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Diagnosis of isolated posterior fossa anomalies in children is biased by the fact that only those that are symptomatic are brought to the attention of the appropriate clinical personnel, and the reported rate is often affected by the adoption of different nomenclature, diagnostic criteria, outcome measures, duration of follow-up and neurodevelopmental tools. The aim of this systematic review was to explore the neurodevelopmental outcome of fetuses with a prenatal diagnosis of isolated posterior fossa anomalies.MEDLINE and EMBASE were searched electronically, utilizing combinations of the relevant medical subject heading terms for 'posterior fossa' and 'outcome'. Studies assessing the neurodevelopmental outcome in children with a prenatal diagnosis of isolated posterior fossa malformations were considered eligible. The posterior fossa anomalies analyzed included Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). Two authors reviewed all abstracts independently. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Meta-analyses of proportions were used to combine data, and between-study heterogeneity was explored using the I(2) statistic.A total of 1640 articles were identified; 95 were assessed for eligibility and a total of 16 studies were included in the systematic review. The overall rate of abnormal neurodevelopmental outcome in children with a prenatal diagnosis of DWM was 58.2% (95% CI, 21.8-90.0%) and varied from 0-100%. In those with a prenatal diagnosis of MCM, the rate of abnormal neurodevelopmental outcome was 13.8% (95% CI, 7.3-21.9%), with a range of 0-50%. There was no significant association between BPC and the occurrence of abnormal neurodevelopmental delay, with a rate of 4.7% (95% CI, 0.7-12.1%) and range of 0-5%. Although affected by the very small number of studies, there was a non-significant occurrence of abnormal neurodevelopmental delay in children with a prenatal diagnosis of VH, with a rate of 30.7% (95% CI, 0.6-79.1%) and range of 0-100%.Fetuses diagnosed with isolated DWM are at high risk of abnormal neurodevelopmental outcome, while isolated MCM or BPC have a generally favorable outcome. The risk of abnormal developmental delay in cases with isolated VH needs to be further assessed. In view of the wide heterogeneity in study design, time of follow-up, neurodevelopmental tests used and the very small number of included cases, further future large prospective studies with standardized and objective protocols for diagnosis and follow-up are needed in order to ascertain the rate of abnormal neurodevelopmental outcome in children with isolated posterior fossa anomalies. Copyright © 2015 ISUOG. Published by John WileySons Ltd.

Phosphatidylinositol (PI) signaling is an essential regulator of cell motility and proliferation. A portion of PI metabolism and signaling takes place in the nuclear compartment of eukaryotic cells, where an array of kinases and phosphatases localize and modulate PI. Among these, Diacylglycerol Kinases (DGKs) are a class of phosphotransferases that phosphorylate diacylglycerol and induce the synthesis of phosphatidic acid. Nuclear DGKalpha modulates cell cycle progression, and its activity or expression can lead to changes in the phosphorylated status of the Retinoblastoma protein, thus, impairing G1/S transition and, subsequently, inducing cell cycle arrest, which is often uncoupled with apoptosis or autophagy induction. Here we report for the first time not only that the DGKalpha isoform is highly expressed in the nuclei of human erythroleukemia cell line K562, but also that its nuclear activity drives K562 cells through the G1/S transition during cell cycle progression. J. Cell. Physiol. 232: 2550-2557, 2017. © 2016 Wiley Periodicals, Inc.

INTRODUCTION: The first aim of this study was to ascertain the diagnostic performance of first trimester ultrasound in detecting congenital anomalies in twins. The secondary aim was to explore the strength of association between different pregnancy characteristics and early detection of structural anomalies in a large unselected population of twin pregnancies. A systematic review of the published literature was also carried out MATERIAL AND METHODS: Retrospective analysis of prospectively collected data from consecutive twin pregnancies booked for antenatal care from 1996 till 2014. Predictive accuracy of those covariates independently associated with the occurrence of fetal anomalies were assessed with logistic regression analysis and ROC curves RESULTS: 1064 twin pregnancies (820 dichorionic and 264 monochorionic) were included in the analysis. 42 pregnancies had one or more fetuses with structural abnormalities. Detection of structural abnormalities using ultrasound was possible in the first trimester in 27.3% (95% CI: 15.0-42.8) of twin pregnancies. Mono-chorionicity (OR 2.3, 95% CI: 1.1-4.7) and discordance in crown-rump length and nuchal translucency were associated with an increased risk of fetal anomalies. However, their predictive accuracy was only moderate (AUC: 0.67, 95% CI: 0.6-0.8 and 0.68, 95% CI: 0.6 - 0.8, for crown-rump length and nuchal translucency discrepancy respectively CONCLUSIONS: First trimester detection of structural abnormalities in twin pregnancies is possible in 27.3% (95% CI: 15.0-42.8) of cases. The likelihood for first trimester detection of structural anomalies in twins was maximum for cranial vault, midline brain and abdominal wall defects. Monochorionicity and increasing discrepancy in crown-rump length and nuchal translucency were associated with fetal structural abnormalities, although their predictive performance was only moderately good. This article is protected by copyright. All rights reserved.

