Superdeformed and Triaxial States in

Shape parameters of a weakly deformed ground-state band and highly deformed slightly triaxial sideband in ^{42}Ca were determined from E2 matrix elements measured in the first low-energy Coulomb excitation experiment performed with AGATA. The picture of two coexisting structures is well reproduced by new state-of-the-art large-scale shell model and beyond-mean-field calculations. Experimental evidence for superdeformation of the band built on 0_{2}^{+} has been obtained and the role of triaxiality in the A∼40 mass region is discussed. Furthermore, the potential of Coulomb excitation as a tool to study superdeformation has been demonstrated for the first time.

Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy.

AIM: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. METHODS AND RESULTS: We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. CONTROLS: Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. CONCLUSIONS: Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.

Isospin Mixing in

The isospin mixing was deduced in the compound nucleus ^{80}Zr at an excitation energy of E^{*}=54 MeV from the γ decay of the giant dipole resonance. The reaction ^{40}Ca+^{40}Ca at E_{beam}=136 MeV was used to form the compound nucleus in the isospin I=0 channel, while the reaction ^{37}Cl+^{44}Ca at E_{beam}=95 MeV was used as the reference reaction. The γ rays were detected with the AGATA demonstrator array coupled with LaBr_{3}:Ce detectors. The temperature dependence of the isospin mixing was obtained and the zero-temperature value deduced. The isospin-symmetry-breaking correction δ_{C} used for the Fermi superallowed transitions was extracted and found to be consistent with ß-decay data.

Isospin character of low-lying pygmy dipole states in 208Pb via inelastic scattering of 17O ions.

The properties of pygmy dipole states in 208Pb were investigated using the 208Pb(17O, 17O'γ) reaction at 340 MeV and measuring the γ decay with high resolution with the AGATA demonstrator array. Cross sections and angular distributions of the emitted γ rays and of the scattered particles were measured. The results are compared with (γ, γ') and (p, p') data. The data analysis with the distorted wave Born approximation approach gives a good description of the elastic scattering and of the inelastic excitation of the 2+ and 3- states. For the dipole transitions a form factor obtained by folding a microscopically calculated transition density was used for the first time. This has allowed us to extract the isoscalar component of the 1- excited states from 4 to 8 MeV.

Coulomb excitation of 104Sn and the strength of the 100Sn shell closure.

A measurement of the reduced transition probability for the excitation of the ground state to the first 2+ state in 104Sn has been performed using relativistic Coulomb excitation at GSI. 104Sn is the lightest isotope in the Sn chain for which this quantity has been measured. The result is a key point in the discussion of the evolution of nuclear structure in the proximity of the doubly magic nucleus 100Sn. The value B(E2; 0+ → 2+) = 0.10(4) e2b2 is significantly lower than earlier results for 106Sn and heavier isotopes. The result is well reproduced by shell model predictions and therefore indicates a robust N = Z = 50 shell closure.

A dual acting compound with latanoprost amide and nitric oxide releasing properties, shows ocular hypotensive effects in rabbits and dogs.

The IOP lowering effects of NCX 139, a new chemical entity comprising latanoprost amide and a NO-donating moiety, were compared to those of the respective des-nitro analog in in vitro assays and in rabbit and dog models of ocular hypertension. The NO donor, molsidomine as well as the prostamide bimatoprost (Lumigan(®)) and the prostaglandin agonist, latanoprost (Xalatan(®)) were also investigated for comparison. NCX 139 but not its des-nitro analog resulted in NO-mediated vascular relaxant effect in pre-contracted rabbit aortic rings (EC(50)=0.70±0.06 µM; E(max)=80.6±2.9%). Like bimatoprost (IC(50)=3.07±1.3 µM) or latanoprost (IC(50)=0.48±0.15 µM), NCX 139 displaced (3)H-PGF2α binding on recombinant human prostaglandin-F (FP) receptors with an estimated potency of 0.77±0.13 µM. In transient ocular hypertensive rabbits, bimatoprost and latanoprost were not effective while molsidomine elicited a dose-dependent reduction of IOP confirming the responsiveness of rabbits to NO but not to FP receptor agonists. NCX 139 tested at a therapeutically relevant dose, significantly lowered IOP while the des-nitro analog was not effective (0.03% NCX 139, Δ(max)=-12.8±2.0 mmHg). In glaucomatous dogs, 0.03% NCX 139 decreased IOP to a greater extent compared to an equimolar dose of the respective des-nitro derivative (Δ(max)=-4.6±1.0 and -2.7±1.3 mmHg, respectively for NCX 139 and its des-nitro analog). Albeit with low potency, NCX 139 also resulted effective in normotensive dogs while it did not reduce IOP in normotensive rabbits. NCX 139, a compound targeting two different and important mechanisms, is endowed with ocular hypotensive effects more evident in hypertensive conditions which may be of interest in the search of more effective treatments for hypertensive glaucoma.

