@article {10761, title = {Causes of Treatment Failure in Children With Inflammatory Bowel Disease Treated With Infliximab: A Pharmacokinetic Study.}, journal = {J Pediatr Gastroenterol Nutr}, volume = {68}, year = {2019}, month = {2019 Jan}, pages = {37-44}, abstract = {

OBJECTIVES: Anti-tumor necrosis factor antibodies have led to a revolution in the treatment of inflammatory bowel diseases (IBD); however, a sizable proportion of patients does not respond to therapy. There is increasing evidence suggesting that treatment failure may be classified as mechanistic (pharmacodynamic), pharmacokinetic, or immune-mediated. Data regarding the contribution of these factors in children with IBD treated with infliximab (IFX) are still incomplete. The aim was to assess the causes of treatment failure in a prospective cohort of pediatric patients treated with IFX.

METHODS: This observational study considered 49 pediatric (median age 14.4) IBD patients (34 Crohn disease, 15 ulcerative colitis) treated with IFX. Serum samples were collected at 6, 14, 22 and 54 weeks, before IFX infusions. IFX and anti-infliximab antibodies (AIA) were measured using enzyme linked immunosorbent assays. Disease activity was determined by Pediatric Crohn{\textquoteright}s Disease Activity Index or Pediatric Ulcerative Colitis Activity Index.

RESULTS: Clinical remission, defined as a clinical score <10, was obtained by 76.3\% of patients at week 14 and by 73.9\% at week 54. Median trough IFX concentration was higher at all time points in patients achieving sustained clinical remission. IFX levels during maintenance correlated also with C-reactive protein, albumin, and fecal calprotectin. After multivariate analysis, IFX concentration at week 14 >3.11 μg/mL emerged as the strongest predictor of sustained clinical remission. AIA concentrations were correlated inversely with IFX concentrations and directly with adverse reactions.

CONCLUSIONS: Most cases of therapeutic failure were associated with low serum drug levels. IFX trough levels at the end of induction are associated with sustained long-term response.

}, issn = {1536-4801}, doi = {10.1097/MPG.0000000000002112}, author = {Naviglio, Samuele and Lacorte, Doriana and Lucaf{\`o}, Marianna and Cif{\`u}, Adriana and Favretto, Diego and Cuzzoni, Eva and Silvestri, Tania and Pozzi Mucelli, Martina and Radillo, Oriano and Decorti, Giuliana and Fabris, Martina and Bramuzzo, Matteo and Taddio, Andrea and Stocco, Gabriele and Alvisi, Patrizia and Ventura, Alessandro and Martelossi, Stefano} } @article {10763, title = {Cervico-vaginal secretion cytokine profile: A non-invasive approach to study the endometrial receptivity in IVF cycles.}, journal = {Am J Reprod Immunol}, volume = {81}, year = {2019}, month = {2019 Jan}, pages = {e13064}, abstract = {

PROBLEM: Cytokines have a significant role in the process of embryo implantation, trophoblast growth, and differentiation by modulating the immune and endocrine system. The aim of this study was to investigate the profile of a large set of cytokines in the cervico-vaginal washing of women undergoing IVF, to explore the association of these proteins with a good receptive endometrium.

METHOD OF STUDY: A cohort of 155 women scheduled for IVF cycle was recruited. All patients were asymptomatic for genitourinary infections and had been screened for chlamydia, mycoplasma, and other bacterial infections. All IVF subjects were treated according to standard clinical and laboratory protocols. A panel of 48 immune factors was analyzed on cervico-vaginal washing, using magnetic bead-based multiplex immunoassays (Bio-Plex, BIO-RAD Laboratories, Milano, Italy).

RESULTS: A total of 99 patients reached embryo transfer, of which 31 had a clinical pregnancy. A pattern of four pro-inflammatory immune molecules, IL-12p40, IFN-a, MIF, and MCP3 (P~<~0.001), was found significantly up-regulated in the cervico-vaginal fluid of women with clinical pregnancy. A significantly increased expression of IL-9, Gro , and SDF-1 (P~<~0.05) was observed in the presence of endometriosis, while high levels of IL-13 and L-15 were associated with ovulatory infertility factor (P~<~0.05).

CONCLUSION: In this pilot study, we demonstrated that the expression of specific cytokines in the cervico-vaginal washing on the day of oocyte retrieval might have a positive correlation with the potential clinical pregnancy. Therefore, cervico-vaginal secretion cytokine profiling might be a new, non-invasive approach to study the endometrial receptivity in IVF management.

}, issn = {1600-0897}, doi = {10.1111/aji.13064}, author = {Zanotta, Nunzia and Monasta, Lorenzo and Skerk, Kristina and Luppi, Stefania and Martinelli, Monica and Ricci, Giuseppe and Comar, Manola} } @article {10764, title = {Changing Epidemiology of Liver Involvement in Children With Celiac Disease.}, journal = {J Pediatr Gastroenterol Nutr}, volume = {68}, year = {2019}, month = {2019 Apr}, pages = {547-551}, abstract = {

OBJECTIVES: Available data indicate that liver involvement is present in a significant proportion of children with celiac disease (CD) at the diagnosis (elevated transaminases 15\%-57\%, autoimmune liver disease 1\%-2\%). We sought to evaluate prevalence, clinical course, and risk factors for liver involvement in a large cohort of children with CD.

METHODS: Children (age 0-18 years) diagnosed with CD from March 2010 to April 2016 were enrolled. Liver involvement was considered to be present when alanine transaminase (ALT) levels were >40 U/L (hypertransaminasemia [HTS]). Patients with HTS were re-evaluated after at least 12 months of a gluten-free diet.

RESULTS: CD was diagnosed in 806 patients during the study period; of these, ALT levels were available for 700 patients (86.9\%), and were elevated in 27 (3.9\%, HTS group); median ALT and aspartate transaminase levels in the HTS group were 57 U/L (interquartile range 49-80 U/L) and 67 U/L (interquartile range 53-85 U/L), respectively. Younger age, malabsorption symptoms, and low hemoglobin or ferritin were significantly more common in the HTS group at univariate analysis. At multivariate analysis, only age <=4.27 years correlated with risk of liver involvement (odds ratio 3.73; 95\% confidence interval: 1.61-8.66). When retested on a gluten-free diet, all but 3 patients normalized ALT levels; of these, 1 was diagnosed with sclerosing cholangitis.

CONCLUSIONS: Liver involvement in celiac children is now less frequent than previously reported, possibly due to changing CD epidemiology. Younger age is the only risk factor. Associated autoimmune liver disease is rare.

}, issn = {1536-4801}, doi = {10.1097/MPG.0000000000002209}, author = {Benelli, Elisa and Naviglio, Samuele and De Leo, Luigina and Stera, Giacomo and Giangreco, Manuela and Ronfani, Luca and Villanacci, Vincenzo and Martelossi, Stefano and Ventura, Alessandro and Not, Tarcisio} } @article {10762, title = {Cell-autonomous and cell non-autonomous downregulation of tumor suppressor DAB2IP by microRNA-149-3p promotes aggressiveness of cancer cells.}, journal = {Cell Death Differ}, volume = {25}, year = {2018}, month = {2018 Jul}, pages = {1224-1238}, abstract = {

The tumor suppressor DAB2IP contributes to modulate the network of information established between cancer cells and tumor microenvironment. Epigenetic and post-transcriptional inactivation of this protein is commonly observed in multiple human malignancies, and can potentially favor progression of tumors driven by a variety of genetic mutations. Performing a high-throughput screening of a large collection of human microRNA mimics, we identified miR-149-3p as a negative post-transcriptional modulator of DAB2IP. By efficiently downregulating DAB2IP, this miRNA enhances cancer cell motility and invasiveness, facilitating activation of NF-kB signaling and promoting expression of pro-inflammatory and pro-angiogenic factors. In addition, we found that miR-149-3p secreted by prostate cancer cells induces DAB2IP downregulation in recipient vascular endothelial cells, stimulating their proliferation and motility, thus potentially remodeling the tumor microenvironment. Finally, we found that inhibition of endogenous miR-149-3p restores DAB2IP activity and efficiently reduces tumor growth and dissemination of malignant cells. These observations suggest that miR-149-3p can promote cancer progression via coordinated inhibition of DAB2IP in tumor cells and in stromal cells.

}, issn = {1476-5403}, doi = {10.1038/s41418-018-0088-5}, author = {Bellazzo, Arianna and Di Minin, Giulio and Valentino, Elena and Sicari, Daria and Torre, Denis and Marchionni, Luigi and Serpi, Federica and Stadler, Michael B and Taverna, Daniela and Zuccolotto, Gaia and Montagner, Isabella Monia and Rosato, Antonio and Tonon, Federica and Zennaro, Cristina and Agostinis, Chiara and Bulla, Roberta and Mano, Miguel and Del Sal, Giannino and Collavin, Licio} } @article {10418, title = {Cerebrospinal Fluid Cytokine Expression Profile in Multiple Sclerosis and Chronic Inflammatory Demyelinating Polyneuropathy.}, journal = {Immunol Invest}, volume = {47}, year = {2018}, month = {2018 Feb}, pages = {135-145}, abstract = {

BACKGROUND: Cerebrospinal fluid (CSF) analysis in patients with particular neurologic disorders is a powerful tool to evaluate specific central nervous system inflammatory markers for diagnostic needs, because CSF represents the specific immune micro-environment to the central nervous system.

METHODS: CSF samples from 49 patients with multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and non-inflammatory neurologic disorders (NIND) as controls were submitted to protein expression profiles of 47 inflammatory biomarkers by multiplex Luminex bead assay to investigate possible differences in the inflammatory process for MS and CIDP.

RESULTS: Our results showed differences in CSF cytokine levels in MS and CIDP; in particular, IL12 (p40) was significantly highly expressed in MS in comparison with CIDP and NIND, while SDF-1α and SCGF-β were significantly highly expressed in CIDP cohort when compared to MS and NIND. IL-9, IL-13, and IL-17 had higher expression levels in NIND if compared with the other groups.

CONCLUSIONS: Our study showed that, despite some common pathogenic mechanisms, central and peripheral nervous system demyelinating diseases, such as MS and CIDP, differ in some specific inflammatory soluble proteins in CSF, underlining differences in the immune response involved in those autoimmune diseases.

}, keywords = {Adult, Aged, Biomarkers, Central Nervous System, Diagnosis, Differential, Female, Hematopoietic Cell Growth Factors, Humans, Interleukin-12, Lectins, C-Type, Male, Middle Aged, Multiple Sclerosis, Peripheral Nervous System, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Proteins}, issn = {1532-4311}, doi = {10.1080/08820139.2017.1405978}, author = {Bonin, Serena and Zanotta, Nunzia and Sartori, Arianna and Bratina, Alessio and Manganotti, Paolo and Trevisan, Giusto and Comar, Manola} } @article {10505, title = {Cervical-length measurement in mid-gestation to predict spontaneous preterm birth in asymptomatic triplet pregnancy.}, journal = {Ultrasound Obstet Gynecol}, volume = {51}, year = {2018}, month = {2018 May}, pages = {614-620}, abstract = {

OBJECTIVE: To assess the predictive value of sonographic cervical-length (CL) measurement in mid-gestation for spontaneous preterm birth (PTB) in asymptomatic triplet pregnancy.

METHODS: This was a retrospective study of asymptomatic triplet pregnancies followed at five Italian tertiary referral centers, between 2002 and 2015. CL was measured transvaginally between 18 and 24 weeks{\textquoteright} gestation. Pregnancies with medically indicated PTB were excluded. Demographic and pregnancy characteristics of pregnancies complicated by PTB were analyzed and the distributions of CL measurements in these patients were calculated. Logistic regression analysis was performed to assess the association between CL and PTB, adjusted for confounders. Performance of CL measurement in prediction of PTB < 28, < 30 and < 32 weeks of gestation was assessed.

RESULTS: A total of 120 triplet pregnancies were included in the final analysis. Median CL was 35 (interquartile range (IQR), 29-40) mm measured at a median gestational age of 20 + 2 (IQR, 20 + 0 to 23 + 4) weeks. Overall, 23 (19.2\%), 17 (14.2\%) and eight (6.7\%) patients had a CL < 25, < 20 and < 15 mm, respectively. Spontaneous PTB < 32 weeks occurred in 41 (34.2\%) cases, < 30 weeks in 23 (19.2\%) and < 28 weeks in 12 (10\%) cases. CL < 15 mm was significantly more frequent in the group of patients who delivered < 28 (P = 0.03) and < 30 (P = 0.01) weeks{\textquoteright} gestation, compared with those who delivered after 28 and after 30 weeks, respectively, while CL < 20 mm was more common in triplet pregnancies with delivery < 32 weeks compared with those delivered >= 32 weeks (P = 0.03). Logistic regression analysis was possible only for PTB < 32 weeks due to the small number of cases that delivered < 30 and < 28 weeks. After adjustment for confounders, CL was not significantly associated with PTB < 32 weeks (adjusted odds ratio, 0.97; 95\% CI, 0.94-1.01). CL measurement had an area under the receiver-operating characteristics curve of 0.41 (95\% CI, 0.20-0.62), 0.41 (95\% CI, 0.26-0.56) and 0.42 (95\% CI, 0.31-0.54) for the prediction of spontaneous PTB < 28, < 30 and < 32 weeks, respectively.

CONCLUSION: CL assessed in mid-gestation is a poor predictor of PTB < 28, < 30 and < 32 weeks{\textquoteright} gestation in asymptomatic triplet pregnancy. Copyright {\textcopyright} 2017 ISUOG. Published by John Wiley \& Sons Ltd.

}, keywords = {Adult, Cervical Length Measurement, Female, Gestational Age, Humans, Infant, Newborn, Logistic Models, Predictive Value of Tests, Pregnancy, Pregnancy, Triplet, Premature Birth, Retrospective Studies}, issn = {1469-0705}, doi = {10.1002/uog.17464}, author = {Fichera, A and Pagani, G and Stagnati, V and Cascella, S and Faiola, S and Gaini, C and Lanna, M and Pasquini, L and Raffaelli, R and Stampalija, T and Tommasini, A and Prefumo, F} } @article {10765, title = {Characterization of multi-locus imprinting disturbances and underlying genetic defects in patients with chromosome 11p15.5 related imprinting disorders.}, journal = {Epigenetics}, volume = {13}, year = {2018}, month = {2018}, pages = {897-909}, abstract = {

The identification of multilocus imprinting disturbances (MLID) appears fundamental to uncover molecular pathways underlying imprinting disorders (IDs) and to complete clinical diagnosis of patients. However, MLID genetic associated mechanisms remain largely unknown. To characterize MLID in Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, we profiled by MassARRAY the methylation of 12 imprinted differentially methylated regions (iDMRs) in 21 BWS and 7 SRS patients with chromosome 11p15.5 epimutations. MLID was identified in 50\% of BWS and 29\% of SRS patients as a maternal hypomethylation syndrome. By next-generation sequencing, we searched for putative MLID-causative mutations in genes involved in methylation establishment/maintenance and found two novel missense mutations possibly causative of MLID: one in NLRP2, affecting ADP binding and protein activity, and one in ZFP42, likely leading to loss of DNA binding specificity. Both variants were paternally inherited. In silico protein modelling allowed to define the functional effect of these mutations. We found that MLID is very frequent in BWS/SRS. In addition, since MLID-BWS patients in our cohort show a peculiar pattern of BWS-associated clinical signs, MLID test could be important for a comprehensive clinical assessment. Finally, we highlighted the possible involvement of ZFP42 variants in MLID development and confirmed NLRP2 as causative locus in BWS-MLID.

}, keywords = {Adaptor Proteins, Signal Transducing, Adolescent, Beckwith-Wiedemann Syndrome, Child, Child, Preschool, Chromosomes, Human, Pair 15, DNA Methylation, Female, Genomic Imprinting, Humans, Infant, Kruppel-Like Transcription Factors, Male, Mutation, Missense, Silver-Russell Syndrome, Young Adult}, issn = {1559-2308}, doi = {10.1080/15592294.2018.1514230}, author = {Fontana, L and Bedeschi, M F and Maitz, S and Cereda, A and Far{\'e}, C and Motta, S and Seresini, A and D{\textquoteright}Ursi, P and Orro, A and Pecile, V and Calvello, M and Selicorni, A and Lalatta, F and Milani, D and Sirchia, S M and Miozzo, M and Tabano, S} } @article {10437, title = {A Child with Diminished Linear Growth and Waddling Gait.}, journal = {J Pediatr}, volume = {201}, year = {2018}, month = {2018 10}, pages = {297-297.e1}, keywords = {Abnormalities, Multiple, Child, Dwarfism, Female, Gait, Humans, Osteochondrodysplasias, Radiography}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2018.04.007}, author = {Tamaro, Gianluca and Pederiva, Federica and Dibello, Daniela and Gregori, Massimo and Carbone, Marco and Pantaleoni, Francesca and Dentici, Maria Lisa and Niceta, Marcello and Barbi, Egidio} } @article {10766, title = {Complete Remission of a Refractory Acute Myeloid Leukemia with Myelodysplastic- and Monosomy 7-Related Changes after a Combined Conditioning Regimen of Plerixafor, Cytarabine and Melphalan in a 4-Year-Old Boy: A Case Report and Review of Literature.}, journal = {Cancers (Basel)}, volume = {10}, year = {2018}, month = {2018 Aug 27}, abstract = {

Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric leukemia associated with very poor disease-free survival. The refractoriness of the disease is due to the protection offered by the bone marrow niche, making leukemic stem cells impervious to whatever chemotherapy or myeloablative regimen is chosen. Using a mobilizing agent for haematopoietic stem cells, Plerixafor, could sensitise leukemic cells to the myeloablative therapy. This approach was not previously used in a pediatric population, and in adult populations, was used in combination with busulphan with no difference in overall survival. We describe the case of a 4-year-old boy affected by refractory acute myeloid leukemia with myelodysplastic changes and monosomy 7. The child had never achieved a remission. We proposed a combined time-scheduled scheme of therapy with plerixafor and melphalan. Combining pharmacokinetics of plerixafor with pharmacokinetics and rapid and elevated myeloablative potential of melphalan in high dosage (200 mg/m{\texttwosuperior}), we succeeded in mobilizing more than 85\% of stem blasts immediately before infusion of Melphalan. The count of residual blasts after 8 h from melphalan infusion was only 1.3 cells/μL. The child achieved an engraftment at day +32 with full donor chimerism. Sixteen months after haematopoietic stem cell transplantation (HSCT), he is well and in complete remission. Our case suggests that the use of plerixafor before a conditioning therapy with melphalan could induce remission in acute myeloid leukemia refractory to the usual conditioning therapy in pediatric patients. This work adds strength to the body of knowledge regarding the "personalized" conditioning regimen for high-risk leukemic patients.

}, issn = {2072-6694}, doi = {10.3390/cancers10090291}, author = {Grasso, Antonio G and Granzotto, Marilena and Zanon, Davide and Maestro, Alessandra and Loiacono, Stefano and Maximova, Natalia} } @article {10849, title = {The Complex Interplay between Lipids, Immune System and Interleukins in Cardio-Metabolic Diseases.}, journal = {Int J Mol Sci}, volume = {19}, year = {2018}, month = {2018 Dec 14}, abstract = {

Lipids and inflammation regulate each other. Early studies on this topic focused on the systemic effects that the acute inflammatory response-and interleukins-had on lipid metabolism. Today, in the era of the obesity epidemic, whose primary complications are cardio-metabolic diseases, attention has moved to the effects that the nutritional environment and lipid derangements have on peripheral tissues, where lipotoxicity leads to organ damage through an imbalance of chronic inflammatory responses. After an overview of the effects that acute inflammation has on the systemic lipid metabolism, this review will describe the lipid-induced immune responses that take place in peripheral tissues and lead to chronic cardio-metabolic diseases. Moreover, the anti-inflammatory effects of lipid lowering drugs, as well as the possibility of using anti-inflammatory agents against cardio-metabolic diseases, will be discussed.

}, keywords = {Anti-Inflammatory Agents, Cardiovascular Diseases, Humans, Hypolipidemic Agents, Immune System, Inflammation, Interleukins, Lipid Metabolism, Lipids, Metabolic Diseases}, issn = {1422-0067}, doi = {10.3390/ijms19124058}, author = {Bernardi, Stella and Marcuzzi, Annalisa and Piscianz, Elisa and Tommasini, Alberto and Fabris, Bruno} } @article {10767, title = {Cooking influence in tolerance acquisition in egg-induced acute food protein enterocolitis syndrome.}, journal = {Allergol Immunopathol (Madr)}, year = {2018}, month = {2018 Oct 10}, abstract = {

BACKGROUND: Few studies on the age of resolution of Food Protein Induced Enterocolitis Syndrome (FPIES) induced by solid foods are available. In particular, for FPIES induced by egg, the mean age of tolerance acquisition reported in the literature ranges from 42 to 63 months.

OBJECTIVE: We have assessed whether the age of tolerance acquisition in acute egg FPIES varies depending on whether the egg is cooked or raw.

METHODS: We conducted a retrospective and multicentric study of children with diagnosis of acute egg FPIES seen in 10 Italian allergy units between July 2003 and October 2017. The collected data regarded sex, presence of other allergic diseases, age of onset of symptoms, kind and severity of symptoms, cooking technique of the ingested egg, outcome of the allergy test, age of tolerance acquisition.

RESULTS: Sixty-one children with acute egg FPIES were enrolled, 34 (56\%) males and 27 (44\%) females. Tolerance to cooked egg has been demonstrated by 47/61 (77\%) children at a mean age of 30.2 months. For 32 of them, tolerance to raw egg has been demonstrated at a mean age of 43.9 months. No episodes of severe adverse reaction after baked egg ingestion have been recorded.

CONCLUSIONS: It is possible to perform an OFC with baked egg, to verify the possible acquisition of tolerance, at about 30 months of life in children with acute egg FPIES.

}, issn = {1578-1267}, doi = {10.1016/j.aller.2018.07.006}, author = {Miceli Sopo, S and Romano, A and Bersani, G and Fantacci, C and Badina, L and Longo, G and Monti, G and Viola, S and Tripodi, S and Barilaro, G and Iacono, I D and Caffarelli, C and Mastrorilli, C and Barni, S and Mori, F and Liotti, L and Cuomo, B and Franceschini, F and Viggiano, D and Monaco, S} } @article {10768, title = {Cx26 partial loss causes accelerated presbycusis by redox imbalance and dysregulation of Nfr2 pathway.}, journal = {Redox Biol}, volume = {19}, year = {2018}, month = {2018 10}, pages = {301-317}, abstract = {

Mutations in GJB2, the gene that encodes connexin 26 (Cx26), are the most common cause of sensorineural hearing impairment. The truncating variant 35delG, which determines a complete loss of Cx26 protein function, is the prevalent GJB2 mutation in several populations. Here, we generated and analyzed Gjb2 mice as a model of heterozygous human carriers of 35delG. Compared to control mice, auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) worsened over time more rapidly in Gjb2 mice, indicating they were affected by accelerated age-related hearing loss (ARHL), or presbycusis. We linked causally the auditory phenotype of Gjb2 mice to apoptosis and oxidative damage in the cochlear duct, reduced release of glutathione from connexin hemichannels, decreased nutrient delivery to the sensory epithelium via cochlear gap junctions and deregulated expression of genes that are under transcriptional control of the nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal regulator of tolerance to redox stress. Moreover, a statistically significant genome-wide association with two genes (PRKCE and TGFB1) related to the Nrf2 pathway (p-value < 4 {\texttimes} 10) was detected in a very large cohort of 4091 individuals, originating from Europe, Caucasus and Central Asia, with hearing phenotype (including 1076 presbycusis patients and 1290 healthy matched controls). We conclude that (i) elements of the Nrf2 pathway are essential for hearing maintenance and (ii) their dysfunction may play an important role in the etiopathogenesis of human presbycusis.

