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Language production has often been described as impaired in psychiatric diseases such as in psychosis. Nevertheless, little is known about the characteristics of linguistic difficulties and their relation with other cognitive domains in patients with a first episode of psychosis (FEP), either affective or non-affective. To deepen our comprehension of linguistic profile in FEP, 133 patients with FEP (95 non-affective, FEP-NA; 38 affective, FEP-A) and 133 healthy controls (HC) were assessed with a narrative discourse task. Speech samples were systematically analyzed with a well-established multilevel procedure investigating both micro- (lexicon, morphology, syntax) and macro-linguistic (discourse coherence, pragmatics) levels of linguistic processing. Executive functioning and IQ were also evaluated. Both linguistic and neuropsychological measures were secondarily implemented with a machine learning approach in order to explore their predictive accuracy in classifying participants as FEP or HC. Compared to HC, FEP patients showed language production difficulty at both micro- and macro-linguistic levels. As for the former, FEP produced shorter and simpler sentences and fewer words per minute, along with a reduced number of lexical fillers, compared to HC. At the macro-linguistic level, FEP performance was impaired in local coherence, which was paired with a higher percentage of utterances with semantic errors. Linguistic measures were not correlated with any neuropsychological variables. No significant differences emerged between FEP-NA and FEP-A (p≥0.02, after Bonferroni correction). Machine learning analysis showed an accuracy of group prediction of 76.36% using language features only, with semantic variables being the most impactful. Such a percentage was enhanced when paired with clinical and neuropsychological variables. Results confirm the presence of language production deficits already at the first episode of the illness, being such impairment not related to other cognitive domains. The high accuracy obtained by the linguistic set of features in classifying groups support the use of machine learning methods in neuroscience investigations.

Background Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16–50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes. Results Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p p p p p p p p p p Conclusion Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants’ prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications.

Aim: This study investigated the different strategies used in 11 European countries to prevent hypothermia, which continues to affect a large proportion of preterm births in the region. Methods: We examined the association between the reported use of hypothermia prevention strategies in delivery rooms and body temperatures on admission to neonatal intensive care units (NICUs) in 5861 infants born at 22 + 0 to 31 +6 weeks of gestation. The use of plastic bags, wraps, caps, exothermic heat and mattresses was investigated. Results: The proportion of infants born in units that systematically used one or more hypothermia prevention strategies was 88.2% and 50.9% of those infants were hypothermic on admission to NICUs. Of the 9.6% born in units without systematic hypothermia prevention, 73.2% were hypothermic. Only 2.2% of infants were born in units with no reported prevention strategies. Lower gestational age increased the probability of hypothermia. No significant differences were found between the various hypothermia prevention strategies. Hyperthermia was seen in 4.8% of all admitted infants. Conclusion: Very preterm infants had lower risks of hypothermia on NICU admission if the unit used systematic prevention strategies. All the strategies had similar effects, possibly due to implementation rather than a strategy's specific efficacy.

International audience; OBJECTIVE: To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates.METHODS: Area-based cohort study of all births before 32 weeks of gestational age.METHODS: 16 regions in 11 European countries in 2011/2012.METHODS: Survivors to discharge from neonatal care (n=6422).METHODS: Severe neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics.RESULTS: 10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%-23.5%) and 13.8% including severe BPD (regional range 10.0%-23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%-18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P

