Impact of allogeneic stem cell transplantation on thyroid function.

PURPOSE: Primary hypothyroidism is a main endocrine complication after allogeneic stem cells transplantation (allo-SCT) in children, but in adults data on post-SCT hypothyroidism are limited. The aims of this observational, cross-sectional study were to assess the prevalence of hypothyroidism in adult allo-SCT recipients according to time from transplantation, and to identify risk factors. METHODS: One hundred and eighty-six patients (M 104; F 82; median age 53.4 years) who underwent allo-SCT between January 2010 and December 2017 were enrolled and divided into three groups, according to time from allo-SCT (1-3 years; 3-5 years; > 5 years). Pre-transplant TSH and fT4 levels were available for all patients. After transplantation, TSH, fT4 and anti-thyroperoxidase antibodies (TPO-Ab) were evaluated. RESULTS: After a follow-up of 3.7 years, 34 (18.3%) patients developed hypothyroidism, with higher prevalence in females (p < 0.001) and in patients who received matched unrelated donor grafts (p < 0.05). No difference in prevalence was found at different time points. Patients who developed hypothyroidism showed higher rate of TPO-Ab positivity (p < 0.05) and higher pre-transplant TSH levels (median 2.34 µU/ml) compared to those with preserved thyroid function (median 1.53 µU/ml; p < 0.001). Multivariable analysis identified higher pre-transplant TSH levels as a positive predictor of hypothyroidism (p < 0.005). The ROC curve analysis identified a pre-SCT TSH cutoff of 1.84 µU/ml, which can predict hypothyroidism with sensitivity 74.1% and specificity 67.2%. CONCLUSIONS: About one out of four patients developed hypothyroidism after allo-SCT, with a greater incidence in females. Pre-transplant TSH levels seem to predict the onset of post-SCT hypothyroidism.

Traumatic renal artery dissection: from imaging to management.

Injury to the renal artery following blunt trauma is detected increasingly due to widespread and early use of multidetector computed tomography (CT), but optimal treatment remains controversial as no guidelines are available. This review illustrates the spectrum of imaging findings of traumatic renal artery dissection based on our experience, with the aim of understanding the physiopathology of ischaemic damage to the kidney, and the process of choosing the best therapeutic strategy (conservative, endovascular, surgical). Five main patterns of traumatic renal artery dissection are described: avulsion of renal hilum; dissection of the segmental renal branches; preocclusive main renal artery dissection; renal artery stenosis without flow limitation; thrombogenic renal artery intimal tear. In the polytrauma patient, management depends on various factors (haemodynamic status, associated lesions, time of diagnosis) rather than on the degree of renal artery stenosis. Non-operative management (NOM) is the preferred option in case of non-flow-limiting dissection of the renal artery and angio-embolisation is an important adjunct to NOM in cases of active bleeding. Embolisation of the renal artery stump may be the best option in cases of occlusive dissection, as catheter manipulation carries a high risk of vessel rupture. The therapeutic window for kidney revascularisation in cases of flow-limiting dissection of main renal artery may be variable. Endovascular stenting >4 h after trauma should be performed only if residual flow with preserved parenchymal perfusion is detected at angiography. Antiplatelet therapy administration is recommended in cases of stenting, but conditioned by the bleeding risk of the patient.

First but not second postoperative day growth hormone assessments as early predictive tests for long-term acromegaly persistence.

PURPOSE: Postoperative assessment of acromegaly activity is typically performed at least 3 months after neurosurgery (NS). Few studies have evaluated the use of early postoperative growth hormone (GH) levels as a test to predict short- and long-term remission of acromegaly. Our objective was to evaluate the diagnostic performance of serum random GH on a postoperative day one (D1-rGH) and two (D2-rGH), particularly in predicting long-term disease persistence. MATERIALS AND METHODS: Forty-one subjects with acromegaly who were undergoing NS were enrolled (mean age ± SD 47.4 ± 13.1 years at diagnosis; women 54%; macroadenomas 71%). The final assessment of disease activity was performed one year after NS. ROC curves were used to evaluate the diagnostic performance of D1-rGH and D2-rGH. RESULTS: After a 1-year follow-up, the overall remission rate was 55%. ROC analysis identified an optimal D1-rGH cut-off value of 2.1 ng/mL for diagnosing long-term disease persistence (55.6% SE; 90.9% SP). The cut-off point became 2.5 ng/mL after maximizing specificity for disease persistence (yielding a 100% positive predictive value) and 0.3 ng/mL after maximizing sensitivity for disease remission. The optimal D2-rGH cut-off value was 0.6 ng/mL (81.8% SE; 50% SP); the cut-off point became 2.9 ng/mL after maximizing specificity and 0.1 ng/mL after maximizing sensitivity, with no clinical utility. CONCLUSIONS: D1-rGH could be a highly specific test for the early diagnosis of long-term acromegaly persistence, which is predicted by a value > 2.5 ng/mL with a great degree of certainty. The diagnostic performance of D2-rGH was insufficient. Further research is required to validate these preliminary results prior to modifying the postoperative management of acromegaly.