}, keywords = {Animals, Apoptosis, Connexin 26, Female, Gene Deletion, Male, Mice, Mice, Inbred C57BL, NF-E2-Related Factor 2, Oxidation-Reduction, Presbycusis, Signal Transduction}, issn = {2213-2317}, doi = {10.1016/j.redox.2018.08.002}, author = {Fetoni, Anna Rita and Zorzi, Veronica and Paciello, Fabiola and Ziraldo, Gaia and Peres, Chiara and Raspa, Marcello and Scavizzi, Ferdinando and Salvatore, Anna Maria and Crispino, Giulia and Tognola, Gabriella and Gentile, Giulia and Spampinato, Antonio Gianmaria and Cuccaro, Denis and Guarnaccia, Maria and Morello, Giovanna and Van Camp, Guy and Fransen, Erik and Brumat, Marco and Girotto, Giorgia and Paludetti, Gaetano and Gasparini, Paolo and Cavallaro, Sebastiano and Mammano, Fabio} } @article {10445, title = {Cytokine profiles of women with vulvodynia: Identification of a panel of pro-inflammatory molecular targets.}, journal = {Eur J Obstet Gynecol Reprod Biol}, volume = {226}, year = {2018}, month = {2018 Jul}, pages = {66-70}, abstract = {

OBJECTIVE: The vulvar pain syndrome (VPS) is a multifactorial disease severely influencing the lifestyle of affected women. Among possible etiological factors, local injury, peripheral and/or central sensitization of the nervous system, and a chronic inflammatory status have been positively associated with the development of VPS. The identification of a constitutive altered local inflammatory profile in VPS women may represent an important point in the characterization of patients{\textquoteright} phenotype as a useful marker influencing the vulvar micro-environment. The aim of this study was to investigative the possible role of the local cytokines production in women with VPS in comparison to healthy women.

STUDY DESIGN: In this study were collected vaginal swabs from 57 healthy women (HC) who never suffered from VPS and from 30 patients diagnosed with vulvodynia (VPS) by at least 3 years and currently symptomatic. All patients included in this study showed the absence of Sexually Transmitted (STD) diseases and Reproductive Tract Infection. Real-time PCR was performed to assess the genomic sequences of ST pathogens. The Luminex Bio-Plex platform was used for the analysis of a panel of 48 immune factors.

RESULTS: Eleven molecules, specifically involved in the pro-inflammatory pathway were significantly modulated in VPS patients in comparison to healthy women, suggesting a persistent inflammatory process.

CONCLUSIONS: Therefore, these inflammatory factors could be possible biological markers involved in this disease. Nevertheless, other studies are needed to consider this specific immune profile as a valid marker of the vulvodynia.

}, keywords = {Adult, Aged, Cytokines, Female, Humans, Inflammation, Middle Aged, Vaginal Smears, Vulva, Vulvodynia, Women{\textquoteright}s Health}, issn = {1872-7654}, doi = {10.1016/j.ejogrb.2018.05.035}, author = {Zanotta, Nunzia and Campisciano, Giuseppina and Scrimin, Federica and Blendi, Ura and Marcuzzi, Annalisa and Vincenti, Ezio and Crovella, Sergio and Comar, Manola} } @article {10461, title = {Cardiac output decreases and systemic vascular resistance increases in newborns placed in the left-lateral position.}, journal = {J Perinatol}, volume = {37}, year = {2017}, month = {2017 May}, pages = {563-565}, abstract = {

OBJECTIVE: The objective of the study was to study the effect of short-term left-lateral position on cardiovascular parameters in hemodynamically stable newborns.

STUDY DESIGN: Cardiac output (CO), stroke volume (SV), systemic vascular resistance index (SVRI) and heart rate (HR) were measured by electric velocimetry in hemodynamically stable newborns without respiratory support in the supine, left-lateral and back-to-supine positions, each kept for 10 min.

RESULTS: Thirty-two newborns were enrolled, birth weight 2134 (1818 to 2460) g, gestational age 34.5{\textpm}2.4 weeks. CO and SV decreased significantly from supine to left-lateral position (CO supine: 193.4 (168.0 to 229.6) ml kgmin; CO left-lateral: 172.0 (154.9 to 201.6) ml kgmin, P<0.0001; SV supine: 3.0 (2.7 to 4.0) ml; SV left-lateral: 2.7 (2.4 to 3.2) ml, P<0.0004). Conversely, SVRI increased in left-lateral position: SVRI supine: 18865{\textpm}9244 dyns cm m; SVRI left-lateral: 21203{\textpm}10059 dyns cm m, P<0.0001). All variables returned to the initial value when infants were back in the supine position. HR and blood pressure did not change.

CONCLUSION: In stable infants, CO and SV decrease and SVRI increases, in left-lateral position.

}, keywords = {Blood Pressure, Cardiac Output, Female, Gestational Age, Heart Rate, Humans, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Italy, Male, Posture, Stroke Volume, Vascular Resistance}, issn = {1476-5543}, doi = {10.1038/jp.2016.251}, author = {Paviotti, G and Todero, S and Demarini, S} } @article {10463, title = {CCR5Δ32 and the genetic susceptibility to rheumatoid arthritis in admixed populations: a multicentre study.}, journal = {Rheumatology (Oxford)}, volume = {56}, year = {2017}, month = {2017 03 01}, pages = {495-497}, keywords = {Arthritis, Rheumatoid, Brazil, Case-Control Studies, Consanguinity, Gene Frequency, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Receptors, CCR5}, issn = {1462-0332}, doi = {10.1093/rheumatology/kew398}, author = {Toson, Bruno and Dos Santos, Eduardo Jos{\'e} and Adelino, Jos{\'e} Eduardo and Sandrin-Garcia, Paula and Crovella, Sergio and Louzada-J{\'u}nior, Paulo and Oliveira, Ren{\^e} Donizete Ribeiro and Pedroza, Larysse Santa Rosa Aquino and de F{\'a}tima Lobato Cunha Sauma, Maria and de Lima, Clayton Pereira Silva and Barbosa, Fabiola Brasil and Brenol, Claiton Viegas and Xavier, Ricardo Machado and Chies, Jos{\'e} Artur Bogo and Veit, Tiago Degani} } @article {10517, title = {Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy.}, journal = {Cochrane Database Syst Rev}, volume = {6}, year = {2017}, month = {2017 06 06}, pages = {CD008991}, abstract = {

BACKGROUND: Cervical cerclage is a well-known surgical procedure carried out during pregnancy. It involves positioning of a suture (stitch) around the neck of the womb (cervix), aiming to give mechanical support to the cervix and thereby reduce risk of preterm birth. The effectiveness and safety of this procedure remains controversial. This is an update of a review last published in 2012.

OBJECTIVES: To assess whether the use of cervical stitch in singleton pregnancy at high risk of pregnancy loss based on woman{\textquoteright}s history and/or ultrasound finding of {\textquoteright}short cervix{\textquoteright} and/or physical exam improves subsequent obstetric care and fetal outcome.

SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth{\textquoteright}s Trials Register (30 June 2016) and reference lists of identified studies.

SELECTION CRITERIA: We included all randomised trials of cervical suturing in singleton pregnancies. Cervical stitch was carried out when the pregnancy was considered to be of sufficiently high risk due to a woman{\textquoteright}s history, a finding of short cervix on ultrasound or other indication determined by physical exam. We included any study that compared cerclage with either no treatment or any alternative intervention. We planned to include cluster-randomised studies but not cross-over trials. We excluded quasi-randomised studies. We included studies reported in abstract form only.

DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion. Two review authors independently assessed risk of bias and extracted data. We resolved discrepancies by discussion. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach.

MAIN RESULTS: This updated review includes a total of 15 trials (3490 women); three trials were added for this update (152 women). Cerclage versus no cerclageOverall, cerclage probably leads to a reduced risk of perinatal death when compared with no cerclage, although the confidence interval (CI) crosses the line of no effect (RR 0.82, 95\% CI 0.65 to 1.04; 10 studies, 2927 women; moderate quality evidence). Considering stillbirths and neonatal deaths separately reduced the numbers of events and sample size. Although the relative effect of cerclage is similar, estimates were less reliable with fewer data and assessed as of low quality (stillbirths RR 0.89, 95\% CI 0.45 to 1.75; 5 studies, 1803 women; low quality evidence; neonatal deaths before discharge RR 0.85, 95\% CI 0.53 to 1.39; 6 studies, 1714 women; low quality evidence). Serious neonatal morbidity was similar with and without cerclage (RR 0.80, 95\% CI 0.55 to 1.18; 6 studies, 883 women; low-quality evidence). Pregnant women with and without cerclage were equally likely to have a baby discharged home healthy (RR 1.02, 95\% CI 0.97 to 1.06; 4 studies, 657 women; moderate quality evidence).Pregnant women with cerclage were less likely to have preterm births compared to controls before 37, 34 (average RR 0.77, 95\% CI 0.66 to 0.89; 9 studies, 2415 women; high quality evidence) and 28 completed weeks of gestation.Five subgroups based on clinical indication provided data for analysis (history-indicated; short cervix based on one-off ultrasound in high risk women; short cervix found by serial scans in high risk women; physical exam-indicated; and short cervix found on scan in low risk or mixed populations). There were too few trials in these clinical subgroups to make meaningful conclusions and no evidence of differential effects. Cerclage versus progesteroneTwo trials (129 women) compared cerclage to prevention with vaginal progesterone in high risk women with short cervix on ultrasound; these trials were too small to detect reliable, clinically important differences for any review outcome. One included trial compared cerclage with intramuscular progesterone (75 women) which lacked power to detect group differences. History indicated cerclage versus ultrasound indicated cerclageEvidence from two trials (344 women) was too limited to establish differences for clinically important outcomes.

AUTHORS{\textquoteright} CONCLUSIONS: Cervical cerclage reduces the risk of preterm birth in women at high-risk of preterm birth and probably reduces risk of perinatal deaths. There was no evidence of any differential effect of cerclage based on previous obstetric history or short cervix indications, but data were limited for all clinical groups. The question of whether cerclage is more or less effective than other preventative treatments, particularly vaginal progesterone, remains unanswered.

}, keywords = {Administration, Intravaginal, Cerclage, Cervical, Cesarean Section, Female, Humans, Injections, Intramuscular, Perinatal Death, Pregnancy, Premature Birth, Progesterone, Randomized Controlled Trials as Topic, Stillbirth, Suture Techniques}, issn = {1469-493X}, doi = {10.1002/14651858.CD008991.pub3}, author = {Alfirevic, Zarko and Stampalija, Tamara and Medley, Nancy} } @article {10524, title = {Child and Adolescent Health From 1990 to 2015: Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2015 Study.}, journal = {JAMA Pediatr}, volume = {171}, year = {2017}, month = {2017 Jun 01}, pages = {573-592}, abstract = {

Importance: Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health.

Objective: To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion.

Evidence Review: Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed (Socio-demographic Index [SDI]) for each geographic unit and year, which evaluates the historical association between SDI and health loss.

Findings: Global child and adolescent mortality decreased from 14.18 million (95\% uncertainty interval [UI], 14.09 million to 14.28 million) deaths in 1990 to 7.26 million (95\% UI, 7.14 million to 7.39 million) deaths in 2015, but progress has been unevenly distributed. Countries with a lower SDI had a larger proportion of mortality burden (75\%) in 2015 than was the case in 1990 (61\%). Most deaths in 2015 occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden. The absolute burden of disability in children and adolescents increased 4.3\% (95\% UI, 3.1\%-5.6\%) from 1990 to 2015, with much of the increase owing to population growth and improved survival for children and adolescents to older ages. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth (eg, neonatal disorders, congenital birth defects, and hemoglobinopathies) and complications of a variety of infections and nutritional deficiencies. Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries.

Conclusions and Relevance: Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.

}, keywords = {Adolescent, Adolescent Health, Age Factors, Cause of Death, Child, Child Health, Child Mortality, Disabled Children, Female, Global Burden of Disease, Global Health, Humans, Male, Pregnancy, Pregnancy Complications, Risk Factors, Sex Factors, Wounds and Injuries}, issn = {2168-6211}, doi = {10.1001/jamapediatrics.2017.0250}, author = {Kassebaum, Nicholas and Kyu, Hmwe Hmwe and Zoeckler, Leo and Olsen, Helen Elizabeth and Thomas, Katie and Pinho, Christine and Bhutta, Zulfiqar A and Dandona, Lalit and Ferrari, Alize and Ghiwot, Tsegaye Tewelde and Hay, Simon I and Kinfu, Yohannes and Liang, Xiaofeng and Lopez, Alan and Malta, Deborah Carvalho and Mokdad, Ali H and Naghavi, Mohsen and Patton, George C and Salomon, Joshua and Sartorius, Benn and Topor-Madry, Roman and Vollset, Stein Emil and Werdecker, Andrea and Whiteford, Harvey A and Abate, Kalkidan Hasen and Abbas, Kaja and Damtew, Solomon Abrha and Ahmed, Muktar Beshir and Akseer, Nadia and Al-Raddadi, Rajaa and Alemayohu, Mulubirhan Assefa and Altirkawi, Khalid and Abajobir, Amanuel Alemu and Amare, Azmeraw T and Antonio, Carl A T and Arnl{\"o}v, Johan and Artaman, Al and Asayesh, Hamid and Avokpaho, Euripide Frinel G Arthur and Awasthi, Ashish and Ayala Quintanilla, Beatriz Paulina and Bacha, Umar and Betsu, Balem Demtsu and Barac, Aleksandra and B{\"a}rnighausen, Till Winfried and Baye, Estifanos and Bedi, Neeraj and Bensenor, Isabela M and Berhane, Adugnaw and Bernabe, Eduardo and Bernal, Oscar Alberto and Beyene, Addisu Shunu and Biadgilign, Sibhatu and Bikbov, Boris and Boyce, Cheryl Anne and Brazinova, Alexandra and Hailu, Gessessew Bugssa and Carter, Austin and Casta{\~n}eda-Orjuela, Carlos A and Catal{\'a}-L{\'o}pez, Ferr{\'a}n and Charlson, Fiona J and Chitheer, Abdulaal A and Choi, Jee-Young Jasmine and Ciobanu, Liliana G and Crump, John and Dandona, Rakhi and Dellavalle, Robert P and Deribew, Amare and deVeber, Gabrielle and Dicker, Daniel and Ding, Eric L and Dubey, Manisha and Endries, Amanuel Yesuf and Erskine, Holly E and Faraon, Emerito Jose Aquino and Faro, Andre and Farzadfar, Farshad and Fernandes, Joao C and Fijabi, Daniel Obadare and Fitzmaurice, Christina and Fleming, Thomas D and Flor, Luisa Sorio and Foreman, Kyle J and Franklin, Richard C and Fraser, Maya S and Frostad, Joseph J and Fullman, Nancy and Gebregergs, Gebremedhin Berhe and Gebru, Alemseged Aregay and Geleijnse, Johanna M and Gibney, Katherine B and Gidey Yihdego, Mahari and Ginawi, Ibrahim Abdelmageem Mohamed and Gishu, Melkamu Dedefo and Gizachew, Tessema Assefa and Glaser, Elizabeth and Gold, Audra L and Goldberg, Ellen and Gona, Philimon and Goto, Atsushi and Gugnani, Harish Chander and Jiang, Guohong and Gupta, Rajeev and Tesfay, Fisaha Haile and Hankey, Graeme J and Havmoeller, Rasmus and Hijar, Martha and Horino, Masako and Hosgood, H Dean and Hu, Guoqing and Jacobsen, Kathryn H and Jakovljevic, Mihajlo B and Jayaraman, Sudha P and Jha, Vivekanand and Jibat, Tariku and Johnson, Catherine O and Jonas, Jost and Kasaeian, Amir and Kawakami, Norito and Keiyoro, Peter N and Khalil, Ibrahim and Khang, Young-Ho and Khubchandani, Jagdish and Ahmad Kiadaliri, Aliasghar A and Kieling, Christian and Kim, Daniel and Kissoon, Niranjan and Knibbs, Luke D and Koyanagi, Ai and Krohn, Kristopher J and Kuate Defo, Barthelemy and Kucuk Bicer, Burcu and Kulikoff, Rachel and Kumar, G Anil and Lal, Dharmesh Kumar and Lam, Hilton Y and Larson, Heidi J and Larsson, Anders and Laryea, Dennis Odai and Leung, Janni and Lim, Stephen S and Lo, Loon-Tzian and Lo, Warren D and Looker, Katharine J and Lotufo, Paulo A and Magdy Abd El Razek, Hassan and Malekzadeh, Reza and Markos Shifti, Desalegn and Mazidi, Mohsen and Meaney, Peter A and Meles, Kidanu Gebremariam and Memiah, Peter and Mendoza, Walter and Abera Mengistie, Mubarek and Mengistu, Gebremichael Welday and Mensah, George A and Miller, Ted R and Mock, Charles and Mohammadi, Alireza and Mohammed, Shafiu and Monasta, Lorenzo and Mueller, Ulrich and Nagata, Chie and Naheed, Aliya and Nguyen, Grant and Nguyen, Quyen Le and Nsoesie, Elaine and Oh, In-Hwan and Okoro, Anselm and Olusanya, Jacob Olusegun and Olusanya, Bolajoko O and Ortiz, Alberto and Paudel, Deepak and Pereira, David M and Perico, Norberto and Petzold, Max and Phillips, Michael Robert and Polanczyk, Guilherme V and Pourmalek, Farshad and Qorbani, Mostafa and Rafay, Anwar and Rahimi-Movaghar, Vafa and Rahman, Mahfuzar and Rai, Rajesh Kumar and Ram, Usha and Rankin, Zane and Remuzzi, Giuseppe and Renzaho, Andre M N and Roba, Hirbo Shore and Rojas-Rueda, David and Ronfani, Luca and Sagar, Rajesh and Sanabria, Juan Ramon and Kedir Mohammed, Muktar Sano and Santos, Itamar S and Satpathy, Maheswar and Sawhney, Monika and Sch{\"o}ttker, Ben and Schwebel, David C and Scott, James G and Sepanlou, Sadaf G and Shaheen, Amira and Shaikh, Masood Ali and She, June and Shiri, Rahman and Shiue, Ivy and Sigfusdottir, Inga Dora and Singh, Jasvinder and Silpakit, Naris and Smith, Alison and Sreeramareddy, Chandrashekhar and Stanaway, Jeffrey D and Stein, Dan J and Steiner, Caitlyn and Sufiyan, Muawiyyah Babale and Swaminathan, Soumya and Tabar{\'e}s-Seisdedos, Rafael and Tabb, Karen M and Tadese, Fentaw and Tavakkoli, Mohammad and Taye, Bineyam and Teeple, Stephanie and Tegegne, Teketo Kassaw and Temam Shifa, Girma and Terkawi, Abdullah Sulieman and Thomas, Bernadette and Thomson, Alan J and Tobe-Gai, Ruoyan and Tonelli, Marcello and Tran, Bach Xuan and Troeger, Christopher and Ukwaja, Kingsley N and Uthman, Olalekan and Vasankari, Tommi and Venketasubramanian, Narayanaswamy and Vlassov, Vasiliy Victorovich and Weiderpass, Elisabete and Weintraub, Robert and Gebrehiwot, Solomon Weldemariam and Westerman, Ronny and Williams, Hywel C and Wolfe, Charles D A and Woodbrook, Rachel and Yano, Yuichiro and Yonemoto, Naohiro and Yoon, Seok-Jun and Younis, Mustafa Z and Yu, Chuanhua and Zaki, Maysaa El Sayed and Zegeye, Elias Asfaw and Zuhlke, Liesl Joanna and Murray, Christopher J L and Vos, Theo} } @article {10528, title = {Children with cancer: a survey on the experience of Italian primary care pediatricians.}, journal = {Ital J Pediatr}, volume = {43}, year = {2017}, month = {2017 May 25}, pages = {48}, abstract = {

BACKGROUND: Cancer is the second cause of death in children and its diagnosis can be difficult, due to the presence of vague and non-specific symptoms. The primary care pediatrician is often involved in the diagnostic process, but no longer in child care once the treatment started. Care models involving both primary care pediatricians and oncologic referral centre highlighted a higher family satisfaction when they worked together. We conducted a survey on primary care pediatricians involved in childhood cancer in order to describe the actual situation.

METHODS: We conducted a retrospective survey enrolling primary care pediatricians from a north-eastern area of Italy. They received a questionnaire that consisted in two parts: the first one aimed to assess the physician{\textquoteright}s seniority and experience and the second one pertained to each case of cancer and explored the relationship between the pediatrician, the family and the referral centre, and pediatricians degree of satisfaction and emotional impact.

RESULTS: We obtained data from 79 pediatricians who described 150 cancer cases. In 99 cases the primary care pediatrician had visited the child at the onset of symptoms and had referred him to the hospital. In 89 cases, he understood the severity of the disease. In 53.3\% of cases the pediatrician was informed by the referral centre. The relationship between the pediatrician and child{\textquoteright}s family improved in 38\% of cases and this was related with their participation to the multidisciplinary meetings on child health.

CONCLUSIONS: Primary pediatricians{\textquoteright} sharing in the management of their patients with cancer was not satisfactory. Development of specific protocols targeted to an integrated care is needed to increase primary pediatricians{\textquoteright} involvement and families{\textquoteright} satisfactions.

}, keywords = {Child, Child, Preschool, Cross-Sectional Studies, Disease-Free Survival, Female, Humans, Italy, Male, Needs Assessment, Neoplasms, Outcome Assessment (Health Care), Pediatricians, Practice Patterns, Physicians{\textquoteright}, Prevalence, Primary Health Care, Retrospective Studies, Risk Assessment, Survival Analysis}, issn = {1824-7288}, doi = {10.1186/s13052-017-0365-9}, author = {Minute, Marta and Cozzi, Giorgio and Plotti, Chiara and Montanari, Giuseppe and Pecile, Paolo and Zanazzo, Giulio Andrea and Ventura, Alessandro and Barbi, Egidio} } @article {10482, title = {Circulating osteoprotegerin is associated with chronic kidney disease in hypertensive patients.}, journal = {BMC Nephrol}, volume = {18}, year = {2017}, month = {2017 Jul 06}, pages = {219}, abstract = {

BACKGROUND: Osteoprotegerin (OPG) is a glycoprotein that plays an important regulatory role in the skeletal, vascular, and immune system. It has been shown that OPG predicts chronic kidney disease (CKD) in diabetic patients. We hypothesized that OPG could be a risk marker of CKD development also in non-diabetic hypertensive patients.

METHODS: A case-control study was carried out to measure circulating OPG levels in 42 hypertensive patients with CKD and in 141 hypertensive patients without CKD. A potential relationship between OPG and the presence of CKD was investigated and a receiver-operating characteristic (ROC) curve was designed thereafter to identify a cut-off value of OPG that best explained the presence of CKD. Secondly, to evaluate whether OPG increase could affect the kidney, 18 C57BL/6J mice were randomized to be treated with saline or recombinant OPG every 3~weeks for 12~weeks.

RESULTS: Circulating OPG levels were significantly higher in hypertensive patients with CKD, and there was a significant inverse association between OPG and renal function, that was independent from other variables. ROC analysis showed that OPG levels had a high statistically predictive value on CKD in hypertensive patients, which was greater than that of hypertension. The OPG best cut-off value associated with CKD was 1109.19~ng/L. In the experimental study, OPG delivery significantly increased the gene expression of pro-inflammatory and pro-fibrotic mediators, as well as the glomerular nitrosylation of proteins.

CONCLUSIONS: This study shows that OPG is associated with CKD in hypertensive patients, where it might have a higher predictive value than that of hypertension for CKD development. Secondly, we found that OPG delivery significantly increased the expression of molecular pathways involved in kidney damage. Further longitudinal studies are needed not only to evaluate whether OPG predicts CKD development but also to clarify whether OPG should be considered a risk factor for CKD.

