Search

In this paper we report the observations of HD189733b, Kepler-41b, Kepler-42b, GJ 436b, WASP-77ab, HAT-P-32b and EPIC 211818569 as measured at the Osservatorio Polifunzionale del Chianti, a new astro-nomical site in Italy. Commissioning observing runs have been done in order to test capabilities, systematics and limits of the system and to improve its accuracy. For this purpose, a software algorithm has been developed to estimate the differential photometric error of any transit observation, so that the integration time can be chosen to reach optimal signal-to-noise ratios, and to obtain a picture of what kind of transits this setup can reveal. Currently, the system is able to reach an accuracy of about 1 mmag and so it is ready for the much needed exoplanetary transit follow-up. [ABSTRACT FROM AUTHOR]

The GERmanium Detector Array (Gerda) is a low background experiment located at the Laboratori Nazionali del Gran Sasso in Italy, which searches for neutrinoless double-beta decay of 76 Ge into 76 Se+2e - . Gerda has been conceived in two phases. Phase II, which started in December 2015, features several novelties including 30 new 76Ge enriched detectors. These were manufactured according to the Broad Energy Germanium (BEGe) detector design that has a better background discrimination capability and energy resolution compared to formerly widely-used types. Prior to their installation, the new BEGe detectors were mounted in vacuum cryostats and characterized in detail in the Hades underground laboratory in Belgium. This paper describes the properties and the overall performance of these detectors during operation in vacuum. The characterization campaign provided not only direct input for Gerda Phase II data collection and analyses, but also allowed to study detector phenomena, detector correlations as well as to test the accuracy of pulse shape simulation codes. [ABSTRACT FROM AUTHOR]

We report on searches for neutrinos and antineutrinos from astrophysical sources performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso in Italy. Electron antineutrinos (ν ¯ e) are detected in an organic liquid scintillator through the inverse β -decay reaction. In the present work we set model-independent upper limits in the energy range 1.8–16.8 MeV on neutrino fluxes from unknown sources that improve our previous results, on average, by a factor 2.5. Using the same data set, we first obtain experimental constraints on the diffuse supernova ν ¯ e fluxes in the previously unexplored region below 8 MeV. A search for ν ¯ e in the solar neutrino flux is also presented: the presence of ν ¯ e would be a manifestation of a non-zero anomalous magnetic moment of the neutrino, making possible its conversion to antineutrinos in the strong magnetic field of the Sun. We obtain a limit for a solar ν ¯ e flux of 384 cm–2 s–1 (90% C.L.), assuming an undistorted solar 8B neutrinos energy spectrum, that corresponds to a transition probability p ν e → ν ¯ e < 7.2 × 10–5 (90% C.L.) for E ν ¯ e > 1.8 MeV. At lower energies, by investigating the spectral shape of elastic scattering events, we obtain a new limit on solar 7Be- ν e conversion into ν ¯ e of p ν e → ν ¯ e < 0.14 (90% C.L.) at 0.862 MeV. Last, we investigate solar flares as possible neutrino sources and obtain the strongest up-to-date limits on the fluence of neutrinos of all flavor neutrino below 3–7 MeV. Assuming the neutrino flux to be proportional to the flare's intensity, we exclude an intense solar flare as the cause of the observed excess of events in run 117 of the Cl-Ar Homestake experiment. [ABSTRACT FROM AUTHOR]

We present the first search for bosonic superweakly interacting massive particles (super-WIMPs) as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-β decay experiment which operates high-purity germanium detectors enriched in 76Ge in an ultralow background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60  keV/c² to 1  MeV/c². No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120  keV/c² have been set. As an example, at a mass of 150  keV/c² the most stringent direct limits on the dimensionless couplings of axionlike particles and dark photons to electrons of gae<3×10-12 and α′/α<6.5×10-24 at 90% credible interval, respectively, were obtained. [ABSTRACT FROM AUTHOR]