Objectives: The use of magnesium sulfate (MgSO4) in European obstetric units is unknown. We aimed to describe reported policies and actual use of MgSO4 in women delivering before 32 weeks of gestation by indication. Methods: We used data from the European Perinatal Intensive Care in Europe (EPICE) population-based cohort study of births before 32 weeks of gestation in 19 regions in 11 European countries. Data were collected from April 2011 to September 2012 from medical records and questionnaires. The study population comprised 720 women with severe preeclampsia, eclampsia or HELLP and 3658 without preeclampsia delivering from 24 to 31 weeks of gestation in 119 maternity units with 20 or more very preterm deliveries per year. Results: Among women with severe pre-eclampsia, eclampsia or HELLP, 255 (35.4%) received MgSO4 before delivery. 41% of units reported use of MgSO4 whenever possible for pre-eclampsia and administered MgSO4 more often than units reporting use sometimes. In women without pre-eclampsia, 95 (2.6%) received MgSO4. 9 units (7.6%) reported using MgSO4 for fetal neuroprotection whenever possible. In these units, the median rate of MgSO4 use for deliveries without severe pre-eclampsia, eclampsia and HELLP was 14.3%. Only 1 unit reported using MgSO4 as a first-line tocolytic. Among women without preeclampsia, MgSO4 use was not higher in women hospitalised before delivery for preterm labour. Conclusions: Severe pre-eclampsia, eclampsia or HELLP are not treated with MgSO4 as frequently as evidence-based medicine recommends. MgSO4 is seldom used for fetal neuroprotection, and is no longer used for tocolysis. To continuously lower morbidity, greater attention to use of MgSO4 is needed.

Aim This study assessed the prevalence of small for gestational age (SGA) among very preterm (VPT) infants using national and European intrauterine references. Methods We generated country-specific and common European intrauterine growth references for 11 European countries, according to Gardosi's approach and Hadlock's fetal growth model, by using national data on birth weights by sex. These references were applied to the Effective Perinatal Intensive Care in Europe (EPICE) cohort, which comprised 7,766 live VPT births without severe congenital anomalies under 32 weeks of gestation in 2011-12, to estimate the prevalence of infants with SGA birth weights, namely those below the 10th percentile. Results The SGA prevalence was 31.8% with country-specific references and 34.0% with common European references. The European references yielded a 10-point difference in the SGA prevalence between countries with lower term birth weights (39.9%) - Portugal, Italy and France - and higher term birth weights, namely Denmark, Netherlands, Sweden (28.9%) (p

Background: Respiratory Syncytial Virus (RSV) is one of the main causes of respiratory infections during the first year of life. Very premature infants may contract more severe diseases and 'late preterm infants' may also be more susceptible to the infection. The aim of this study is to evaluate the risk factors for hospitalization during the first year of life in children born at different gestational ages in Italy. Methods: A cohort of 33-34 weeks gestational age (wGA) newborns matched by sex and age with two cohort of newborns born at 35-37 wGA and >37 wGA were enrolled in this study for a three-year period (2009-2012). Hospitalization for bronchiolitis (ICD-9 code 466.1) during the first year of life was assessed through phone interview at the end of the RSV season (November-March) and at the completion of the first year of life. Results: The study enrolled 2314 newborns, of which 2210 (95.5 %) had a one year follow-up and were included in the analysis; 120 (5.4 %) were hospitalized during the first year of life for bronchiolitis. Children born at 33-34 wGA had a higher hospitalization rate compared to the two other groups. The multivariate analysis carried out on the entire population associated the following factors with higher rates for bronchiolitis hospitalization: male gender; prenatal treatment with corticosteroids; prenatal exposure to maternal smoking; singleton delivery; respiratory diseases in neonatal period; surfactant therapy; lack of breastfeeding; siblings

