was to determine a possible relationship between mode of delivery and risk of atopic phenotypes and, to assess the critical role of some pre-and post-natal parameters as a link between mode of delivery and risk of atopy.1516 children were assessed by skin prick tests, serum total and specific IgE levels. Parental reports on demographic and clinical data were also recorded.Of the 1516 children enrolled for the study, clinical and laboratory informations were obtained from 917 children. 460 children of them were born via CD and 457 via VD. Mode of delivery did not modify the prevalence of immune sensitization and/or allergic diseases. However, CD was associated with increased risk of atopy (p0.001). Moreover, some parameters such as familiar history of atopy (p0.001), habits smoking (p0.05), exclusive artificial feeding (p0.001); and breast-feeding time (3months) (p0.001) were associated with a major risk of atopy in CD group. Additionally, although our study confirmed that breast-feeding is associated to lower serum total IgE levels than artificial-feeding (p0.001), it seems that the protective role of breast-feeding is negatively influenced from CD. Also in artificial-feeding subjects CD is related to a significant higher levels of IgE than VD (p0.001).Our findings suggest that CD influences only the risk of atopy but no prevalence of immune sensitization and allergic diseases.

Although extensive epidemiological and laboratory studies have been performed to identify the environmental and immunological causes of atopy, genetic predisposition seems to be the biggest risk factor for allergic diseases. The onset of atopic diseases may be the result of heritable changes of gene expression, without any alteration in DNA sequences occurring in response to early environmental stimuli. Findings suggest that the establishment of a peculiar epigenetic pattern may also be generated by oxidative stress (OS) and perpetuated by the activation of OS-related genes. Analyzing the role of maternal and neonatal oxidative stress and oxidative stress-inducible genes, the purpose of this review was to summarize what is known about the relationship between maternal and neonatal OS-related genes and the development of atopic diseases.

To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis.Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease.The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P0.05).This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.

YKL-40 is a chitinase-like protein present in serum of healthy subjects and its levels are increased in several human inflammatory diseases. The aim of this study was to evaluate the levels of both serum and sputum YKL-40 in cystic fibrosis (CF) patients.Serum and sputum YKL-40 levels were measured in a cohort of twenty-eight patients with a diagnosis of CF and twenty healthy controls.Serum YKL-40 levels were significantly higher in CF patients (88.8±56.7 vs 18.6±2.9ng/ml, P0.001), as well as sputum YKL-40 levels (138.5±132.7 vs 28.2±24.34, P0.001) than in healthy controls. Serum YKL-40 levels were closely related to YKL-40 levels assessed in sputum samples (r=0.71; P0.01).YKL-40 is elevated in CF patients and is further elevated during severe exacerbations. Longitudinal studies in infant are needed to establish its role in disease pathogenesis.

Renal artery embolism (RAE) is a rare disease, and its clinical features and diagnostic tools are mysterious to most physicians. Anticoagulants, surgery, and thrombolytic therapies have been used to treat patients with RAE. However, there is no universal protocol for the proper management of RAE and the timing of treatment. This variation in treatment management further impairs the comparison of different therapies, complications and prognoses. We reported a RAE patient who underwent intra-arterial urokinase treatment. A detailed literature search found that the most common presentations of RAE are localized pain in the flank/abdomen, nausea and vomiting, and fever. A few laboratory abnormalities, including elevations of lactic dehydrogenase, C-reactive protein, and white cell count, as well as unexplained proteinuria and hematuria, are useful screening tools for RAE. A contrast-enhanced computed tomographic scan of the abdomen is currently the best diagnostic tool. Anticoagulants are an effective and safe treatment, resulting in a fair prognosis for RAE cases. The rates of mortality and long-term hemodialysis are low. Surgery and intra-arterial thrombolytic therapy should be reserved in cases where the aggressive preservation of residual renal function is necessary in patients with deteriorated renal function or only one functional kidney. In addition, concurrent and subsequent thrombolytic events in other organs are common in patients with RAE.