Among Italian hospital physicians and general practitioners, 17.9% endorsed euthanasia or assisted suicide for terminally ill patients and 79.4% endorsed withholding or withdrawal of treatment. Need for attention to quality of life and pain control also emerged. [ABSTRACT FROM AUTHOR]

To reach fusion conditions and control the plasma configuration in ITER, the next step in tokamak fusion research, two neutral beam injectors (NBIs) will supply 16.5 MW each, by neutralizing accelerated negative hydrogen or deuterium ions. The requirements of ITER NBIs (40A/1 MeV D- ions for ≤1 h, 46A/870 keV H- ions for ≤1000 s) have never been simultaneously attained. So in the Neutral Beam Test Facility (NBTF, Consorzio RFX, Italy) the operation of the full-scale ITER NBI prototype (MITICA) will be tested and optimised up to full performances, focussing on accelerator (including voltage holding), beam optics, neutralisation, residual ion removal. The NBTF includes also the full-scale prototype of the ITER NBI source with 100 keV particle energy (SPIDER), for early investigation of: negative ion production and extraction, source uniformity, negative ion current density and beam optics. This paper will describe the main results of the first two years of SPIDER operation, devoted to characterizing plasma and beam parameters, including investigation of RF-plasma coupling efficiency and magnetic filter field effectiveness in reducing co-extracted electrons. SPIDER is progressing towards the first caesium injection, which aims at increasing the negative ion density. A major shutdown, planned for 2021, to solve the issues identified during the operation and to carry out programmed modifications, will be outlined. The installation of each MITICA power supply and auxiliary system is completed; in-vessel mechanical components are under procurement by Fusion for Energy (F4E). Integration, commissioning and test of the power supplies, procured by F4E and QST, as the Japanese Domestic Agency (JADA), will be presented. In particular, 1.0MV insulating tests were carried out step-by-step and successfully completed. In 2020 integrated tests of the power supplies on the accelerator dummy load started, including the assessment of their resilience to accelerator grid breakdowns using a short-circuit device located in vacuum. The aggressive programme, to validate the NBI design at NBTF and to meet ITER schedule (requiring NBIs in operation in 2032), will be outlined. Unfortunately, in 2020 the coronavirus disease infection affected the NBTF activities. A solution to proceed with integrated power tests despite the coronavirus is presented. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted Arm Therapy (RAT) has been increasingly applied in the last years for promoting functional recovery in patients with disabilities related to neurological health conditions. Evidence of a knowledge-to-action gap for applying robot-assisted technologies in the rehabilitation of patients with neurological health conditions and the difficulty to apply and tailor the knowledge to the local contexts solicited the need for a national consensus conference on these interventions., Aim: The aim of this paper was to explain the methodology used by the working group dedicated to synthesizing evidence on the effectiveness of RAT in neurological health conditions in the context of the CICERONE Italian Consensus Conference., Design: The methodological approach of the working group., Setting: All rehabilitation settings., Population: Patients with disability following a neurological health condition., Methods: Following the indications proposed by the Methodological Manual published by the Italian National Institute of Health, a Promoting Committee and a Technical Scientific Committee have been set up. Six working groups (WGs) have been composed to collect evidence on different questions, among which WG2.2 was focused on the effectiveness of RAT in neurological health conditions., Results: WG2.2 started its work defining the specific research questions. It was decided to adopt the ICF as the reference framework for the reporting of all outcomes. Literature search, data extraction and qualitative assessment, evidence analysis and synthesis have been performed., Conclusions: This paper summarized the methodological approaches used by the WG2.2 of the CICERONE Italian Consensus Conference to define the effectiveness of RAT in the management of patients with neurological health conditions., Clinical Rehabilitation Impact: WG2.2 synthesis might help clinicians, researchers, and all rehabilitation stakeholders to address the use of RAT in the Individualized Rehabilitation Plan, to guide the allocation of resources and define clinical protocols and indications for the management of patients with different neurological health conditions.