New constraint on the existence of the µ+ → e+ γ decay.

The analysis of a combined data set, totaling 3.6 × 10(14) stopped muons on target, in the search for the lepton flavor violating decay µ(+) → e(+)γ is presented. The data collected by the MEG experiment at the Paul Scherrer Institut show no excess of events compared to background expectations and yield a new upper limit on the branching ratio of this decay of 5.7 × 10(-13) (90% confidence level). This represents a four times more stringent limit than the previous world best limit set by MEG.

Reaction surface approach to multimode vibronic coupling problems: general framework and application to furan.

A new general framework for treating the dynamics on intersecting multidimensional potential energy surfaces is presented. It rests on a sub-division of the nuclear coordinates into different classes, one of primary importance with large-amplitude displacements during the process of interest and another one with smaller displacements, thus permitting a more approximate description. The latter are treated within the well-known linear + quadratic vibronic coupling scheme, where, however, the expansion "coefficients" are general functions of the "primary" coordinates. This may be augmented by an effective-mode approach for further degrees of freedom acting as an environment for the dynamics of the original modes. Following the general considerations, the approach is applied to the nonadiabatic photodynamics of furan and is shown to allow for an eight-dimensional quantum treatment, of higher dimension than was possible so far. The influence of the various degrees of freedom on the dynamics and lifetime of furan due to nonadiabatic ring-opening is discussed.

New limit on the lepton-flavor-violating decay µ+→e+γ.

We present a new result based on an analysis of the data collected by the MEG detector at the Paul Scherrer Institut in 2009 and 2010, in search of the lepton-flavor-violating decay µ(+)e(+)γ. The likelihood analysis of the combined data sample, which corresponds to a total of 1.8×10(14) muon decays, gives a 90% C.L. upper limit of 2.4×10(-12) on the branching ratio of the µ(+)→e(+)γ decay, constituting the most stringent limit on the existence of this decay to date.

Ab initio quantum dynamical study of photoinduced ring opening in furan.

The nonadiabatic photoinduced ring opening occurring in the two lowest excited singlet states of furan is investigated theoretically, using wave-packet propagation techniques. The underlying multidimensional potential energy surfaces (PESs) are obtained from ab initio computations, using the equation-of-motion coupled cluster method restricted to single and double excitations (EOM-CCSD), reported in earlier recent work [E. V. Gromov, A. B. Trofimov, F. Gatti, and H. Köppel, J. Chem. Phys. 133, 164309 (2010)]. Up to five nuclear degrees of freedom are considered in the quantum dynamical treatment. Four of them represent in-plane motion for which the electronic states in question (correlating with the valence (1)B(2)(V) and Rydberg (1)A(2)(3s) states at the C(2v) ground-state molecular configuration) have different symmetries, A(') and A(''), respectively. The fifth mode, representing out-of-plane bending of the oxygen atom against the carbon-atom plane, leads to an interaction of these states, as is crucial for the photoreaction. The nonadiabatic coupling and conical intersection cause an electronic population transfer on the order of ∼10 fs. Its main features, and that of the wave-packet motion, are interpreted in terms of properties of the PES. The lifetime due to the ring-opening process has been estimated to be around 2 ps. The dependence of this estimate on the nuclear degrees of freedom retained in the computations is discussed.

Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naïve patients.

