Spritz: a server for the prediction of intrinsically disordered regions in protein sequences using kernel machines

Intrinsically disordered proteins have long stretches of their polypeptide chain, which do not adopt a single native structure composed of stable secondary and tertiary structure in the absence of binding partners. The prediction of intrinsically disordered regions in proteins from sequence is increasingly becoming of interest, as the presence of many such regions in the complete genome sequences are discovered and important functional roles are associated with them. We have developed a machine learning approach based on two support vector machines (SVM) to discriminate disordered regions from sequence. The SVM are trained and benchmarked on two sets, representing long and short disordered regions. A preliminary version of Spritz was shown to perform consistently well at the recent biannual CASP-6 experiment [Critical Assessment of Techniques for Protein Structure Prediction (CASP), 2004]. The fully developed Spritz method is freely available as a web server at and

Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20–44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991–1993; n56,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998–2000; n518,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007–2010; n510,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19–1.59) from 1998–2000 to 2007–2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhiniti

ANTHROPOMETRY AND MOTOR FITNESS IN CHILDREN AGED 6-12 YEARS

This study aimed at evaluating motor abilities and anthropometric parameters in children aged 6-12 years and their interrelationships. One hundred fifty-two children underwent standard anthropometry (BMI, waist circumference, waist-to-hip ratio, sum of five skinfolds) and motor fitness tests (standing long jump and 30m dash). Data were stratified by age (6-7, 8-9, 10-12 years) and sex (M/F), and the Spearman correlation coefficient was used to evaluate the correlation between BMI and the other anthropometric measurements in each class as well as the correlation between anthropometric parameters and fitness tests. The effect of age, sex, and individual anthropometric measurement on velocity or jump length was evaluated by ANOVA. BMI positively correlated with waist circumference and subcutaneous fat, and negatively correlated with body density. Motor fitness was not significantly affected by BMI, while sum of five skinfolds negatively associated with velocity in males aged 6-7 years and with jump length in females aged 8-12 years. Motor fitness significantly correlated with age, and performance was higher in males. Moreover, motor fitness tests positively correlated with each other, especially in females. In the 6-12 years period motor performance improves with age and improvement is partially sex-related; this correlation is higher in boys, possibly because of their lesser amount of fat. Subcutaneous fat is a better predictor of physical fitness than BMI or waist circumference. Results also suggest that explosive strength and velocity are related the 6-12 years age span, possibly because both are power events, which involve horizontal movement of the centre of mass

Liver injury due to amoxicillin vs. amoxicillin/clavulanate: a subgroupnalysis of a drug-induced liver injury case-control study in Italy

Several studies showed that amoxicillin plus clavulanic acid (co-amoxiclav) is one of the most common agents associated to serious Drug Induced Liver Injury (DILI). We estimated the risk of acute serious DILI associated with amoxicillin alone compared with co-amoxiclav, through a multicenter case-control study carried out in nine Italian hospitals from October 2010 to January 2014.Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders, not related to chronic conditions and not involving the liver. Adjusted Odds Ratio (ORs) with 95% CI were calculated initially with a bivariate and then multivariate analysis. We analysed 179 cases matched to 1770 controls. Seven cases were exposed to amoxicillin (adjusted OR 1.69, 95% CI 0.72-3.98) and 22 cases to co-amoxiclav (adjusted OR 3.00, 95% CI 1.76-5.40). Co-amoxiclav almost doubled the risk of serious acute liver injury compared to amoxicillin alone. The incidence of co-amoxiclav induced DILI is very low but the widespread use of this drug by the general population makes the risk clinically relevant. The often inappropriate prescription of antimicrobial agents, and in particular of co-amoxiclav, could expose a given patient to a life-threatening risk compared to a negligible clinical benefit

The Local Complement Activation on Vascular Bed of Patients with Systemic Sclerosis : A Hypothesis-Generating Study

Peer reviewe

Comparative Proteomic Analysis of Serum from Patients with Systemic Sclerosis and Sclerodermatous GVHD. Evidence of Defective Function of Factor H