Dear Editor, A poorer response to hepatitis B vaccination, in coeliac subjects, compared to healthy subjects, has been largely debated. Almost all authors postulated that human leukocyte antigen (HLA) genotype DQ2, found in 90 - 95% of coeliac patients, could represent the main cause in determining the impaired antibody response to recombinant HBV vaccine (1), as well as observed also in healthy not responder subjects. However it has been supposed that gluten intake could represent the main factor in influencing a poorer response to vaccine, since in several studies, it has been observed that the percentage of responders in patients compliant with a gluten free diet (GFD) was similar to healthy subjects (2, 3). Since type I diabetes (T1DM) and coeliac disease (CD) have the same genetic background, given by the HLA molecules that have also been identified as haplotypes associated with unresponsiveness to hepatitis B virus (HBV) vaccination (DR3 and DR4 for T1DM, DQ2 and DQ8 for CD), we firstly compared three different groups of patients, corresponding to T1DM, CD and DMT1-CD, that had in common the same HLA haplotypes, to establish the weight of specific haplotypes of HLA and/or gluten that could favor a poorer response to HBV vaccine. In 30 children suffering from both CD and DMT1, vaccinated by the administration of three doses of vaccine (Engerix-B, Glaxo Smith Kline, London, United Kingdome) at the age of 3, 5 and 11 months of life, according to the national vaccination schedule, we discovered 16 (53.3%) non-responders. This percentage was similar to a previous study on 60 coeliac patients (4), although not significantly higher, compared to a previous study on 100 diabetics (5) (Table 1). Table 1. Characteristics of Patients With Type 1 Diabetes Mellitus, Celiac Disease and Associated Type 1 Diabetes Mellitus/Coeliac Disease a As the mean age and the anti-HBs antibodies titers was similar between coeliacs and coeliacs/diabetics, we consider that the presence of T1DM and its HLA haplotype seems to not decrease anti-HBs antibodies production and percentage of responders. The open question is: what is the role of gluten in this matter? Comparing the T1DM/CD and T1DM, in which both groups had a similar HLA haplotype, we found a higher non-significant percentage of non-responders in T1DM/CD than in T1DM (53.3% vs. 38.2%), although the first group even had a significantly lower mean age (P < 0.0001), which usually is associated to a higher titer of anti HBs antibodies (P < 0.02) and a higher percentage of responders, as we also found in our study (Table 1). The question still remains open: what is the role of gluten in this matter? First of all, we observed that the percentage of non-responders is higher in T1DM/CD patients, compared with diabetics (53.3% vs. 38.2%). However, if we compare the first group with coeliacs, the percentage of non-responders is similar (53.3% vs. 50%). As the genetic substrate of HLA haplotypes, in the two diseases, is the same, this comparison indirectly confirms that gluten certainly represents a second variable, which favors a further decrease of efficacy to HBV vaccine, beyond the HLA system. As written in 1890 by in the chapter “The Science of Deduction” of the book “The Sign of Four, eliminate all other factors and the one which remains must be the truth (6).”

Nemaline myopathy is a rare, non progressive congenital skeletal muscle disorder defined by the presence of inclusions known as nemaline rods in muscle fibers. Several clinical subtypes have been described, according to degree of muscle weakness, severity and age at onset. The course of nemaline myopathy is very slowly progressive, and death is usually due to respiratory failure. Cardiac involvement is rare and generally considered to be the result of ACTA1 mutations.We report the case of a 6 year old boy with typical congenital nemaline myopathy. Nemaline myopathy was confirmed at 3 years of age by muscle biopsy. No mutation of ACTA1, TPM2 and TNNT1 genes was detected. The child died suddenly of cardiac arrest and associated hypoxic-ischemic brain injury, in absence of acute respiratory failure or swallowing difficulties.Nemaline cardiomyopathy was suspected, but post mortem cardiac biopsy did not show findings consistent with nemaline myopathy.Congenital typical nemaline myopathy is not necessarily a static or very slowly progressive disorder and acute cardiac deterioration can lead to early death.