}, keywords = {Aged, Animals, Biomarkers, Case-Control Studies, Female, Follow-Up Studies, Humans, Hypertension, Male, Mice, Mice, Inbred C57BL, Middle Aged, Osteoprotegerin, Random Allocation, Renal Insufficiency, Chronic}, issn = {1471-2369}, doi = {10.1186/s12882-017-0625-3}, author = {Bernardi, Stella and Toffoli, Barbara and Bossi, Fleur and Candido, Riccardo and Stenner, Elisabetta and Carretta, Renzo and Barbone, Fabio and Fabris, Bruno} } @article {10541, title = {Climate change, emerging infections and blood donations.}, journal = {J Travel Med}, volume = {24}, year = {2017}, month = {2017 05 01}, keywords = {Blood Transfusion, Climate Change, Communicable Diseases, Emerging, Global Health, Humans, Travel}, issn = {1708-8305}, doi = {10.1093/jtm/taw098}, author = {Cegolon, L and Heymann, W C and Lange, J H} } @article {10465, title = {[Clinical and molecular study in a family with autosomal dominant hypohidrotic ectodermal dysplasia].}, journal = {Arch Argent Pediatr}, volume = {115}, year = {2017}, month = {2017 02 01}, pages = {e34-e38}, abstract = {

Hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized by deficiency in development of structure derived from the ectoderm and is caused by mutations in the genes EDA, EDAR, or EDARADD. Phenotypes caused by mutations in these three may exhibit similar clinical features, explained by a common signaling pathway. Mutations in EDA gene cause X linked HED, which is the most common form. Mutations in EDAR and EDARADD genes cause autosomal dominant and recessive form of HED. The most striking clinical findings in HED are hypodontia, hypotrichosis and hypohidrosis that can lead to episodes of hyperthermia. We report on clinical findings in a child with HED with autosomal dominant inheritance pattern with a heterozygous mutation c.1072C>T (p.Arg358X) in the EDAR gene. A review of the literature with regard to other cases presenting the same mutation has been carried out and discussed.

}, keywords = {Child, Preschool, Ectodermal Dysplasia 1, Anhidrotic, Edar Receptor, Humans, Male, Mutation, Pedigree}, issn = {1668-3501}, doi = {10.5546/aap.2017.e34}, author = {Callea, Michele and Cammarata-Scalisi, Francisco and Willoughby, Colin E and Giglio, Sabrina R and Sani, Ilaria and Bargiacchi, Sara and Traficante, Giovanna and Bellacchio, Emanuele and Tadini, Gianluca and Yavuz, Izzet and Galeotti, Angela and Clarich, Gabriella} } @article {10552, title = {Combined use of AFM and soft X-ray microscopy to reveal fibres{\textquoteright} internalization in mesothelial cells.}, journal = {Analyst}, volume = {142}, year = {2017}, month = {2017 May 30}, pages = {1982-1992}, abstract = {

Nanotoxicology and nanomedicine investigations often require the probing of nano-objects such as fibres and particles in biological samples and cells, whilst internalization and intracellular destiny are the main issues for in vitro cellular studies. Various high resolution microscopy techniques are well suited for providing this highly sought-after information. However, sample preparation, nanomaterial composition and sectioning challenges make it often difficult to establish whether the fibres or particles have been internalized or they are simply overlaying or underlying the biological matter. In this paper we suggest a novel suitable combination of two different microscopic techniques to reveal in intact cells the uptake of asbestos fibres by mesothelial cells. After exposure to asbestos fibres and fixation, cells were first analysed under the AFM instrument and then imaged under the TwinMic soft X-ray microscope at Elettra Sincrotrone. The suggested approach combines standard soft X-ray microscopy imaging and AFM microscopy, with a common non-invasive sample preparation protocol which drastically reduces the experimental uncertainty and provides a quick and definitive answer to the nanoparticle cellular and tissue uptake.

}, keywords = {Asbestos, Cell Line, Epithelial Cells, Epithelium, Humans, Microscopy, Atomic Force, X-Rays}, issn = {1364-5528}, doi = {10.1039/c6an02661c}, author = {Gianoncelli, Alessandra and Kourousias, George and Cammisuli, Francesca and Cassese, Damiano and Rizzardi, Clara and Radillo, Oriano and Lazzarino, Marco and Pascolo, Lorella} } @article {10568, title = {Common variants in CLDN14 are associated with differential excretion of magnesium over calcium in urine.}, journal = {Pflugers Arch}, volume = {469}, year = {2017}, month = {2017 01}, pages = {91-103}, abstract = {

The nature and importance of genetic factors regulating the differential handling of Ca and Mg by the renal tubule in the general population are poorly defined. We conducted a genome-wide meta-analysis of urinary magnesium-to-calcium ratio to identify associated common genetic variants. We included 9320 adults of European descent from four genetic isolates and three urban cohorts. Urinary magnesium and calcium concentrations were measured centrally in spot urine, and each study conducted linear regression analysis of urinary magnesium-to-calcium ratio on ~2.5 million single-nucleotide polymorphisms (SNPs) using an additive model. We investigated, in mouse, the renal expression profile of the top candidate gene and its variation upon changes in dietary magnesium. The genome-wide analysis evidenced a top locus (rs172639, p~=~1.7~{\texttimes}~10), encompassing CLDN14, the gene coding for claudin-14, that was genome-wide significant when using urinary magnesium-to-calcium ratio, but not either one taken separately. In mouse, claudin-14 is expressed in the distal nephron segments specifically handling magnesium, and its expression is regulated by chronic changes in dietary magnesium content. A genome-wide approach identified common variants in the CLDN14 gene exerting a robust influence on the differential excretion of Mg over Ca in urine. These data highlight the power of urinary electrolyte ratios to unravel genetic determinants of renal tubular function. Coupled with mouse experiments, these results support a major role for claudin-14, a gene associated with kidney stones, in the differential paracellular handling of divalent cations by the renal tubule.

}, keywords = {Animals, Calcium, Claudins, Humans, Kidney Tubules, Magnesium, Polymorphism, Single Nucleotide, Urine}, issn = {1432-2013}, doi = {10.1007/s00424-016-1913-7}, author = {Corre, Tanguy and Olinger, Eric and Harris, Sarah E and Traglia, Michela and Ulivi, Sheila and Lenarduzzi, Stefania and Belge, Hendrica and Youhanna, Sonia and Tokonami, Natsuko and Bonny, Olivier and Houillier, Pascal and Polasek, Ozren and Deary, Ian J and Starr, John M and Toniolo, Daniela and Gasparini, Paolo and Vollenweider, Peter and Hayward, Caroline and Bochud, Murielle and Devuyst, Olivier} } @article {10537, title = {Comparison of Efficacy and Safety of Caspofungin Versus Micafungin in Pediatric Allogeneic Stem Cell Transplant Recipients: A Retrospective Analysis.}, journal = {Adv Ther}, volume = {34}, year = {2017}, month = {2017 05}, pages = {1184-1199}, abstract = {

INTRODUCTION: The high morbidity and mortality associated with invasive fungal infections (IFIs) provide the rationale for antifungal prophylaxis in immuno-compromised pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Caspofungin and micafungin are antifungal agents of interest for prophylaxis of IFIs because of their potency against Candida and minimal toxicity or interactions with other drugs. Few studies have demonstrated the safety and efficacy of such echinocandins as prophylaxis for IFIs in patients undergoing HSCT.

METHODS: This retrospective cohort study compared caspofungin and micafungin for prevention of IFIs in 93 pediatric patients undergoing HSCT for oncological or non-oncological disease. The observation began with the first dose of antifungal agent and ended 3~months after transplantation.

RESULTS: Patients in the micafungin group had a higher overall treatment success rate of 87.2 versus 84.8\% in the caspofungin group, but the difference was not significant. There were no statistically significant differences in the incidence or type of proven/probable IFIs between the 2 groups. The low incidence of death did not differ statistically between the groups. Patients in the caspofungin group presented more frequently with fever, during and after neutropenia. In both groups, we observed an expected worsening of blood chemistry parameters. There were no adverse events definitely attributable to the two antifungal agents.

CONCLUSION: These results demonstrate good efficacy and tolerability for caspofungin and micafungin. However, better results with respect to the incidence and resolution of fever in the micafungin group may suggest its use in preference to that of caspofungin.

}, keywords = {Adolescent, Antifungal Agents, Caspofungin, Child, Child, Preschool, Cohort Studies, Echinocandins, Female, Hematopoietic Stem Cell Transplantation, Humans, Infant, Infant, Newborn, Lipopeptides, Male, Micafungin, Mycoses, Neutropenia, Retrospective Studies}, issn = {1865-8652}, doi = {10.1007/s12325-017-0534-7}, author = {Maximova, Natalia and Schillani, Giulia and Simeone, Roberto and Maestro, Alessandra and Zanon, Davide} } @article {10591, title = {Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth.}, journal = {Front Immunol}, volume = {8}, year = {2017}, month = {2017}, pages = {1559}, abstract = {

C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid (HA) its globular domain. C1q bound to HA was able to induce adhesion and proliferation of mesothelioma cells (MES) enhancement of ERK1/2, SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organization of the globular domain, we demonstrated that C1q may bind to HA through ghA module, whereas it may interact with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds to HA and enhances the tumor growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM.

}, issn = {1664-3224}, doi = {10.3389/fimmu.2017.01559}, author = {Agostinis, Chiara and Vidergar, Romana and Belmonte, Beatrice and Mangogna, Alessandro and Amadio, Leonardo and Geri, Pietro and Borelli, Violetta and Zanconati, Fabrizio and Tedesco, Francesco and Confalonieri, Marco and Tripodo, Claudio and Kishore, Uday and Bulla, Roberta} } @article {10515, title = {A complete duplication of X chromosome resulting in a tricentric isochromosome originated by centromere repositioning.}, journal = {Mol Cytogenet}, volume = {10}, year = {2017}, month = {2017}, pages = {22}, abstract = {

BACKGROUND: Neocentromeres are rare and considered chromosomal aberrations, because a non-centromeric region evolves in an active centromere by mutation. The literature reported several structural anomalies of X chromosome and they influence the female reproductive capacity or are associated to Turner syndrome in the presence of monosomy X cell line.

CASE PRESENTATION: We report a case of chromosome X complex rearrangement found in a prenatal diagnosis. The fetal karyotype showed a mosaicism with a 45,X cell line and a 46 chromosomes second line with a big marker, instead of a sex chromosome. The marker morphology and fluorescence in situ hybridization (FISH) characterization allowed us to identify a tricentric X chromosome constituted by two complete X chromosome fused at the p arms telomere and an active neocentromere in the middle, at the union of the two Xp arms, where usually are the telomeric regions. FISH also showed the presence of a paracentric inversion of both Xp arms. Furthermore, fragility figures were found in 56\% of metaphases from peripheral blood lymphocytes culture at birth: a shorter marker chromosome and an apparently acentric fragment frequently lost.

CONCLUSIONS: At our knowledge, this is the first isochromosome of an entire non-acrocentric chromosome. The neocentromere is constituted by canonical sequences but localized in an unusual position and the original centromeres are inactivated. We speculated that marker chromosome was the result of a double rearrangement: firstly, a paracentric inversion which involved the Xp arm, shifting a part of the centromere at the p end and subsequently a duplication of the entire X chromosome, which gave rise to an isochromosome. It is possible to suppose that the first event could be a result of a non-allelic homologous recombination mediated by inverted low-copy repeats. As expected, our case shows a Turner phenotype with mild facial features and no major skeletal deformity, normal psychomotor development and a spontaneous development of puberty and menarche, although with irregular menses since the last follow-up.

}, issn = {1755-8166}, doi = {10.1186/s13039-017-0323-7}, author = {Villa, N and Conconi, D and Benussi, D Gambel and Tornese, G and Crosti, F and Sala, E and Dalpr{\`a}, L and Pecile, V} } @article {8311, title = {A congenital purplish tumour.}, journal = {Arch Dis Child Educ Pract Ed}, volume = {102}, year = {2017}, month = {2017 Apr}, pages = {79-81}, keywords = {Congenital Abnormalities, Humans, India, Infant, Infant, Newborn, Knee, Male, Neonatology, Neoplasms, Treatment Outcome}, issn = {1743-0593}, doi = {10.1136/archdischild-2015-309475}, author = {Matarazzo, L and Delise, A and Zennaro, F and Bussani, R and Demarini, S and Berti, I and Ventura, A} } @article {10474, title = {Cubosomes for in vivo fluorescence lifetime imaging.}, journal = {Nanotechnology}, volume = {28}, year = {2017}, month = {2017 Feb 03}, pages = {055102}, abstract = {

Herein we provided the first proof of principle for in vivo fluorescence optical imaging application using monoolein-based cubosomes in a healthy mouse animal model. This formulation, administered at a non-cytotoxic concentration, was capable of providing both exogenous contrast for NIR fluorescence imaging with very high efficiency and chemospecific information upon lifetime analysis. Time-resolved measurements of fluorescence after the intravenous injection of cubosomes revealed that the dye rapidly accumulated mainly in the liver, while lifetimes profiles obtained in vivo allowed for discriminating between free dye or dye embedded within the cubosome nanostructure after injection.

}, keywords = {Animals, Carbocyanines, Cell Survival, Drug Compounding, Erythrocytes, Female, Fluorescent Dyes, Glycerides, Humans, Injections, Intravenous, Liposomes, Liver, Mice, Mice, Inbred BALB C, Nanoparticles, NIH 3T3 Cells, Optical Imaging, Particle Size, Spectroscopy, Near-Infrared, Time-Lapse Imaging}, issn = {1361-6528}, doi = {10.1088/1361-6528/28/5/055102}, author = {Biffi, Stefania and Andolfi, Laura and Caltagirone, Claudia and Garrovo, Chiara and Falchi, Angela M and Lippolis, Vito and Lorenzon, Andrea and Macor, Paolo and Meli, Valeria and Monduzzi, Maura and Obiols-Rabasa, Marc and Petrizza, Luca and Prodi, Luca and Rosa, Antonella and Schmidt, Judith and Talmon, Yeshayahu and Murgia, Sergio} } @article {10518, title = {Curcumin Anti-Apoptotic Action in a Model of Intestinal Epithelial Inflammatory Damage.}, journal = {Nutrients}, volume = {9}, year = {2017}, month = {2017 Jun 06}, abstract = {

The purpose of this study is to determine if a preventive treatment with curcumin can protect intestinal epithelial cells from inflammatory damage induced by IFNγ. To achieve this goal we have used a human intestinal epithelial cell line (HT29) treated with IFNγ to undergo apoptotic changes that can reproduce the damage of intestinal epithelia exposed to inflammatory cytokines. In this model, we measured the effect of curcumin (curcuminoid from ) added as a pre-treatment at different time intervals before stimulation with IFNγ. Curcumin administration to HT29 culture before the inflammatory stimulus IFNγ reduced the cell apoptosis rate. This effect gradually declined with the reduction of the curcumin pre-incubation time. This anti-apoptotic action by curcumin pre-treatment was paralleled by a reduction of secreted IL7 in the HT29 culture media, while there was no relevant change in the other cytokine levels. Even though curcumin pre-administration did not impact the activation of the NF-κB pathway, a slight effect on the phosphorylation of proteins in this inflammatory signaling pathway was observed. In conclusion, curcumin pre-treatment can protect intestinal cells from inflammatory damage. These results can be the basis for studying the preventive role of curcumin in inflammatory bowel diseases.

}, keywords = {Anti-Inflammatory Agents, Non-Steroidal, Apoptosis, Cell Survival, Curcuma, Curcumin, Cytokines, Epithelial Cells, HT29 Cells, Humans, Inflammation, Interferon-gamma, Interleukin-7, Intestinal Mucosa, NF-kappa B, Phosphorylation, Signal Transduction}, issn = {2072-6643}, doi = {10.3390/nu9060578}, author = {Loganes, Claudia and Lega, Sara and Bramuzzo, Matteo and Vecchi Brumatti, Liza and Piscianz, Elisa and Valencic, Erica and Tommasini, Alberto and Marcuzzi, Annalisa} } @article {10558, title = {CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment.}, journal = {Environ Int}, volume = {105}, year = {2017}, month = {2017 08}, pages = {34-42}, abstract = {

BACKGROUND: Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes.

OBJECTIVES: We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development.

METHODS: The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n=1160, 20 and 30months of age, studied during the years 2001-2012), two subcohorts from Spain (INMA) (n=625, 14months of age, 2003-2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18months of age, 2006-2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4).

RESULTS: There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (β[95\% CI]:=2.9[1.53,4.27] for CYP3A7 rs2257401 GG+GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA+AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG+AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p<0.05) in European cohorts only.

CONCLUSIONS: Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development.

}, keywords = {Adult, Child Development, Child, Preschool, Cohort Studies, Cytochrome P-450 CYP3A, Female, Fetal Blood, Genotype, Greece, Humans, Infant, Italy, Male, Mercury, Methylmercury Compounds, Neurodevelopmental Disorders, Neuropsychological Tests, Polymorphism, Genetic, Pregnancy, Prenatal Exposure Delayed Effects, Seychelles, Spain}, issn = {1873-6750}, doi = {10.1016/j.envint.2017.04.013}, author = {Llop, Sabrina and Tran, Van and Ballester, Ferran and Barbone, Fabio and Sofianou-Katsoulis, Aikaterini and Sunyer, Jordi and Engstr{\"o}m, Karin and Alhamdow, Ayman and Love, Tanzy M and Watson, Gene E and Bustamante, Mariona and Murcia, Mario and I{\~n}iguez, Carmen and Shamlaye, Conrad F and Rosolen, Valentina and Mariuz, Marika and Horvat, Milena and Tratnik, Janja S and Mazej, Darja and van Wijngaarden, Edwin and Davidson, Philip W and Myers, Gary J and Rand, Matthew D and Broberg, Karin} } @article {8302, title = {C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation.}, journal = {Nat Commun}, volume = {7}, year = {2016}, month = {2016}, pages = {10346}, abstract = {

Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa(-/-)) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa(-/-) mice. Bone marrow (BM) chimeras between C1qa(-/-) and WT mice identify non-BM-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings support a role for locally synthesized C1q in promoting tumour growth.

}, keywords = {Animals, Apoptosis, Cell Line, Tumor, Cell Movement, Cell Proliferation, Complement Activation, Complement C1q, Complement C3, Complement C5, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasms}, issn = {2041-1723}, doi = {10.1038/ncomms10346}, author = {Bulla, Roberta and Tripodo, Claudio and Rami, Damiano and Ling, Guang Sheng and Agostinis, Chiara and Guarnotta, Carla and Zorzet, Sonia and Durigutto, Paolo and Botto, Marina and Tedesco, Francesco} } @article {8321, title = {Candidate Soluble Immune Mediators in Young Women with High-Risk Human Papillomavirus Infection: High Expression of Chemokines Promoting Angiogenesis and Cell Proliferation.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0151851}, abstract = {

BACKGROUND: The causal interpretation of cervical immune response to Human Papillomavirus (HPV) infection is complex and poorly characterized mainly due to the delicate balance that exists between viral infection, increase of inflammatory cytokines and host risk factors. This study aims to explore the significance of cervical immune mediators associated to cell survival, angiogenesis and interaction with immune response, in predicting the risk to develop HPV-related intraepithelial lesions.

METHODS: A panel of 48 cytokines and growth factors were explored in a selected cohort of 168 immunocompetent women including 88 diagnosed with low (LSIL) or high (HSIL) squamous intraepithelial lesions of the cervix and 80 with normal cervical cytology (NIL). HPV genotyping was performed by Linear Array HPV test and the soluble concentration of 48 immune molecules was analyzed using the Bio-Plex platform.

RESULTS: The prevalence of single HR-HPV infection was 30\% in NIL and 100\% in LSIL and HSIL women. The expression of 13 cytokines, including interleukins IL-6, IL-3, IL-12p40, IL-12p70, IL-16, IL-18, LIF, of chemokines CCL7 (MCP-3), CXCL9 (MIG), CXCL12 (SDF-1α) and of the tropic factors VEGF, G-CSF, M-CSF were significantly associated with the presence of infection, with levels being higher in women with precancerous lesions compared to NIL HPV negative women. Only the growth factor GM-CSF was positively associated with the cytological abnormalities.

CONCLUSIONS: The ability of HR-HPV to escape from innate immune recognition and to orchestrate the production of specific inflammatory and growth factors, involved in early inflammatory response and in the cell-proliferating phase of intraepithelial damage, was documented in women before the development of cervical lesions.

}, keywords = {Adult, Cell Survival, Cervix Uteri, Chemokines, Cohort Studies, Female, Humans, Neovascularization, Pathologic, Papillomaviridae, Papillomavirus Infections}, issn = {1932-6203}, doi = {10.1371/journal.pone.0151851}, author = {Zanotta, Nunzia and Tornesello, Maria Lina and Annunziata, Clorinda and Stellato, Giovanni and Buonaguro, Franco Maria and Comar, Manola} } @article {8512, title = {Carbamazepine-induced thrombocytopenic purpura in a child: Insights from a genomic analysis.}, journal = {Blood Cells Mol Dis}, volume = {59}, year = {2016}, month = {2016 Jul}, pages = {97-9}, issn = {1096-0961}, doi = {10.1016/j.bcmd.2016.05.001}, author = {Abate, Maria Valentina and Stocco, Gabriele and Devescovi, Raffaella and Carrozzi, Marco and Pierobon, Chiara and Valencic, Erica and Lucaf{\`o}, Marianna and Di Silvestre, Alessia and d{\textquoteright}Adamo, Pio and Tommasini, Alberto and Decorti, Giuliana and Ventura, Alessandro} } @article {8482, title = {A Case of Prenatal Neurocytoma Associated With ATR-16 Syndrome.}, journal = {J Ultrasound Med}, volume = {35}, year = {2016}, month = {2016 Jun}, pages = {1359-61}, issn = {1550-9613}, doi = {10.7863/ultra.15.07045}, author = {Quadrifoglio, Mariachiara and Faletra, Flavio and Bussani, Rossana and Pecile, Vanna and Zennaro, Floriana and Grasso, Alessandra and Zandon{\`a}, Lorenzo and Alberico, Salvatore and Stampalija, Tamara} } @article {8326, title = {CCR2 and CCR5 genes polymorphisms in women with cervical lesions from Pernambuco, Northeast Region of Brazil: a case-control study.}, journal = {Mem Inst Oswaldo Cruz}, volume = {111}, year = {2016}, month = {2016 Mar}, pages = {174-80}, abstract = {

Polymorphisms in chemokine receptors play an important role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Our study examined the association of CCR2-64I (rs1799864) andCCR5-Δ32 (rs333) polymorphisms with susceptibility to develop cervical lesion (CIN and CC) in a Brazilian population. The genotyping of 139 women with cervical lesions and 151 women without cervical lesions for the CCR2-64I and CCR5-Δ32 polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. The individuals carrying heterozygous or homozygous genotypes (GA+AA) for CCR2-64I polymorphisms seem to be at lower risk for cervical lesion [odds ratio (OR) = 0.37, p = 0.0008)]. The same was observed for the A allele (OR = 0.39, p = 0.0002), while no association was detected (p > 0.05) with CCR5-Δ32 polymorphism. Regarding the human papillomavirus (HPV) type, patients carrying the CCR2-64Ipolymorphism were protected against infection by HPV type 16 (OR = 0.35, p = 0.0184). In summary, our study showed a protective effect ofCCR2-64I rs1799864 polymorphism against the development of cervical lesions (CIN and CC) and in the susceptibility of HPV 16 infection.