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by immunological and vascular abnormalities. Until now, the cause of SSc remains unclear. Sclerodermatous graft-versus-host disease (ScGVHD) is one of the most severe complications following bone marrow transplantation (BMT) for haematological disorders. Since the first cases, the similarity of ScGVHD to SSc has been reported. However, both diseases could have different etiopathogeneses. The objective of this study was to identify new serum biomarkers involved in SSc and ScGVHD. METHODOLOGY: Serum was obtained from patients with SSc and ScGVHD, patients without ScGVHD who received BMT for haematological disorders and healthy controls. Bi-dimensional electrophoresis (2D) was carried out to generate maps of serum proteins from patients and controls. The 2D maps underwent image analysis and differently expressed proteins were identified. Immuno-blot analysis and ELISA assay were used to validate the proteomic data. Hemolytic assay with sheep erythrocytes was performed to evaluate the capacity of Factor H (FH) to control complement activation on the cellular surface. FH binding to endothelial cells (ECs) was also analysed in order to assess possible dysfunctions of this protein. PRINCIPAL FINDINGS: Fourteen differentially expressed proteins were identified. We detected pneumococcal antibody cross-reacting with double stranded DNA in serum of all bone marrow transplanted patients with ScGVHD. We documented higher levels of FH in serum of SSc and ScGVHD patients compared healthy controls and increased sheep erythrocytes lysis after incubation with serum of diffuse SSc patients. In addition, we observed that FH binding to ECs was reduced when we used serum from these patients. CONCLUSIONS: The comparative proteomic analysis of serum from SSc and ScGVHD patients highlighted proteins involved in either promoting or maintaining an inflammatory state. We also found a defective function of Factor H, possibly associated with ECs damage

Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.ClinicalTrials.gov NCT00730509

Multicentre, double-blind, crossover trial to identify the Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus (OPTION-DM): study protocol for a randomised controlled trial

BACKGROUND: The number of people with diabetes is growing rapidly. Diabetes can cause nerve damage leading to severe pain in the feet, legs and hands, which is known as diabetic peripheral neuropathic pain (DPNP). In the UK, the National Institute for Health and Care Excellence (NICE) recommends amitriptyline, duloxetine, pregabalin or gabapentin as initial treatment for DPNP. If this is not effective, adding one of the other drugs in combination with the first is recommended. NICE points out that these recommendations are not based on robust evidence. The OPTION-DM randomised controlled trial has been designed to address this evidence deficit, with the aims of determining the most clinically beneficial, cost-effective and tolerated treatment pathway for patients with DPNP. METHODS/DESIGN: A multicentre, double-blind, centre-stratified, multi-period crossover study with equal allocation to sequences (1:1:1:1:1:1) of treatment pathways. Three hundred and ninety-two participants will be recruited from secondary care DPNP centres in the UK. There are three treatment pathways: amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline and duloxetine supplemented with pregabalin. All participants will receive all three pathways and randomisation will determine the order in which they are received. The primary outcome is the difference between 7-day average 24-h pain scores on an 11-point NRS scale measured during the final follow-up week of the treatment pathway. Secondary outcomes for efficacy, cost-effectiveness, safety, patient-perceived tolerability and subgroup analysis will be measured at week 6 and week 16 of each pathway. DISCUSSION: The study includes direct comparisons of the mainstay treatment for DPNP. This novel study is designed to examine treatment pathways and capture clinically relevant outcomes which will make the results generalisable to current clinical practice. The study will also provide information on health economic outcomes and will include a subgroup study to provide information on whether patient phenotypes predict response to treatment. TRIAL REGISTRATION: ISRCTN17545443 . Registered on 12 September 2016

Identifying allergic rhinitis cases from a screening questionnaire: the GEIRD project

