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Background: Soluble mesothelin-related peptide (SMRP) is a promising diagnostic biomarker for malignant pleural mesothelioma (MPM), but various confounders hinder its usefulness in surveillance programmes. We previously showed that a single nucleotide polymorphism (SNP) within the 3'untranslated region (3'UTR) of the mesothelin ( MSLN ) gene could affect the levels of SMRP., Objectives: To focus on SNPs located within MSLN promoter as possible critical genetic variables in determining SMRP levels., Methods: The association between SMRP and SNPs was tested in 689 non-MPM subjects and 70 patients with MPM. Reporter plasmids carrying the four most common haplotypes were compared in a dual luciferase assay, and in silico analyses were performed to investigate the putative biological role of the SNPs., Results: We found a strong association between serum SMRP and variant alleles of rs3764247, rs3764246 (in strong linkage disequilibrium with rs2235504) and rs2235503 in non-MPM subjects. Inclusion of the genotype information led to an increase in SMRP specificity from 79.9% to 85.5%. Although not statistically significant, the group with MPM showed the same trend of association. According to the in vitro luciferase study, rs3764247 itself had a functional role. In silico approaches showed that the binding sites for transcription factors such as Staf and ZNF143 could be affected by this SNP. The other SNPs were shown to interact with each other in a more complex way., Conclusions: These data support the suggestion that SMRP performance is affected by individual (ie, genetic) variables and that MSLN expression is influenced by SNPs located within the promoter regulatory region., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Antigens contained in vaccines are inherently unstable biologically; such a characteristic is conferred by their three-dimensional structure. Preserving the ability of the vaccines to protect against disease is necessary to ensure the supervision and monitoring of all steps of the cold chain. DTPa-HBV-IPV/Hib vaccine (Infanrix hexaTM, GSK Vaccines, Belgium) is designed to prevent disease due to diphtheria, tetanus, pertussis (DTP), hepatitis B virus (HBV), poliomyelitis and Haemophilus influenzae type b (Hib); it was first licensed for use in Europe in 2000 and is currently licensed in at least 95 countries. Since October 2013, more than 102 million doses of GSK's DTPa-HBV-IPV/Hib vaccine have been distributed globally, with nearly 15 million doses distributed in Italy. DTPa-HBV-IPV/Hib components are stable up to a temperature of 25°C for 72 hours. Lacking of officially approved stability data may generate some concern in case of cold chain accidents., Methods: An analysis based on collected data was carried out to estimate potential costs attributable to events of "out-of-temperature" in the stockpiling of hexavalent vaccines occurring in Italy in 2014., Results: The analysis, based on real data, documented that the loss for the National Health Service (NHS) was in the range of 100,000 - 400,000 euros in one year. However, the amount of money that in principle could have been lost would have ranged between nearly half and one million euros/year., Conclusions: A substantial loss of money was avoided thanks to the availability of officially approved stability data for GSK's DTPa-HBV-IPV/Hib vaccine.

Objective: The diagnosis restless legs syndrome (RLS) in children depends on the history told by the child and his parents. The description of symptoms given by the child himor herself is most important. Additional criteria are, among others, the results of polysomnography (PSG). Description of the presenting symptoms is the aim of the study., Methods: Survey in two European pediatric sleep centers of presenting symptoms in children who after a detailed work-up proved to have RLS., Results: Fifty-two percent of the 31 children presented with symptoms similar to those mentioned in the "four questions" relevant for the diagnosis of RLS. In the other patients the description included often very colourful wordings, such as "ants or spiders in the legs, legs want to kick, need to stretch." All children were tired or sleepy during daytime and nearly all reported an urge to move. Insomnia was mentioned by 61% of the patients. The presenting symptoms did not differ significantly from those mentioned in a previous study in the US, but did so when compared to adults with RLS. PSG revealed an abnormal periodic limb movement index in 81% of the children., Conclusions: The description of presenting symptoms in children with the final diagnosis of RLS differs from that in adults. The results of this European study corroborate those from the US.

Background: Sleep related problems affect approximately 25-40% of children and adolescents. The acquisition of sleep patterns characterised by later bedtimes, insomnia and excessive daytime sleepiness is related to poorer school performance, daytime drowsiness, physical tiredness and a higher rate of psychiatric illnesses. Many studies have investigated the correlation between sleep and mood in children and adolescents and overall, show a positive association between sleep problems and psychiatric disorders. However, little is known about adolescents' personal perception of their psychological status as it is linked with the occurrence of mood changes and sleep-related problems., Aims of the Study: The aim of the study is to explore the impact of variables such as age, gender, education and the perception of their own psychological status (evaluated through suitable questionnaires) on the simultaneous presence of sleep disturbances and affective symptoms in a sample of adolescents. A positive correlation between these two dependent variables signals the need to intervene with proper support programs., Methods: A recursive bivariate probit model has been employed. This method allows us to take into account two dependent dummy variables and to consider the relationship between the two, presuming that one may also influence the other. The analysis has been carried out on a sample of 2,005 adolescents out of a total of 4,000 who declared their willingness to be telephonically interviewed using a questionnaire in two parts designed to obtain information about the participants sleep habits and affective symptoms., Results: There is a positive correlation between sadness and daytime drowsiness. The estimated joint probability ranging from 5.5% to 9% in girls demonstrates a greater tendency for girls to experience both depression and altered sleep patterns. DISCUSSION AND LIMITATIONS OF THE STUDY: Just as sadness is a key symptom of affective disorders, daytime drowsiness indicates the presence of sleep disorders caused by sleep habits that are likely to evolve into affective symptoms. This assumption is confirmed by the results of this analysis. However, since the interviews were conducted during the years 2003 and 2004, a replication of the analysis would outline whether this evidence is still the same or whether changes in habits and behaviours have intervened to modify substantially this pattern in recent years. As the analysis considers a sample of adolescents living in two southern Italian regions, the study should be replicated in other geographical areas. IMPLICATIONS FOR HEALTH CARE PROVISIONS AND USE: The early detection of affective symptoms in adolescents may presumably lead to a diminished use of antidepressants and an improvement in learning abilities and school results along with strengthening of personal motivations., Implications for Health Policies: Counselling and educational programs directed towards those adolescents demonstrating poor sleep habits should be planned and implemented to avoid further complications and impact on their mental health.

Study Objectives: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors., Design: Prospective, multicenter, case-control epidemiologic survey., Settings: Twenty sleep centers certified by the Italian Association of Sleep Medicine., Patients: Eight hundred and sixty-one patients affected by MS and 649 control subjects., Interventions: N/A., Measures and Results: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56-8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects., Conclusions: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.