}, issn = {1678-8060}, doi = {10.1590/0074-02760150367}, author = {Santos, Erinaldo Ubirajara Damasceno Dos and Lima, G{\'e}ssica Dayane Cordeiro de and Oliveira, Micheline de Lucena and Her{\'a}clio, Sandra de Andrade and Silva, Hildson Dornelas Angelo da and Crovella, Sergio and Maia, Maria de Mascena Diniz and Souza, Paulo Roberto Eleut{\'e}rio de} } @article {8502, title = {CD209 promoter polymorphisms associate with HCV infection and pegylated-interferon plus ribavirin treatment response.}, journal = {Mol Immunol}, volume = {76}, year = {2016}, month = {2016 Aug}, pages = {49-54}, abstract = {

Hepatitis C is a severe liver disease caused by hepatitis C virus that could persist in the host causing progression towards chronic disease in about 80\% of the cases. Pegylated-interferon plus ribavirin was the gold standard therapy, however treatment{\textquoteright}s response was quite variable among individuals and different host/viral factors may play a role in disease outcome. The cluster of differentiation 209 (CD209 antigen) is a component of the innate immune system able to recognize HCV and consequently activating the immune response. We enrolled 203 Italian HCV infected patients and 220 healthy controls investigating if five promoter polymorphisms within CD209 gene (encoding for CD209 antigen) correlated with HCV infection susceptibility, spontaneous viral clearance and interferon treatment response. CD209 -939G>A and -871A>G polymorphisms associated with HCV infection susceptibility, while, CD209 -871A>G and -336A>G polymorphisms associated with response to treatment. In conclusion, CD209 polymorphisms could play a role in the susceptibility to HCV infection as well as interferon treatment response in our study population from North-East of Italy.

}, issn = {1872-9142}, doi = {10.1016/j.molimm.2016.06.009}, author = {Zupin, Luisa and Polesello, Vania and Alberi, Giulia and Moratelli, Giulia and Croc{\`e}, Saveria Lory and Masutti, Flora and Pozzato, Gabriele and Crovella, Sergio and Segat, Ludovica} } @article {8324, title = {Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma.}, journal = {Lung Cancer}, volume = {94}, year = {2016}, month = {2016 Apr}, pages = {61-7}, abstract = {

OBJECTIVES: Immune mediators are likely to be relevant for the biological response to asbestos exposure. The aim of this study was to investigate the association between immune mediators involved in inflammation, cell survival and angiogenesis, and asbestos-related diseases in workers from a coastal area of North-East Italy with a high incidence of pleural malignant mesothelioma (PMM).

MATERIALS AND METHODS: A selected custom set of 12 soluble mediators was evaluated with a Luminex platform in sera, pleural fluid and mesothelioma biopsies from 123 asbestos-exposed workers (38 free from pleural-pulmonary disorders, 46 with non-malignant asbestos diseases, 39 with PMM) and in sera from 33 healthy controls from the same territorial area.

RESULTS: Increased immune mediator concentrations were observed in the sera of the asbestos-exposed workers compared to controls for human fibroblast growth factor (FGF-b), vascular endothelial growth factor (VEGF), CCL5 (RANTES), CXCL10 (IP-10), CLEC11A (SCGF-b), CCL27 (CTACK), CCL11 (EOTAXIN), IL-5 and IL-6 (p<0.001). The chemokines IP-10 and RANTES were associated with the severity of asbestos-related diseases. In the workers with PMM, the immune proteins secreted by mesothelioma biopsies showed detectable levels of RANTES, VEGF, and IP-10. In the same workers with PMM, a significant relationship between serum and pleural fluid concentrations was found for RANTES alone.

CONCLUSIONS: Occupational exposure to asbestos seems to drive the production of specific growth factors dually involved in the early inflammatory response and in pro-tumoral activity before clinical evidence of related disorders, suggesting that their over-expression may precede the onset of asbestos-related diseases. These findings suggest that some chemokines may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by non-malignant asbestos-related diseases.

}, issn = {1872-8332}, doi = {10.1016/j.lungcan.2016.01.020}, author = {Comar, M and Zanotta, N and Zanconati, F and Cortale, M and Bonotti, A and Cristaudo, A and Bovenzi, M} } @article {8296, title = {Chemokines SNPs in HIV-1+ Patients and Healthy Controls from Northeast Brazil: Association with Protection against HIV-1 Infection.}, journal = {Curr HIV Res}, volume = {14}, year = {2016}, month = {2016}, pages = {340-5}, abstract = {

BACKGROUND: HIV-1 virus is known to infect the host mainly through CD4+ T-lymphocyte cells, by interactions among the viral envelope proteins, CD4 receptor and HIV-1 coreceptors, such as chemokines receptors. Variations in the genes encoding HIV-1 coreceptors and their natural ligands have been shown to modify HIV-1 infection susceptibility and disease progression.

METHODS AND RESULTS: We analysed the distribution of SNPs in chemokines (CCL3, CCL4, CCL5, CXCL12) and chemokine receptor (CXCR6) genes, in 268 HIV-1 infected patients (HIV-1+) and 221 healthy controls from Northeast Brazil, and their possible connection with susceptibility to HIV-1 infection. The genotyping were performed through allele specific fluorogenic probes using real time PCR. We observed that the T alleles and AT genotype of rs1719153 CCL4 SNP were more frequent in healthy controls (19.8\% and 35.0\%, respectively) than in HIV-1+ patients (T allele: 14.1\%; OR=0.67; 95\%CI=0.47-0.95; p-value=0.020; and AT genotype: 24.4\%; OR=0.61; 95\%CI=0.40- 0.93; p-value=0.021) after correcting for age and sex. The rs1719134 (CCL3) and rs1719153 (CCL4) SNPs presented linkage disequilibrium (D{\textquoteright}=0.83). The AT haplotype frequency was increased in healthy controls (17.3\%) in relation to HIV-1+ patients (11.0\%; OR=0.62; 95\%CI=0.42-0.93; p-value=0.020).

CONCLUSION: Since our results revealed an increased frequency of alleles and genotypes of CCL3/CCL4 SNPs and haplotype (CCL3-CCL4) among healthy controls, we suggest that these variations might have a potential protective role against HIV-1 infection.

}, issn = {1873-4251}, author = {Celerino da Silva, Ronaldo and Victor Campos Coelho, Antonio and Cl{\'a}udio Arraes, Luiz and Andr{\'e} Cavalcanti Brand{\~a}o, Lucas and Lima Guimar{\~a}es, Rafael and Crovella, Sergio} } @article {8509, title = {A Child with Severe Developmental Delay and Growth Retardation.}, journal = {J Pediatr}, volume = {175}, year = {2016}, month = {2016 Aug}, pages = {241-241.e1}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2016.05.006}, author = {Rossetto, Elena and Matarazzo, Lorenza and Maschio, Massimo and Taddio, Andrea and Costa, Paola and Ventura, Alessandro} } @article {8336, title = {Childhood hearing surveillance activity in Italy: preliminary recommendations.}, journal = {Acta Otorhinolaryngol Ital}, volume = {36}, year = {2016}, month = {2016 Feb}, pages = {15-20}, abstract = {

Following the positive outcomes of the newborn hearing screening programmes already underway in several Italian regions, it is now necessary to address the identification of childhood hearing impairments that missed the neonatal screening programme or have delayed onset. Within the framework of the Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for early Identification, Intervention and Care of Hearing Impaired Children", a group of professionals identified three main recommendations that can be useful to improve hearing surveillance activity within the regional and state Italian Health System. The family paediatrician is recognised as having a key role in ongoing monitoring of hearing capacity and development of the growing child.

}, issn = {1827-675X}, doi = {10.14639/0392-100X-1073}, author = {Orzan, E and Ruta, F and Bolzonello, P and Marchi, R and Ceschin, F and Ciciriello, E} } @article {8332, title = {Chronic nonbacterial osteomyelitis may be associated with renal disease and bisphosphonates are a good option for the majority of patients.}, journal = {Acta Paediatr}, volume = {105}, year = {2016}, month = {2016 Jul}, pages = {e328-33}, abstract = {

AIM: The aim of this Italian study was to describe the clinical features, treatment options and outcomes of a cohort of patients with chronic nonbacterial osteomyelitis (CNO).

METHODS: This was a retrospective cohort study. Laboratory data, diagnostic imaging, histological features and clinical course are reported.

RESULTS: We enrolled 47 patients diagnosed with CNO. Bone pain was the leading symptom, and multifocal disease was present in 87\% of the patients. The majority of the bone lesions were located in the appendicular skeleton (58\%). Extraosseous manifestations were present in 34\% of the patients, and renal involvement was detected in four patients. Inflammatory indices were increased in 80\%, and bone x-rays were negative in 15\% of the patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the first therapy for all patients, achieving clinical remission in 27\%. A good response to NSAIDs was significantly associated with a better prognosis. Bisphosphonates were used in 26 patients, with remission in 73\%. Only six patients (13\%), all with spine involvement, developed sequelae.

CONCLUSION: We found a possible association between CNO and renal disease. Bisphosphonates were more likely to lead to clinical remission when NSAIDs and corticosteroids had failed. Vertebral localisation was the only risk factor for potential sequelae.

}, issn = {1651-2227}, doi = {10.1111/apa.13420}, author = {Pastore, Serena and Ferrara, Giovanna and Monasta, Lorenzo and Meini, Antonella and Cattalini, Marco and Martino, Silvana and Alessio, Maria and La Torre, Francesco and Teruzzi, Barbara and Gerloni, Valeria and Breda, Luciana and Taddio, Andrea and Lepore, Loredana} } @article {8342, title = {Circulating levels of TNF-related apoptosis inducing-ligand are decreased in patients with large adult-type granulosa cell tumors-implications for therapeutic potential.}, journal = {Tumour Biol}, year = {2016}, month = {2016 Apr 11}, abstract = {

Targeted treatments are needed for advanced adult-type granulosa cell tumors (AGCTs). We set out to assess tumor tissue and circulating levels of TNF-related apoptosis-inducing ligand (TRAIL), a promising anti-cancer cytokine, in patients affected by AGCT. We analyzed tissue expression of TRAIL in 127 AGCTs using immunohistochemistry or RT-PCR. Soluble TRAIL was measured by means of ELISA from 141 AGCT patient serum samples, as well as the conditioned media of 15 AGCT patient-derived primary cell cultures, and the KGN cell line. Tissue and serum TRAIL levels were analyzed in relationship with clinical parameters, and serum estradiol, FSH, and LH levels. We found that AGCT samples expressed TRAIL mRNA and protein at levels comparable to normal granulosa cells. AGCT cells did not release soluble TRAIL. TRAIL protein levels were decreased in tumors over 10~cm in diameter (p = 0.04). Consistently, circulating TRAIL levels correlated negatively to tumor dimension (p = 0.01). Circulating TRAIL levels negatively associated with serum estradiol levels. In multiple regression analysis, tumor size was an independent factor contributing to the decreased levels of soluble TRAIL in AGCT patients. AGCTs associate with significantly decreased tumor tissue and serum TRAIL levels in patients with a large tumor mass. These findings encourage further study of agonistic TRAIL treatments in patients with advanced or recurrent AGCT.

}, issn = {1423-0380}, doi = {10.1007/s13277-016-5042-x}, author = {F{\"a}rkkil{\"a}, Anniina and Zauli, Giorgio and Haltia, Ulla-Maija and Pihlajoki, Marjut and Unkila-Kallio, Leila and Secchiero, Paola and Heikinheimo, Markku} } @article {8503, title = {Clinical and pathogenetic features of ETV6 related thrombocytopenia with predisposition to acute lymphoblastic leukemia.}, journal = {Haematologica}, year = {2016}, month = {2016 Jun 30}, abstract = {

ETV6-related thrombocytopenia (ETV6-RT) is an autosomal dominant thrombocytopenia that has been recently identified in a few families and has been suspected to predispose to hematological malignancies. To gain further information on this disorder, we searched for ETV6 mutations in the 130 families with inherited thrombocytopenia of unknown origin from our cohort of 274 consecutive pedigrees with familial thrombocytopenia. We identified 20 ETV6-RT patients from 7 pedigrees. They have 5 different ETV6 variants, including three novel mutations affecting the highly conserved E26 transformation-specific domain. The relative frequency of ETV6-RT resulted 2.6\% in the whole case series and 4.6\% among the families with known forms of inherited thrombocytopenia. The degree of thrombocytopenia and bleeding tendency of ETV6-RT patients were mild, but 4 subjects developed B-cell acute lymphoblastic leukemia during childhood, resulting in a significantly increased incidence compared to the general population. Clinical and laboratory findings did not identify any peculiar defects that can be used to suspect this disorder by routine diagnostic workup. However, at variance with most inherited thrombocytopenias, platelet size was not enlarged. In vitro studies revealed that patients megakaryocytes have defective maturation and impaired proplatelet formation. Moreover, ETV6-RT platelets have reduced ability to spread on fibrinogen. Since also the dominant thrombocytopenias due to mutations in RUNX1 and ANKRD26 are characterized by normal platelet size and predispose to hematological malignancies, we suggest that mutation screening of ETV6, RUNX1 and ANKRD26 should be performed in all the subjects with autosomal dominant thrombocytopenia and normal platelet size.

}, issn = {1592-8721}, doi = {10.3324/haematol.2016.147496}, author = {Melazzini, Federica and Palombo, Flavia and Balduini, Alessandra and De Rocco, Daniela and Marconi, Caterina and Noris, Patrizia and Gnan, Chiara and Pippucci, Tommaso and Bozzi, Valeria and Faleschini, Michela and Barozzi, Serena and Doubek, Michael and Di Buduo, Christian A and Stano Kozubik, Katerina and Radova, Lenka and Loffredo, Giuseppe and Pospisilova, Sarka and Alfano, Caterina and Seri, Marco and Balduini, Carlo L and Pecci, Alessandro and Savoia, Anna} } @article {8331, title = {Clinical Characteristics of Patients Carrying the Q703K Variant of the NLRP3 Gene: A 10-year Multicentric National Study.}, journal = {J Rheumatol}, volume = {43}, year = {2016}, month = {2016 Jun}, pages = {1093-100}, abstract = {

OBJECTIVE: The aim of our study was to analyze the clinical and functional effect of the p.Q703K (p. Q705K, c. 2107C>A) variant of the NLRP3 gene in a population of patients screened for suspected cryopyrin-associated periodic syndrome (CAPS).

METHODS: Since 2002, 580 patients underwent molecular analysis for NLRP3. Data on clinical presentation, response to treatment, and longterm followup were collected using a uniform questionnaire. The pattern of cytokine secretion after lipopolysaccharide stimulation from isolated monocytes was analyzed in 3 patients carrying the p.Q703K variant and 1 patient with a chronic infantile neurologic, cutaneous, articular syndrome phenotype carrying both the p.M406I and p.Q703K, and compared with 7 patients with CAPS with sure pathogenic variants and 6 healthy controls.

RESULTS: The p.Q703K variant was found in 57 screened patients with an overall allelic frequency of 5\%. The frequency in normal controls was 5.5\%. Clinical data at the moment of molecular analysis and at followup were available in 36 patients. Two patients displayed additional mutations of NLRP3. The mean followup was 2.5 years. Thirteen patients (39\%) had a final diagnosis different from the original suspicion of CAPS. The remaining 21 patients displayed a mild phenotype mainly characterized by recurrent episodes of urticarial rash and arthralgia. Only 8 patients were treated with anti-interleukin (IL)-1 treatment, with a complete response in 5 patients. The pattern of secretion of IL-1β and other cytokines (IL-6 and IL-1 receptor antagonist) in patients did not display the aberrancies observed in patients with CAPS and was similar to that observed in healthy controls.

CONCLUSION: The present study confirms the weak clinical and functional effect of the p.Q703K variant.

}, issn = {0315-162X}, doi = {10.3899/jrheum.150962}, author = {Naselli, Aldo and Penco, Federica and Cantarini, Luca and Insalaco, Antonella and Alessio, Mariolina and Tommasini, Alberto and Maggio, Cristina and Obici, Laura and Gallizi, Romina and Cimmino, Marco and Signa, Sara and Lucherini, Orso Maria and Carta, Sonia and Caroli, Francesco and Martini, Alberto and Rubartelli, Anna and Ceccherini, Isabella and Gattorno, Marco} } @article {8348, title = {Clinical Spectrum of PRKAG2 Syndrome.}, journal = {Circ Arrhythm Electrophysiol}, volume = {9}, year = {2016}, month = {2016 Jan}, pages = {e003121}, keywords = {AMP-Activated Protein Kinases, DNA, Heart Conduction System, Humans, Mutation, Wolff-Parkinson-White Syndrome}, issn = {1941-3084}, doi = {10.1161/CIRCEP.115.003121}, author = {Porto, Andrea Giuseppe and Brun, Francesca and Severini, Giovanni Maria and Losurdo, Pasquale and Fabris, Enrico and Taylor, Matthew R G and Mestroni, Luisa and Sinagra, Gianfranco} } @article {8352, title = {CNV analysis in 169 patients with bladder exstrophy-epispadias complex.}, journal = {BMC Med Genet}, volume = {17}, year = {2016}, month = {2016}, pages = {35}, abstract = {

BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology.

METHODS: To detect further CNVs, array analysis was performed in 169 BEEC patients. Prior to inclusion, 22q11.21 duplications were excluded using multiplex ligation-dependent probe amplification.

RESULTS: Following the application of stringent filter criteria, seven rare CNVs were identified: n = 4, not present in 1307 in-house controls; n = 3, frequency of <0.002 in controls. These CNVs ranged from 1 to 6.08~Mb in size. To identify smaller CNVs, relaxed filter criteria used in the detection of previously reported BEEC associated chromosomal regions were applied. This resulted in the identification of six additional rare CNVs: n = 4, not present in 1307 in-house controls; n = 2, frequency <0.0008 in controls. These CNVs ranged from 0.03-0.08~Mb in size. For 10 of these 13 CNVs, confirmation and segregation analyses were performed (5 of maternal origin; 5 of paternal origin). Interestingly, one female with classic bladder extrophy carried a 1.18~Mb duplication of 22q11.1, a chromosomal region that is associated with cat eye syndrome.

CONCLUSIONS: A number of rare CNVs were identified in BEEC patients, and these represent candidates for further evaluation. Rare inherited CNVs may constitute modifiers of, or contributors to, multifactorial BEEC phenotypes.

}, issn = {1471-2350}, doi = {10.1186/s12881-016-0299-x}, author = {von Lowtzow, Catharina and Hofmann, Andrea and Zhang, Rong and Marsch, Florian and Ebert, Anne-Karoline and R{\"o}sch, Wolfgang and Stein, Raimund and Boemers, Thomas M and Hirsch, Karin and Marcelis, Carlo and Feitz, Wouter F J and Brusco, Alfredo and Migone, Nicola and Di Grazia, Massimo and Moebus, Susanne and N{\"o}then, Markus M and Reutter, Heiko and Ludwig, Michael and Draaken, Markus} } @article {8318, title = {Consensus Conference on Clinical Management of pediatric Atopic Dermatitis.}, journal = {Ital J Pediatr}, volume = {42}, year = {2016}, month = {2016}, pages = {26}, abstract = {

The Italian Consensus Conference on clinical management of atopic dermatitis in children reflects the best and most recent scientific evidence, with the aim to provide specialists with a useful tool for managing this common, but complex clinical condition. Thanks to the contribution of experts in the field and members of the Italian Society of Pediatric Allergology and Immunology (SIAIP) and the Italian Society of Pediatric Dermatology (SIDerP), this Consensus statement integrates the basic principles of the most recent guidelines for the management of atopic dermatitis to facilitate a practical approach to the disease. The therapeutical approach should be adapted to the clinical severity and requires a tailored strategy to ensure good compliance by children and their parents. In this Consensus, levels and models of intervention are also enriched by the Italian experience to facilitate a practical approach to the disease.

}, issn = {1824-7288}, doi = {10.1186/s13052-016-0229-8}, author = {Galli, Elena and Neri, Iria and Ricci, Giampaolo and Baldo, Ermanno and Barone, Maurizio and Belloni Fortina, Anna and Bernardini, Roberto and Berti, Irene and Caffarelli, Carlo and Calamelli, Elisabetta and Capra, Lucetta and Carello, Rossella and Cipriani, Francesca and Comberiati, Pasquale and Diociaiuti, Andrea and El Hachem, Maya and Fontana, Elena and Gruber, Michaela and Haddock, Ellen and Maiello, Nunzia and Meglio, Paolo and Patrizi, Annalisa and Peroni, Diego and Scarponi, Dorella and Wielander, Ingrid and Eichenfield, Lawrence F} } @article {8349, title = {The cortical response to a noxious procedure changes over time in preterm infants.}, journal = {Pain}, volume = {157}, year = {2016}, month = {2016 Sep}, pages = {1979-87}, abstract = {

The aim of the study was to investigate whether cortical response to a repeated noxious procedure may change over time in preterm infants. Possible reasons for change are: (1) advancing maturation of central nervous system; and (2) increasing experience with noxious procedures during hospital stay. Sixteen preterm infants were recruited, with a postmenstrual age (PMA) ranging between 29 and 36 weeks. Newborns were assessed during a heel-prick procedure, once a week for at least 3 consecutive times. Multichannel near-infrared spectroscopy was used to detect cortical activation, by measuring increase in cortical oxy-haemoglobin (HbO2). Parietal, temporal, and posterior frontal areas were monitored bilaterally. By regression analysis, we studied the effect of (1) increasing PMA and (2) increasing number of heel pricks, on the magnitude of cortical activation. We observed a bilateral nociceptive event-related activation of the posterior frontal cortex, mainly contralateral to the side pricked. Additionally, we found a significant positive effect of PMA, as HbO2 progressively increased in the posterior frontal cortex (P < 0.001), bilaterally, over time. Conversely, the degree of cortical activation decreased as the number of noxious events increased (P < 0.002). We conclude the following: (1) Preterm newborns showed a significant activation of the posterior frontal cortex in association with noxious stimuli; (2) Cortical activation was progressively greater with increasing PMA; (3) There was an inverse relationship between cortical activation and the number of heel pricks. We speculate that such findings may be due to both endogenous cortical maturation and experience-dependent neuroplasticity of the developing brain (eg, synaptogenesis, synaptic pruning).

}, issn = {1872-6623}, doi = {10.1097/j.pain.0000000000000605}, author = {Bembich, Stefano and Marrazzo, Francesca and Barini, Alice and Ravalico, Paola and Cont, Gabriele and Demarini, Sergio} } @article {8505, title = {Cross-sectional study of coeliac autoimmunity in a population of Vietnamese children.}, journal = {BMJ Open}, volume = {6}, year = {2016}, month = {2016}, pages = {e011173}, abstract = {

OBJECTIVE: The prevalence of coeliac disease (CD) in Vietnam is unknown. To fill this void, we assessed the prevalence of serological markers of CD autoimmunity in a population of children in Hanoi.

SETTING: The outpatient blood drawing laboratory of the largest paediatric hospital in North Vietnam was used for the study, which was part of an international project of collaboration between Italy and Vietnam.

PARTICIPANTS: Children having blood drawn for any reason were included. Exclusion criteria were age younger than 2 years, acquired or congenital immune deficiency and inadequate sample. A total of 1961 children (96\%) were enrolled (838 females, 1123 males, median age 5.3 years).

OUTCOMES: Primary outcome was the prevalence of positive autoimmunity to both IgA antitransglutaminase antibodies (anti-tTG) assessed with an ELISA test and antiendomysial antibodies (EMA). Secondary outcome was the prevalence of CD predisposing human leucocyte antigens (HLA) (HLA DQ2/8) in the positive children and in a random group of samples negative for IgA anti-tTG.

RESULTS: The IgA anti-tTG test was positive in 21/1961 (1\%; 95\% CI 0.61\% to 1.53\%); however, EMA antibodies were negative in all. HLA DQ2/8 was present in 7/21 (33\%; 95\% CI 14.5\% to 56.9\%) of the anti-tTG-positive children and in 72/275 (26\%; 95\% CI 21\% to 32\%) of those who were negative.

CONCLUSIONS: Coeliac autoimmunity is rare in Vietnam, although prevalence of HLA DQ2/8 is similar to that of other countries. We hypothesise that the scarce exposure to gluten could be responsible for these findings.