Background Tobacco smoke exposure (TSE) is a worldwide health problem and it is considered a risk factor for pregnant women’s and children’s health, particularly for respiratory morbidity during the first year of life. Few significant birth cohort studies on the effect of prenatal TSE via passive and active maternal smoking on the development of severe bronchiolitis in early childhood have been carried out worldwide. Methods From November 2009 to December 2012, newborns born at ≥33 weeks of gestational age (wGA) were recruited in a longitudinal multi-center cohort study in Italy to investigate the effects of prenatal and postnatal TSE, among other risk factors, on bronchiolitis hospitalization and/or death during the first year of life. Results Two thousand two hundred ten newborns enrolled at birth were followed-up during their first year of life. Of these, 120 (5.4 %) were hospitalized for bronchiolitis. No enrolled infants died during the study period. Prenatal passive TSE and maternal active smoking of more than 15 cigarettes/daily are associated to a significant increase of the risk of offspring children hospitalization for bronchiolitis, with an adjHR of 3.5 (CI 1.5–8.1) and of 1.7 (CI 1.1–2.6) respectively. Conclusions These results confirm the detrimental effects of passive TSE and active heavy smoke during pregnancy for infants’ respiratory health, since the exposure significantly increases the risk of hospitalization for bronchiolitis in the first year of life. Electronic supplementary material The online version of this article (doi:10.1186/s12931-015-0312-5) contains supplementary material, which is available to authorized users.

BACKGROUND:Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P

A group of 103 sicilian patients with hereditary and familiar breast and/or ovarian cancer were screened for Breast Cancer 1 gene (BRCA1) mutations by direct sequencing PCR products spanning the coding region and partial intronic regions of the BRCA1 gene. In this study, we report a new germline mutation in BRCA1 gene, not previously reported in the BIC database, in a woman with ovarian cancer at 46 years old. Mother's proband has been diagnosed the same histotype of ovarian cancer at 42 age. The mutational analyses that shown a 4843delC frameshift mutation in exon 16 of BRCA1 gene was extended to other family members including the proband's brother and her two sons. Direct automatic sequencing of DNA extracted from the lymphocytes showed exactly the same 4843delC frameshift mutation only in the brother. In conclusion, the characterization of this mutation could help in the identification of a founder mutation of sicilian area and this may provide significant advantages for genetic counselling.

Background Neonatal units’ volume of activity, and other quantitative and qualitative variables, such as staffing, workload, work environment, care organization and geographical location, may influence the outcome of high risk newborns. Data about the distribution of these variables and their relationships among Italian neonatal units are lacking. Methods Between March 2010-April 2011, 63 neonatal intensive care units adhering to the Italian Neonatal Network participated in the SONAR Nurse study. Their main features and work environment were investigated by questionnaires compiled by the chief and by physicians and nurses of each unit. Twelve cross-sectional monthly-repeated surveys on different shifts were performed, collecting data on number of nurses on duty and number and acuity of hospitalized infants. Results Six hundred forty five physicians and 1601 nurses compiled the questionnaires. In the cross-sectional surveys 702 reports were collected, with 11082 infant and 3226 nurse data points. A high variability was found for units’ size (4–50 total beds), daily number of patients (median 14.5, range 3.4-48.7), number of nurses per shift (median 4.2, range 0.7-10.8) and number of team meetings per month. Northern regions performed better than Central and Southern regions for frequency of training meetings, qualitative assessment of performance, motivation within the unit and nursing work environment; mean physicians’ and nurses’ age increased moving from North to South. After stratification by terciles of the mean daily number of patients, the median number of nurses per shift increased at increasing volume of activity, while the opposite was found for the nurse-to-patient ratio adjusted by patients’ acuity. On average, in units belonging to the lower tercile there was 1 nurse every 2.5 patients, while in those belonging to the higher tercile the ratio was 1 nurse every 5 patients. Conclusions In Italy, there is a high variability in organizational characteristics and work environment among neonatal units and an uneven distribution of human resources in relation to volume of activity, suggesting that the larger the unit the greater the workload for each nurse. Urgent modifications in planning and organization of services are needed in order to pursue more efficient, homogeneous and integrated regionalized neonatal care systems.

