Constructible Functions on 2-dimensional Analytic Manifolds

We present a characterization of sums of signs of global analytic functions on a real analytic manifold M of dimension two. Unlike the algebraic case, obstructions at infinity are not relevant: a function is a sum of signs on M if and only if this is true on each compact subset of M. This characterization gives a necessary and sufficient condition for an analytically constructible function, i.e. a linear combination with integer coefficients of Euler characteristic of fibres of proper analytic morphisms, to be such a sum of signs

Il Registro Toscano delle Malattie Rare

In meno di 10 anni l\u27attenzione per le malattie rare (MR) ha registrato una crescita cos? rapida da costituire un intervento prioritario tra le iniziative di sanit? pubblica. Fin dal 2001 il progetto regionale sulle MR si ? sviluppato in Toscana con la costante e significativa collaborazione delleAssociazioni dei malati, raccolte in un Forum. Si ? costituita una rete regionale di Presidi dedicati alla diagnosi e cura di queste patologie e delle strutture di coordinamento. Al fine di garantire la qualit? dei servizi prestati e l\u27informazione sui servizi erogati la Regione Toscana ha rinnovato il suo impegno sulle MR nel Piano Sanitario Regionale 2008-2010.In meno di 10 anni l\u27attenzione per le malattie rare (MR) ha registrato una crescita cos? rapida da costituire un intervento prioritario tra le iniziative di sanit? pubblica. Fin dal 2001 il progetto regionale sulle MR si ? sviluppato in Toscana con la costante e significativa collaborazione delleAssociazioni dei malati, raccolte in un Forum. Si ? costituita una rete regionale di Presidi dedicati alla diagnosi e cura di queste patologie e delle strutture di coordinamento. Al fine di garantire la qualit? dei servizi prestati e l\u27informazione sui servizi erogati la Regione Toscana ha rinnovato il suo impegno sulle MR nel Piano Sanitario Regionale 2008-2010

Rare diseases and congenital malformations integrated registry in Tuscany-Italy

Aims: Rare diseases (RD) are life-threatening or chronically debilitating diseases with prevalence of fewer than 5 cases among 10,000. For these conditions there is lack of scientific information, research, diagnosis, and treatment. To obtain epidemiological information the Italian Network of RD was set up in 2001. The Network is formed by Presidia specifically identified by each Region for diagnosis/treatment and by regional and national Registries. Among the 583 RDs eligible for free healthcare treatment, congenital malformation (CM) is the most frequent group with 254 diseases. Analysis of data and information available from both registries is therefore crucial to improve knowledge on the actual size of the CMs phenomenon also by activating an integrated system of registration. Methods: Linkage analysis was performed on data of the Tuscany Registries of CMs (RTDC) and of RDs (RTMR) for cases observed from 1992 to 2006 over approximately 420,000 surveilled resident births. Five specific rare CMs were selected: microcephaly, acrocephalosyndactyly, lissencephaly, oesophageal atresia, Down syndrome. Variables used for linkage were CM, names, date of birth, and residence. Results: Undernotification of rare CM cases more difficult to diagnose at birth like the lissencephaly was observed in the RTDC compared to the RTMR, while overlapping of record of cases emerged for other anomalies such as the Down syndrome. Linkage has allowed in some cases to better specify the diagnosis and to provide missing information. Conclusions: Use of different information sources has enabled to reduce undernotification of cases and to mutually validate information

Manuale utente - Screening audiologico neonatale (SCRAUN)

not availableLo scopo di questo documento-manuale utente ? di descrivere ad un utente come utilizzare via Internet il Sistema per il Screening Audiologico Neonatale (SCRAUN). Il sistema SCRAUN ? un sistema accessibile via web e costituisce l\u27implementazione della procedura di Screening descritta nel documento "ProgettoScreening.doc" scaricabile dal sito stesso. Il sistema SCRAUN sar? utilizzato da un insieme di utenti autorizzati, facenti parte della rete di neonatologi e di specialisti in otorinolaringoiatria e audiologia del Servizio Sanitario della Toscana, per registrare le nascite e gli esami di screening effettuati e per rilevare eventuali diagnosi di ipoacusia

Amyotrophic Lateral Sclerosis: results from Tuscany Registry of Rare Diseases.