Magnetic resonance imaging of primary breast lymphoma.

PURPOSE: Primary lymphomas of the breast (PBNHL) are uncommon. Magnetic resonance imaging (MRI) features of these malignancies can be relevant in establishing the extent of disease and planning the appropriate therapeutic strategy, usually represented by chemo- and radiotherapy, rather than surgery. The purpose of this study was to assess MRI features of PBNHL. MATERIALS AND METHODS: MRI examinations performed on seven patients with known PBNHL were retrospectively evaluated. Lesions were analysed for both morphology and kinetics and classified according to the Breast Imaging Reporting and Data System (BI-RADS) categories. RESULTS: The mean MRI maximum diameter was 44 mm (range 12-69). Six lesions showed a mass-like enhancement; one lesion showed a non-mass-like enhancement. For mass-like lesions, kinetic curve assessment of initial rise showed slow enhancement in one lesion, rapid enhancement in four lesions and medium enhancement in one lesion. Assessment of delayed enhancement showed plateau in five lesions and washout in one lesion. MRI BI-RADS categories were distributed as follows: one BI-RADS II, one BI-RADS III, three BI-RADS IV and two BI-RADS V. CONCLUSIONS: MRI features of primary breast lymphomas in this study cohort suggest that the occurrence of a PBNHL should be considered in the presence of large enhancing lesions of the breast, especially if associated with skin thickening. MRI may also have an important role in the assessment of response to therapy and diagnosis of recurrence.

Search for the pygmy dipole resonance in 68Ni at 600 MeV/nucleon.

The gamma decay from Coulomb excitation of 68Ni at 600 MeV/nucleon on a Au target was measured using the RISING setup at the fragment separator of GSI. The 68Ni beam was produced by a fragmentation reaction of 86Kr at 900 MeV/nucleon on a 9Be target and selected by the fragment separator. The gamma rays produced at the Au target were measured with HPGe detectors at forward angles and with BaF2 scintillators at backward angles. The measured spectra show a peak centered at approximately 11 MeV, whose intensity can be explained in terms of an enhanced strength of the dipole response function (pygmy resonance). Such pygmy structure has been predicted in this unstable neutron-rich nucleus by theory.

Probing the order-to-chaos region in superdeformed 151Tb and 196Pb nuclei with continuum gamma transitions.

The gamma decay associated with the warm rotation of the superdeformed nuclei 151Tb and 196Pb has been measured with the EUROBALL IV array. Several independent quantities provide a stringent test of the population and decay dynamics in the superdeformed well. A Monte Carlo simulation of the gamma decay based on microscopic calculations gives remarkable agreement with the data only assuming a large enhancement of the B(E1) strength for 1-2 MeV gamma rays, which may be related to the evidence for octupole vibrations in both mass regions.

Giant dipole resonance in the hot and thermalized 132Ce nucleus: damping of collective modes at finite temperature.

The gamma decay of the giant dipole resonance (GDR) in the 132Ce compound nucleus with temperature up to approximately 4 MeV has been measured, using the reaction 64Ni + 68Zn at E(beam) = 300, 400, and 500 MeV. The gamma and charged particles measured in coincidence with recoils are consistent with a fully equilibrated compound nucleus emission. The GDR width, obtained with the statistical model analysis, is found to increase almost linearly with temperature. This increase is rather well reproduced within a model including thermal shape fluctuations and the lifetime of the compound nucleus.

Decommissioning procedures for an 11 MeV self-shielded medical cyclotron after 16 years of working time.