The monitoring of asthma is based mainly on clinical history, physical examination, and lung function test evaluation. To improve knowledge of the disease, new biomarkers of airway inflammation, including high mobility group box-1 (HMGB1), are being developed.To evaluate sputum HMGB1 levels in children with stable, off-therapy, allergic asthma and to evaluate the relation between HMGB1 levels and lung function parameters.Fifty children with asthma (28 boys and 22 girls, median age 11.56 ± 1.41 years) and 44 healthy children (22 boys and 22 girls, median age 11.07 ± 2.12 years) were enrolled. Sputum HMGB1 was assessed in the cohort study. Lung function (predicted percentage of forced expiratory volume in 1 second [FEV1%] and forced expiratory flow between 25% and 75% [FEF25%-75%]), serum total IgE levels, and asthma severity by validated Global Initiative for Asthma criteria were recorded.Sputum HMGB1 levels were higher in children with asthma than in healthy controls (100.68 ± 10.03 vs 9.60 ± 3.76 ng/mL, P.0001). Sputum HMGB1 levels also were positively related to total IgE levels in children with asthma (r = 0.6567, P.0001). An inverse and strict correlation between sputum HMGB1 levels and pulmonary function indices also were observed in children with mild (FEV1%, r = -0.86544, P.0001; FEF25%-75%, r = -0.53948, P.05), moderate (FEV1%, r = -0.99548, P.0001; FEF25%-75%, r = -0.48668, P .05), and severe (FEV1%, r = -0.90191, P.0001; FEF25%-75%, r = -0.66777, P.05) asthma.The present study provides evidence that sputum HMGB1 is a sensitive biomarker of allergic asthma in children because it was increased and correlated directly with asthma severity and inversely with lung function indices.

Background Necrotizing enterocolitis is a gastrointestinal surgical emergency in premature neonates. Free radicals have been linked to the development of the disease in infants. Ischemia, hypoxia–reperfusion, infection, and inflammation produce elevated levels of reactive oxygen species, impairing the redox balance and shifting cells into a state of oxidative stress. Melatonin, an effective direct free-radical scavenger and indirect antioxidant agent, exerts pleiotropic action on the human body. Several studies have tested the efficacy of melatonin in counteracting oxidative injury in diseases of newborns. Melatonin has been widely used in newborns including cases of asphyxia, respiratory distress syndrome, and sepsis, and no significant toxicity or treatment-related side effects with long-term melatonin therapy have been reported. Conclusion Therefore, melatonin, besides standard therapies, could be considered as a potentially safe approach to prevent and treat necrotizing enterocolitis in premature infants. This review summarizes what is known about the role of oxidative stress, and potentially beneficial effects of antioxidants, such as melatonin, in necrotizing enterocolitis.

To date cytokines profile in AEDS is poorly described in children. We evaluated the interleukin (IL)-17, IL-23, and IL-10 levels in atopic eczema/dermatitis syndrome (AEDS) children and healthy controls, in atopic AEDS (aAEDS) and nonatopic (naAEDS) subtypes and their relationship with disease severity. A total of 181 children with aAEDS and 93 healthy children were evaluated. According to the skin-prick test (SPT) for allergens and serum total IgE, all patients were subdivided in two groups: 104 aAEDS and 77 naAEDS. In all patients, serum IL-17, IL-23, and IL-10 levels were detected. Serum IL-17 and IL-23 levels were significantly higher, and serum IL-10 levels were significantly lower in AEDS children than healthy group (p < 0.001). Moreover, serum IL-17 and IL-23 levels were significantly higher in aAEDS than in naAEDS subtypes (p < 0.001). Differently, serum IL-10 levels resulted similar in both subtypes. There was a correlation between Score Atopic Dermatitis (SCORAD) index and both IL-17 and IL-23 and an inverse correlation between SCORAD index and IL-10 in aAEDS and naAEDS types. Serum IL-17 and IL-23 values were positively related to total IgE levels (p < 0.0001) in aAEDS. Further increase of IL-17 and IL-23 levels was detected in aAEDS subjects with atopic diseases such as asthma and rhinitis than children with only allergic sensitization. Our study confirms the role of IL-17, IL-23, and IL-10 and their relationship with the severity of AEDS. We firstly found a correlation between high IL-17/IL-23 axis levels and different phenotypes of AEDS in children, suggesting its role as marker of "atopic march" and disease severity.