Background: Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to examine the etiological factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available., Methods: Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks., Results: The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks., Conclusion: The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.

Pertussis vaccination coverage in the Marche region is one of the lowest in Italy, with the province of Pesaro-Urbino remaining stable below 95% coverage since at least 2013. In this paper, we retrospectively analyzed all whooping cough notification cards arriving at the prevention department of the Area Vasta 1 Health Office in the Marche region and relating to the Pesaro-Urbino province (Italy). Between 2012 and 2017, there were 28 reported cases of pertussis with a peak in 2016 (11 cases, of which seven were in Urbino). The 28 patients were mostly male (65%), and had a mean age of 9 years. Three of these were not Italian. Between 2012 and 2017, the district of Pesaro reported the highest number of cases (almost 46.5% of the total), followed by Urbino (28.5%) and Fano (25%). The average incidence in the province in the period in question, still under 2 cases/100,000 inhabitants, arrived in 2016 at 4 cases/100,000 inhabitants. In particular, in Urbino there was an unforeseen incidence >8 cases/100,000 inhabitants. There were no deaths, although two children (both under 12 months of age) were hospitalized. Our data confirm that in 2016 there was a pertussis epidemic in Urbino (Italy).

Background: Insulin-resistance and hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion Barrett's Esophagus (BE). HER2 activation has also a pivotal role in EAC carcinogenesis but no data correlate these two phenomena in this disease context., Aims: To investigate the role of hyperinsulinemia in BE-dysplasia-adenocarcinoma sequence and the possible relationship between insulin-mediated and HER2 signaling in EAC development., Methods: Serum insulin, C-peptide, IGF1, glucagon, IL-6, TNF-alpha, leptin, adiponectin and Insulin-Resistance-index were analyzed in 19 patients with gastro-esophageal reflux disease, 51 with BE, 24 with dysplastic-BE and 14 with EAC. Insulin/IGF1/HER2 pathways were analyzed in esophageal biopsies using Luminex ® Technology. Insulin effect was also evaluated in EAC-derived OE19 cells. Data were analyzed by Fisher's exact test, Kruskal-Wallis test, Mann-Whitney U-test, Cuzick's test and Spearman correlation coefficient calculation., Results: Insulin-Resistance-index, insulin and C-peptide levels increased along with disease progression (p=0.019, p=0.002, p<0.0001, respectively) and correlated with HER2 expression and with downstream mediators phospho-Akt and phospho-mTOR in esophageal tissue. In vitro, insulin was also able to induce cell proliferation through HER2 activation., Conclusions: Our data pinpoint a possible role of hyperinsulinemia in the Barrett's Esophagus metaplasia-dysplasia-adenocarcinoma sequence through HER2 activation in esophageal epithelial cells., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Data from large case series of children with cerebral thrombotic events are pivotal to improve prevention, early recognition and treatment of these conditions. The Italian Registry of Pediatric Thrombosis (R. I. T. I.) was established in 2007 by a multidisciplinary team, aiming for a better understanding of neonatal and paediatric thrombotic events in Italy and providing a preliminary source of data for the future development of specific clinical trials and diagnostic-therapeutic protocols. We analysed data relative to the paediatric cerebral thrombotic events of the R. I. T. I. which occurred between January 2007 and June 2012. In the study period, 79 arterial ischaemic stroke (AIS) events (49 in males) and 91 cerebral sinovenous thrombosis (CSVT) events (65 in males) were enrolled in the R. I. T. I. Mean age at onset was 4.5 years in AIS, and 7.1 years in CSVT. Most common modes of presentation were hemiparesis, seizures and speech disturbances in AIS, and headache, seizures and lethargy in CSVT. Most common etiologies were underlying chronic diseases, vasculopathy and cardiopathy in AIS, and underlying chronic diseases and infection in CSVT. Time to diagnosis exceeded 24 hours in 46 % AIS and 59 % CSVT. Overall data from the Italian Registry are in substantial agreement with those from the literature, despite small differences. Among these, a longer time to diagnosis compared to other registries and case series poses the accent to the need of an earlier recognition of paediatric cerebrovascular events in Italy, in order to enable prompt and effective treatment strategies.