The present article describes the decommissioning of a compact, self-shielded, 11 MeV medical cyclotron. A Monte Carlo simulation of the possible nuclear reactions was performed in order to plan the decommissioning activities. In the course of the cyclotron dismantling, cyclotron components, shields, and floor concrete samples were measured. Residual activities were analyzed with a Ge(Li) detector and compared with simulation data. Doses to staff involved in the decommissioning procedure were monitored by individual TL dosimeters. The simulations identified five radioactive nuclides in shields and floor concrete: 55Fe and 45Ca (beta emitters, total specific activity: 2.29 x 10(4) Bq kg) and 152Eu, 154Eu, 60Co (gamma emitters, total specific activity: 1.62 x 10(3) Bq kg-1). Gamma-ray spectrometry confirmed the presence of gamma emitters, corresponding to a total specific activity of 3.40 x 10(2) Bq kg-1. The presence of the radioisotope 124Sb in the lead contained in the shield structure, corresponding to a simulated specific activity of 9.38 x 10(3) Bq kg-1, was experimentally confirmed. The measured dose from external exposure of the involved staff was <20 muSv, in accordance with the expected range of values between 10 and 20 muSv. The measured dose from intake was negligible. Finally, the decommissioning of the 11 MeV cyclotron does not represent a risk for the involved staff, but due to the presence of long-lived radioisotopes, the cyclotron components are to be treated as low level radioactive waste and stored in an authorized storage area.

Prevention of venous thromboembolism in spinal surgery.

Deep vein thrombosis (DVT), and its most feared complication, pulmonary embolism (PE), still have a high incidence with high risk for patients' health. Proven prophylactic measures are available but are generally underused, and DVT is still considered the most common cause of preventable death among hospitalized patients. The rationale for prophylaxis of venous thromboembolism is based on the clinically silent nature of the disease, the relatively high prevalence among hospitalized patients and the potentially tragic consequences of a missed diagnosis. During the last 15-20 years, spine surgery has changed radically, developing into a well-defined area of specialist surgery, and some attention is now being given to DVT events in spine surgery. The incidence of DVT during spine surgery is not documented in the literature, because only case reports or retrospective studies are reported. It would therefore be very helpful to initiate a multicenter study in order to understand this problem better and to develop, if possible, some guidelines on prophylactic measures in spine surgery. In doing so, we need to consider each patient's pattern, any risk factors and every kind of surgical technique related to DVT, in order to improve the outcome of the patient and to reduce any medicolegal problems that could arise from a thrombotic complication or an epidural hematoma, with its high potential for irreversible consequences.

Low frequency of elevated serum transferrin saturation in elderly subjects.

Serum transferrin saturation (TS) values were calculated on the basis of serum iron and transferrin (protein) measurements in a total of 2425 serum samples from six groups of subjects: individuals applying for selection as blood donors (M and F, median age 34 and 32 years); patients referring to the hospital laboratory for routine testing (M and F, median age 45 and 48 years); and elderly subjects living in a specialized institute (M and F, median age 76 and 82 years). In the first four groups the frequency of TS values <15% and >62% respectively, was substantially as expected, considering the average health conditions and sex. These results indirectly support the reliability of the measurement procedure. In the elderly group, however, the frequency of TS values >62% was zero. Mean TS values in the elderly group (males and females) were significantly lower (P<0. 0001) than in the blood donors group and in the hospital patients one. This observation suggests a shortened survival in the presence of (unrecognized) iron overload, pointing out at the usefulness of iron overload screening using simple biochemical tests.

Effects of iron on extracellular and intracellular growth of Penicillium marneffei.

Killing of intracellular Penicillium marneffei conidia is demonstrated in gamma interferon-lipopolysaccharide-activated human THP1 and mouse J774 cells. Iron overload significantly reduces the antifungal activity of macrophages. Likewise, exogenous iron enhances and iron chelators inhibit the extracellular growth of P. marneffei. These results suggest that iron availability critically affects immunity to and the pathogenicity of P. marneffei.

Antibody responses to hepatitis C virus hypervariable region 1: evidence for cross-reactivity and immune-mediated sequence variation.