OBJECTIVES: The aim of the study was to determine whether the incidence of first-line treatment discontinuations and their causes changed according to the time of starting highly active antiretroviral therapy (HAART) in an Italian cohort. METHODS: We included in the study patients from the Italian COhort Naïve Antiretrovirals (ICoNA) who initiated HAART when naïve to antiretroviral therapy (ART). The endpoints were discontinuation within the first year of >or= 1 drug in the first HAART regimen for any reason, intolerance/toxicity, poor adherence, immunovirological/clinical failure and simplification. We investigated whether the time of starting HAART (stratified as 'early', 1997-1999; 'intermediate', 2000-2002; 'recent', 2003-2007) was associated with the probability of reaching the endpoints by a survival analysis. RESULTS: Overall, the 1-year probability of discontinuation of >or= 1 drug in the first regimen was 36.1%. The main causes of discontinuation were intolerance/toxicity (696 of 1189 patients; 58.5%) and poor adherence (285 of 1189 patients; 24%). The hazards for all-reason change were comparable according to calendar period [2000-2002, adjusted relative hazard (ARH) 0.82, 95% confidence interval (CI) 0.69-0.98; 2003-2007, ARH 0.94, 95% CI 0.76-1.16, vs. 1997-1999; global P-value = 0.08]. Patients who started HAART during the 'recent' period were less likely to change their initial regimen because of intolerance/toxicity (ARH 0.67, 95% CI 0.51-0.89 vs. 'early' period). Patients who started in the 'intermediate' and 'recent' periods had a higher risk of discontinuation because of simplification (ARH 15.26, 95% CI 3.21-72.45, and ARH 37.97, 95% CI 7.56-190.64, vs. 'early' period, respectively). CONCLUSIONS: It seems important to evaluate reason-specific trends in the incidence of discontinuation in order to better understand the determinants of changes over time. The incidence of discontinuation because of intolerance/toxicity has declined over time while simplification strategies have become more frequent in recent years. Intolerance/toxicity remains the major cause of drug discontinuation.

Theoretical study of photoinduced ring-opening in furan.

The potential energy surfaces (PESs) of the two lowest excited singlet states of furan [correlating with the Rydberg (1)A(2)(3s) and valence (1)B(2)(V) states at the C(2v) ground-state molecular configuration] have been studied in some detail with regard to the photoinduced ring-opening reaction. The surfaces have been characterized in terms of their stationary points and points of minimum energy conical intersections along the ring-opening pathway. The optimization of the geometrical parameters has been performed with the equation of motion coupled cluster singles and doubles method. The ab initio PESs have been modeled by energy grids and Taylor series. The resulting 11-dimensional PESs reproduce the ab initio results to a good accuracy and can be used in dynamical calculations.

Quantum dynamics of dissociative chemisorption of CH(4) on Ni(111): Influence of the bending vibration.

Two-dimensional, three-dimensional, and four-dimensional quantum dynamic calculations are performed on the dissociative chemisorption of CH(4) on Ni(111) using the multiconfiguration time-dependent Hartree (MCTDH) method. The potential energy surface used for these calculations is 15-dimensional (15D) and was obtained with density functional theory for points which are concentrated in the region that is dynamically relevant to reaction. Many reduced dimensionality calculations were already performed on this system, but the molecule was generally treated as pseudodiatomic. The main improvement of our model is that we try to describe CH(4) as a polyatomic molecule by including a degree of freedom describing a bending vibration in our three-dimensional and four-dimensional models. Using a polyspherical coordinate system, a general expression for the 15D kinetic energy operator is derived, which discards all the singularities in the operator and includes rotational and Coriolis coupling. We use seven rigid constraints to fix the CH(3) umbrella of the molecule to its gas phase equilibrium geometry and to derive two-dimensional, three-dimensional, and four-dimensional Hamiltonians, which were used in the MCTDH method. Only four degrees of freedom evolve strongly along the 15D minimum energy path: the distance of the center of mass of the molecule to the surface, the dissociative C[Single Bond]H bond distance, the polar orientation of the molecule, and the bending angle between the dissociative C[Single Bond]H bond and the umbrella. A selection of these coordinates is included in each of our models. The polar rotation is found to be important in determining the mode selective behavior of the reaction. Furthermore, our calculations are in good agreement with the finding of Xiang et al. [J. Chem. Phys. 117, 7698 (2002)] in their reduced dimensional calculation that the helicopter motion of the umbrella symmetry axis is less efficient than its cartwheel motion for promoting the reaction. The effect of pre-exciting the bend modes is qualitatively incorrect at higher energies, suggesting the necessity of including additional rotational and vibrational degrees of freedom in the model.

Photoinduction of fast, reversible translational motion in a hydrogen-bonded molecular shuttle.