MUTYH variants are differently distributed in geographical areas of the world. In MUTYH-associated polyposis (MAP) patients from North-Eastern Italy, c.933+3A>C (IVS10+3A>C), a transversion causing an aberrant splicing process, accounts for nearly 1/5 of all mutations. The aim of this study was to verify whether its high frequency in North-Eastern Italy is due to a founder effect and to clarify its impact on MUTYH transcripts and protein. Haplotype analysis and age estimate performed on members of eleven Italian MAP families and cancer-free controls provided evidence that c.933+3A>C is a founder mutation originated about 83 generations ago. In addition, the Italian haplotype associated with the c.933+3A>C was also found in German families segregating the same mutation, indicating it had a common origin in Western Europe. Altogether c.933+3A>C and the two common Caucasian mutations p.Tyr179Cys and p.Gly396Asp represent about 60% of MUTYH alterations in MAP patients from North-Eastern Italy, suggesting the opportunity to perform targeted molecular screening for these variants in the diagnostic setting. Expression analyses performed on lymphoblastoid cell lines supported the notion that MUTYH c.933+3A>C alters splicing causing the synthesis of a non functional protein. However, some primary transcripts escape aberrant splicing, producing traces of full-length transcript and wild-type protein in a homozygote; this is in agreement with clinical findings that suggest a relatively mild phenotypic effect for this mutation. Overall, these data, that demonstrate a founder effect and further elucidate the splicing alterations caused by the MUTYH c.933+3A>C mutation, have important implications for genetic counseling and molecular diagnosis of MAP., (Copyright © 2012 UICC.)

Background: Attenuated familial adenomatous polyposis (AFAP) is characterized by the presence of 10-99 colorectal adenomas. The disease may be associated with mutations in either APC or MUTYH genes. We purposed to evaluate the contribution of adenomatous polyposis coli (APC) and MutY homologue (MUTYH) germline alterations to the AFAP phenotype and to identify genotype/phenotype correlations., Methods: During counselling for familial adenomatous polyposis (FAP), 91 probands (and 107 affected individuals) who met the criteria of AFAP were identified. Eighty-two families were screened for constitutional mutations of the APC and MUTYH genes., Results: MUTYH mutations were detected in 21 families (25.6 % of the 82 tested), and APC mutations in 7 (8.5 %). Overall, constitutional alterations were found in 34.1 % of the probands. Patients with APC mutations were younger at cancer onset and had a higher mean number of polyps (48.5 ± 33.0 in APC+ individuals vs. 35.7 ± 24.9 in MUTYH+ individuals, and 33.2 ± 18.4 in the "no mutation" group). Clinical features rendered the "no mutation" group closer to MUTYH+ than to the APC+ group. Colorectal cancer at diagnosis was detected in 40 % of AFAP individuals., Conclusions: AFAP is a new clinical entity with its frequency in the general population still undefined. The number of adenomas varies greatly, with an average of 30-40 lesions. The molecular basis of AFAP can be established in approximately 1/3 of the patients. Both MUTYH and APC genes are implicated in AFAP, though the role of MUTYH is of considerably greater relevance.