Oxidative stress is caused by an imbalance between the production of reactive oxygen (free radicals) and the body’s ability (antioxidant capacity) to readily detoxify the reactive intermediates or easily repair the resulting damage. An adequate diet, characterized by daily intake of foods associated with improvements in the total antioxidant capacity of individuals and reduced incidence of diseases related to oxidation, can modulate the degree of oxidative stress. In fact, diet-derived micronutrients may be direct antioxidants, or are components of antioxidant enzymes, leading to improvement of some indicators of hepatic function. However, although their increased dietary intake might be beneficial, literature data are still controversial. This review summarizes what is known about the effects of diet nutrients on oxidative stress, inflammation and liver function. Moreover, we have analyzed: (1) the main nutritional components involved in the production and/or removal of free radicals; and (2) the role of free radicals in the pathogenesis of several hepatic diseases and related comorbidities.

Rapid maxillary expansion (RME) is an orthodontic procedure that separates the two maxillary bones at the mid palatine suture level. RME is commonly used in the pediatric age group to reduce and/or eliminate a transverse maxillary deficiency. At our institution we followed up an 11-year-old adolescent who was diagnosed with a class III malocclusion and was treated by RME with the combined use of expansion appliances (i.e., Hyrax) in addition to maxillary protraction devices (i.e., Delaire facemask). Three months after the start of treatment, he complained of headache and double vision, and was admitted to our hospital. A funduscopic examination revealed papilledema. Magnetic resonance imaging of the brain showed intraocular protrusion of the optic nerve head and enlarged perioptic subarachnoid space. Cerebrospinal fluid opening pressure during lumbar puncture was elevated (+370 mm H2O), confirming the diagnosis of the pseudotumor cerebri syndrome (PTCS). Removal of the maxillary expander and facemask led to the complete resolution of clinical symptoms in 1 week. The association of RME and PTCS-related manifestations was first reported by Timms in 1986, but, to the best of our knowledge, further cases have been not described in the medical literature. This overlooks PTCS as a potential RME-associated complication. We suggest that clinicians should carefully consider PTCS in all pediatric patients that complain of headache and/or visual disturbances during a treatment by RME. We also speculate on the possible changes of the cerebral venous circulation during RME, potentially leading to an impaired venous drainage that may cause increased intracranial pressure and PTCS.

Obesity and attendant co-morbidities are an emergent problem in public health. Much attention has focused on prevention, especially during the perinatal period. Breastfeeding is considered a possible protective factor for obesity in childhood, influencing gene–neuroendocrine–environment–lifestyle interaction. Therefore, breastfeeding and its longer duration are probably associated with lower development of childhood obesity. Through human milk, but not formula, the child assumes greater bioactive factors contributing to immunological, endocrine, development, neural and psychological benefits. Contrarily, other studies did not confirm a critical role of breast milk. Confounding factors, especially maternal pre-pregnancy overweight, may influence breastfeeding effects. This review summarises what is known about the possible relationship between breastfeeding and prevention of obesity development. Conclusion Breastfeeding appears to represent a protective factor for obesity in childhood, although evidence is still controversial and underlying mechanisms unclear. Further research is needed to improve knowledge on overweight/obesity and breastfeeding.

Adipose tissue is considered an endocrine organ secreting numerous neuroendocrine and peripheral peptides, also known as “adipokines.” Although, the role of adipokines, precisely visfatin, is still controversial, it was recently discovered their involvement in different mechanisms, including metabolism, inflammation, and endocrine-immunologic system. A literature search of electronic databases was undertaken for the major studies published from 1957 to present. The databases searched were: PubMed, EMBASE, Orphanet, Midline, and Cochrane Library. This review aims to emphasize the molecular and endocrine mechanisms of visfatin and its role in fetal development. This review also reviews the role of adipocytokine in the pathogenesis of inflammatory-endocrine disorders. Further research will bring new insight into linkage between visfatin and humans, during pregnancy and perinatal period.