The Erice Charter was unanimously approved at the conclusion of the 47th Residential Course "Adapted Physical Activity in Sport, Wellness and Fitness: New Challenges for Prevention and Health Promotion", held on 20-24 April 2015 in Erice, Italy, at the "Ettore Majorana" Foundation and Centre for Scientific Culture, and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group on Movement Sciences for Health of the Italian Society of Hygiene, Preventive Medicine and Public Health. After an intense discussion the participants identified the main points associated with the relevance of physical activity for Public Health, claiming the pivotal role of the Department of Prevention in coordinating and managing preventive actions. The participants underlined the importance of the physicians specialized in Hygiene, Preventive Medicine and Public Health. The contribution of other operators such as physicians specialized in Sport Medicine was stressed. Further, the holders of the new degree in Human Movement and Sport Sciences were considered fundamental contributors for the performance of physical activity and their presence was seen as a promising opportunity for the Departments of Prevention. Primary prevention based on recreational physical activities should become easily accessible for the population, avoiding obstacles such as certification steps or complex bureaucracy. The Sport Doctor is recognized as the principal referent for preliminary physical evaluation and clinical monitoring in secondary and tertiary prevention actions based on adapted physical activities. Developing research in the field is essential as well as implementing higher education on physical activity management in Schools of Public Health.

Introduction. It was recognized early on that an Evidence-Based Medicine (EBM) approach could be applied to Public Health (PH), including the area of Occupational Health (OH). The aim of Evidence-Based Occupational Health (EBOH) is to ensure safety, health, and well-being in the workplace. Currently, high-quality research is necessary in order to provide arguments and scientific evidence upon which effective, efficient, and sustainable preventive measures and policies are to be developed in the workplace in Western countries. Occupational physicians need to integrate available scientific evidence and existing recommendations with a framework of national employment laws and regulations. Objective. This paper addresses the state of the art of scientific evidence available in the field (i.e., efficacy of interventions, usefulness of education and training of workers, and need of a multidisciplinary strategy integrated within the national PH programs) and the main critical issues for their implementation. Conclusions. Promoting good health is a fundamental part of the smart, inclusive growth objectives of Europe 2020 - Europe's growth strategy: keeping people healthy and active for longer has a positive impact on productivity and competitiveness. It appears clear that health quality and safety in the workplace play a key role for smart, sustainable, and inclusive growth in Western countries.