}, issn = {2044-6055}, doi = {10.1136/bmjopen-2016-011173}, author = {Zanella, Sara and De Leo, Luigina and Nguyen-Ngoc-Quynh, Le and Nguyen-Duy, Bo and Not, Tarcisio and Tran-Thi-Chi, Mai and Phung-Duc, Son and Le-Thanh, Hai and Malaventura, Cristina and Vatta, Serena and Ziberna, Fabiana and Mazzocco, Martina and Volpato, Stefano and Phung-Tuyet, Lan and Le-Thi-Minh, Huong and Borgna-Pignatti, Caterina} } @article {7693, title = {Current concepts in management of pain in children in the emergency department.}, journal = {Lancet}, volume = {387}, year = {2016}, month = {2016 Jan 2}, pages = {83-92}, abstract = {

Pain is common in children presenting to emergency departments with episodic illnesses, acute injuries, and exacerbation of chronic disorders. We review recognition and assessment of pain in infants and children and discuss the manifestations of pain in children with chronic illness, recurrent pain syndromes, and cognitive impairment, including the difficulties of pain management in these patients. Non-pharmacological interventions, as adjuncts to pharmacological management for acute anxiety and pain, are described by age and development. We discuss the pharmacological management of acute pain and anxiety, reviewing invasive and non-invasive routes of administration, pharmacology, and adverse effects.

}, keywords = {Acute Pain, Analgesics, Opioid, Anesthetics, Local, Anti-Inflammatory Agents, Non-Steroidal, Anxiety, Child, Emergency Medicine, Emergency Service, Hospital, Humans, Pain Management, Pediatrics, Stress, Psychological}, issn = {1474-547X}, doi = {10.1016/S0140-6736(14)61686-X}, author = {Krauss, Baruch S and Calligaris, Lorenzo and Green, Steven M and Barbi, Egidio} } @article {7757, title = {A case of Rubinstein-Taybi syndrome associated with growth hormone deficiency in childhood.}, journal = {Clin Endocrinol (Oxf)}, volume = {83}, year = {2015}, month = {2015 Sep}, pages = {437-9}, issn = {1365-2265}, doi = {10.1111/cen.12748}, author = {Tornese, Gianluca and Marzuillo, Pierluigi and Pellegrin, Maria Chiara and Germani, Claudio and Faleschini, Elena and Zennaro, Floriana and Grandone, Anna and Miraglia Del Giudice, Emanuele and Perrone, Laura and Ventura, Alessandro} } @article {3618, title = {Central venous access devices in pediatric malignancies: a position paper of Italian Association of Pediatric Hematology and Oncology.}, journal = {J Vasc Access}, volume = {16}, year = {2015}, month = {2015 Mar-Apr}, pages = {130-6}, abstract = {

INTRODUCTION: Treatment of pediatric malignancies is becoming progressively more complex, implying the adoption of multimodal therapies. A reliable, long-lasting venous access represents one of the critical requirements for the success of those treatments. Recent technical innovations-such as minimally invasive procedures for placement, new devices and novel materials-have rapidly spread for clinical use in adult patients, but are still not consistently used in the pediatric population.

METHODS: The Supportive Therapy Working Group of Italian Association of Hematology and Oncology (AIEOP) reviewed medical literature focusing on new aspects of central venous access devices (VADs) in pediatric patients affected by oncohematological diseases.

RESULTS: Appropriate recommendations for clinical use in these patients have been discussed and formulated.

CONCLUSIONS: The importance of the correct choice, management and use of VADs in pediatric oncohematological patients is a necessary prerequisite for an adequate standard of care, also considering the increased chances of cure and the longer life expectancy of those patients with modern therapies.

}, issn = {1724-6032}, doi = {10.5301/jva.5000314}, author = {Crocoli, Alessandro and Tornesello, Assunta and Pittiruti, Mauro and Barone, Angelica and Muggeo, Paola and Inserra, Alessandro and Molinari, Angelo Claudio and Grillenzoni, Valeria and Durante, Viviana and Cicalese, Maria Pia and Zanazzo, Giulio Andrea and Cesaro, Simone} } @article {3604, title = {Cerebral oxygenation with different nasal continuous positive airway pressure levels in preterm infants.}, journal = {Arch Dis Child Fetal Neonatal Ed}, volume = {100}, year = {2015}, month = {2015 Mar}, pages = {F165-8}, abstract = {

OBJECTIVES: This study evaluates the effect of varying nasal continuous positive airway pressure (NCPAP) level on cerebral blood flow (CBF) and oxygenation in preterm infants.

METHODS: Oxy-haemoglobin (HbO2) and total haemoglobin (HbTot), as CBF estimates, and the ratio between HbO2 and HbTot (HbO2/HbTot), as cerebral oxygenation estimate, were assessed by near-infrared spectroscopy in 26 stable preterm newborns at a postmenstrual age between 26 and 33 weeks. Baseline HbO2, HbTot and HbO2/HbTot values were initially collected with NCPAP at 5 cm H2O and then compared with values obtained with NCPAP levels at both 3 and 8 cm H2O.

RESULTS: Compared with 5 cm H2O, cerebral HbO2, HbTot and HbO2/HbTot remained unchanged both after increasing (to 8 cm H2O) and decreasing (to 3 cm H2O) the NCPAP level. This result was observed both in regional areas (24 sites) and in the overall monitored area (frontal and parietal cortex). Compared with 8 cm H2O, peripheral oxygen saturation significantly decreased at 3 cm H2O (p=0.021). Heart rate did not change.

CONCLUSIONS: No differences in CBF and cerebral oxygenation were observed with NCPAP levels in the range 3-8 cm H2O despite a decrease in peripheral oxygenation with 3 cm H2O.

}, keywords = {Cerebrovascular Circulation, Continuous Positive Airway Pressure, Female, Hemoglobins, Humans, Infant, Newborn, Infant, Premature, Intensive Care, Neonatal, Male, Nasal Cavity, Oxygen, Oxygen Consumption, Oxyhemoglobins, Spectroscopy, Near-Infrared}, issn = {1468-2052}, doi = {10.1136/archdischild-2014-306356}, author = {Bembich, Stefano and Travan, Laura and Cont, Gabriele and Bua, Jenny and Strajn, Tamara and Demarini, Sergio} } @article {7783, title = {Characterization of 14 novel deletions underlying Rubinstein-Taybi syndrome: an update of the CREBBP deletion repertoire.}, journal = {Hum Genet}, volume = {134}, year = {2015}, month = {2015 Jun}, pages = {613-26}, abstract = {

Rubinstein-Taybi syndrome (RSTS) is a rare, clinically heterogeneous disorder characterized by cognitive impairment and several multiple congenital anomalies. The syndrome is caused by almost private point mutations in the CREBBP (~55\% of cases) and EP300 (~8\%) genes. The CREBBP mutational spectrum is variegated and characterized by point mutations (30-50 \%) and deletions (~10\%). The latter are diverse in size and genomic position and remove either the whole CREBBP gene and its flanking regions or only an intragenic portion. Here, we report 14 novel CREBBP deletions ranging from single exons to the whole gene and flanking regions which were identified by applying complementary cytomolecular techniques: fluorescence in situ hybridization, multiplex ligation-dependent probe amplification and array comparative genome hybridization, to a large cohort of RSTS patients. Deletions involving CREBBP account for 23\% of our detected CREBBP mutations, making an important contribution to the mutational spectrum. Genotype-phenotype correlations revealed that patients with CREBBP deletions extending beyond this gene did not always have a more severe phenotype than patients harboring CREBBP point mutations, suggesting that neighboring genes play only a limited role in the etiopathogenesis of CREBBP-centerd contiguous gene syndrome. Accordingly, the extent of the deletion is not predictive of the severity of the clinical phenotype.

}, keywords = {Adolescent, Adult, Base Sequence, Child, Child, Preschool, Cohort Studies, CREB-Binding Protein, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Point Mutation, Rubinstein-Taybi Syndrome, Sequence Deletion}, issn = {1432-1203}, doi = {10.1007/s00439-015-1542-9}, author = {Rusconi, Daniela and Negri, Gloria and Colapietro, Patrizia and Picinelli, Chiara and Milani, Donatella and Spena, Silvia and Magnani, Cinzia and Silengo, Margherita Cirillo and Sorasio, Lorena and Curtisova, Vaclava and Cavaliere, Maria Luigia and Prontera, Paolo and Stangoni, Gabriela and Ferrero, Giovanni Battista and Biamino, Elisa and Fischetto, Rita and Piccione, Maria and Gasparini, Paolo and Salviati, Leonardo and Selicorni, Angelo and Finelli, Palma and Larizza, Lidia and Gervasini, Cristina} } @article {8086, title = {[Clinical and molecular study in a child with X-linked hypohidrotic ectodermal dysplasia].}, journal = {Arch Argent Pediatr}, volume = {113}, year = {2015}, month = {2015 Dec 1}, pages = {e341-4}, abstract = {

Ectodermal dysplasia encompasses more than 200 clinically distinct entities, which affect at least two structures derived from the ectoderm, including the skin, hair, nails, teeth, sweat glands, and sebaceous glands. X-linked hypohidrotic ectodermal dysplasia is the most common type and is caused by mutation of the EDA gene that encodes Ectodysplasin-A. It occurs in less than 1 in 100 000 individuals and is clinically characterized by hypodontia, hypohidrosis, hypotrichosis, and eye dis orders. We present a child evaluated in a multidisciplinary manner with clinical and molecular diagnosis of X-linked hypohidrotic ectodermal dysplasia with type missense mutation c.1133C> T; p.T378M in EDA gene.

}, issn = {1668-3501}, author = {Callea, Michele and Yavuz, Izzet and Clarich, Gabriella and Cammarata-Scalisi, Francisco} } @article {7698, title = {Clinical aspects of Fanconi anemia individuals with the same mutation of FANCF identified by next generation sequencing.}, journal = {Birth Defects Res A Clin Mol Teratol}, volume = {103}, year = {2015}, month = {2015 Dec}, pages = {1003-1010}, abstract = {

BACKGROUND: Fanconi anemia (FA) is a rare genetic disease characterized by congenital malformations, aplastic anemia and increased risk of developing malignancies. FA is genetically heterogeneous as it is caused by at least 17 different genes. Among these, FANCA, FANCC, and FANCG account for approximately 85\% of the patients whereas the remaining genes are mutated in only a small percentage of cases. For this reason, the molecular diagnostic process is complex and not always extended to all the FA genes, preventing the characterization of individuals belonging to rare groups.

METHODS: The FA genes were analyzed using a next generation sequencing approach in two unrelated families.

RESULTS: The analysis identified the same, c.484_485del, homozygous mutation of FANCF in both families. A careful examination of three electively aborted fetuses in one family and one affected girl in the other indicated an association of the FANCF loss-of-function mutation with a severe phenotype characterized by multiple malformations.

CONCLUSION: The systematic use of next generation sequencing will allow the recognition of individuals from rare complementation groups, a better definition of their clinical phenotypes, and consequently, an appropriate genetic counseling. Birth Defects Research (Part A) 103:1003-1010, 2015. {\textcopyright} 2015 Wiley Periodicals, Inc.

}, issn = {1542-0760}, doi = {10.1002/bdra.23388}, author = {Nicchia, Elena and Benedicenti, Francesco and Rocco, Daniela De and Greco, Chiara and Bottega, Roberta and Inzana, Francesca and Faleschini, Michela and Bonin, Serena and Cappelli, Enrico and Mogni, Massimo and Stanzial, Franco and Svahn, Johanna and Dufour, Carlo and Savoia, Anna} } @article {8079, title = {Coeliac disease in the ERA of the new ESPGHAN and BSPGHAN guidelines: a prospective cohort study.}, journal = {Arch Dis Child}, year = {2015}, month = {2015 Nov 17}, abstract = {

OBJECTIVE: To evaluate the consequences of the last European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) guidelines for the diagnosis of coeliac disease (CD) by means of a prospective study.

DESIGN: Prospective cohort study.

SETTING: Institute for Maternal and Child Health IRCCS Burlo Garofolo (Trieste, Italy).

PATIENTS: Children diagnosed with CD without a duodenal biopsy (group 1), following the last ESPGHAN and BSPGHAN guidelines, and children diagnosed with a duodenal biopsy, matched for sex, age and year of diagnosis (group 2), were prospectively enrolled over a 3-year period. All patients were put on a gluten-free diet (GFD) and were followed up for clinical conditions and laboratory testing at 6 months every year since diagnosis (median follow up: 1.9 years).

OUTCOME MEASURES: Resolution of symptoms, body mass index, laboratory testing (haemoglobin, anti-transglutaminase IgA), adherence to a GFD, quality of life, and supplementary post-diagnosis medical consultations.

RESULTS: 51 out of 468 (11\%) patients were diagnosed without a duodenal biopsy (group 1; median age 2.1 years) and matched to 92 patients diagnosed with a biopsy (group 2; median age 2.4 years). At the end of follow-up the two groups were statistically comparable in terms of clinical and nutritional status, anti-transglutaminase IgA antibody titres, quality of life, adherence to a GFD, and number of supplementary medical consultations.

CONCLUSIONS: On the basis of this prospective study, diagnosis of CD can be reliably performed without a duodenal biopsy in approximately 11\% of cases. At least during a medium-term follow-up, this approach has no negative consequences relating to clinical remission, adherence to diet, and quality of life of children with CD.

}, issn = {1468-2044}, doi = {10.1136/archdischild-2015-309259}, author = {Benelli, Elisa and Carrato, Valentina and Martelossi, Stefano and Ronfani, Luca and Not, Tarcisio and Ventura, Alessandro} } @article {7685, title = {The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis.}, journal = {Mediators Inflamm}, volume = {2015}, year = {2015}, month = {2015}, pages = {918089}, abstract = {

To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory "marker" VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis.

}, issn = {1466-1861}, doi = {10.1155/2015/918089}, author = {Agostinis, C and Zorzet, S and De Leo, R and Zauli, G and De Seta, F and Bulla, R} } @article {8062, title = {Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma.}, journal = {Lung Cancer}, year = {2015}, month = {2015 Sep 25}, abstract = {

OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as {\textquoteright}soluble mesothelin-related proteins{\textquoteright} (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage.

MATERIALS AND METHODS: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the {\textquoteright}3-biomarker classifier{\textquoteright} was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated.

RESULTS AND CONCLUSION: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.

}, issn = {1872-8332}, doi = {10.1016/j.lungcan.2015.09.021}, author = {Santarelli, Lory and Staffolani, Sara and Strafella, Elisabetta and Nocchi, Linda and Manzella, Nicola and Grossi, Paola and Bracci, Massimo and Pignotti, Elettra and Alleva, Renata and Borghi, Battista and Pompili, Cecilia and Sabbatini, Armando and Rubini, Corrado and Zuccatosta, Lina and Bichisecchi, Elisabetta and Valentino, Matteo and Horwood, Keith and Comar, Manola and Bovenzi, Massimo and Dong, Lan-Feng and Neuzil, Jiri and Amati, Monica and Tomasetti, Marco} } @article {8061, title = {Comment on: {\textquoteright}Anthropometric parameters in relation to glycaemic status and lipid profile in a multi-ethnic sample in Italy{\textquoteright} by Gualdi-Russo et al.}, journal = {Public Health Nutr}, year = {2015}, month = {2015 Oct 28}, pages = {1}, issn = {1475-2727}, doi = {10.1017/S1368980015003122}, author = {Monasta, Lorenzo and Knowles, Alessandra} } @article {7746, title = {Comment to Santos et al., "hyper-IgD and periodic fever syndrome: a new MVK mutation (p.R277G) associated with a severe phenotype".}, journal = {Gene}, volume = {559}, year = {2015}, month = {2015 Mar 15}, pages = {99-101}, abstract = {

We performed molecular modeling analysis onto a novel mutation in the gene MVK, described by Santos et al., found to be causative of a severe form of Hyper-IgD/Mevalonate Kinase Deficiency. The mutation p.R277G, in our analysis, lowers the binding affinity for some enzyme{\textquoteright}s substrates. Interestingly, we found that p.R277G mutation inhibits binding of Isopentenyl Pyrophosphate (IPP) (binding free energy=0 kcal/mol), one of isoprenoids responsible for feedback-inhibition of MVK. IPP is known to be an activator of a specific class of T-cells and we can hypothesize that increased levels of this metabolite generate an aberrant immune system response. Indeed other experiments are needed to verify this hypothesis; however, this work demonstrates usefulness of molecular modeling in generating novel pathogenic hypothesis.

}, keywords = {Fever, Humans, Immunoglobulin D, Male, Mutation, Missense, Phosphotransferases (Alcohol Group Acceptor)}, issn = {1879-0038}, doi = {10.1016/j.gene.2015.01.029}, author = {Santos, Ruda de Luna Almeida and Crovella, Sergio and Celsi, Fulvio} } @article {3598, title = {Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation.}, journal = {APMIS}, volume = {123}, year = {2015}, month = {2015 Jan}, pages = {77-80}, abstract = {

Varicella zoster virus (VZV), a threat for hematopoietic stem cell transplantation (HSCT) recipients, is still one of the most common viral pathogens that affect these patients with a reported incidence ranging between 17\% and 50\% in the post transplantation period. Valganciclovir (V-GCV), a valine ester pro-drug of GCV orally administrable, has recently shown great activity against CMV infections, but there are no reports of its clinical efficacy against VZV. We here report a case history of a patient with positive serologic test for VZV, who underwent allogeneic HSCT and developed an atypical varicella-like illness. First-line therapy with foscarnet had to be discontinued due rapid development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and therefore was switched to V-GCV. The renal impairment and skin lesions of the patient fully recovered after few days of therapy, even though the patient had complete lymphocyte depletion. This is the first case of a patient with chickenpox-like illness treated successfully with V-GCV.

}, keywords = {Acute Kidney Injury, Adolescent, Bone Marrow Transplantation, Fatal Outcome, Female, Ganciclovir, Herpes Zoster, Herpesvirus 3, Human, Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Viral Load}, issn = {1600-0463}, doi = {10.1111/apm.12303}, author = {Maximova, Natalia and Antonio, Pizzol and Marilena, Granzotto and Rovere, Francesca and Tamaro, Paolo} } @article {7753, title = {Comprehensive analysis of polymorphisms in the HLA-G 5{\textquoteright} upstream regulatory and 3{\textquoteright} untranslated regions in Brazilian patients with systemic lupus erythematosus.}, journal = {Tissue Antigens}, volume = {85}, year = {2015}, month = {2015 Jun}, pages = {458-65}, abstract = {

This study aims to comprehensively analyze human leucocyte antigen (HLA)-G polymorphisms association with susceptibility to systemic lupus erythematosus (SLE) development and clinical manifestations. The HLA-G 5{\textquoteright} upstream regulatory region (URR), 3{\textquoteright} untranslated region (UTR) and a cytosine deletion at exon 3 (ΔC, HLA-G*0105N allele) were analyzed in 114 SLE patients and 128 healthy controls from North East Brazil. The +3003T>C (rs1707) C allele and the HG010101c extended HLA-G allele were significantly more frequent in SLE patients than healthy controls (+3003C allele frequency: 12\% in SLE patients vs 6\% in controls; odds ratio (OR), 2.10, 95\% confidence interval (CI), 1.06-4.28, P = 0.026; HG010101c frequency: 11.8\% in SLE patients and 6.3\% in controls; OR, 2.14, 95\% CI, 1.01-4.51, P = 0.046) and were associated with susceptibility for disease development. Other polymorphisms were associated with different clinical manifestations. Although HLA-G role in SLE disease is far from being elucidated yet, our association study results along with a systematic review and meta-analysis suggest that HLA-G might be able to slightly modulate the complex SLE phenotype (pooled OR, 1.14, 95\% CI, 1.02-1.27, P = 0.021).

}, issn = {1399-0039}, doi = {10.1111/tan.12545}, author = {Catamo, E and Addobbati, C and Segat, L and Sotero Fragoso, T and Tavares Dantas, A and de Ata{\'\i}de Mariz, H and Ferreira da Rocha Junior, L and Branco PintoDuarte, A L and Coelho, A V C and de Moura, R R and Polesello, V and Crovella, S and Sandrin Garcia, P} } @article {3584, title = {Connexin 26 variant carriers have a better gastrointestinal health: is this the heterozygote advantage?}, journal = {Eur J Hum Genet}, volume = {23}, year = {2015}, month = {2015 May}, pages = {563-4}, issn = {1476-5438}, doi = {10.1038/ejhg.2014.151}, author = {Vuckovic, Dragana and Dallapiccola, Bruno and Franz{\`e}, Annamaria and Mauri, Lucia and Perrone, Maria Dolores and Gasparini, Paolo} } @article {3561, title = {C1q as a unique player in angiogenesis with therapeutic implication in wound healing.}, journal = {Proc Natl Acad Sci U S A}, volume = {111}, year = {2014}, month = {2014 Mar 18}, pages = {4209-14}, abstract = {

We have previously shown that C1q is expressed on endothelial cells (ECs) of newly formed decidual tissue. Here we demonstrate that C1q is deposited in wound-healing skin in the absence of C4 and C3 and that C1q mRNA is locally expressed as revealed by real-time PCR and in situ hybridization. C1q was found to induce permeability of the EC monolayer, to stimulate EC proliferation and migration, and to promote tube formation and sprouting of new vessels in a rat aortic ring assay. Using a murine model of wound healing we observed that vessel formation was defective in C1qa(-/-) mice and was restored to normal after local application of C1q. The mean vessel density of wound-healing tissue and the healed wound area were significantly increased in C1q-treated rats. On the basis of these results we suggest that C1q may represent a valuable therapeutic agent that can be used to treat chronic ulcers or other pathological conditions in which angiogenesis is impaired, such as myocardial ischemia.

}, keywords = {Animals, Cell Proliferation, Complement C1q, DNA Primers, Endothelial Cells, Enzyme-Linked Immunosorbent Assay, Human Umbilical Vein Endothelial Cells, Humans, Immunoblotting, Immunohistochemistry, In Situ Hybridization, Mice, Mice, Inbred C57BL, Mice, Knockout, Neovascularization, Physiologic, Rats, Rats, Wistar, Real-Time Polymerase Chain Reaction, Wound Healing}, issn = {1091-6490}, doi = {10.1073/pnas.1311968111}, author = {Bossi, Fleur and Tripodo, Claudio and Rizzi, Lucia and Bulla, Roberta and Agostinis, Chiara and Guarnotta, Carla and Munaut, Carine and Baldassarre, Gustavo and Papa, Giovanni and Zorzet, Sonia and Ghebrehiwet, Berhane and Ling, Guang Sheng and Botto, Marina and Tedesco, Francesco} } @article {3496, title = {Can body mass index accurately predict adiposity in newborns?}, journal = {Arch Dis Child Fetal Neonatal Ed}, volume = {99}, year = {2014}, month = {2014 May}, pages = {F238-9}, abstract = {

Body mass index (BMI) is correlated with body fatness and risk of related diseases in children and adults. Proportionality indexes such as BMI and ponderal index (PI) have been suggested as complementary measures in neonatal growth assessment. Yet, they are still not used in neonates and their correlation with fatness is unknown. The aim of the study was to test the hypothesis that BMI z-score would predict neonatal adiposity. Body composition measurements (ie, fat mass, fat-free mass) by air displacement plethysmography (PEA POD, LMI, Concord-USA), weight and length were obtained in 200 infants >=36 weeks{\textquoteright} gestational age (GA) at birth. Linear regression analysis showed a direct association between BMI z-score and \%fat mass (r(2)=0.43, p<0.0001). This association was confirmed independently from sex, GA and maternal prepregnancy BMI. BMI z-score predicted adiposity better than PI. However, both BMI z-score and PI were poor predictors of adiposity at birth.