Melatonin has been proposed as a premedication alternative to midazolam, preceding anaesthesia induction. However, to our knowledge, data concerning interaction between melatonin and intravenous anaesthetic drugs in children are not available. The aim of this prospective, randomized, double-blind pilot study was to investigate the possible effect of melatonin premedication, in comparison to midazolam, on the required infusion of propofol in children undergoing surgery. As a secondary outcome, the effect of oral melatonin on the preoperative sedation level and on the post anaesthesia recovery score was evaluated.Children between the age of 5 and 14 years, scheduled for elective surgery, were prospectively enrolled between January 2012 and December 2013, and randomly assigned to two groups based on whether they received oral melatonin (0.5 mg/kg) or oral midazolam (0.5 mg/kg) premedication before induction of anaesthesia with propofol. Degree of sedation before and after anaesthesia was also evaluated.Ninety-two patients were studied, 46 for each group. We found that oral administration of melatonin significantly reduced doses of propofol required for induction of anaesthesia in paediatric patients, more than midazolam (P0.001). No statistically significant differences were found in the pre- and post-anaesthesia sedation score (P = 0.387 and P = 0.525, respectively) between the two groups.The present study demonstrates that melatonin enhances the potency of propofol also in paediatric patients. Moreover, considering the paediatric level of sedation, melatonin was equally as effective as midazolam. These data support the use of melatonin as a premedicant in paediatric surgical patients.

Atopic diseases are a major public health problem worldwide, and several factors are thought to contribute to this rapid increase. The observed association between mode of delivery and risk of atopy in childhood has had a great deal of interest during the past few decades. In fact, even during delivery, exposure to antigens can index immune system in newborn, which induces the release of biologically active molecules, which are polarizing immune responses toward the T-helper 2 atopic profile. However, to date, studies on the relationship between mode of delivery and atopy have produced conflicting findings. The aim of this review was to summarize what is known about the relationship between mode of delivery and risk of atopic diseases in children. A literature search of electronic databases was undertaken for the major studies published from 1994 to today. The databases searched were PubMed, EMBASE, Medline, and Cochrane Library. The following key words were used: mode of delivery, cesarean section, vaginal delivery, atopy, and atopic diseases.

Higher total homocysteine (tHcy) levels, and C677T and A1298C methylenetetrahydrofolate (MTHFR) polymorphisms, have been reported in preterm or full term newborns with neonatal encephalopathy following perinatal hypoxic-ischemic insult. This study investigated the causal role of tHcy and MTHFR polymorphisms together with other acquired risk factors on the occurrence of brain white matter abnormalities (WMA) detected by cranial ultrasound scans (cUS) in a population of late preterm and full term infants. A total of 171 newborns (81 M, 47.4%), 45 (26.3%) born (P<0.014), lower GA(P<0.000), lower Apgar score at 1 minutes(P<0.000)and 5 minutes(P<0.000), and 1298AC and 677CT/1298AC genotypes (P<0.000andP<0.000). In conclusion, both acquired and genetic predisposing antenatal factors were significantly associated with adverse neonatal outcome and WMA. The role of A1298C polymorphism may be taken into account for prenatal assessment and treatment counseling.