Sequence heterogeneity of hepatitis C virus (HCV) is unevenly distributed along the genome, and maximal variation is confined to a short sequence of the HCV second envelope glycoprotein (E2), designated hypervariable region 1 (HVR1), whose biological function is still undefined. We prospectively studied serological responses to synthetic oligopeptides derived from HVR1 sequences of patients with acute and chronic HCV infection obtained at baseline and after a defined follow-up period. Extensive serological cross-reactivity for unrelated HVR1 peptides was observed in the majority of the patients. Antibody response was restricted to the IgG1 isotype and was focused on the carboxyterminal end of the HVR1 region. Cross-reactive antibodies could be readily elicited following immunization of mice with multiple antigenic peptides carrying HVR1 sequences derived from our patients. The vigor and heterogeneity of cross-reactive antibody responses were significantly higher in patients with chronic hepatitis compared with those with acute hepatitis and in patients infected with HCV type 2 compared with patients infected with other viral genotypes (predominantly type 1), which suggest that higher time-related HVR1 sequence diversification previously described for type 2 may result from immune selection. The finding of a statistically significant correlation between HVR1 sequence variation, and intensity, and cross-reactivity of humoral immune responses provided stronger evidence in support of the contention that HCV variant selection is driven by the host's immune pressure.

Serum proteins by capillary zone electrophoresis: approaches to the definition of reference values.

The Paragon CZE 2000 (Beckman Analytical, Milan, Italy) is an automatic dedicated capillary zone electrophoresis (CZE) system, producing a five-zone serum protein pattern with quantitative estimation of the zones. With the view of substituting this instrument for two previously used serum protein electrophoresis techniques, we planned to produce reference values for the "new" systems leading to compatible interpretation of the results. High resolution cellulose acetate electrophoresis with visual inspection and descriptive reporting (HR-CAE) and five-zone cellulose acetate electrophoresis with densitometry (CAE-D) were the previously used techniques. Serum samples (n = 167) giving "normal pattern" with HR-CAE were assayed with the CZE system, and the results were statistically assessed to yield 0.95 reference intervals. One thousand normal and pathological serum samples were then assayed with the CAE-D and the CZE techniques, and the regression equations of the CAE-D values over the CZE values for the five zones were used to transform the CAE-D reference limits into the CZE reference limits. The two sets of reference values thereby produced were in good agreement with each other and also with reference values previously reported for the CZE system. Thus, reference values for the CZE techniques permit interpretation of results coherent with the previously used techniques and reporting modes.

Dynamics of hypervariable region 1 variation in hepatitis C virus infection and correlation with clinical and virological features of liver disease.

Hepatitis C virus (HCV) infection is a dynamic process during which molecular variants are continuously selected as the result of virus adaptation to the host. Understanding the nature of HCV genetic variation is central to current theories of pathogenesis and immune response. We prospectively studied hypervariable region 1 (HVR1) variation in the E2 gene of 36 hepatitis C patients, including 10 asymptomatic carriers, followed up for 1 to 2 years. Sequence changes in single and consecutive serum samples were assessed and correlated with clinical and virological parameters of liver disease. A region of the E1 gene was sequenced for comparison in 3 subjects. HVR1 heterogeneity at single time points widely varied in individual patients, did not increase cumulatively over the follow-up period, and did not correlate with HVR1 evolutionary rates. Conversely, the process of HVR1 sequence diversification, although differed considerably among patients, was stable over time and directly correlated with infections by HCV type 2, lower alanine aminotransferase (ALT) levels, and absence of cirrhosis. HCV carriers showed the highest HVR1 variation rates. Our findings indicate that HVR1 variation has an adaptive significance and is associated with favorable features of liver disease and suggest that prospective, rather than static, observations are required to model the process of HCV variation.

Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a case-control study.

BACKGROUND & AIMS: Viral genotypes have been associated with different severity and outcome of hepatitis C virus (HCV)-related liver disease. The aim of this study was to determine whether HCV genotypes may influence the cirrhosis-related risk of the development of hepatocellular carcinoma (HCC). METHODS: Three groups of patients were studied: 593 patients with chronic hepatitis, 166 patients with HCC and cirrhosis, and 219 patients with cirrhosis but without HCC. A cross-sectional study of frequency distribution and a case-control analysis were performed. HCV genotypes were detected according to Okamoto. RESULTS: HCV type 1b infection was more prevalent among patients with HCC compared with patients with cirrhosis but without HCC (P < 0.01) and chronic hepatitis (P < 0.001). Age, male sex, and HCV type 1b significantly influenced the risk of cancer in cirrhosis by univariate analysis. A pairwise comparison performed on 162 patients with HCC and an equal number of patients with cirrhosis matched by age, sex, and Child's class showed that HCV type 1b was independently associated with HCC (odds ratio, 1.7; P = 0.026). CONCLUSIONS: HCV type 1b is overrepresented in patients with cirrhosis and HCC and significantly influences the risk of HCC in cirrhosis, independent of sex, age, and Child's class.