Objective: To provide the first Italian data on pathogens causing early-onset sepsis (EOS) and their antimicrobial susceptibility, after the successfully prevention of Group B streptococcus (GBS) EOS. Methods: Retrospective area-based cohort study from Emilia-Romagna (Italy). Cases of EOS registered (from 2009 to 2012) in all gestational age neonates were reviewed. Results: Live births (LB) numbered 146 682. Ninety neonates had EOS and 12 died (incidence rates of 0.61 and 0.08/1000 LB, respectively). EOS and mortality were the highest among neonates with a birth weight n = 27, 0.18/1000 LB) and Escherichia coli (n = 19, 0.13/1000 LB). Most infants affected by E. coli EOS were born preterm (n = 13), had complications (n = 4) or died (n = 7). Among 90 isolates tested, only 3 were resistant to both first line empirical antibiotics. Multivariate logistic regression analysis showed that low gestational age, caesarean section and low platelet count at presentation were significantly associated with death or brain lesions (area under ROC curve = 0.939, H-L = 0.944, sensitivity 76.0%, specificity 90.7%). Conclusions: GBS slightly exceeds E. coli as a cause of EOS. However, E. coli is the prominent cause of death, complications and in most cases affects preterm neonates. Empirical antimicrobial therapy of EOS seems appropriate.

Background: Gastric cancer (GC) development is a multistep process, during which numerous alterations accumulate in nuclear and mitochondrial DNA. A deficiency of repair machinery brings about an accumulation of errors introduced within simple repetitive microsatellite sequences during replication of DNA. Aberrant methylation is related to microsatellite instability (MSI) by the silencing of the hMLH1 gene. The aim of this study is to investigate a possible relationship between the RUNX3 promoter methylation, nuclear microsatellite instability (nMSI) and mitochondrial microsatellite instability (mtMSI), in order to clarify its biological role in GC. Patients and methods: nMSI and mtMSI were evaluated in a consecutive series of 100 GC patients. For the analysis of the nMSI, we followed the National Cancer Institute guidelines. mtMSI was assessed by analyzing a portion of the displacement-loop region. The aberrant methylation of RUNX3 was analyzed in 40 GC patients by methylation-specific PCR. Results: Overall, 55% of GC demonstrated methylation of the RUNX3 promoter; 82% of GC was classified as stable microsatellite instability, 5% as low-level microsatellite instability and 13% as high-level microsatellite instability (MSI-H); mtMSI was detected in 11 % of GC. A significant association was found between mtMSI and tumor-node-metastasis staging, furthermore an interesting association between MSI-H status, mtMSI and RUNX3 methylation. Conclusion: These data suggest that RUNX3 is an important target of methylation in the evolution of mtMSI and nMSI-H GC.

PURPOSE: To evaluate the contribution of germline BRCA1 mutations in the incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer (OC) in patients from Southern Italy (in the region of Sicily) and to identify a possible association between the higher frequency of BRCA1 mutations and a specific familial profile. EXPERIMENTAL DESIGN: A consecutive series of 650 patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from the Southern Italian region of Sicily, after interview at the "Regional Reference Centre for the Characterization and Genetic Screening of Hereditary Tumors" at the University of Palermo. Genetic counselling allowed us to recruit a total of 106 unrelated families affected with breast and/or ovarian cancer screened for mutations occurring in the whole BRCA1 gene by automatic direct sequencing. RESULTS: Germline BRCA1 mutations were found in 17 of 106 (16%) Sicilian families. The HBOC profile had a major frequency (66%) of mutations (P < 0.01). A total of 28 sequence variants was identified. Seven of these were pathogenic, 5 unknown biological variant (UV) and 16 polymorphisms. We also identified a pathological mutation (4843delC) as a possible Sicilian founder mutation. CONCLUSIONS: The present study is the first BRCA1 disease-associated mutations analysis in Southern Italian families. The early age of onset of such tumors and the association with the HBOC familial profile could be two valid screening factors for the identification of BRCA1 mutation carriers. Finally, we identified a BRCA1 mutation with a possible founder effect

The putative role of TP53 and p16INK4A tumor suppressor genes and Ras oncogenes in the development and progression of salivary gland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case of carcinoma ex-PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/Single Strand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific-PCR (MS-PCR). Mutations in TP53 were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H-Ras and K-Ras were identified in4%(1/28) and7% (2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutations in K-Ras. p16INK4A promoter hypermethylation was found in 14% (4/28) of PAs and 100% (5/5) carcinomas. All genetic and epigenetic alterations were detected exclusively in the epithelial and transitional tumor components, and were absent in the mesenchymal parts. Our analysis suggests that TP53 mutations and p16INK4A promoter methylation, but not alterations in the H-Ras and K-Ras genes, might be involved in the malignant progression of PA into carcinoma. J. Cell. Physiol. 207: 654–659, 2006. 2006 Wiley-Liss, Inc.

BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P

Background Over 600 different pathogenic mutations have been identified in the BRCA1 gene. Nevertheless, numerous missense mutations of unknown biological function still exist. Understanding of biological significance of these mutations should help in genetic counselling to carriers and their families. Patients and methods A total of 104 patients with breast and/or ovarian cancer whose genetic counselling answered the criteria of the American Society of Clinical Oncology (ASCO 2003), were prospectively screened for mutations in all coding exons of the BRCA1 gene by automatic direct sequencing. Results During these mutational screening procedures one case presented three mutations classified in the Breast Cancer Information Core Database as unknown variants. These were 655A/G found in exon 8 of BRCA1, 1575T/C and 1767A/C found in exon 11 of the same gene. The identification of the three unknown variants in the proband (16SIRIO) and in her mother and sister indicates that such alterations exist in cis. Conclusions Our results suggest that the charge and stechiometry variations determined by the changes in the amino acids Y179C, F486L and N550H might produce an effect on the conformation of the protein and, consequently, on its function.

Background: The role of nasal continuous positive airways pressure (nCPAP) in the management of respiratory distress syndrome in preterm infants is not completely defined. Objective: To evaluate the benefits and risks of prophylactic nCPAP in infants of 28–31 weeks gestation. Design: Multicentre randomised controlled clinical trial. Setting: Seventeen Italian neonatal intensive care units. Patients: A total of 230 newborns of 28–31 weeks gestation, not intubated in the delivery room and without major malformations, were randomly assigned to prophylactic or rescue nCPAP. Interventions: Prophylactic nCPAP was started within 30 minutes of birth, irrespective of oxygen requirement and clinical status. Rescue nCPAP was started when FIO2 requirement was > 0.4, for more than 30 minutes, to maintain transcutaneous oxygen saturation between 93% and 96%. Exogenous surfactant was given when FIO2 requirement was > 0.4 in nCPAP in the presence of radiological signs of respiratory distress syndrome. Main outcome measures: Primary end point: need for exogenous surfactant. Secondary end points: need for mechanical ventilation and incidence of air leaks. Results: Surfactant was needed by 22.6% in the prophylaxis group and 21.7% in the rescue group. Mechanical ventilation was required by 12.2% in both the prophylaxis and rescue group. The incidence of air leaks was 2.6% in both groups. More than 80% of both groups had received prenatal steroids. Conclusions: In newborns of 28–31 weeks gestation, there is no greater benefit in giving prophylactic nCPAP than in starting nCPAP when the oxygen requirement increases to a FIO2 > 0.4.

INTRODUCTION: Variation of respiratory care is described between centers around the world. The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. METHODS: We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. RESULTS: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. CONCLUSIONS. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement.