The aim of the study was to identify which groups of women contribute to interinstitutional variation of caesarean delivery (CD) rates and which are the reasons for this variation. In this regard, 15,726 deliveries from 11 regional centers were evaluated using the 10-group classification system. Standardized indications for CD in each group were used. Spearman's correlation coefficient was used to calculate (1) relationship between institutional CD rates and relative sizes/CD rates in each of the ten groups/centers; (2) correlation between institutional CD rates and indications for CD in each of the ten groups/centers. Overall CD rates correlated with both CD rates in spontaneous and induced labouring nulliparous women with a single cephalic pregnancy at term (P = 0.005). Variation of CD rates was also dependent on relative size and CD rates in multiparous women with previous CD, single cephalic pregnancy at term (P < 0.001). As for the indications, "cardiotocographic anomalies" and "failure to progress" in the group of nulliparous women in spontaneous labour and "one previous CD" in multiparous women previous CD correlated significantly with institutional CD rates (P = 0.021, P = 0.005, and P < 0.001, resp.). These results supported the conclusion that only selected indications in specific obstetric groups accounted for interinstitutional variation of CD rates.

The experimental findings herein reported are aimed at gaining a perspective on the complex neural events that follow lesions of the motor cortical areas. Cortical damage, whether by trauma or stroke, interferes with the flow of descending signals to the modular interneuronal structures of the spinal cord. These spinal modules subserve normal motor behaviors by activating groups of muscles as individual units (muscle synergies). Damage to the motor cortical areas disrupts the orchestration of the modules, resulting in abnormal movements. To gain insights into this complex process, we recorded myoelectric signals from multiple upper-limb muscles in subjects with cortical lesions. We used a factorization algorithm to identify the muscle synergies. Our factorization analysis revealed, in a quantitative way, three distinct patterns of muscle coordination-including preservation, merging, and fractionation of muscle synergies-that reflect the multiple neural responses that occur after cortical damage. These patterns varied as a function of both the severity of functional impairment and the temporal distance from stroke onset. We think these muscle-synergy patterns can be used as physiological markers of the status of any patient with stroke or trauma, thereby guiding the development of different rehabilitation approaches, as well as future physiological experiments for a further understanding of postinjury mechanisms of motor control and recovery.

The reported incidence of hereditary colorectal cancers (CRCs) is widely variable. The principal aim of the study was to prospectively evaluate the incidence of familial CRCs in a region of northern Italy using a standardized method. Consecutive CRC patients were prospectively enrolled from October 2002 to December 2003. Patients underwent a structured family history, the microsatellite instability (MSI) test and a screen for MUTYH mutations. Following family history patients were classified as belonging to high, moderate and mild risk families. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins and investigation for MLH1/MSH2 mutations, for MLH1 promoter methylation and for the V600E hotspot BRAF mutation were performed in high MSI (MSI-H) cases. Of the 430 patients enrolled, 17 (4%) were high risk [4 hereditary non-polyposis colorectal cancer (HNPCC), 12 suspected HNPCC and 1 MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. The MSI test was performed on 393 tumours, and 46 (12%) of them showed MSI-H. In these patients, one MLH1 pathogenetic mutations and two MSH2 pathogenetic mutations were found. Thirty-two (70%) MSI-H cases demonstrated MLH1 methylation and/or BRAF mutation: None of them showed MLH1/MSH2 mutation. Two biallelic germline MUTYH mutations were found, one with clinical features of MAP. A strong family history of CRC was present in 4% of the enrolled cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3% and of MSI-H phenotype was 12%. MLH1 methylation and BRAF mutation can exclude 70% of MSI-H cases from gene sequencing.