Objectives The nuclear protein high mobility group protein box 1 (HMGB1) is a proinflammatory mediator that belongs to the alarmin family of proinflammatory mediators, and it has recently emerged as a key player in different acute and chronic immune disorders. Several lines of evidence demonstrate that HMGB1 is actively released extracellularly from immune cells or passively released from necrotic cells. Because of the ability of HMGB1 to sustain chronic inflammation, we investigated whether the protein is present in nasal fluids of patients with different forms of rhinitis. Methods HMGB1 levels were evaluated in nasal fluids of healthy subjects or rhinitis patients who were treated or not treated with different treatments. Results We report that the level of HMGB1 was significantly increased in nasal fluids of patients with allergic rhinitis, patients with NARES (nonallergic rhinitis with eosinophiliac syndrome), as well as patients with polyps. We also found that a formulation containing the HMGB1-binding compound glycyrrhizin (GLT) reduced the HMGB1 content in nasal fluids of rhinitis patients to an extent similar to that with nasal budesonide treatment. We also found that among the cultured human leukocyte populations, eosinophils released higher amounts of HMGB1. Based on the ability of HMGB1 to sustain eosinophil survival and the ability of GLT to inactivate HMGB1, we report that GLT selectively killed cultured eosinophils and had no effect on neutrophils, macrophages, and lymphocytes. Conclusion Collectively, these data underscore the role of HMGB1 in rhinitis pathogenesis and the therapeutic potential of GLT formulations in treatment of chronic inflammatory disorders of the nasal mucosa.

Exogenous melatonin is used in a number of situations, first and foremost in the treatment of sleep disorders and jet leg. However, the hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a drug that modulates effects of anesthetic agents, supporting its potential use at different stages during anesthetic procedures, in both adults and children. In light of these properties, melatonin has been administered to children undergoing diagnostic procedures requiring sedation or general anesthesia, such as magnetic resonance imaging, auditory brainstem response tests and electroencephalogram. Controversial data support the use of melatonin as anxiolytic and antinociceptive agents in pediatric patients undergoing surgery. The aim of this review was to evaluate available evidence relating to efficacy and safety of melatonin as an analgesic and as a sedative agent in children. Melatonin and its analogs may have a role in antinociceptive therapies and as an alternative to midazolam in premedication of adults and children, although its effectiveness is still controversial and available data are clearly incomplete.

Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH.

Allergen immunotherapy is a disease-modifying therapy, effective for the treatment of allergic rhinitis, allergic asthma, conjunctivitis or stinging insect allergy. Allergen immunotherapy involves the administration of increasing doses of allergens with the aim of ameliorating the allergic response. Although precise underlying mechanisms of the induction of immune tolerance remain unclear, immunotherapy has been associated with the induction of distinct subsets of Tregs that eventually lead to peripheral tolerance by inducing a deviation from Th2 to Th1 immune responses. This review focuses on the current knowledge of the mechanisms of immunotherapy in relationship to different routes of administration and also provides a unifying view.

Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS). Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases.

Melatonin may have important immunostimulatory actions in allergic diseases, in addition to its well-known antioxidant and cytoprotective effects in several inflammatory conditions. The activation of the immune system leads to free radical production associated with decreased melatonin levels and depressed antioxidant enzyme activities in several inflammatory diseases. Many skin disorders, including atopic dermatitis, are accompanied by infiltration and activation of mast cells, which release vasoactive and proinflammatory mediators. Experimental data suggest that melatonin inhibits development of atopic eczema and reduces serum total IgE and IL-4. Allergic asthma is a condition characterized by bronchial hyperresponsiveness and the presence of IgE antibodies in response to inhaled allergens; often there is also enhanced total serum IgE levels. Melatonin regulates smooth muscle tone and influences the immune response. Melatonin may, however, act as a pro-inflammatory agent in asthma leading to bronchial constriction. The safety of melatonin as a sleep-inducing agent has been confirmed in asthmatic subjects, but its routine use is not recommended in bronchial asthma. This review summarizes what is known about the role of melatonin as an immunomodulatory agent in asthma and atopic eczema.

An accessory mouth is a very rare condition, with approximately 15 cases reported in the literature to date. We describe another unique case and discuss its possible embryopathogenesis.

Oxidative stress contributes to the severity of several newborn conditions to the extent that Saugstad coined the phrase “oxygen radical diseases of neonatology.” In order to counteract free radicals damage many strategies to augment antioxidant status in ill-term and preterm infants have been proposed and several medications have been experimented with mixed results. Several studies have tested the efficacy of melatonin to counteract oxidative damage in diseases of newborns such as chronic lung disease, perinatal brain injury, necrotizing enterocolitis, and retinopathy of prematurity, giving promising results. The peculiar perinatal susceptibility to oxidative stress indicates that prophylactic use of antioxidants as melatonin could help to prevent or at least reduce oxidative stress related diseases in newborns. However, more studies are needed to confirm these beneficial effects.