A rotaxane is described in which a macrocycle moves reversibly between two hydrogen-bonding stations after a nanosecond laser pulse. Observation of transient changes in the optical absorption spectrum after photoexcitation allows direct quantitative monitoring of the submolecular translational process. The rate of shuttling was determined and the influence of the surrounding medium was studied: At room temperature in acetonitrile, the photoinduced movement of the macrocycle to the second station takes about 1 microsecond and, after charge recombination (about 100 microseconds), the macrocycle shuttles back to its original position. The process is reversible and cyclable and has properties characteristic of an energy-driven piston.

Renner-Teller effect in linear tetra-atomic molecules. II. Rovibronic levels analysis of the X 2Pi(u) electronic state of HCCH+.

The variational approach detailed in the previous paper (Paper I) for the treatment of the Renner-Teller effect in linear tetra-atomic molecules including all degrees of freedom and couplings between angular momenta is applied for HCCH(+). The accurate six-dimensional potential energy surfaces of the X (2)Pi(u) electronic state, presented in Paper I is incorporated in the variational treatment in order to obtain all rovibronic levels including the spin-orbit coupling for 1/2 < or = J < or = 7/2 and up to 2600 cm(-1) above the global zero point energy. The "pure" stretching levels are calculated up to 11,000 cm(-1) from the stretching zero point energy. The calculated rovibronic energies are compared with previous theoretical and experimental data. The mean agreement with the zero kinetic energy photoelectron measurements of Tang et al. [J. Chem. Phys. 125, 133201 (2006)] is of 16.7 cm(-1). The Renner-Teller parameters have been determined at nu(trans) = 690.0 cm(-1), epsilon(trans) = 0.30, nu(cis) = 715.0 cm(-1), and epsilon(cis) = -0.063. A detailed analysis of the rovibronic Hund's cases is presented and the rotational structures of some vibronic bands recorded by Yang and Mo [J. Phys. Chem. A 110, 11001 (2006)] are given.

Renner-Teller effect in linear tetra-atomic molecules. I. Variational method including couplings between all degrees of freedom on six-dimensional potential energy surfaces.

For electronically degenerate states of linear tetra-atomic molecules, a new method is developed for the variational treatment of the Renner-Teller and spin-orbit couplings. The approach takes into account all rotational and vibrational degrees of freedom, the dominant couplings between the corresponding angular momenta as well as the couplings with the electronic and electron spin angular momenta. The complete rovibrational kinetic energy operator is expressed in Jacobi coordinates, where the rovibrational angular momenta J(N) have been replaced by J-L(ez)-S and the spin-orbit coupling has been described by the perturbative term A(SO) x L(ez)S(z). Attention has been paid on the electronic wave functions, which require additional phase for linear tetra-atomic molecules. Our implemented rovibrational basis functions and the integration of the different parts of the total Hamiltonian operator are described. This new variational approach is tested on the electronic ground state X (2)Pi(u) of HCCH(+) for which new six-dimensional potential energy surfaces have been computed using the internally contracted multireference configuration interaction method and the cc-pV5Z basis set. The calculated rovibronic energies and their comparisons with previous theoretical and experimental works are presented in the next paper.

Production and separation of 163Ho for nuclear physics experiments.

This paper describes the production and chemical separation of the 163Ho isotope that will be used in several nuclear physics experiments aiming at measuring the neutrino mass as well as the neutron cross section of the 163Ho isotope. For this purpose, several batches of enriched 162Er have been irradiated at the Institut Laue-Langevin high flux reactor to finally produce 6 mg or 100 MBq of the desired 163Ho isotope. A portion of the Er/Ho mixture is then subjected to a sophisticated chemical separation involving ion exchange chromatography to isolate the Ho product from the Er target material. Before irradiation, a thorough analysis of the impurity content was performed and its implication on the produced nuclide inventory will be discussed.

Intestinal permeability in patients with adverse reactions to food.

BACKGROUND: An abnormal intestinal permeability could contribute to establish an altered sensitivity to food-allergen. AIM: To evaluate the intestinal permeability in subjects with adverse reactions to food on allergen-free diet. SUBJECTS: Twenty-one patients with food allergy and 20 with food hypersensitivity on allergen-free diet were enrolled and divided in four groups according to the seriousness of their referred clinical symptoms when they were on a free diet. METHODS: Intestinal permeability was evaluated by Lactulose/Mannitol ratio urinary detection determined by anion-exchange chromatography. RESULTS: Statistically significant different Lactulose/Mannitol ratio was evidenced in subjects with food allergy (p=0.003) or hypersensitivity (p=0.0008) compared to control patients. The correlation between Lactulose/Mannitol ratio and the seriousness of clinical symptoms, by using Spearman test, was statistically significant for food allergy (p=0.0195) and hypersensitivity (p=0.005) patients. CONCLUSIONS: The present data demonstrate that impaired intestinal permeability, measured in our conditions, is present in all subjects with adverse reactions to food. In addition, for the first time, we report a statistically significant association between the severity of referred clinical symptoms and the increasing of Intestinal Permeability Index. These data reveal that intestinal permeability is not strictly dependent on IgE-mediated processes but could better be related to other mechanisms involved in early food sensitisation, as breast-feeding, or microbial environment that influence the development of oral tolerance in early infancy.