Introduction: DianaWeb is a community-based participatory project open to Italian breast cancer patients. The aim of the study was to assess the effectiveness of a lifestyle intervention in improving the prognosis after patients received diagnosis and surgery/chemotherapy. The DianaWeb study uses an interactive Web site (www.dianaweb.org) to monitor patients’ lifestyles, and to obtain clinical and anthropometric data. Although detailed instructions for measuring height, body weight, waist circumference, and blood pressure (BP) are provided, individuals might tend to overestimate or underestimate those parameters. The aims of the present study were: (1) to compare self-recorded data with those from standardized ambulatory measurements; (2) to determine the trueness of a subject classification in the overweight/obesity or hypertensive subgroup on the basis of the patients’ own measurements and estimates; and (3) to identify confounding variables. Patients and Methods: We compared self-reported with ambulatory measurements in a subgroup of 200 randomly selected women of approximately 1000 enrolled in the DianaWeb study (from September 2016 to March 2018). Results: Bland–Altman analysis showed a close agreement for self-reported and ambulatory-measured height, weight, and body mass index (BMI). On the contrary, women overestimated waist circumference and underestimated BP. Cohen κ statistics showed fair agreement only for hypertension. Binary logistic regression analysis showed that BMI and diastolic BP self-measurements were biased according to age. Conclusion: The results suggest that self-reported height, weight, and BMI are satisfactorily accurate for patients in the DianaWeb study, such as accuracies of overweight/obese and central obesity classification, and that these data can be useful for our research. We evaluated the validity of self-reported anthropometric measures in 200 women of approximately 1000 participating the DianaWeb study, a community-based participatory research offered to Italian breast cancer patients. Self-reported height, weight, and body mass index resulted to be satisfactorily accurate, and self-reported weight, height, and waist circumference were appropriate to estimate overweight/obese and central obesity in participants of the DianaWeb study.

Objective: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. Study design: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. Results: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. Conclusion: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. Trial registration: isrctn.org: ISRCTN53107700.

Metabolic syndrome (MS), conventionally defined by the presence of at least three out of five dysmetabolic traits (abdominal obesity, hypertension, low plasma HDL-cholesterol, high plasma glucose and high triglycerides), has been associated with an increased risk of several age-related chronic diseases, including breast cancer (BC). This may have prognostic implications for BC survivors. 2,092 early stage BC survivors aged 35-70, recruited in eleven Italian centres 0-5 years after surgical treatment (1.74 years on average), were followed-up over 2.8 years on average for additional BC-related events, including BC-specific mortality, distant metastasis, local recurrences and contralateral BC. At recruitment, 20 % of the patients had MS. Logistic regression models were carried out to generate OR and 95 % confidence intervals (CI) for new BC events associated with MS, adjusting for baseline pathological prognostic factors. New BC events occurred in 164 patients, including 89 distant metastases. The adjusted ORs for women with MS versus women without any MS traits were 2.17 (CI 1.31-3.60) overall, and 2.45 (CI 1.24-4.82) for distant metastasis. The OR of new BC events for women with only one or two MS traits was 1.40 (CI 0.91-2.16). All MS traits were positively associated with new BC events, and significantly so for low HDL and high triglycerides. MS is an important prognostic factor in BC. As MS is reversible through lifestyle changes, interventions to decrease MS traits in BC patients should be implemented in BC clinics.

During childhood and adolescence, a game could be an effective educational tool to learn healthy eating habits. We developed Kaledo, a new board game, to promote nutrition education and to improve dietary behavior. A two-group design with one pre-treatment assessment and two post-treatment assessments was employed. A total of 3,110 subjects (9-19years old) from 20 schools in Campania, Italy, were included in the trial. In the treated group, the game was introduced each week over 20 consecutive weeks. Control group did not receive any intervention. The primary outcomes were (i) score on the "Adolescent Food Habits Checklist" (AFHC), (ii) scores on a dietary questionnaire, and (iii) BMI z-score. At the first post-assessment (6months), the treated group obtained significantly higher scores than the control group on the AFHC (14.4 (95% confidence interval (CI) 14.0 to 14.8) vs 10.9 (95% CI 10.6 to -11.2); F(1,20) = 72.677; p

Multiple Sulfatase Deficiency (MSD; OMIM 272200) is a rare autosomal recessive inborn error of metabolism caused by mutations in the sulfatase modifying factor 1 gene, encoding the formylglycine-generating enzyme (FGE), and resulting in tissue accumulation of sulfatides, sulphated glycosaminoglycans, sphingolipids and steroid sulfates. Less than 50 cases have been published so far. We report a new case of MSD presenting in the newborn period with hypotonia, apnoea, cyanosis and rolling eyes, hepato-splenomegaly and deafness. This patient was compound heterozygous for two so far undescribed SUMF1 mutations (c.191C > A; p.S64X and c.818A > G; p.D273G).