Purpose: The risk of cancer or severe polyposis of the rectal stump after total colectomy for MutYH-associated polyposis is scarcely defined. To evaluate this risk, we describe the findings of endoscopic surveillance of the rectal stump in a series of patients with biallelic MutYH mutations and polyposis., Methods: This is a retrospective, observational, multicenter case series derived from 2 familial cancer registries. Biallelic, germ-line MutYH mutations were found in 14 patients with no adenomatous polyposis coli gene mutations. Eleven of them underwent total colectomy with ileorectal anastomosis and yearly proctoscopic surveillance thereafter. Phenotype and histology of rectal polyps were recorded at diagnosis and during follow-up. Development of adenomas and carcinomas during endoscopic surveillance of the rectal stump was observed., Results: At diagnosis, 6 patients had attenuated polyposis (10-100 adenomas), 5 patients had classical polyposis, 8 patients had colon carcinoma, and no patient had rectal carcinoma. The mean number of rectal polyps at diagnosis was 2.64 ± 2.11 (range, 0-6). No patients had rectal cancer. The most frequent MutYH mutations were Y165C/Y165C and G382D/G382D in 6 and 2 patients, respectively. During surveillance of the rectal stump after surgery (median duration, 5 y; range, 2-23 y), no patient developed rectal cancer. The mean number of adenomas per proctoscopy was 1.23 ± 2.19 (range, 0-10 adenomas per proctoscopy). This study was limited by the small size and retrospective nature of the case series., Conclusion: Total colectomy with ileorectal anastomosis may be appropriate for patients with MutYH-associated polyposis, provided that they have no rectal cancer or severe rectal polyposis at presentation and that they undergo yearly endoscopic surveillance thereafter.

We describe seven cases of meningitis in a group of young Italian travelers coming back from India. Virologic studies identified echovirus-4 as the cause of this cluster of cases, the first imported echovirus outbreak in Italy. Enteroviruses may play an important role in undiagnosed fevers in travelers.

Background and Aim of the Study: The aim of this study was to evaluate the early and mid-term off-pump coronary artery bypass surgery (OPCAB) results in a single surgical unit, assessing the impact of completeness of revascularization., Methods: Three hundred and twelve patients underwent OPCAB between August 2000 and January 2005. In-hospital data were collected prospectively for all patients undergoing OPCAB. Complete revascularization (CR) was derived by comparing significantly stenotic vessels at cardiac catheterization with surgically grafted coronary vessels. Grafting of all the significantly stenotic coronary vessels was considered CR. In-hospital outcomes were compared between patients with CR and incomplete revascularization (IR). A multivariate analysis based on the Cox proportional hazards regression model was performed., Results: Patients receiving IR (105 patients, 43.7%) presented a worse preoperative risk profile then those having CR (mean Euroscore 6.8 +/- 2.9 vs. 4.3 +/- 2.8, p < 0.0001). IR was not associated with a higher incidence of early adverse events. Five-year freedom from death and major adverse cardiac events (MACE) were 0.88 (0.02 SE) and 0.86 (0.03 SE), respectively. Complete revascularization was protective for mid-term unstable angina recurrence [heart rate (HR) = 0.24, 95% confidence interval (CI) 0.10 to 0.58], acute myocardial infarction (HR = 0.25, 95% CI 0.09 to 0.73), all-cause repeat revascularization (HR = 0.35, 95% CI 0.13 to 0.90), and MACE (HR = 0.2, 95% CI 0.1 to 0.5)., Conclusion: Our study suggests that, although incomplete revascularization may not result in increased short-term morbidity and mortality, it increases the incidence of mid-term MACE.

Background: The aim of this study was to evaluate the midterm results of the initial phase of off-pump coronary artery bypass (OPCAB) surgery adoption in a single surgical unit, assessing the impact of procedural volume., Methods: Study participants were 312 patients who underwent OPCAB during the period between August 2000 and January 2005 at S. Croce Hospital. Of these patients, 126 patients with an indication selected for comorbidities or 1-vessel disease underwent OPCAB performed by 4 low-volume surgeons, and 186 unselected patients underwent OPCAB performed by a single high-volume surgeon., Results: OPCAB performed by low-volume surgeons was associated with less complete revascularization and less arterial conduit use. Early result analysis showed a low rate of in-hospital or 30-day adverse events. The 5-year survival was 0.88 (0.02 SE). OPCAB performance by a high-volume surgeon and complete revascularization were shown have a protective effect for midterm major adverse cardiac events (respectively, hazard ratio = 0.28, 95% confidence interval 0.11-0.74 and hazard ratio = 0.33, 95% confidence interval 0.15-0.73)., Conclusion: Our study on the initial phase of OPCAB adoption suggests a benefit on midterm outcome from surgery performed by a high-volume surgeon.