Objective High plasma homocysteine (Hcy) levels and, C677T and A1298C MTHFR polymorphysms, have been reported in preterm or full term newborns with neonatal encephalopathy following an hypoxic-ischemic insult. Beyond the well-defined pattern of white matter injury such as periventricular leukomalacia, several qualitative neonatal white matter abnormalities (WMA) may account for different degrees of neurobehavioral impairment at long-term observation, either in very preterm or full term infants. Environmental factors may contribute to WMA. We assessed the causal role of Hcy and MTHFR polymorphisms together with acquired risk factors on the occurrence of WMA detected by cranial ultrasound scans (cUS) in a population of late preterm and full term infants. Methods Newborn infants were recruited at the Intensive Care Unit of University Hospital of Messina. Antenatal, perinatal and neonatal details were obtained. Hcy levels were assessed in whole blood within the first week of life. The assessment of C677T and A1298C MTHFR genotypes was carried out. Cerebral ultrasound was performed to all newborns from 1 to 3 days of life and 44 postmenstrual age. Results 171 newborns (81 M, 47.4%), 45 (26.3%) born Conclusion Hcy and MTHFR polymorphisms significantly predisposed to WMA, either full-term or late preterm newborns, in our study. However, WMA was also significantly associated to acquired factors as GA and perinatal status, measured by Apgar scores. The role of A1298C polymorphism might be taken into account for prenatal assessment and treatment counseling.

Although the outcome of newborns with surgical congenital diseases (e.g., diaphragmatic hernia; esophageal atresia; omphalocele; gastroschisis) has improved rapidly with recent advances in perinatal intensive care and surgery, infant survivors often require intensive treatment after birth, have prolonged hospitalizations, and, after discharge, may have long-term sequelae including gastro-intestinal comorbidities, above all, gastroesophageal reflux (GER). This condition involves the involuntary retrograde passage of gastric contents into the esophagus, with or without regurgitation or vomiting. It is a well-recognized condition, typical of infants, with an incidence of 85%, which usually resolves after physiological maturation of the lower esophageal sphincter and lengthening of the intra-abdominal esophagus, in the first few months after birth. Although the exact cause of abnormal esophageal function in congenital defects is not clearly understood, it has been hypothesized that common (increased intra-abdominal pressure after closure of the abdominal defect) and/or specific (e.g., motility disturbance of the upper gastrointestinal tract, damage of esophageal peristaltic pump) pathological mechanisms may play a role in the etiology of GER in patients with birth defects. Improvement of knowledge could positively impact the long-term prognosis of patients with surgical congenital diseases. The present manuscript provides a literature review focused on pathological and clinical characteristics of GER in patients who have undergone surgical treatment for congenital abdominal malformations.

Recently, there has been growing interest in the relationship between allergic and autoimmune diseases. Allergy and autoimmunity can be considered two potential outcomes of dysregulated immunity and analysis of literature data shows a strong positive association between a history of Th2-mediated allergic disorders and Th1-mediated autoimmune disorders. Autoimmune thyroid diseases are the most common of all autoimmune pathological conditions. Currently, the mechanisms explaining an association among atopy, autoimmunity, and thyroid diseases are not fully understood. There are data in literature pointing to the relationship between melatonin and thyroid activity. Several studies have suggested a paracrine role for this molecule in the regulation of thyroid activity, documenting that administration, as an antioxidant, in thyroid tissues under conditions of increased oxidative stress, could be helpful to reduce the oxidative processes involved in autoimmune thyroid diseases. Although thyroid autoimmunity has been regularly associated with atopic conditions in children, the possible protective role of melatonin has not yet been investigated. This review summarizes what is known regarding the connection between atopy and autoimmune thyroid diseases, and analyses the probable beneficial action of melatonin.