}, keywords = {Adiposity, Adult, Anthropometry, Body Composition, Body Mass Index, Cross-Sectional Studies, Female, Gestational Age, Humans, Infant, Newborn, Male, Mothers, Plethysmography, Predictive Value of Tests, Regression Analysis, Reproducibility of Results, Sex Factors}, issn = {1468-2052}, doi = {10.1136/archdischild-2013-305386}, author = {De Cunto, Angela and Paviotti, Giulia and Ronfani, Luca and Travan, Laura and Bua, Jenny and Cont, Gabriele and Demarini, Sergio} } @article {3597, title = {Can Lactobacillus fermentum LF10 and Lactobacillus acidophilus LA02 in a slow-release vaginal product be useful for prevention of recurrent vulvovaginal candidiasis?: A clinical study.}, journal = {J Clin Gastroenterol}, volume = {48 Suppl 1}, year = {2014}, month = {2014 Nov-Dec}, pages = {S102-5}, abstract = {

OBJECTIVE: To assess the effectiveness of the association of 2 specific strains, Lactobacillus fermentum LF10 (DSM 19187) and Lactobacillus acidophilus LA02 (DSM 21717), specifically formulated in slow-release effervescent tablets, in patients with recurrent vulvovaginal candidiasis.

STUDY DESIGN: The study was a clinical trial of 58 women diagnosed with recurrent VVC (>=4 culture-confirmed episodes in a 12-mo period). All patients were given 200 mg of fluconazole orally as an induction dose for 3 alternate days during the first treatment week. Afterward, the patients were given a new product formulated in slow-release vaginal tablets containing at least 0.4 billion live cells of each of lactobacillus L. fermentum LF10 and L. acidophilus LA02 (first phase of the prophylactic period), on alternate days for 10 consecutive nights. Patients who were still free of symptoms were given 1 vaginal tablet every week for the next 10 weeks (second phase of the prophylactic period). Patients asymptomatic after the total duration of the observation phase (7 mo) were considered as responders.

RESULTS: During the second 10-week prophylactic phase, 49 of 57 (86.0\%) patients remained free of clinical recurrence, whereas symptomatic VVC occurred in 8 patients (14.0\%). During the 7-month follow-up, 42 patients of 49 (85.7\%) were symptom free at the end of the protocol, whereas clinical recurrences occurred in 7 women (14.3\%). Overall, 42 of 58 women enrolled in the study (72.4\%) experienced no clinical recurrence throughout the 7-month observation phase (responders).

CONCLUSIONS: This study strengthens the evidence supporting the use of specific lactobacilli with well-demonstrated activities associated with the creation and maintenance of a vaginal biofilm that hinders the persistence of an infection caused by Candida.

}, keywords = {Administration, Intravaginal, Adult, Biofilms, Candidiasis, Vulvovaginal, Delayed-Action Preparations, Female, Humans, Italy, Lactobacillus acidophilus, Lactobacillus fermentum, Middle Aged, Probiotics, Recurrence, Tablets, Time Factors, Treatment Outcome, Vagina, Vulva, Young Adult}, issn = {1539-2031}, doi = {10.1097/MCG.0000000000000225}, author = {Murina, Filippo and Graziottin, Alessandra and Vicariotto, Franco and De Seta, Francesco} } @article {3601, title = {Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study.}, journal = {Blood}, volume = {123}, year = {2014}, month = {2014 Mar 6}, pages = {1470-8}, abstract = {

The outcome of high-risk (HR) acute lymphoblastic leukemia patients enrolled in the AIEOP-BFM ALL 2000 study in Italy is described. HR criteria were minimal residual disease (MRD) levels >=10(-3) at day 78 (MRD-HR), no complete remission (CR) at day 33, t(4;11) translocation, and prednisone poor response (PPR). Treatment (2 years) included protocol I, 3 polychemotherapy blocks, delayed intensification (protocol IIx2 or IIIx3), cranial radiotherapy, and maintenance. A total of 312 HR patients had a 5-year event-free survival (EFS) of 58.9\% (standard error [SE] = 2.8) and an overall survival of 68.9\% (SE = 2.6). In hierarchical order, EFS was 45.9\% (4.4) in 132 MRD-HR patients, 41.2\% (11.9) in 17 patients with no CR at day 33, 36.4\% (14.5) in 11 patients with t(4;11), and 74.0\% (3.6) in 152 HR patients only for PPR. No statistically significant difference was found for disease-free survival in patients with very HR features [MRD-HR, no CR at day 33, t(4;11) translocation], given hematopoietic stem cell transplantation (HSCT) (n = 66) or chemotherapy only (n = 88), after adjusting for waiting time to HSCT (5.7 months). Patients at HR only for PPR have a favorable outcome. MRD-HR is associated with poor outcome despite intensive treatment and/or HSCT and may qualify for innovative therapies. The study was registered at www.clinicaltrials.gov as $\#$NCT00613457.

}, keywords = {Adolescent, Antineoplastic Combined Chemotherapy Protocols, Child, Child, Preschool, Combined Modality Therapy, Female, Hematopoietic Stem Cell Transplantation, Humans, Infant, Male, Neoplasm, Residual, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Radiotherapy, Remission Induction, Treatment Outcome}, issn = {1528-0020}, doi = {10.1182/blood-2013-10-532598}, author = {Conter, Valentino and Valsecchi, Maria Grazia and Parasole, Rosanna and Putti, Maria Caterina and Locatelli, Franco and Barisone, Elena and Lo Nigro, Luca and Santoro, Nicola and Aric{\`o}, Maurizio and Ziino, Ottavio and Pession, Andrea and Testi, Anna Maria and Micalizzi, Concetta and Casale, Fiorina and Zecca, Marco and Casazza, Gabriella and Tamaro, Paolo and La Barba, Gaetano and Notarangelo, Lucia Dora and Silvestri, Daniela and Colombini, Antonella and Rizzari, Carmelo and Biondi, Andrea and Masera, Giuseppe and Basso, Giuseppe} } @article {3484, title = {Class IV laser therapy as treatment for chemotherapy-induced oral mucositis in onco-haematological paediatric patients: a prospective study.}, journal = {Int J Paediatr Dent}, volume = {24}, year = {2014}, month = {2014 Nov}, pages = {441-9}, abstract = {

BACKGROUND: Oral mucositis is a debilitating side effect of chemotherapy. Laser therapy has recently demonstrated efficacy in the management of oral mucositis (OM).

AIM: This prospective study was conducted to evaluate the efficacy of class IV laser therapy in patients affected by OM.

DESIGN: Eighteen onco-haematological paediatric patients receiving chemotherapy and/or haematopoietic stem cell transplantation, prior to total body irradiation, affected by OM, were enrolled in this study. Patients were treated with class IV laser therapy for four consecutive days; the assessment of OM was performed through WHO Oral Mucositis Grading Objective Scale, and pain was evaluated through visual analogue scale. Patients completed a validated questionnaire, and photographs of lesions were taken during each session. Patients were re-evaluated 11 days after the first day of laser therapy.

RESULTS: All patients demonstrated improvement in pain sensation, and all mucositis was fully resolved at the 11-day follow-up visit, with no apparent side effects. Laser therapy was well tolerated with remarkable reduction in pain associated with oral mucositis after 1-2 days of laser therapy.

CONCLUSIONS: Given class IV laser therapy appears to be safe, non-invasive, and potentially effective, prospective, randomized, controlled trials are necessary to further assess efficacy and to determine optimal treatment parameters.

}, issn = {1365-263X}, doi = {10.1111/ipd.12090}, author = {Chermetz, Maddalena and Gobbo, Margherita and Ronfani, Luca and Ottaviani, Giulia and Zanazzo, Giulio A and Verzegnassi, Federico and Treister, Nathaniel S and Di Lenarda, Roberto and Biasotto, Matteo and Zacchigna, Serena} } @article {3602, title = {Clinical features and follow-up in patients with 22q11.2 deletion syndrome.}, journal = {J Pediatr}, volume = {164}, year = {2014}, month = {2014 Jun}, pages = {1475-80.e2}, abstract = {

OBJECTIVE: To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease.

STUDY DESIGN: A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis.

RESULTS: The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71\% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations (P = .015) and speech disorders (P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis.

CONCLUSIONS: Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management.

}, keywords = {Abnormalities, Multiple, Adolescent, Adult, Age Factors, Child, Child, Preschool, Chromosomes, Human, Pair 22, Delayed Diagnosis, Developmental Disabilities, DiGeorge Syndrome, Disease Progression, Early Diagnosis, Female, Follow-Up Studies, Genetic Testing, Humans, Infant, Infant, Newborn, Male, Monitoring, Physiologic, Prospective Studies, Retrospective Studies, Risk Assessment, Severity of Illness Index, Sex Factors, Time Factors, Young Adult}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2014.01.056}, author = {Cancrini, Caterina and Puliafito, Pamela and Digilio, Maria Cristina and Soresina, Annarosa and Martino, Silvana and Rondelli, Roberto and Consolini, Rita and Ruga, Ezia Maria and Cardinale, Fabio and Finocchi, Andrea and Romiti, Maria Luisa and Martire, Baldassarre and Bacchetta, Rosa and Albano, Veronica and Carotti, Adriano and Specchia, Fernando and Montin, Davide and Cirillo, Emilia and Cocchi, Guido and Trizzino, Antonino and Bossi, Grazia and Milanesi, Ornella and Azzari, Chiara and Corsello, Giovanni and Pignata, Claudio and Aiuti, Alessandro and Pietrogrande, Maria Cristina and Marino, Bruno and Ugazio, Alberto Giovanni and Plebani, Alessandro and Rossi, Paolo} } @article {3571, title = {Clinical significance of hyper-IgA in a paediatric laboratory series.}, journal = {Arch Dis Child}, volume = {99}, year = {2014}, month = {2014 Dec}, pages = {1114-6}, abstract = {

The causes of extremely elevated IgA, whether isolated or associated with an increase in other classes of immunoglobulin, are poorly defined in paediatrics. We reviewed the diagnostic significance of very high IgA levels (greater than 3 SD above the mean for age) in a cohort of patients referred to a tertiary care children{\textquoteright}s hospital. Hyper-IgA was found in 91 of 6364 subjects (1.4\%) and in 68 cases was not associated with an increased IgG and/or IgM level. Most subjects with hyper-IgA (73.5\%) had a severe immune defect, a chronic rheumatic disease or inflammatory bowel disease, while these conditions were very rare in a control group with normal IgA values (8\%). Although our results may in part reflect the experience of a tertiary care centre, we suggest that hyper-IgA in children should always arouse suspicion of a serious disease.

}, keywords = {Adolescent, Child, Child, Preschool, Female, Hospitals, Pediatric, Humans, Hypergammaglobulinemia, Immunoglobulin A, Infant, Italy, Male, Tertiary Care Centers}, issn = {1468-2044}, doi = {10.1136/archdischild-2014-306607}, author = {Copetti, Valentina and Pastore, Serena and De Pieri, Carlo and Radillo, Oriano and Taddio, Andrea and Ventura, Alessandro and Tommasini, Alberto} } @article {3506, title = {Common variants in UMOD associate with urinary uromodulin levels: a meta-analysis.}, journal = {J Am Soc Nephrol}, volume = {25}, year = {2014}, month = {2014 Aug}, pages = {1869-82}, abstract = {

Uromodulin is expressed exclusively in the thick ascending limb and is the most abundant protein excreted in normal urine. Variants in UMOD, which encodes uromodulin, are associated with renal function, and urinary uromodulin levels may be a biomarker for kidney disease. However, the genetic factors regulating uromodulin excretion are unknown. We conducted a meta-analysis of urinary uromodulin levels to identify associated common genetic variants in the general population. We included 10,884 individuals of European descent from three genetic isolates and three urban cohorts. Each study measured uromodulin indexed to creatinine and conducted linear regression analysis of approximately 2.5 million single nucleotide polymorphisms using an additive model. We also tested whether variants in genes expressed in the thick ascending limb associate with uromodulin levels. rs12917707, located near UMOD and previously associated with renal function and CKD, had the strongest association with urinary uromodulin levels (P<0.001). In all cohorts, carriers of a G allele of this variant had higher uromodulin levels than noncarriers did (geometric means 10.24, 14.05, and 17.67 μg/g creatinine for zero, one, or two copies of the G allele). rs12446492 in the adjacent gene PDILT (protein disulfide isomerase-like, testis expressed) also reached genome-wide significance (P<0.001). Regarding genes expressed in the thick ascending limb, variants in KCNJ1, SORL1, and CAB39 associated with urinary uromodulin levels. These data indicate that common variants in the UMOD promoter region may influence urinary uromodulin levels. They also provide insights into uromodulin biology and the association of UMOD variants with renal function.

}, keywords = {Creatinine, European Continental Ancestry Group, Genetic Variation, Humans, Polymorphism, Single Nucleotide, Uromodulin}, issn = {1533-3450}, doi = {10.1681/ASN.2013070781}, author = {Olden, Matthias and Corre, Tanguy and Hayward, Caroline and Toniolo, Daniela and Ulivi, Sheila and Gasparini, Paolo and Pistis, Giorgio and Hwang, Shih-Jen and Bergmann, Sven and Campbell, Harry and Cocca, Massimiliano and Gandin, Ilaria and Girotto, Giorgia and Glaudemans, Bob and Hastie, Nicholas D and Loffing, Johannes and Polasek, Ozren and Rampoldi, Luca and Rudan, Igor and Sala, Cinzia and Traglia, Michela and Vollenweider, Peter and Vuckovic, Dragana and Youhanna, Sonia and Weber, Julien and Wright, Alan F and Kutalik, Zolt{\'a}n and Bochud, Murielle and Fox, Caroline S and Devuyst, Olivier} } @article {3572, title = {A comparison of three scales for measuring pain in children with cognitive impairment.}, journal = {Acta Paediatr}, volume = {103}, year = {2014}, month = {2014 Nov}, pages = {e495-500}, abstract = {

AIM: Pain is a neglected problem in children with cognitive impairments, and few studies compare the clinical use of specific pain scales. We compared the Non-Communicating Children{\textquoteright}s Pain Checklist Postoperative Version (NCCPC-PV), the Echelle Douleur Enfant San Salvador (DESS) and the Children{\textquoteright}s Hospital of Eastern Ontario Pain Scale (CHEOPS). The first two were developed for children with cognitive impairment, and the third is a more general pain scale.

METHODS: Two external observers and the child{\textquoteright}s caregiver assessed 40 children with cognitive impairment for pain levels. We assessed inter-rater agreement, correlation, dependence on knowledge of the child{\textquoteright}s behaviour, simplicity and adequacy in pain rating according to the caregiver for all three scales.

RESULTS: The correlation between the NCCPC-PV and the DESS was strong (Spearman correlation coefficient = 0.76) and better than between each scale and the CHEOPS. Although the DESS showed better inter-rater agreement, it was more dependent on familiarity with the child and was judged more difficult to use by all observers. The NCCPC-PV was the easiest use and the most appropriate for rating the child{\textquoteright}s pain.

CONCLUSION: The NCCPC-PV was the easiest to use for pain assessment in cognitively impaired children and should be adopted in clinical settings.

}, issn = {1651-2227}, doi = {10.1111/apa.12748}, author = {Massaro, Marta and Ronfani, Luca and Ferrara, Giovanna and Badina, Laura and Giorgi, Rita and D{\textquoteright}Osualdo, Flavio and Taddio, Andrea and Barbi, Egidio} } @article {3575, title = {Consanguinity and hereditary hearing loss in Qatar.}, journal = {Hum Hered}, volume = {77}, year = {2014}, month = {2014}, pages = {175-82}, abstract = {

Qatar is a sovereign state located on the Eastern coast of the Arabian Peninsula in the Persian Gulf. Its native population consists of 3 major subgroups: people of Arabian origin or Bedouins, those from an Eastern or Persian ancestry and individuals with African admixture. Historically, all types of consanguineous marriages have been and still are common in the Qatari population, particularly among first and double-first cousins. Thus, there is a higher risk for most inherited diseases including hereditary hearing loss (HHL). In particular, a hearing loss prevalence of 5.2\% has been reported in Qatar, with parental consanguinity being more common among affected individuals as compared with unaffected ones. Our recent molecular results confirm a high homogeneity and level of inbreeding in Qatari HHL patients. Among all HHL genes, GJB2, the major player worldwide, accounts for a minor proportion of cases and at least 3 additional genes have been found to be mutated in Qatari patients. Interestingly, one gene, BDP1, has been described to cause HHL only in this country. These results point towards an unexpected level of genetic heterogeneity despite the high level of inbreeding. This review provides an up-to-date picture of HHL in Qatar and of the impact of consanguinity on this disease.

}, keywords = {Consanguinity, Hearing Loss, Homozygote, Humans, Inheritance Patterns, Pedigree, Prevalence, Principal Component Analysis, Qatar, Transcription Factor TFIIIB}, issn = {1423-0062}, doi = {10.1159/000360475}, author = {Girotto, Giorgia and Mezzavilla, Massimo and Abdulhadi, Khalid and Vuckovic, Dragana and Vozzi, Diego and Khalifa Alkowari, Moza and Gasparini, Paolo and Badii, Ramin} } @article {3493, title = {Cow{\textquoteright}s milk allergy in children, from avoidance to tolerance.}, journal = {Endocr Metab Immune Disord Drug Targets}, volume = {14}, year = {2014}, month = {2014 Mar}, pages = {47-53}, abstract = {

Food allergy is the primary cause of anaphylaxis in paediatric age affecting roughly 4\% of children and their families worldwide, and requiring changes in dietary habits. The prognosis for food allergy in children has traditionally been regarded as good for the most frequent allergens, however the prognosis for cow{\textquoteright}s milk allergy in the pediatric age is currently considered to be worse than previously believed. There is now enough evidence that measures of avoidance for children at risk did not have any preventive effect whatsoever, but they still came to be counterproductive by avoiding the physiological interaction between food allergens and gastrointestinal mucosal immune system. Programs of specific oral tolerance induction (SOTI) have obtained interesting results in the treatment of food allergy supporting the idea that antigen exposure through gastrointestinal section is important to allow the development of tolerance. Nevertheless this approach is not yet considered "ready" for community recommendations. In this paper we describe our experience in the field of SOTI in children with cow{\textquoteright}s milk allergy.

}, keywords = {Animals, Cattle, Child, Child, Preschool, Desensitization, Immunologic, Humans, Immune Tolerance, Milk Hypersensitivity, Milk Substitutes, Retrospective Studies}, issn = {2212-3873}, author = {Calligaris, Lorenzo and Longo, Giorgio and Badina, Laura and Berti, Irene and Barbi, Egidio} } @article {3627, title = {Curcumin and inflammatory bowel disease: potential and limits of innovative treatments.}, journal = {Molecules}, volume = {19}, year = {2014}, month = {2014}, pages = {21127-53}, abstract = {

Curcumin belongs to the family of natural compounds collectively called curcuminoids and it possesses remarkable beneficial anti-oxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Moreover it is commonly assumed that curcumin has also been suggested as a remedy for digestive diseases such as inflammatory bowel diseases (IBD), a chronic immune disorder affecting the gastrointestinal tract and that can be divided in two major subgroups: Crohn{\textquoteright}s disease (CD) and Ulcerative Colitis (UC), depending mainly on the intestine tract affected by the inflammatory events. The chronic and intermittent nature of IBD imposes, where applicable, long-term treatments conducted in most of the cases combining different types of drugs. In more severe cases and where there has been no good response to the drugs, a surgery therapy is carried out. Currently, IBD-pharmacological treatments are generally not curative and often present serious side effects; for this reason, being known the relationship between nutrition and IBD, it is worthy of interesting the study and the development of new dietary strategy. The curcumin principal mechanism is the suppression of IBD inflammatory compounds (NF-κB) modulating immune response. This review summarizes literature data of curcumin as anti-inflammatory and anti-oxidant in IBD, trying to understand the different effects in CD e UC.

}, keywords = {Animals, Anti-Inflammatory Agents, Non-Steroidal, Chemistry, Pharmaceutical, Clinical Trials as Topic, Curcumin, Humans, Inflammatory Bowel Diseases, Molecular Targeted Therapy, Nanotechnology, Treatment Outcome}, issn = {1420-3049}, doi = {10.3390/molecules191221127}, author = {Vecchi Brumatti, Liza and Marcuzzi, Annalisa and Tricarico, Paola Maura and Zanin, Valentina and Girardelli, Martina and Bianco, Anna Monica} } @article {1901, title = {A comparative analysis of serologic parameters and oxidative stress in osteoarthritis and rheumatoid arthritis: reply to Mishra and colleagues.}, journal = {Rheumatol Int}, volume = {33}, year = {2013}, month = {2013 Sep}, pages = {2445-6}, abstract = {

In chronic diseases such as rheumatoid arthritis and osteoarthritis, the progression of the disease is characterized by stress oxidative, inflammation, and elevated levels of cholesterol. In mevalonate kinase deficiency, an auto-inflammatory disease, the correlation between inflammation and cholesterol levels is opposite. The metabolic pathway that underlies the production of cholesterol is the mevalonate pathway; it is also essential for the biosynthesis of isoprenoids involved in the control of several cell functions. This divergence of cholesterol levels, associated with these two inflammatory disorders, is probably due to a different etiology, pathogenesis, and progression.

}, keywords = {Arthritis, Rheumatoid, Female, Humans, Inflammation Mediators, Lipids, Male, Osteoarthritis, Oxidative Stress}, issn = {1437-160X}, doi = {10.1007/s00296-012-2436-y}, author = {Girardelli, M and Bianco, A M and Marcuzzi, A and Crovella, S} } @article {1950, title = {A case of familial hemiplegic migraine associated with a novel ATP1A2 gene mutation.}, journal = {Pediatr Neurol}, volume = {47}, year = {2012}, month = {2012 Aug}, pages = {133-6}, abstract = {

Hemiplegic migraine constitutes an unusual form, characterized by periodic attacks of migraine with a motor component (hemiplegia). Familial forms are dominantly inherited, and are attributable to mutations in genes encoding proteins involved in ion transportation, including ATP1A2, which codes for the α-2 isoform of the sodium-potassium adenosine triphosphatase, a P-type cation transport adenosine triphosphatase, and responsible for the so-called familial hemiplegic migraine type 2. We describe a 9-year-old boy affected by familial hemiplegic migraine, with a novel ATP1A2 gene mutation (c.1799T>C p.V600A) in exon 13. Long-term treatment with flunarizine resulted in a good clinical response and the prevention of further attacks.

}, keywords = {Amino Acid Sequence, Child, Preschool, Humans, Male, Migraine with Aura, Molecular Sequence Data, Mutation, Pedigree, Sodium-Potassium-Exchanging ATPase}, issn = {1873-5150}, doi = {10.1016/j.pediatrneurol.2012.04.012}, author = {De Cunto, Angela and Bensa, Marco and Tonelli, Alessandra} } @article {1880, title = {CD14 polymorphisms correlate with an augmented risk for celiac disease in Italian patients.}, journal = {Genes Immun}, volume = {13}, year = {2012}, month = {2012 Sep}, pages = {489-95}, abstract = {

Celiac disease (CD) is a T-cell-mediated chronic inflammatory disease characterized by autoimmune, immunological and environmental components, where genetic factors in addition to the main known risk factors (gliadin and human leukocyte antigen (HLA)-DQ haplotypes) are supposed to be involved. CD14 is a multifunctional receptor involved in the bacterial lipopolysaccharides-dependent signal transduction. The CD14 gene maps on the long arm of chromosome 5 (5q22-q32), a {\textquoteright}hotbed{\textquoteright} region for CD; promoter polymorphisms are known to influence its expression. In this study we analyzed three CD14 promoter polymorphisms (c.-1359G>T, c.-1145A>G and c.-159C>T, ) in 938 CD Italian patients and 533 healthy controls, with known HLA-DQ haplotypes, with the aim of evaluating their possible association with the disease. The c.-1145A>G G and c.-159C>T T alleles (as well as the combination of the two alleles in the GT haplotype), were identified as susceptibility factors for CD development, being significantly more frequent in CD patients than in healthy controls. This association was also confirmed when the analysis was restricted to only those subjects characterized by HLA-DQ risk haplotypes. Our results indicate the involvement of CD14 gene polymorphisms in the susceptibility to CD.