Resistance to thyroid hormone (RTH) is almost invariably associated with mutations of the thyroid hormone (TH) receptor beta (hTR beta) gene and is inherited as an autosomal dominant disease. Mutations of hTR beta identified in patients affected by RTH cluster generally at two spots of the ligand binding domain. We investigated whether an Italian kindred with RTH had a mutation in the thyroid hormone (TH) receptor beta gene. Blood samples were obtained from the available family members for biochemical and genetic analyses. Thyroid function tests in basal conditions, and in the case of the propositus also following incremental doses of T3, were performed. Exon 4 to 10 of hTR beta gene were amplified using the polymerase chain reaction (PCR) and the mutation was identified by direct sequence analysis. The affinity constant of this mutated receptor for T3 was measured by in vitro transcription-translation and was then compared with that of wild type. We identified a heterozygous G to A transition at nucleotide 1037 of exon 8 at codon 251, resulting in a glycine (G) to glutamic acid (E) substitution (G251E) in the patient affected by RTH and in his affected offspring, but not in the normal family members. This novel mutation represents a de novo mutation since both parents of the index case were unaffected and did not have this genomic mutation. When expressed in vitro, the mutant protein (G251E) showed a marked decrease of the affinity for T3, suggesting an impaired ligand-dependent transactivation activity of this mutant receptor. In vivo studies with incremental doses of L-T3 demonstrated a reduced sensitivity to TH in the index case, in particular at the pituitary level where the thyrotrophs' activity was not completely inhibited even by 200 micrograms/day of L-T3. G251E mutation represents the fourth mutation described up to now in exon 8 of hTR beta among the subjects affected by RTH. A third cluster of mutations of the c-erbA beta gene located proximally with respect to the other two so far described begins to emerge in RTH patients.

The whole male population with indwelling catheter of the Trento health district has been included in a survey of the quality of the home nursing services. The epidemiological and in depth analysis of the characteristics and motivation of the high degree of heterogeneity of medical prescribing behaviors and of the nursing practices suggest that an important effort of rationalization (on the basis of pre adopted protocols) is both needed and possible.

Blood group systems ABO, KEL, MN, RH, secretor status for ABH blood group substances, red cell enzymes ACP1, ESD, AK1, 6-PGD, PGM1 subtypes, serum markers GC, TF, PI, AHSG, ORM1 and chromosomal heteromorphism Q, C, DA/DAPI were examined in a population sample of the Garfagnana, a semi-isolated mountainous area in the province of Lucca (Tuscany, Italy). The total sample was subdivided and analysed according to the more recent historical events which have occurred in Garfagnana. The observed phenotype and gene frequencies were discussed in the context of other population samples from the same province and of the same region. As a whole, the results concur in pointing out a certain degree of heterogeneity within the area and a high differentiation from the rest of Tuscany. Such peculiar genetic features of the population have to be related to the historical, geographic and cultural isolation of the Garfagnana.

DA/DAPI and C chromosomal heteromorphic sites (1q, 9q, 15p, 16q, Yq) in a sample of 136 unrelated individuals from the Garfagnana valley (Tuscany, Italy) have been analyzed quantitatively and qualitatively. The variations in length, between-homolog heteromorphisms, and intensity of fluorescence of the heterochromatic bands have been compared in two subsamples of the population (upper and middle valley) individualized according to geodemographic criteria. DA/DAPI heterochromatin differed significantly from C heterochromatin, showing a lower average amount and a higher variability at each site. This suggests a differential staining of DNA of the two banding systems. Furthermore, DA/DAPI heterochromatin was less uniformly distributed in the population than C heterochromatin and the regions 16q and Yq discriminated better between subsamples. The variations of DA/DAPI fluorescence at the 15p site demonstrated an excess of homomorphic individuals in the upper valley, which could be related to the mating structure of the population living in this area.