Amyotrophic Lateral Sclerosis: results from Tuscany Registry of Rare Diseases. Anna Pierini, Federica Pieroni, Fabrizio Minichilli, Michela Rial and Fabrizio Bianchi Unit of Environmental Epidemiology, Institute of Clinical Physiology-CNR, Pisa Introduction: Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease with an incidence in Europe of approximately 2 per 100,000 per year. As the average disease duration from clinical onset is 3 years, prevalence is estimated at 6 per 100,000. In 90-95% of cases ALS occurs sporadically while 5-10% of cases are familiar. The specific cause of sporadic ALS is unknown while it has been hypothesized that some interactions can occur between genetic, environmental, and age-dependent risk factors. The Tuscany Registry of Rare Diseases (TRRD) was set up in 2005 and involves in data collection all public health centers in Tuscany. The Institute of Clinical Physiology-National Research Council (IFC-CNR) manages the TRRD which is part of the National Network for Rare Diseases leaded by Italian Health Institute. Objectives: To produce knowledge on ALS epidemiology: prevalence/incidence/survival, in Tuscany region. Methods: Age-standardized prevalence and incidence were calculated. Survival analysis was carried out by Kaplan-Meier method. Analysis was performed by Stata v.10. Results: In the period 2005-2009, it comes out in the TRDD are included 282 new patients with definite ALS, 234 of whom resident in Tuscany (122 men-112 women). The standardized average annual incidence in the study period (153 patients, age 20-99) is 0.81/100,000, the highest is 1.15/100,000 in 2006; the highest average incidence rate (2.41/100,000) is amongst patients aged 60-79. On 31 December 2009 (mortality data updated to 2008), the standardized prevalence was 5.36/100,000 (the highest registered is 5.87/100,000 in 2007). Survival rates at 1, 2, 3, 4 and 5 years after the onset were 86%, 70%, 58%, 48% and 44%, respectively. Conclusions: The results of the present study indicate that the incidence and prevalence of ALS in the Tuscany population seems to be lower compared to other populations and the survival of patients was longer than previously reported

Il Registro Regionale Malattie Rare della Toscana

Rare diseases (RDs) are life-threatening or chronically debilitating diseases with a prevalence lower than 5 cases among 10,000. For these conditions there is a lack of scientific information, research, diagnosis, treatment and expert availability. In 2001 the Italian Network for RDs was set up in order to obtain epidemiological information on these diseases. Presidia specifically identified by the Regions for diagnosis/treatment and by the Regional and National Registries are part of the national Network. Some RDs Registries were also created at the regional level. The Tuscany Registry for Rare Diseases (RTMR) is a network of presidia identified by the regional administration. The single presidium refers to a coordination centre for each group of RDs. The "G. Monasterio" Foundation for Medical Research and Public Health, formerly Institute of Clinical Physiology of the CNR, in charge of the Registry management, has produced a protocol, a questionnaire and a software allowing electronic registration of RD cases treated in Tuscany health centres via the Internet. Additionally, the local Register uploads local cases into the National Registry for RDs, coordinated by the Istituto Superiore di Sanit? (ISS). The registration questionnaire is divided in several sections and seeks information on patient, disease, diagnosis, tests performed for diagnosis, besides health condition and treatment. Cases are patients, dead or alive, diagnosed and followed by the Tuscan Presidia of the Regional Health System, including those residing outside the Region, properly diagnosed with one of the RDs included in the 279/2001 Ministerial Decree\u27s list. To ensure privacy, data can only be accessed using a login username and password assigned to each user. Further information is available on the Tuscan Registry for Rare Diseases website: www.rtmr.i

a metaproteomic pipeline to identify newborn mouse gut phylotypes

Abstract In order to characterize newborn mouse gut microbiota phylotypes in very early-life stages, an original metaproteomic pipeline, based on LC–MS 2 -spectra and Mascot driven NCBI non-redundant repository database interrogation was developed. An original computational analysis assisted in the generation of a taxonomic gut architecture from protein hits to operational taxonomic units (OTUs) and related functional categories. Regardless of the mouse's genetic background, a prevalence of Firmicutes (Lactobacillaceae) and Proteobacteria (Enterobacteriaceae) was observed among the entire Eubacteria taxonomic node. However, a higher abundance of Firmicutes was retrieved for Balb/c gut microbiota compared to Rag2 ko mice, the latter was mainly characterized by a Proteobacteria enriched microbiota. The metaproteomic-obtained OTUs were supported, for the identification (ID) of the cultivable bacteria fraction, corroborated by axenic culture-based MALDI-TOF MS IDs. Particularly, functional analysis of Rag2 ko mice gut microbiota proteins revealed the presence of abundant glutathione, riboflavin metabolism and pentose phosphate pathway components, possibly related to genetic background. The metaproteomic pipeline herein presented may represent a useful tool to investigate the highly debated onset of the human gut microbiota in the first days of life, when the bacterial composition, despite its very low diversity (complexity), is still very far from an exhaustive description and other complex microbial consortia. Biological significance The manuscript deals with a "frontier" topic regarding the study of the gut microbiota and the application of a metaproteomic pipeline to unveil the complexity of this fascinating ecosystem at the very early stages of life. Indeed during these phases, its diversity is very low but the bacterial content is highly "instable", and the relative balance between mucosal and fecal bacteria starts its dynamics of "fight" to get homeostasis. However, in the neonatal period, especially immediately after birth, a comprehensive description of this microbial eco-organ is still lacking, while it should be mandatory to highlight its first mechanisms of homeostasis and perturbation, while it co-develops with and within the host species. In order to unravel its low but almost unknown microbial community multiplicity, the newborn mouse gut, characterized by a "very" low complexity, was herein selected as model to design a LC–MS 2 -based shotgun metaproteomic approach, potentially suitable to study onset and shaping in human newborns. A microbiological semi-automatic computational analysis was performed to infer gut phylotypes; such as proof of evidence, related OTUs were compared to axenic-culture-based MALDI-TOF MS IDs showing consistency at family and phyla levels for the bacterial cultivable fraction. This article is part of a Special Issue entitled: Trends in Microbial Proteomics