HOLMES: The electron capture decay of [Formula: see text]Ho to measure the electron neutrino mass with sub-eV sensitivity.

The European Research Council has recently funded HOLMES, a new experiment to directly measure the neutrino mass. HOLMES will perform a calorimetric measurement of the energy released in the decay of [Formula: see text]Ho. The calorimetric measurement eliminates systematic uncertainties arising from the use of external beta sources, as in experiments with beta spectrometers. This measurement was proposed in 1982 by A. De Rujula and M. Lusignoli, but only recently the detector technological progress allowed to design a sensitive experiment. HOLMES will deploy a large array of low temperature microcalorimeters with implanted [Formula: see text]Ho nuclei. The resulting mass sensitivity will be as low as 0.4 eV. HOLMES will be an important step forward in the direct neutrino mass measurement with a calorimetric approach as an alternative to spectrometry. It will also establish the potential of this approach to extend the sensitivity down to 0.1 eV. We outline here the project with its technical challenges and perspectives.

Fluvoxamine alone in the treatment of delusional depression.

OBJECTIVE: The aim of this study was to evaluate the efficacy of fluvoxamine in the treatment of delusional depression. METHOD: Fifty-nine inpatients who met the DSM-III-R criteria for major depression with psychotic features were treated with fluvoxamine for 6 weeks. Patients were assessed at baseline and weekly thereafter with the Hamilton Depression Rating Scale and the Dimensions of Delusional Experience rating scale. RESULTS: Of the 57 subjects completed the trial, 84.2% (N=48) recovered. The index episodes of the patients who did not respond to fluvoxamine were of significantly longer duration than those of the responders. CONCLUSIONS: Fluvoxamine has a response rate similar to that of the currently most efficacious treatments for delusional depression, including antidepressants plus antipsychotics and ECT.

Nimesulide as a downregulator of the activity of the neutrophil myeloperoxidase pathway. Focus on the histoprotective potential of the drug during inflammatory processes.

Neutrophils, recruited to tissue sites of inflammation, release a variety of oxidants and enzymes, which are responsible for tissue damage. Among the oxidants released are potent chlorinated compounds, such as hypochlorous acid and chloramines, which induce tissue cell damage and inactivate protease inhibitors, particularly alpha 1-antitrypsin, the specific inhibitor of neutrophil elastase. In studying a rational approach to the pharmacological control of neutrophil-mediated tissue injury, we investigated the activity of the anti-inflammatory drug nimesulide. This agent reduced the function of the myeloperoxidase pathway (which generates hypochlorous acid), by exerting a cell-directed inhibitory activity, as shown by measurement of superoxide anion and hydrogen peroxide production. Nimesulide also inactivated hypochlorous acid directly and protected alpha 1-antitrypsin from the neutrophil-mediated oxidation. Thus, neutrophil elastolytic activity may be attenuated by nimesulide-spared alpha 1-antitrypsin. The prevention of oxidative inactivation of alpha 1-antitrypsin by nimesulide strictly correlates with the drug's ability to suppress the extracellular availability of hypochlorous acid. Taken together, these data suggest that nimesulide may prevent tissue injury at sites of inflammation by maintaining natural host protective systems.

A comparison between delusional and non-delusional depressives.

Delusional depressive episodes may represent more sever degrees of depressive manifestations or a distinct subtype of depressive illness. To test these two alternative hypotheses, characteristics on demographic, clinical and symptomatic variables, presence of personality disorders and familial loading were compared in 57 delusional and 57 non-delusional depressive patients. The delusional group did not differ on symptomatological intensity degree, clinical and familial loading characteristics. They did differ on higher distribution of Cluster 1 personality disorders. In the delusional sample the presence of mood incongruent psychotic features and hallucinations were evaluated as possible indicators of different subtypes of delusional depression.