Background: Per una buona fenotipizzazione della rinite allergica (AR) \ue8 necessario utilizzare sia test diagnostici che l\u2019anamnesi medica, poich\ue9 la diagnosi basata su un solo metodo pu\uf2 produrre molti falsi positivi e negativi. Obiettivo: Analizzare la validit\ue0 del processo di selezione per identificare i casi di AR e valutare il fenotipo di AR nell\u2019ambito del progetto GEIRD (Gene-Environment Interaction in Respiratory Diseases), uno studio multi-centrico, multi caso-controllo nidificato. Metodi: I soggetti che riportavano allergie nasali oppure problemi dovuti a \u201cfrequenti starnuti o naso che cola o naso chiuso al di fuori dei comuni raffreddori o dell\u2019influenza\u201d (Probabili casi di AR; n=136) in un questionario di screening e probabili controlli (n=262) di et\ue0 20-64 anni sono stati mandati in clinica per la fenotipizzazione. I soggetti sono stati poi etichettati come controlli, soggetti AR e soggetti che riportavano rinite non allergica (NAR) in base all\u2019anamnesi del paziente e alle prove allergologiche cutanee (skin prick test). Risultati: I probabili controlli e i probabili casi di AR sono stati fenotipizzati come 205 controlli, 112 casi di AR e 65 casi di NAR. E\u2019 stata riscontrata una buona validit\ue0 del processo di selezione: il valore predittivo positivo della definizione di probabile caso di AR era 68.5%. Una buona ripetibilit\ue0 \ue8 stata riscontrata per le allergie nasali tra quanto riportato nel questionario di screening e nell\u2019intervista clinica (K=0.73; C.I. 95%=0.61-0.85) mentre un accordo minore \ue8 stato riscontrato per il sintomo \u201cnaso chiuso/naso che cola\u201d (K=0.52; C.I. 95%=0.42-0.61). I soggetti con AR presentavano un profilo differente dai soggetti con NAR sia al questionario di screening che all\u2019intervista clinica. In particolare, la proporzione di sintomi da \u201craffreddore da fieno\u201d era pi\uf9 alta sia nel questionario di screening (50.9% vs 16.9%, p<0.001) che nell\u2019intervista clinica (53.6% vs 6.15%). Conclusioni: Il processo di selezione dei casi di AR \ue8 stato efficiente e adeguato per fini epidemiologici. Le domande utilizzate per selezionare i casi di AR sono risultate valide e ripetibili. Il fenotipo di AR \ue8 risultato differente dal fenotipo NARBackground: Both diagnostic tests and medical history are necessary to provide a good phenotypization of Allergic Rhinitis (AR) since diagnosis using one method alone can produce a lot of false positives and false negatives. Objective: To investigate the validity of the process of selection in identifying AR cases and to evaluate AR phenotype in the frame of GEIRD (Gene-Environment Interaction in Respiratory Diseases), a multi-center nested multi-case-control study. Methods: Subjects reporting nasal allergies or having ever had a problem with sneezing, or a runny or a blocked nose in the absence of a cold or flu (probable cases of AR; n=136) in a screening questionnaire and probable controls (n=262) aged 20-64 years were sent to clinic for phenotypization. Subjects were then labeled as controls, AR subjects and non allergic rhinitis (NAR) subjects depending on patient history and skin prick test. Results: Probable controls and probable cases of AR were phenotyped as 205 controls, 112 AR cases and 65 NAR cases. A good validity of the process of selection was found: the positive predictive value of the definition of probable case of AR was 68.5%. The repeatability was good for nasal allergies between the screening questionnaire and the clinical interview (K=0.73; C.I. 95%=0.61-0.85) while a lower agreement was for \u201crunny/blocked nose\u201d symptom (K=0.52; C.I. 95%=0.42-0.61). AR subjects presented a different profile from NAR subjects both in the screening questionnaire and in the clinical interview: in particular, they reported a higher proportion of \u201cHay fever\u201d symptoms both in the screening questionnaire (50.9% vs 16.9%, p<0.001) and in the clinical interview (53.6% vs 6.15%). Conclusions: The process of selection of AR cases was efficient and adequate for epidemiological purpose. Questions used to select AR cases were valid and repeatable. AR phenotype was different from NAR phenotype