Relationship between hemoglobin, hemolysis, and transcranial Doppler velocities in children with sickle cell disease: Results from a long-term natural history study in Italy in the era of multimodal therapy

Background: Stroke and cerebral vasculopathy are leading causes of morbidity and mortality in patients with sickle cell disease (SCD). Transcranial Doppler (TCD) is a reliable and validated predictor of stroke risk. Children with conditional or abnormal TCD are at an increased risk for stroke, which can be mitigated by red blood cell transfusion or hydroxyurea. Elucidating the relationship between cerebral hemodynamics and hemolytic anemia can help identify novel therapeutic approaches to reduce stroke risk and transfusion dependence.Methods: This long-term, real-world study was designed to evaluate the prevalence of TCD imaging (TCDi)-assessed flow velocities in children and to interrogate their relationship with markers of anemia and hemolysis.Results: In total, 155 children (median follow-up 79.8 months, 1358.44 patient-years) had 583 evaluable TCDi results. Only patients with HbSS or HbS beta(0) had abnormal (1.6%) or conditional (10.9%) TCDi. Children with abnormal or conditional TCDi had lower hemoglobin (Hb) and higher hemolysis markers. A linear correlation was detected between TCD velocity and Hb: an Hb increase of 1 g/dL corresponded to decreases in velocity in the internal carotid and middle cerebral arteries (6.137 cm/s and 7.243 cm/s). Moreover, patients with Hb >9 g/dL presented a lower risk of TCDi-associated events.Conclusion: These results support the need to optimize disease-modifying treatments that increase Hb and reduce hemolysis for stroke prevention in young children with SCD

Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

Background: In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related cognitive decline, with the most consistent effects against Alzheimer’s disease (AD) confined especially in the early or prodromal stages of the pathology. In the present study, we investigated the action of n-3 PUFA supplementation on behavioral performances and hippocampal neurogenesis, volume, and astrogliosis in aged mice subjected to a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valuable model to mimic one of the most reliable hallmarks of early AD neuropathology. Methods: Aged mice first underwent mu-p75-saporin immunotoxin intraventricular lesions to obtain a massive cholinergic depletion and then were orally supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks. Four weeks after the beginning of the dietary supplementation, anxiety levels as well as mnesic, social, and depressive-like behaviors were evaluated. Subsequently, hippocampal morphological and biochemical analyses and n-3 PUFA brain quantification were carried out. Results: The n-3 PUFA treatment regulated the anxiety alterations and reverted the novelty recognition memory impairment induced by the cholinergic depletion in aged mice. Moreover, n-3 PUFA preserved hippocampal volume, enhanced neurogenesis in the dentate gyrus, and reduced astrogliosis in the hippocampus. Brain levels of n-3 PUFA were positively related to mnesic abilities. Conclusions: The demonstration that n-3 PUFA are able to counteract behavioral deficits and hippocampal neurodegeneration in cholinergically depleted aged mice promotes their use as a low-cost, safe nutraceutical tool to improve life quality at old age, even in the presence of first stages of AD

Impact of Pharmacological Inhibition of Hydrogen Sulphide Production in the SOD1G93A-ALS Mouse Model

A number of factors can trigger amyotrophic lateral sclerosis (ALS), although its precise pathogenesis is still uncertain. In a previous study done by us, poisonous liquoral levels of hydrogen sulphide (H2S) in sporadic ALS patients were reported. In the same study very high concentrations of H2S in the cerebral tissues of the familial ALS (fALS) model of the SOD1G93A mouse, were measured. The objective of this study was to test whether decreasing the levels of H2S in the fALS mouse could be beneficial. Amino-oxyacetic acid (AOA)\u2014a systemic dual inhibitor of cystathionine--synthase and cystathionine- lyase (two key enzymes in the production of H2S)\u2014was administered to fALS mice. AOA treatment decreased the content of H2S in the cerebral tissues, and the lifespan of female mice increased by approximately ten days, while disease progression in male mice was not aected. The histological evaluation of the spinal cord of the females revealed a significant increase in GFAP positivity and a significant decrease in IBA1 positivity. In conclusion, the results of the study indicate that, in the animal model, the inhibition of H2S production is more eective in females. The findings reinforce the need to adequately consider sex as a relevant factor in AL