}, keywords = {Adolescent, Adult, Aged, Antigens, CD14, Case-Control Studies, Celiac Disease, Child, Child, Preschool, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, HLA Antigens, Humans, Infant, Italy, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Young Adult}, issn = {1476-5470}, doi = {10.1038/gene.2012.23}, author = {Catamo, E and Segat, L and Lenarduzzi, S and Petix, V and Morgutti, M and Crovella, S} } @article {1948, title = {Chemerin regulates NK cell accumulation and endothelial cell morphogenesis in the decidua during early pregnancy.}, journal = {J Clin Endocrinol Metab}, volume = {97}, year = {2012}, month = {2012 Oct}, pages = {3603-12}, abstract = {

CONTEXT: Although decidual natural killer (NK) cell accumulation and vascular remodeling are critical steps to ensure successful pregnancy, the molecular mechanisms controlling these events are poorly defined.

OBJECTIVE: Herein we analyzed whether chemerin, a recently identified chemoattractant involved in many pathophysiological processes, could be expressed in the uterine compartment and could regulate events relevant for the good outcome of pregnancy.

DESIGN: Chemerin expression in human primary culture of stromal (ST) cells, extravillous trophoblast cells, and decidual endothelial cells (DEC) was analyzed by RT-PCR, ELISA, and Western blot. Migration through ST or DEC of peripheral blood and decidual (d) NK cells from pregnant women was performed using a transwell assay. A DEC capillary-like tube formation assay was used to evaluate endothelial morphogenesis.

RESULTS: Chemerin is differentially expressed by decidual cells during early pregnancy being present at high levels in ST and extravillous trophoblast cells but not in DEC. Notably, ST cells from pregnant women exhibit and release higher levels of chemerin as compared with ST cells from menopausal or fertile nonpregnant women. Chemerin can support peripheral blood NK cell migration through both DEC and ST cells. Although dNK cells exhibit lower chemerin receptor (CMKLR1) expression than their blood counterpart, CMKLR1 engagement on dNK cells resulted in both ERK activation and migration through decidual ST cells. Interestingly, DEC also express CMKLR1 and undergo ERK activation and capillary-like tube structure formation upon exposure to chemerin.

CONCLUSIONS: Our data indicate that chemerin is up-regulated during decidualization and might contribute to NK cell accumulation and vascular remodeling during early pregnancy.

}, keywords = {Capillaries, Cell Movement, Chemokines, Decidua, Endothelial Cells, Female, Humans, Killer Cells, Natural, MAP Kinase Signaling System, Neovascularization, Physiologic, Pregnancy, Pregnancy Trimester, First, Receptors, Chemokine, RNA, Messenger, Stromal Cells, Trophoblasts}, issn = {1945-7197}, doi = {10.1210/jc.2012-1102}, author = {Carlino, Claudia and Trotta, Eleonora and Stabile, Helena and Morrone, Stefania and Bulla, Roberta and Soriani, Alessandra and Iannitto, Maria Luisa and Agostinis, Chiara and Mocci, Carlo and Minozzi, Massimo and Aragona, Cesare and Perniola, Giorgia and Tedesco, Francesco and Sozzani, Silvano and Santoni, Angela and Gismondi, Angela} } @article {1951, title = {A child with edema, lower limb deformity, and recurrent diarrhea.}, journal = {J Pediatr}, volume = {161}, year = {2012}, month = {2012 Dec}, pages = {1177}, keywords = {Bone Retroversion, Capsule Endoscopy, Child, Preschool, Diarrhea, Edema, Humans, Knee Joint, Lymphangiectasis, Intestinal, Lymphedema, Male, Recurrence}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2012.06.022}, author = {Gortani, Giulia and Maschio, Massimo and Ventura, Alessandro} } @article {1865, title = {A child with severe pneumomediastinum and ABCA3 gene mutation: a puzzling connection.}, journal = {Arch Bronconeumol}, volume = {48}, year = {2012}, month = {2012 Apr}, pages = {139-40}, keywords = {Anemia, ATP-Binding Cassette Transporters, Child, Preschool, Dyspnea, Genetic Predisposition to Disease, Heterozygote, Humans, Intensive Care, Leukocytosis, Male, Mediastinal Emphysema, Mutation, Missense, Point Mutation, Pulmonary Emphysema, Respiratory Tract Infections, Subcutaneous Emphysema, Tomography, X-Ray Computed}, issn = {1579-2129}, doi = {10.1016/j.arbres.2011.11.008}, author = {Copertino, Marco and Barbi, Egidio and Poli, Furio and Zennaro, Floriana and Ferrari, Maurizio and Carrera, Paola and Ventura, Alessandro} } @article {1904, title = {Clarification of the pleiotropic effects of statins on mevalonate pathway and the feedback regulation of isoprenoids requires more comprehensive investigation.}, journal = {Cell Biochem Funct}, volume = {30}, year = {2012}, month = {2012 Mar}, pages = {176}, keywords = {Carcinoma, Hepatocellular, Enzyme Inhibitors, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Liver Neoplasms, Simvastatin, Terpenes}, issn = {1099-0844}, doi = {10.1002/cbf.2798}, author = {Bianco, Anna Monica and Zanin, Valentina and Marcuzzi, Annalisa and Crovella, Sergio} } @article {1922, title = {Clinical and laboratory features of 103 patients from 42 Italian families with inherited thrombocytopenia derived from the monoallelic Ala156Val mutation of GPIbα (Bolzano mutation).}, journal = {Haematologica}, volume = {97}, year = {2012}, month = {2012 Jan}, pages = {82-8}, abstract = {

BACKGROUND: Bernard-Soulier syndrome is a very rare form of inherited thrombocytopenia that derives from mutations in GPIbα, GPIbβ, or GPIX and is typically inherited as a recessive disease. However, some years ago it was shown that the monoallelic c.515C>T transition in the GPIBA gene (Bolzano mutation) was responsible for macrothrombocytopenia in a few Italian patients.

DESIGN AND METHODS: Over the past 10 years, we have searched for the Bolzano mutation in all subjects referred to our institutions because of an autosomal, dominant form of thrombocytopenia of unknown origin.

RESULTS: We identified 42 new Italian families (103 cases) with a thrombocytopenia induced by monoallelic Bolzano mutation. Analyses of the geographic origin of affected pedigrees and haplotypes indicated that this mutation originated in southern Italy. Although the clinical expression was variable, patients with this mutation typically had a mild form of Bernard-Soulier syndrome with mild thrombocytopenia and bleeding tendency. The most indicative laboratory findings were enlarged platelets and reduced GPIb/IX/V platelet expression; in vitro platelet aggregation was normal in nearly all of the cases.

CONCLUSIONS: Our study indicates that monoallelic Bolzano mutation is the most frequent cause of inherited thrombocytopenia in Italy, affecting 20\% of patients recruited at our institutions during the last 10 years. Because many people from southern Italy have emigrated during the last century, this mutation may have spread to other countries.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Bernard-Soulier Syndrome, Child, Child, Preschool, Family Health, Female, Heterozygote, Humans, Infant, Italy, Male, Membrane Glycoproteins, Middle Aged, Mutation, Missense, Platelet Aggregation, Platelet Count, Platelet Glycoprotein GPIb-IX Complex, Polymorphism, Genetic, Thrombocytopenia, Thrombopoietin, Tubulin, Young Adult}, issn = {1592-8721}, doi = {10.3324/haematol.2011.050682}, author = {Noris, Patrizia and Perrotta, Silverio and Bottega, Roberta and Pecci, Alessandro and Melazzini, Federica and Civaschi, Elisa and Russo, Sabina and Magrin, Silvana and Loffredo, Giuseppe and Di Salvo, Veronica and Russo, Giovanna and Casale, Maddalena and De Rocco, Daniela and Grignani, Claudio and Cattaneo, Marco and Baronci, Carlo and Dragani, Alfredo and Albano, Veronica and Jankovic, Momcilo and Scianguetta, Saverio and Savoia, Anna and Balduini, Carlo L} } @article {1946, title = {The clinical interpretation and significance of electronic fetal heart rate patterns 2 h before delivery: an institutional observational study.}, journal = {Arch Gynecol Obstet}, volume = {286}, year = {2012}, month = {2012 Nov}, pages = {1153-9}, abstract = {

PURPOSE: To evaluate the clinical significance of intrapartum fetal heart rate (FHR) monitoring in low-risk pregnancies according to guidelines and specific patterns.

METHODS: An obstetrician, blinded to neonatal outcome, retrospectively reviewed 198 low-risk cases that underwent continuous electronic fetal monitoring (EFM) during the last 2 h before delivery. The tracings were interpreted as normal, suspicious or pathological, according to specific guidelines of EFM and by grouping the different FHR patterns considering baseline, variability, presence of decelerations and bradycardia. The EFM groups and the different FHR-subgroups were associated with neonatal acid base status at birth, as well as the short-term neonatal composite outcome. Comparisons between groups were performed with Kruskal-Wallis test. Differences among categorical variables were evaluated using Fisher{\textquoteright}s exact test. Significance was set at p < 0.05 level.

RESULTS: Significant differences were found for mean pH values in the three EFM groups, with a significant trend from "normal" [pH 7.25, 95 \% confidence interval (CI) 7.28-7.32] to "pathological" tracings (pH 7.20, 95 \% CI 7.17-7.13). Also the rates of adverse composite neonatal outcome were statistically different between the two groups (p < 0.005). Among the different FHR patterns, tracings with atypical variable decelerations and severe bradycardia were more frequently associated with adverse neonatal composite outcome (11.1 and 26.7 \%, respectively). However, statistically significant differences were only observed between the subgroups with normal tracings and bradycardia.

CONCLUSIONS: In low-risk pregnancies, there is a significant association between neonatal outcome and EFM classification. However, within abnormal tracings, neonatal outcome might differ according to specific FHR pattern.

}, keywords = {Acidosis, Bradycardia, Female, Fetal Blood, Fetal Monitoring, Heart Rate, Fetal, Humans, Hydrogen-Ion Concentration, Infant, Newborn, Labor, Obstetric, Predictive Value of Tests, Pregnancy, Pregnancy Outcome, Retrospective Studies, Single-Blind Method, Statistics, Nonparametric, Time Factors}, issn = {1432-0711}, doi = {10.1007/s00404-012-2446-8}, author = {Maso, Gianpaolo and Businelli, Caterina and Piccoli, Monica and Montico, Marcella and De Seta, Francesco and Sartore, Andrea and Alberico, Salvatore} } @article {1774, title = {Coeliac disease diagnosis: ESPGHAN 1990 criteria or need for a change? Results of a questionnaire.}, journal = {J Pediatr Gastroenterol Nutr}, volume = {54}, year = {2012}, month = {2012 Jan}, pages = {15-9}, abstract = {

BACKGROUND AND OBJECTIVES: A revision of criteria for diagnosing coeliac disease (CD) is being conducted by The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). In parallel, we have performed a survey aimed to evaluate present practices for CD among paediatric gastroenterologists and to learn their views on the need for modification of present criteria for CD diagnosis.

PATIENTS AND METHODS: Questionnaires were distributed to experienced paediatric gastroenterologists (ESPGHAN members) via the Internet.

RESULTS: Overall, 95 valid questionnaires were available for analysis, pertaining to 28 different countries, with the majority of responders treating patients with CD for >15 years. Only about 12\% of the responders comply with present criteria, noncompliance being related mainly to the challenge policy. Approximately 90\% request a revision and modification of the present criteria. Forty-four percent want to omit the small bowel biopsy in symptomatic children with positive anti-tissue transglutaminase immunoglobulin (Ig) A or endomysial IgA antibodies, especially if they are DQ2/DQ8 positive. For silent cases detected by screening with convincingly positive anti-tissue transglutaminase IgA or EMA IgA, about 30\% consider that no small bowel biopsy should be required in selected cases. Adding human leukocyte antigen typing in the diagnostic workup was asked for by 42\% of the responders. As for gluten challenge, a new policy is advocated restricting its obligation to cases whenever the diagnosis is doubtful or unclear.

CONCLUSIONS: Based on these opinions, revision of the ESPGHAN criteria for diagnosing CD is urgently needed.

}, keywords = {Adolescent, Adult, Biopsy, Celiac Disease, Child, Child, Preschool, Glutens, Guideline Adherence, Guidelines as Topic, Health Care Surveys, Humans, Immunoglobulin A, Intestine, Small, Physician{\textquoteright}s Practice Patterns, Questionnaires, Societies, Medical, Transglutaminases, Young Adult}, issn = {1536-4801}, doi = {10.1097/MPG.0b013e31822a00bb}, author = {Ribes-Koninckx, C and Mearin, M L and Korponay-Szab{\'o}, I R and Shamir, R and Husby, S and Ventura, A and Branski, D and Catassi, C and Koletzko, S and M{\"a}ki, M and Troncone, R and Zimmer, K P} } @article {1893, title = {Cognitive assessment of very preterm infants at 2-year corrected age: performance of the Italian version of the PARCA-R parent questionnaire.}, journal = {Early Hum Dev}, volume = {88}, year = {2012}, month = {2012 Mar}, pages = {159-63}, abstract = {

BACKGROUND: Serial assessments of cognitive and language development are recommended for very preterm children, but standardized neuropsychological testing is time-consuming and expensive, as well as tiring for the child.

AIMS: To validate the Italian version of the PARCA-R parent questionnaire and test its clinical effectiveness in assessing cognitive development of very preterm children at 2 years of corrected age.

METHODS: 120 consecutive Italian very preterm children (mean gestational age 28.8 weeks, standard deviation 2.1) were assessed in four hospitals through the Mental Development Index (MDI) of the Bayley Scales of Infant Development (BSID-II). Parents completed the PARCA-R questionnaire, designed to measure children{\textquoteright}s non-verbal and verbal (vocabulary and sentence complexity) cognitive level. The correlation between the MDI and the PARCA-R Parent Report Composite (PRC) was tested through the Pearson correlation coefficient, and the receiver operating characteristic (ROC) curve was used to identify optimal PRC cut-offs.

RESULTS: Significant correlation between the PRC score and MDI (r=0.60, p<0.001) indicated good concurrent validity. The area under the ROC curve was 0.83, and the cut-off of 46 lead to 72.7\% sensitivity and 77.1\% specificity in identifying children with moderate/severe cognitive delay (MDI<70). Negative predictive value was 96.6 (90.3-99.3). Screening through PARCA-R would reduce the number of children with MDI>=70 undergoing BSID-II or equivalent standardized tool from 109 to 25.

CONCLUSIONS: The Italian version of PARCA-R retains good discriminative power for identifying cognitive delay in 2-year very preterm children. It is well accepted by parents, and represents a valid and efficient alternative for developmental screening and outcome measurement.

}, keywords = {Cognition, Female, Humans, Infant, Infant, Newborn, Infant, Premature, Italy, Male, Parents, Questionnaires, ROC Curve}, issn = {1872-6232}, doi = {10.1016/j.earlhumdev.2011.07.022}, author = {Cuttini, Marina and Ferrante, Pierpaolo and Mirante, Nadia and Chiandotto, Valeria and Fertz, Mariacristina and Dall{\textquoteright}Oglio, Anna Maria and Coletti, Maria Franca and Johnson, Samantha} } @article {1842, title = {Comments to the editor concerning the paper entitled "Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways" Shiekh Tanveer Ahmad et al.}, journal = {Toxicology}, volume = {293}, year = {2012}, month = {2012 Mar 11}, pages = {123-4}, keywords = {Animals, Antineoplastic Agents, Kidney Neoplasms, Male, Signal Transduction, Terpenes}, issn = {1879-3185}, doi = {10.1016/j.tox.2011.12.008}, author = {Vuch, Josef and Marcuzzi, Annalisa and Zanin, Valentina and Crovella, Sergio} } @article {1864, title = {A common genetic background could explain early-onset Crohn{\textquoteright}s disease.}, journal = {Med Hypotheses}, volume = {78}, year = {2012}, month = {2012 Apr}, pages = {520-2}, abstract = {

Crohn{\textquoteright}s disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn{\textquoteright}s disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.

}, keywords = {Crohn Disease, Genetic Linkage, Genetic Predisposition to Disease, Humans, Models, Biological}, issn = {1532-2777}, doi = {10.1016/j.mehy.2012.01.023}, author = {Bianco, Anna Monica and Zanin, Valentina and Girardelli, Martina and Magnolato, Andrea and Martelossi, Stefano and Martellossi, Stefano and Tommasini, Alberto and Marcuzzi, Annalisa and Crovella, Sergio} } @article {1972, title = {Comparison of hybrid capture II, linear array, and a bead-based multiplex genotyping assay for detection of human papillomavirus in women with negative pap test results and atypical squamous cells of undetermined significance.}, journal = {J Clin Microbiol}, volume = {50}, year = {2012}, month = {2012 Dec}, pages = {4041-6}, abstract = {

Many methods with different levels of analytical sensitivity and clinical specificity have been developed to detect the presence of high-risk (HR) types of the human papillomavirus (HPV) in cervical samples. The Hybrid Capture II (HC-II) assay is broadly used for primary screening. In addition, several HPV genotyping assays, based on PCR methods, display higher sensitivity than the HC-II and are also used in screening programs. We evaluated the performance of three HPV DNA tests, namely, the HC-II, the Linear Array (LA) HPV genotyping assay, and an HPV type-specific E7 PCR bead-based multiplex genotyping assay (TS-MPG) that is a laboratory-developed method for the detection of HPV, in 94 women with atypical squamous cells of undetermined significance (ASC-US) and in cytological samples from 86 women with a negative Pap test. The HPV prevalence with the TS-MPG assay was increased compared to the prevalence with the LA and HC-II assays. The HPV DNA prevalence in women with ASC-US was greater with the TS-MPG assay (46.2\%) than with the LA (36.3\%) and HC-II (29.7\%) assays. The HPV DNA prevalence in the control group was greater with the TS-MPG assay (32.1\%) than with the LA assay (10.7\%). Two women with ASC-US who were HPV DNA negative by the HC-II and positive by the TS-MPG or/and LA assays had lesions that progressed to low-grade squamous intraepithelial and high-grade squamous intraepithelial lesions. This study shows that the TS-MPG assay exhibited higher analytical sensitivity than the LA and HC-II assays for the detection of HPV DNA, which reduces the potential to incorrectly identify a woman{\textquoteright}s HPV infection status.

}, keywords = {Adult, DNA, Viral, Female, Humans, Molecular Diagnostic Techniques, Papillomavirus Infections, Sensitivity and Specificity, Uterine Cervical Neoplasms, Virology}, issn = {1098-660X}, doi = {10.1128/JCM.02105-12}, author = {Comar, Manola and Iannacone, Michelle R and Casalicchio, Giorgia and McKay-Chopin, Sandrine and Tommasino, Massimo and Gheit, Tarik} } @article {1801, title = {Congenital hemangiopericytoma.}, journal = {J Pediatr}, volume = {160}, year = {2012}, month = {2012 May}, pages = {878}, keywords = {Biopsy, Needle, Female, Gestational Age, Hemangiopericytoma, Humans, Immunohistochemistry, Infant, Newborn, Magnetic Resonance Imaging, Pregnancy, Prognosis, Risk Assessment, Soft Tissue Neoplasms, Treatment Outcome, Ultrasonography, Prenatal}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2011.11.023}, author = {Travan, Laura and Demarini, Sergio and Del Frate, Giovanni and Zacchi, Alberto} } @article {1802, title = {Contribution of SNP arrays in diagnosis of deletion 2p11.2-p12.}, journal = {Gene}, volume = {492}, year = {2012}, month = {2012 Jan 15}, pages = {315-8}, abstract = {

Deletions of the short arm of chromosome 2 are exceedingly rare, having been reported in few patients. Furthermore most cases with deletion in 2p11.2-p12 have been studied using standard karyotype and so it is not possible to delineate the precise size of deletions. Here, we describe a 9-year-old girl with a 9.4 Mb de novo interstitial deletion of region 2p11.2-p12 identified by SNP array analysis. The deleted region encompasses over 40 known genes, including LRRTM1, CTNNA2 and REEP1, haploinsufficiency of which could explain some clinical features of this patient such as mental retardation, speech delay and gait abnormalities. A comparison of our case with previously reported patients who present deletions in 2p11.2-p12 was carried out. Our case adds new information to the deletion of 2p11.2-p12, improving the knowledge on this rearrangement.

}, keywords = {Abnormalities, Multiple, Child, Chromosomes, Human, Pair 2, Female, Humans, Intellectual Disability, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Sequence Deletion}, issn = {1879-0038}, doi = {10.1016/j.gene.2011.10.035}, author = {Rocca, Maria Santa and Fabretto, Antonella and Faletra, Flavio and Carlet, Ombretta and Skabar, Aldo and Gasparini, Paolo and Pecile, Vanna} } @article {1768, title = {A coughing spine.}, journal = {Emerg Med J}, volume = {29}, year = {2012}, month = {2012 Jan}, pages = {14}, keywords = {Cervical Vertebrae, Child, Dyspnea, Humans, Male, Mediastinal Emphysema, Spinal Diseases, Subcutaneous Emphysema, Tomography, X-Ray Computed}, issn = {1472-0213}, doi = {10.1136/emermed-2011-200108}, author = {Norbedo, Stefania and Perini, Roberto and Amaddeo, Alessandro} } @article {1757, title = {Celiac disease and immigration in Northeastern Italy: the "drawn double nostalgia" of "cozonac" and "panettone" slices.}, journal = {Clin Exp Gastroenterol}, volume = {4}, year = {2011}, month = {2011}, pages = {121-5}, abstract = {

Many investigators consider children{\textquoteright}s drawings to be an important test in the evaluation of stress and anxiety, but few studies have examined the reliability and validity of indicators of emotional distress in children{\textquoteright}s projective drawings. In this report, we describe screening tests in children coming to the Friuli Venezia Giulia region in Northeastern Italy from non-European Union regions and suspected to have celiac disease, the problems involved in diagnosis of the disease, and the "drawn double nostalgia" of Romanian children for both Italian food and traditional Romanian foods. Of 3150 Western European cases, we found 712 with positive antibodies for IgA/IgG antitransglutaminase, 174 with a positive antiendomysium antibody confirmation test, and 20 with an IgA deficit. Of the children examined, 93\% were children native to Western Europe, 4\% were immigrants from Eastern Europe, and 1.6\% originated from Africa. Among these, four Romanian children with celiac disease brought in their drawings, as requested in a hospital questionnaire. The prevalence of celiac disease is destined to increase among immigrants. Economic problems are common, and the twin nostalgia of immigrant children for foods and tastes that are "cozonac" (from the native country) and "panettone" (Italian cake flavor) represents a problem that will be difficult to resolve. Only some children{\textquoteright}s hospitals in Italy, ie, Burlo Garofolo and Gaslini, public and private foundations, or volunteer associations would be able to deal with this problem.

}, issn = {1178-7023}, doi = {10.2147/CEG.S19225}, author = {Parco, Sergio and Citt{\`a}, Angelo and Vascotto, Fulvia and Tamaro, Giorgio} } @article {1855, title = {Childhood chronic anterior uveitis associated with vernal keratoconjunctivitis (VKC): successful treatment with topical tacrolimus. Case series.}, journal = {Pediatr Rheumatol Online J}, volume = {9}, year = {2011}, month = {2011}, pages = {34}, abstract = {

Uveitis treatment involves topical corticosteroids along with cycloplegic-mydriatics. Particularly severe cases may require systemic corticosteroids and immunosuppressive drugs. Vernal keratoconjunctivitis (VKC) treatment consists of a brief period of topical corticosteroids and/or cyclosporine. In patients refractory to traditional treatment, the use of 0.1\% topical ophtalmic FK- 506 (tacrolimus) ointment has been occasionally reported.This is the first report of the coexistence of uveitis and VKC. The documented response to topical tacrolimus eyedrop of uveitis and VKC is also of interest, in particular since to our knowledge there are no published reports on its clinical use in uveitis.

}, issn = {1546-0096}, doi = {10.1186/1546-0096-9-34}, author = {Taddio, Andrea and Cimaz, Rolando and Caputo, Roberto and de Libero, Cinzia and Di Grande, Laura and Simonini, Gabriele and Mori, Francesca and Novembre, Elio and Pucci, Neri} } @article {1800, title = {Circulating TRAIL shows a significant post-partum decline associated to stressful conditions.}, journal = {PLoS One}, volume = {6}, year = {2011}, month = {2011}, pages = {e27011}, abstract = {

BACKGROUND: Since circulating levels of TNF-related apoptosis inducing ligand (TRAIL) may be important in the physiopathology of pregnancy, we tested the hypothesis that TRAIL levels change at delivery in response to stressful conditions.