Background: Lenalidomide is currently used in the treatment of del(5q) lowrisk MDS patients, where it may suppress the del(5q) clone and restore a normal erythropoiesis. The exact molecular mechanisms underlying the effect of Lenalidomide in MDS patients are not completely understood, even though it has been demonstrated that in Lenalidomide-sensitive del(5q) cell lines, Akt phosphorylation is inhibited. Interestingly, Akt signalling is activated both in high-risk MDS, where it activates cell proliferation, and in low-risk MDS, where it is associated with response to erythropoietin. Aims: To detect the specific effect of Lenalidomide on clonal del(5q) and normal (5q+) cells, in low-risk MDS patients and in cell lines, mainly focusing on erythropoiesis, cell cycle and signal transduction pathways involved in cell proliferation and differentiation. Methods: This study included 6 patients diagnosed with del(5q) MDS (IPSS: Low or Int-1) treated with Lenalidomide. Given the limited number of cells, we quantified the expression of Akt in bone marrow total mononuclear cells by immunocytochemistry only. In particular, we analyzed Akt and RPS14 co-localization, in order to specifically detect the del(5q) clone. Moreover, by Real-Time PCR analyses, we also assessed the expression of Globin genes, to evaluate the effect of the drug on erythropoiesis. To better discriminate between del(5q) and normal (5q+) cells, we studied the effect of Lenalidomide on Namalwa cells, showing a del(5q) karyotype, and in U937 cells, showing a normal 5q chromosome. In both cell lines, we quantified the expression of Globin genes, cell cycle and inositide signalling molecules, by Real-Time PCR, immunocytochemistry, Western blot and flow cytometry. Results: In our case series, 4/6 del(5q) low-risk MDS patients responded to Lenalidomide, whereas the 2 non responder patients early discontinued Lenalidomide for adverse events, and for these patients neither a clinical assessment of Lenalidomide effect, nor a molecular analysis, were possible. Responder patients showed an activation of erythropoiesis, in that Beta-Globin levels increased, as compared with baseline. Moreover, these subjects displayed a specific phosphorylation of Akt in cells not showing the 5q deletion. As for cell lines, Lenalidomide specifically induced an accumulation of Namalwa cells in G0/G1 phase, which corresponded to a slight decrease of p-Akt, an increase of p27 and a decreased expression of cyclin B1, cyclin E and cyclin D3. On the contrary, in normal (5q+) cells, Lenalidomide did not affect cell cycle, but induced both p-Akt and Gamma-Globin. Summary and Conclusions: Our data show that Lenalidomide can induce a selective arrest of cell cycle in G1 phase of del(5q) cells, therefore slowing the proliferation rate of this clonal cell population. On the contrary, cyclins, Akt and Gamma-Globin are specifically activated in normal (5q+) cells, possibly stimulating a normal cell proliferation and erythroid differentiation. Taken together, these findings could lead to a better comprehension of the effect of Lenalidomide in MDS and pave the way to innovative targeted therapies in low-risk MDS patients without del(5q).

To explore the outcome of fetuses with a prenatal diagnosis of ovarian cyst.The electronic databases MEDLINE and EMBASE were searched using keywords and word variants for 'ovarian cysts', 'ultrasound' and 'outcome'. The following outcomes in fetuses with a prenatal diagnosis of ovarian cyst were explored: resolution of the cyst, change of ultrasound pattern of the cyst, occurrence of ovarian torsion and intracystic hemorrhage, need for postnatal surgery, need for oophorectomy, accuracy of prenatal ultrasound examination in correctly identifying ovarian cyst, type of ovarian cyst at histopathological analysis and intrauterine treatment. Meta-analyses using individual data random-effects logistic regression and meta-analyses of proportions were performed. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale.Thirty-four studies (954 fetuses) were included. In 53.8% (95% CI, 46.0-61.5%) of cases for which resolution of the cyst was evaluated (784 fetuses), the cyst regressed either during pregnancy or after birth. The likelihood of resolution was significantly lower in complex vs simple cysts (odds ratio (OR), 0.15 (95% CI, 0.10-0.23)) and in cysts measuring ≥ 40 mm vs 40 mm (OR, 0.03 (95% CI, 0.01-0.06)). Change in ultrasound pattern of the cyst was associated with an increased risk of ovarian loss (surgical removal or autoamputation) (pooled proportion, 57.7% (95% CI, 42.9-71.8%)). The risk of ovarian torsion was significantly higher for cysts measuring ≥ 40 mm compared with 40 mm (OR, 30.8 (95% CI, 8.6-110.0)). The likelihood of having postnatal surgery was higher in patients with cysts ≥ 40 mm compared with 40 mm (OR, 64.4 (95% CI, 23.6-175.0)) and in complex compared with simple cysts, irrespective of cyst size (OR, 14.6 (95% CI, 8.5-24.8)). In cases undergoing prenatal aspiration of the cyst, rate of recurrence was 37.9% (95% CI, 14.8-64.3%), ovarian torsion and intracystic hemorrhage were diagnosed after birth in 10.8% (95% CI, 4.4-19.7%) and 12.8% (95% CI, 3.8-26.0%), respectively, and 21.8% (95% CI, 0.9-40.0%) had surgery after birth.Size and ultrasound appearance are the major determinants of perinatal outcome in fetuses with ovarian cysts. Copyright © 2016 ISUOG. Published by John WileySons Ltd.