Aims and BackgroundThe DIANA (Diet and Androgens)-5 study is a multi-institutional randomized controlled trial of the effectiveness of a diet based on Mediterranean and macrobiotic recipes and principles, associated with moderate physical activity, in reducing additional breast cancer events in women with early stage invasive breast cancer at high risk of recurrence because of metabolic or endocrine milieu. The intervention is expected to reduce serum insulin and sex hormones, which were associated with breast prognosis in previous studies.MethodsBetween 2008 and 2010, the study randomly assigned 1208 patients to an intensive diet and exercise intervention or to a comparison group, to be followed-up through 2015. General lifestyle recommendations for the prevention of cancer are given to both groups, and the intervention group is being offered a comprehensive lifestyle intervention, including cooking classes, conferences, common meals and exercise sessions. Adherence assessments occurred at baseline and at 12 months and are planned at 36 and 60 months. They include food frequency diaries, anthropometric measures, body fat distribution assessed with impedance scale, one week registration of physical activity with a multisensor arm-band monitor, metabolic and endocrine blood parameters. Outcome breast cancer events are assessed through self report at semi annual meetings or telephone interview and are validated through medical record verification.ResultsThe randomized groups were comparable for age (51.8 years), proportion of ER-negative tumors (22%), axillary node metastasis (42%), reproductive variables, tobacco smoking, blood pressure, anthropometric measurements and hormonal and metabolic parameters.ConclusionsDIANA-5 has the potential to establish whether a Mediterranean-macrobiotic lifestyle may reduce breast cancer recurrences. We will assess evidence of effectiveness, first by comparing the incidence of additional breast cancer events (local or distant recurrence, second ipsilateral or contralateral cancer) in the intervention and in the control group, by an intention-to-treat analysis, and second by analyzing the incidence of breast cancer events in the total study population by compliance assessment score.

A computer-aided detection (CAD) system for the selection of lung nodules in computer tomography (CT) images is presented. The system is based on region growing (RG) algorithms and a new active contour model (ACM), implementing a local convex hull, able to draw the correct contour of the lung parenchyma and to include the pleural nodules. The CAD consists of three steps: (1) the lung parenchymal volume is segmented by means of a RG algorithm; the pleural nodules are included through the new ACM technique; (2) a RG algorithm is iteratively applied to the previously segmented volume in order to detect the candidate nodules; (3) a double-threshold cut and a neural network are applied to reduce the false positives (FPs). After having set the parameters on a clinical CT, the system works on whole scans, without the need for any manual selection. The CT database was recorded at the Pisa center of the ITALUNG-CT trial, the first Italian randomized controlled trial for the screening of the lung cancer. The detection rate of the system is 88.5% with 6.6 FPs/CT on 15 CT scans (about 4700 sectional images) with 26 nodules: 15 internal and 11 pleural. A reduction to 2.47 FPs/CT is achieved at 80% efficiency. © 2007 American Association of Physicists in Medicine.

Introduction: An apparent re-emergence of kernicterus has been recently reported, with some cases occurring in otherwise healthy breastfed newborn. Methods: We describe a case of kernicterus in a term Caucasian newborn. Results: An exceptional polymorphism of UGT1A1 gene promoter co-existed with asymptomatic inherited spherocytosis, due to erythroid anion exchange (band-3) deficiency. Both concurred to the development of severe neonatal hyperbilirubinaemia. Conclusion: As some cases of kernikterus remain unresolved, haemolytic diseases and bilirubin metabolism disorders should be carefully investigated in unexplained severe neonatal hyperbilirubinaemia.