METHODS/PRINCIPAL FINDINGS: We conducted a longitudinal study in a cohort of 73 women examined at week 12, week 16, delivery and in the corresponding cord blood (CB). Serum TRAIL was assessed in relationship with maternal characteristics and to biochemical parameters. TRAIL did not vary between 12 (67.6{\textpm}27.6 pg/ml, means{\textpm}SD) and 16 (64.0{\textpm}16.2 pg/ml) weeks{\textquoteright} gestation, while displaying a significant decline after partum (49.3{\textpm}26.4 pg/ml). Using a cut-off decline >20 pg/ml between week 12 and delivery, the subset of women with the higher decline of circulating TRAIL (41.7\%) showed the following characteristics: i) nullipara, ii) higher age, iii) operational vaginal delivery or urgent CS, iv) did not receive analgesia during labor, v) induced labor. CB TRAIL was significantly higher (131.6{\textpm}52 pg/ml) with respect to the corresponding maternal TRAIL, and the variables significantly associated with the first quartile of CB TRAIL (<90 pg/ml) were higher pre-pregnancy BMI, induction of labor and fetal distress. With respect to the biochemical parameters, maternal TRAIL at delivery showed an inverse correlation with C-reactive protein (CRP), total cortisol, glycemia and insulin at bivariate analysis, but only with CRP at multivariate analysis.

CONCLUSIONS: Stressful partum conditions and elevated CRP levels are associated with a decrease of circulating TRAIL.

}, keywords = {Adult, Biological Markers, C-Reactive Protein, Female, Fetal Blood, Fetal Distress, Humans, Labor, Obstetric, Logistic Models, Multivariate Analysis, Postpartum Period, Pregnancy, Pregnancy Outcome, Statistics, Nonparametric, Stress, Physiological, TNF-Related Apoptosis-Inducing Ligand}, issn = {1932-6203}, doi = {10.1371/journal.pone.0027011}, author = {Zauli, Giorgio and Monasta, Lorenzo and Rimondi, Erika and Vecchi Brumatti, Liza and Radillo, Oriano and Ronfani, Luca and Montico, Marcella and D{\textquoteright}Ottavio, Giuseppina and Alberico, Salvatore and Secchiero, Paola} } @article {1697, title = {Clinical and genetic aspects of Bernard-Soulier syndrome: searching for genotype/phenotype correlations.}, journal = {Haematologica}, volume = {96}, year = {2011}, month = {2011 Mar}, pages = {417-23}, abstract = {

BACKGROUND: Bernard-Soulier syndrome is a severe bleeding disease due to a defect of GPIb/IX/V, a platelet complex that binds the von Willebrand factor. Due to the rarity of the disease, there are reports only on a few cases compromising any attempt to establish correlations between genotype and phenotype. In order to identify any associations, we describe the largest case series ever reported, which was evaluated systematically at the same center.

DESIGN AND METHODS: Thirteen patients with the disease and seven obligate carriers were enrolled. We collected clinical aspects and determined platelet features, including number and size, expression of membrane glycoproteins, and ristocetin induced platelet aggregation. Mutations were identified by direct sequencing of the GP1BA, GP1BB, and GP9 genes and their effect was shown by molecular modeling analyses.

RESULTS: Patients all had a moderate thrombocytopenia with giant platelets and a bleeding tendency whose severity varied among individuals. Consistent with expression levels of GPIbα always lower than 10\% of control values, platelet aggregation was absent or severely reduced. Homozygous mutations were identified in the GP1BA, GP1BB and GP9 genes; six were novel alterations expected to destabilize the conformation of the respective protein. Except for obligate carriers of a GP9 mutation with a reduced GPIb/IX/V expression and defective aggregation, all the other carriers had no obvious anomalies.

CONCLUSIONS: Regardless of mutations identified, the patients{\textquoteright} bleeding diathesis did not correlate with thrombocytopenia, which was always moderate, and platelet GPIbα expression, which was always severely impaired. Obligate carriers had features similar to controls though their GPIb/IX/V expression showed discrepancies. Aware of the limitations of our cohort, we cannot define any correlations. However, further investigations should be encouraged to better understand the causes of this rare and underestimated disease.

}, keywords = {Adolescent, Adult, Amino Acid Sequence, Bernard-Soulier Syndrome, Blood Platelets, Cell Shape, Child, Child, Preschool, Female, Genetic Association Studies, Genetic Markers, Hemorrhage, Homozygote, Humans, Italy, Male, Membrane Glycoproteins, Middle Aged, Molecular Sequence Data, Platelet Aggregation, Platelet Count, Platelet Glycoprotein GPIb-IX Complex, Point Mutation, Polymerase Chain Reaction, Ristocetin, Thrombocytopenia, von Willebrand Factor, Young Adult}, issn = {1592-8721}, doi = {10.3324/haematol.2010.032631}, author = {Savoia, Anna and Pastore, Annalisa and De Rocco, Daniela and Civaschi, Elisa and Di Stazio, Mariateresa and Bottega, Roberta and Melazzini, Federica and Bozzi, Valeria and Pecci, Alessandro and Magrin, Silvana and Balduini, Carlo L and Noris, Patrizia} } @article {1613, title = {Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.}, journal = {Clin Immunol}, volume = {139}, year = {2011}, month = {2011 Apr}, pages = {6-11}, abstract = {

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3\% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7\% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.

}, keywords = {Adolescent, Adult, Child, Child, Preschool, Heterozygote, Homozygote, Humans, Middle Aged, Mutation, Polyendocrinopathies, Autoimmune, Time Factors, Young Adult}, issn = {1521-7035}, doi = {10.1016/j.clim.2010.12.021}, author = {Mazza, Cinzia and Buzi, Fabio and Ortolani, Federica and Vitali, Alberto and Notarangelo, Lucia D and Weber, Giovanna and Bacchetta, Rosa and Soresina, Annarosa and Lougaris, Vassilios and Greggio, Nella A and Taddio, Andrea and Pasic, Srdjan and de Vroede, Monique and Pac, Malgorzata and Kilic, Sara Sebnem and Ozden, Sanal and Rusconi, Roberto and Martino, Silvana and Capalbo, Donatella and Salerno, Mariacarolina and Pignata, Claudio and Radetti, Giorgio and Maggiore, Giuseppe and Plebani, Alessandro and Notarangelo, Luigi D and Badolato, Raffaele} } @article {1600, title = {Comments on {\textquoteright}{\textquoteright}Geranylgeraniol--a new potential therapeutic approach to bisphosphonate associated osteonecrosis of the jaw" by Ziebart T et al. (2011).}, journal = {Oral Oncol}, volume = {47}, year = {2011}, month = {2011 May}, pages = {436-7; author reply 438}, keywords = {Bone Density Conservation Agents, Diphosphonates, Diterpenes, Humans, Jaw Diseases, Osteonecrosis}, issn = {1879-0593}, doi = {10.1016/j.oraloncology.2011.02.017}, author = {Marcuzzi, Annalisa and Zanin, Valentina and Crovella, Sergio and Pontillo, Alessandra} } @article {1775, title = {Comparison of propofol versus propofol-ketamine combination in pediatric oncologic procedures performed by non-anesthesiologists.}, journal = {Pediatr Blood Cancer}, volume = {57}, year = {2011}, month = {2011 Dec 15}, pages = {1163-7}, abstract = {

BACKGROUND: Limited data are available on the best option (short acting sedatives, opioids, or ketamine) in oncologic procedural sedation performed by non-anesthesiologists. The aim of the present prospective study is to compare the safety and efficacy of propofol-ketamine versus propofol alone, managed by trained pediatricians, in children with cancer undergoing painful procedures.

PROCEDURES: Data on 121 children with acute lymphatic leukemia (ALL) undergoing procedural sedations (lumbar punctures and bone marrow aspirations) were prospectively collected and included drug doses, side effects, pain assessment, and sedation degree. Children were randomly assigned to one of the two groups: P (n = 62) receiving propofol alone and K (n = 59) in whom a ketamine-propofol combination was used.

RESULTS: In group K, the total dose of propofol required was significantly lower than in group P (3.9 {\textpm} 3.6 mg/kg vs. 5.1 {\textpm} 3.6 mg/kg; P < 0.001). The incidence of hypotension was also significantly lower (11\% vs. 39\%; P < 0.001). Major O(2) desaturations (defined as SatO(2) < 88\%) occurred principally in group P (7 vs. 1; P = 0.05). Both best analgesia and shorter recovery time were obtained with the propofol-ketamine association. No differences were observed in the degree of sedation and in the awakening quality score between the two groups.

CONCLUSIONS: The combination of propofol and ketamine produced statistically significant clinical advantages combined with a higher profile of safety in children with cancer undergoing painful procedures.

}, keywords = {Biopsy, Needle, Bone Marrow Examination, Child, Conscious Sedation, Female, Humans, Hypnotics and Sedatives, Ketamine, Male, Neoplasms, Pediatrics, Physicians, Propofol, Spinal Puncture}, issn = {1545-5017}, doi = {10.1002/pbc.23170}, author = {Chiaretti, Antonio and Ruggiero, Antonio and Barbi, Egidio and Pierri, Filomena and Maurizi, Palma and Fantacci, Claudia and Bersani, Giulia and Riccardi, Riccardo} } @article {1596, title = {Compliance with the gluten-free diet: the role of locus of control in celiac disease.}, journal = {J Pediatr}, volume = {158}, year = {2011}, month = {2011 Mar}, pages = {463-466.e5}, abstract = {

OBJECTIVES: To verify whether subjects with celiac disease (CD) have a different locus of control (LoC) compared with healthy subjects, and to evaluate the relationship between LoC and compliance with a prescribed gluten-free diet (GFD) and quality of life (QoL).

STUDY DESIGN: We studied 156 subjects on a GFD (mean age, 10 years) and 353 healthy controls (mean age, 12 years). All subjects completed tests on the Nowicki-Strickland Locus of Control Scale; the subjects with CD also completed a questionnaire to measure compliance with dietary treatment and the disease{\textquoteright}s impact on QoL.

RESULTS: There was no difference in LoC values between patients with CD and controls. Subjects with CD with good dietary compliance had a more internal LoC compared with those who were not compliant (P = .01). Patients who reported a satisfactory QoL had a more internal LoC compared with those who reported negative affects on QoL due to CD (P = .01).

CONCLUSIONS: Our study confirms the usefulness of the LoC concept for identifying those patients who might be at risk for dietary transgression. Given the enhanced, psychological, and social well being that can result from adherence to a GFD, educational and psychological support can help internalize the LoC in those patients at risk for dietary transgression.

}, keywords = {Adolescent, Age Factors, Case-Control Studies, Celiac Disease, Child, Diet, Gluten-Free, Female, Humans, Internal-External Control, Italy, Male, Patient Compliance, Quality of Life}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2010.08.034}, author = {Bellini, Anna and Zanchi, Chiara and Martelossi, Stefano and Di Leo, Grazia and Not, Tarcisio and Ventura, Alessandro} } @article {1603, title = {Concentrated midazolam for intranasal administration: a pilot study.}, journal = {Pediatr Emerg Care}, volume = {27}, year = {2011}, month = {2011 Mar}, pages = {245-7}, keywords = {Administration, Intranasal, Child, Child, Preschool, Conscious Sedation, Dose-Response Relationship, Drug, Female, Humans, Hypnotics and Sedatives, Infant, Male, Midazolam, Pain, Pilot Projects, Preoperative Care}, issn = {1535-1815}, doi = {10.1097/PEC.0b013e31820db93b}, author = {Calligaris, Lorenzo and Davide, Zanon and Alessandra, Maestro and De Bortoli, Romina and Chiaretti, Antonio and Barbi, Egidio} } @article {1776, title = {Congenital aplasia of the optic chiasm and esophageal atresia: a case report.}, journal = {J Med Case Rep}, volume = {5}, year = {2011}, month = {2011}, pages = {335}, abstract = {

INTRODUCTION: The complete absence of the chiasm (chiasmal aplasia) is a rare clinical condition. Hypoplasia of the optic nerve and congenital nystagmus are almost invariably associated characteristics. Microphthalmos or anophthalmos are common features in chiasmal aplasia, while central nervous system abnormalities are less frequent. Esophageal atresia can be isolated or syndromic. In syndromic cases, it is frequently associated with cardiac, limb, renal or vertebral malformations and anal atresia. More rarely, esophageal atresia can be part of anophthalmia-esophageal-genital syndrome, which comprises anophthalmia or microphthalmia, genital abnormalities, vertebral defects and cerebral malformations. Here, a previously unreported case of chiasmal aplasia presenting without microphthalmos and associated with esophageal atresia is described.

CASE PRESENTATION: Aplasia of the optic chiasm was identified in a Caucasian Italian 8-month-old boy with esophageal atresia. An ultrasound examination carried out at 21 weeks{\textquoteright} gestation revealed polyhydramnios. Intrauterine growth retardation, esophageal atresia and a small atrial-septal defect were subsequently detected at 28 weeks{\textquoteright} gestation. Repair of the esophageal atresia was carried out shortly after birth. A jejunostomy was carried out at four months to facilitate enteral feeding. The child was subsequently noted to be visually inattentive and to be neurodevelopmentally delayed. Magnetic resonance imaging revealed chiasmal aplasia. No other midline brain defects were found. His karyotype was normal.

CONCLUSION: If achiasmia is a spectrum, our patient seems to depict the most severe form, since he appears to have an extremely severe visual impairment. This is in contrast to most of the cases described in the literature, where patients maintain good--or at least useful-- visual function. To the best of our knowledge, the association of optic nerve hypoplasia, complete chiasmal aplasia, esophageal atresia and atrial-septal defect, choanal atresia, hypertelorism and psychomotor retardation has never been described before.

}, issn = {1752-1947}, doi = {10.1186/1752-1947-5-335}, author = {Pensiero, Stefano and Cecchini, Paolo and Michieletto, Paola and Pelizzo, Gloria and Madonia, Maurizio and Parentin, Fulvio} } @article {1762, title = {Consensus on diagnosis and empiric antibiotic therapy of febrile neutropenia.}, journal = {Pediatr Rep}, volume = {3}, year = {2011}, month = {2011 Feb 24}, pages = {e4}, abstract = {

Controversial issues on the management of empiric therapy and diagnosis of febrile neutropenia (FN) were faced by a Consensus Group of the Italian Association of Pediatric Hematology-Oncology (AIEOP). In this paper we report the suggestions of the consensus process regarding the role of aminoglycosides, glycopeptides and oral antibiotics in empiric therapy of FN, the rules for changing or discontinuing the therapy as well as the timing of the blood cultures.

}, issn = {2036-7503}, doi = {10.4081/pr.2011.e4}, author = {Giurici, Nagua and Zanazzo, Giulio A} } @article {1655, title = {Corneal curvature and thickness development in premature infants.}, journal = {J Pediatr Ophthalmol Strabismus}, volume = {48}, year = {2011}, month = {2011 Jan-Feb}, pages = {25-9}, abstract = {

PURPOSE: Analysis of postnatal changes in central corneal thickness (CCT) and corneal curvature (CC) in premature infants, their relation, and their possible influence on eye growth and intraocular pressure (IOP) evaluation.

METHODS: CCT and CC were assessed in both eyes of 56 premature infants, born at 24 to 32 weeks of gestational age (GA), and then two or three times at post-conceptional ages (PCAs) of 28 to 42 weeks.

RESULTS: CC changed from 65.83 diopters at 28 weeks of PCA to 49.38 diopters at 42 weeks of PCA. CCT decreased from 794 to 559 μm at the same ages. The reductions of these two corneal parameters seem to be related to each other and begin immediately after birth.

CONCLUSION: In light of the few data available in the literature, these data provide more certainty about the CCT values of premature infants. The importance of CCT and CC fast variations after premature birth concerns both the knowledge of anterior segment development and the correct evaluation of IOP in immature eyes; the influence of these two parameters on the methods of IOP evaluation could be more remarkable at the lowest PCAs.

}, keywords = {Child Development, Cornea, Corneal Pachymetry, Eye, Female, Gestational Age, Humans, Infant, Newborn, Infant, Premature, Intraocular Pressure, Male, Premature Birth}, issn = {1938-2405}, doi = {10.3928/01913913-20100318-02}, author = {De Silva, Silvana and Parentin, Fulvio and Michieletto, Paola and Pensiero, Stefano} } @article {1741, title = {Cryptic genetic gluten intolerance revealed by intestinal antitransglutaminase antibodies and response to gluten-free diet.}, journal = {Gut}, volume = {60}, year = {2011}, month = {2011 Nov}, pages = {1487-93}, abstract = {

BACKGROUND AND OBJECTIVE: Antitransglutaminase (anti-TG2) antibodies are synthesised in the intestine and their presence seems predictive of future coeliac disease (CD). This study investigates whether mucosal antibodies represent an early stage of gluten intolerance even in the absence of intestinal damage and serum anti-TG2 antibodies.

METHODS: This study investigated 22 relatives of patients with CD genetically predisposed to gluten intolerance but negative for both serum anti-TG2 antibodies and intestinal abnormalities. Fifteen subjects were symptomatic and seven were asymptomatic. The presence of immunoglobulin A anti-TG2 antibodies in the intestine was studied by creating phage-antibody libraries against TG-2. The presence of intestinal anti-TG2 antibodies was compared with the serum concentration of the intestinal fatty acid-binding protein (I-FABP), a marker for early intestinal mucosal damage. The effects of a 12-month gluten-free diet on anti-TG2 antibody production and the subjects{\textquoteright} clinical condition was monitored. Twelve subjects entered the study as controls.

RESULTS: The intestinal mucosa appeared normal in 18/22; 4 had a slight increase in intraepithelial lymphocytes. Mucosal anti-TG2 antibodies were isolated in 15/22 subjects (68\%); in particular symptomatic subjects were positive in 13/15 cases and asymptomatic subjects in 2/7 cases (p=0.01). No mucosal antibodies were selected from the controls{\textquoteright} biopsies. There was significant correlation between the presence of intestinal anti-TG2 antibodies and positive concentrations of I-FABP (p=0.0008). After a gluten-free diet, 19/22 subjects underwent a second intestinal biopsy, which showed that anti-TG2 antibodies had disappeared in 12/15 (p=0.002), while I-FABP decreased significantly (p<0.0001). The diet resolved both extraintestinal and intestinal symptoms.

CONCLUSIONS: A new form of genetic-dependent gluten intolerance has been described in which none of the usual diagnostic markers is present. Symptoms and intestinal anti-TG2 antibodies respond to a gluten free-diet. The detection of intestinal anti-TG2 antibodies by the phage-antibody libraries has an important diagnostic and therapeutic impact for the subjects with gluten-dependent intestinal or extraintestinal symptoms. Clinical trial number NCT00677495.

}, keywords = {Adolescent, Adult, Antibodies, Anti-Idiotypic, Asymptomatic Diseases, Celiac Disease, Child, Child, Preschool, Diet, Gluten-Free, Fatty Acid-Binding Proteins, Female, Genetic Predisposition to Disease, GTP-Binding Proteins, Health Status, Humans, Intestinal Mucosa, Male, Middle Aged, Peptide Library, Transglutaminases, Young Adult}, issn = {1468-3288}, doi = {10.1136/gut.2010.232900}, author = {Not, Tarcisio and Ziberna, Fabiana and Vatta, Serena and Quaglia, Sara and Martelossi, Stefano and Villanacci, Vincenzo and Marzari, Roberto and Florian, Fiorella and Vecchiet, Monica and Sulic, Ana-Marija and Ferrara, Fortunato and Bradbury, Andrew and Sblattero, Daniele and Ventura, Alessandro} } @article {1660, title = {A case of lymphedema-distichiasis syndrome carrying a new de novo frameshift FOXC2 mutation.}, journal = {Ophthalmic Genet}, volume = {31}, year = {2010}, month = {2010 Jun}, pages = {98-100}, abstract = {

PURPOSE: Lymphedema-Distichiasis (LD, OMIM 153400) is an autosomal dominant disorder with variable expression. The mutated gene implicated is FOXC2, which encodes for a forkhead transcription factor involved in the development of the lymphatic and vascular system. LD is characterized by late childhood or pubertal onset lymphedema of the limbs and distichiasis. Other associations have been reported, including congenital heart disease, ptosis, scoliosis.

CONCLUSIONS: Here we describe a case of LD carrying a de novo frameshift mutation of FOXC2 who presented a prepubertal onset of lower limbs lymphedema and mild distichiasis associated with other anomalies such as webbing neck and ptosis.

}, keywords = {Abnormalities, Multiple, Adolescent, Eye Abnormalities, Eyelashes, Face, Forkhead Transcription Factors, Frameshift Mutation, Humans, Lymphedema, Male, Syndrome}, issn = {1744-5094}, doi = {10.3109/13816811003620517}, author = {Fabretto, Antonella and Shardlow, Alison and Faletra, Flavio and Lepore, Loredana and Hladnik, Uros and Gasparini, Paolo} } @article {1671, title = {A child with pain after mild trauma.}, journal = {J Pediatr}, volume = {157}, year = {2010}, month = {2010 Oct}, pages = {693}, keywords = {Antigens, CD, Antigens, CD31, Antigens, CD34, Antigens, Differentiation, Myelomonocytic, Biopsy, Child, Factor VIII, Fingers, Hand Injuries, Hemangioendothelioma, Humans, Immunohistochemistry, Injury Severity Score, Male, Osteolysis, Pain, Pain Measurement, S100 Proteins, Vascular Neoplasms}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2010.04.028}, author = {Londero, Margherita and Pastore, Serena and Zanazzo, Giulio A and Bruno, Irene and Ventura, Alessandro} } @article {1642, title = {Circulating levels of frizzled-related protein (FRZB) are increased in patients with early rheumatoid arthritis and decrease in response to disease-modifying antirheumatic drugs.}, journal = {Ann Rheum Dis}, volume = {69}, year = {2010}, month = {2010 Sep}, pages = {1733-4}, keywords = {Antirheumatic Agents, Arthritis, Rheumatoid, Biological Markers, Glycoproteins, Humans}, issn = {1468-2060}, doi = {10.1136/ard.2009.125732}, author = {Corallini, Federica and Secchiero, Paola and Castellino, Gabriella and Montecucco, Maurizio and Trotta, Francesco and Zauli, Giorgio} } @article {1641, title = {Corticosteroids do not cause harmful increase of viral load in severe H1N1 virus infection.}, journal = {Intensive Care Med}, volume = {36}, year = {2010}, month = {2010 Oct}, pages = {1780-1}, keywords = {Adult, Antiviral Agents, Bronchoalveolar Lavage Fluid, Extracorporeal Membrane Oxygenation, Glucocorticoids, Humans, Influenza A Virus, H1N1 Subtype, Influenza, Human, Male, Methylprednisolone, Oseltamivir, Respiration, Artificial, Severity of Illness Index, Viral Load, World Health Organization}, issn = {1432-1238}, doi = {10.1007/s00134-010-1964-8}, author = {Confalonieri, Marco and D{\textquoteright}Agaro, Pierlanfranco and Campello, Cesare} } @article {10449, title = {Comparison between procaine and isocarboxazid metabolism in vitro by a liver microsomal amidase-esterase.}, journal = {Biochem Pharmacol}, volume = {24}, year = {1975}, month = {1975 Aug 15}, pages = {1517-21}, keywords = {Amidohydrolases, Animals, Esterases, Hydrogen-Ion Concentration, In Vitro Techniques, Isocarboxazid, Kinetics, Male, Metals, Microsomes, Liver, Phospholipids, Procaine, Proteins, Rats, Subcellular Fractions, Temperature}, issn = {1873-2968}, author = {Moroi, K and Sato, T} }