Hypomethylating agents, such as 5-Azacytidine (AZA), significantly modified the therapeutic approach to MDS, primarily in older patients with higher risk disease for whom intensive chemotherapy and allogeneic stem cell transplantation are not an option. In low-risk MDS, 5- AZA aims to reduce transfusion dependency, improve quality of life and hopefully the survival, but it is still unclear if this therapeutic approach would be cost-effective. At a molecular level, the mechanisms underlying the effect of epigenetic therapy are not completely understood, although it is well known that DNA methyltransferase inhibitors can induce the expression of Phosphoinositide-Phospholipase C (PIPLC) beta1 in high-risk MDS. Here, we prospectively investigated the efficacy and safety of AZA in low-risk MDS patients. AZA was administered at a lower intensity schedule, that is 75 mg/sqm/day subcutaneous for 5 days every 28, for a total of 8 cycles, and response was assessed at the 4th and 8th cycle of AZA. Moreover, PI-PLCbeta1 promoter methylation and gene expression levels were quantified before and after each cycle of 5-AZA. The study included 32 patients, and 26 cases completed 8 cycles of AZA. ORR was 47% (15/32) on intention to treat and 58% (15/26) for patients completing the treatment program. In this latter group, 5 (19%) cases achieved CR and 10 (38%) had HI, according to the IWG criteria. Interestingly, three patients have maintained their HI after 37, 34 and 33 months without other treatments. At a molecular level, although baseline PI-PLCbeta1 levels were not correlated to clinical response, 5d-AZA induced a statistically significant decrease in PI-PLCbeta1 promoter methylation in 14/15 responders, which corresponded to a significant increase in PI-PLCbeta1 mRNA. In 9/14 (64%) responsive patients, the first molecular increase in PI-PLCbeta1 level was observed between the 3rd and 4th cycle, therefore anticipating the clinical evaluation. In addition, 8 cases showed a loss of the response after the end of therapy (8th cycle) and these cases displayed a significant reduction of PI-PLCbeta1 levels, below the pre-treatment values, already before the clinical loss of the response. Taken together, our results show that 5d-AZA is safe and effective in a proportion of low risk MDS patients. PI-PLCbeta1 gene expression is a reliable and dynamic marker of response that can be useful to optimize AZA therapy.

Background Our study aimed to estimate the prevalence of pregnancy e-health seekers in a large Italian sample; to explore the factors influencing the choices of the childbearing women regarding their lifestyles after internet consultation; and finally to investigate potential differences between primiparous and multiparous women in internet use to find information about pregnancy. Methods A multicentre survey was carried out in seven Italian cities. Data were collected through a validated questionnaire administered in waiting rooms of outpatient departments by medical doctors. Respondents were questioned about their sociodemographic status, their use of the internet to seek pregnancy information and their consequent choices to modify their lifestyles. Data were analysed using descriptive statistics and logistic regression. Results Almost all women were pregnancy e-health seekers (95%), including those who also received information from healthcare professionals. Indeed, the main reason for searching the web was the need of further knowledge on pregnancy-related topic, over and beyond other key advantages of the net such as anonymity, simplicity and rapidity. A higher likelihood of changing lifestyle after pregnancy e-health was observed among the women who searched institutional websites; declared more confidence in the information retrieved; participated into pregnancy-centred forum online; and were residents in Italy. Conclusions To reduce the likelihood for women of both finding erroneous information or misinterpreting correct ones, healthcare professionals should commit to fill the information gap and guide pregnant women in the online searches. Also, future studies are strongly needed to analyse the quality and accuracy of health information found on the web.

Background:There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families.Methods:This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community.Results:The societal burden of AD, composed of public, patient, and informal care costs, was about €20,000/yr. Out of this, the cost borne by the public sector was €4,534/yr. The main driver of public cost was the national cash-for-care allowance (€2,324/yr), followed by drug prescriptions (€1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at €13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure.Conclusion:The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556).

It was recognized early on that an Evidence-Based Medicine (EBM) approach could be applied to Public Health (PH), including the area of Occupational Health (OH). The aim of Evidence-Based Occupational Health (EBOH) is to ensure safety, health, and well-being in the workplace. Currently, high-quality research is necessary in order to provide arguments and scientific evidence upon which effective, efficient, and sustainable preventive measures and policies are to be developed in the workplace in Western countries. Occupational physicians need to integrate available scientific evidence and existing recommendations with a framework of national employment laws and regulations.This paper addresses the state of the art of scientific evidence available in the field (i.e., efficacy of interventions, usefulness of education and training of workers, and need of a multidisciplinary strategy integrated within the national PH programs) and the main critical issues for their implementation.Promoting good health is a fundamental part of the smart, inclusive growth objectives of Europe 2020 - Europe's growth strategy: keeping people healthy and active for longer has a positive impact on productivity and competitiveness. It appears clear that health quality and safety in the workplace play a key role for smart, sustainable, and inclusive growth in Western countries.