[Mentally ill people with means-tested benefits at the job center : Diagnosis spectrum and care-First results from the LIPSY project]. / Psychisch erkrankte Menschen mit Arbeitslosengeld-II-Bezug im Jobcenter : Diagnosespektrum und Versorgung ­ erste Ergebnisse aus dem LIPSY-Projekt.

BACKGROUND: Although people receiving means-tested benefits are regularly taken care of at the job center, little is known about their mental health situation and mental health care. OBJECTIVE: The aim of the study was to describe the diagnostic spectrum and the functional status as well as the mental health care utilization of individuals with mental illnesses who are receiving means-tested benefits. METHODS: Mentally ill people with means-tested benefits were recruited at the job center as part of the "Leipzig Individual Placement and Support for Mentally Ill People" (LIPSY) project, where they were initially diagnosed according to ICD-10 and included in the project if they had a mental disorder. Mental healthcare utilization was recorded. In the present study, data from n = 583 consecutively included persons were analyzed descriptively and by multivariate statistics. RESULTS: Of the study participants 60.7% (n = 583; 51.5% female; average age 36 years; unemployed for an average of 4.8 years) suffered from affective disorders, followed by neurotic, stress and somatoform disorders (42.5%). With a mean global assessment of functioning (GAF) value of 49.4 (SD 7.7), there was on average a serious impairment. Nearly half of the subjects (48.5%) had never received psychotherapeutic, psychiatric or neurological treatment in the 6 months prior to inclusion in the project. DISCUSSION: It could be shown that there is a broad spectrum of mental disorders with substantial functional impairment. The data suggest that this group is significantly undertreated and difficult to reach.

Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy.

Histidyl-tRNA synthetase (HARS) ligates histidine to cognate tRNA molecules, which is required for protein translation. Mutations in HARS cause the dominant axonal peripheral neuropathy Charcot-Marie-Tooth disease type 2W (CMT2W); however, the precise molecular mechanism remains undefined. Here, we investigated three HARS missense mutations associated with CMT2W (p.Tyr330Cys, p.Ser356Asn, and p.Val155Gly). The three mutations localize to the HARS catalytic domain and failed to complement deletion of the yeast ortholog (HTS1). Enzyme kinetics, differential scanning fluorimetry (DSF), and analytical ultracentrifugation (AUC) were employed to assess the effect of these substitutions on primary aminoacylation function and overall dimeric structure. Notably, the p.Tyr330Cys, p.Ser356Asn, and p.Val155Gly HARS substitutions all led to reduced aminoacylation, providing a direct connection between CMT2W-linked HARS mutations and loss of canonical ARS function. While DSF assays revealed that only one of the variants (p.Val155Gly) was less thermally stable relative to wild-type, all three HARS mutants formed stable dimers, as measured by AUC. Our work represents the first biochemical analysis of CMT-associated HARS mutations and underscores how loss of the primary aminoacylation function can contribute to disease pathology.

The reactivity of cyclopropyl cyanide in titan's atmosphere: a possible pre-biotic mechanism.

Cyclopropyl cyanide and other simple nitriles detected in Titan's atmosphere could be precursors leading to the formation of organic macromolecules in the atmosphere of Saturn's largest satellite. Proposing a thermodynamically possible mechanism that explains their formation and supports experimental results represents a difficult challenge. Experiments done in the Atomic and Molecular Physics Laboratory at the University of Trento (AMPL) have studied the ion-molecule reaction between cyclopropyl cyanide and its protonated form, with reaction products being characterized by mass spectrometry. In addition to the expected ion-molecule adduct stabilized by non-covalent long-range interactions, in this work we prove that another distinct species having the same mass to charge ratio (m/z) of 135 is also produced. Moreover, from a previous study of the neutral cyclopropyl cyanide potential energy surface (PES) which shows a partial biradical character it has been possible to characterize the formation through the bimolecular reaction of a new covalent cyclic organic molecule. Calculations have been carried out at the ab initio Møller-Plesset (MP2) level of theory, ensuring the connectivity of the stationary points by using the intrinsic reaction coordinate (IRC) procedure. In order to characterize the reaction transition state, multireference calculations were done using a complete active space involving six electrons and six molecular orbitals [CAS (6 e-, 6 m.o.)]. This study opens the possibility of exploring the formation of new organic molecules by gaseous phase ion-molecule interaction schemes, with such molecules having relevance in interstellar space and in astrobiology (and may be involved in prebiotic molecular evolution).

The role of Li+ ions in the gas phase dehydrohalogenation and dehydration reactions of i-C3H7Br and i-C3H7OH molecules studied by radiofrequency-guided ion beam techniques and ab initio methods.

Gas phase reactive collisions between lithium ions and i-C3H7X (X = Br, OH) molecules have been studied under single collision conditions in the center of mass (CM) 0.01-10.00 eV energy range using a radiofrequency-guided ion beam apparatus. Mass spectrometry analysis of the products did show the presence of [C3H6-Li]+, [HX-Li]+, C3H7+, and C2H3+ as well as of the [Li-i-C3H7Br]+ adduct while [Li-i-C3H7OH]+ was hardly detected. For all these reactive processes, the corresponding cross sections have been measured in absolute units as a function of the CM collision energy. Quantum chemistry ab initio calculations done at the second order Möller Plesset level have provided relevant information on the topology of the potential energy surfaces (PESs) where a reaction takes place allowing the characterization of the stationary points on the respective PESs along their reaction pathways. The connectivity of the different stationary points localized on the PESs was ensured by using the intrinsic reaction coordinate (IRC) method, confirming the adiabatic character of the reactions. The main topology features of the reactive PESs, in the absence of dynamical calculations, were used to interpret at the qualitative level the behavior of the experimental excitations functions, evidencing the role played by the potential energy barriers on the experimental dynamics of the reactions. Reaction rate constants at 303.2 K for different reactions have been calculated from measured excitation functions.

Molecular Dynamics Simulations of Small Clusters and Liquid Hydrogen Sulfide at Different Thermodynamic Conditions.

A new force field for the intermolecular H2S-H2S interaction has been used to study the most relevant properties of the hydrogen sulfide system from gaseous to liquid phases by means of molecular dynamics (MD) simulations. In order to check the validity of the interaction formulation, ab initio CCSD(T)/aug-cc-pVTZ calculations, including the counterpoise correction on the H2S, (H2S)2, and (H2S)3 structures optimized at the MP2/aug-cc-pVDZ level, have been performed. The (H2S)2,3 systems have been characterized by performing NVE MD simulations at decreasing values of the temperature, while the liquid sulfide behavior has been investigated considering a NpT ensemble of 512 molecules at several thermodynamic states, defined by different pressure and temperature values. Additional calculations using an ensemble of 2197 molecules at two different temperatures have been performed to investigate the liquid/vapor interface of the system. The S-S, S-H, and H-H radial distribution functions and the coordination number, calculated at the same conditions used in X-ray and neutron diffraction experiments, and the evaluated thermodynamic and structural properties have been compared successfully with experimental data, thus confirming the reliability of the force field formulation and of the MD predictions.

Dehydrohalogenation and Dehydration Reactions of i-C3H7Br and i-C3H7OH by Sodium Ions Studied by Guided Ion Beam Techniques and Quantum Chemical Methods.

Dehydrohalogenation and dehydration reactions of gas-phase i-C3H7Br and i-C3H7OH molecules induced by collision with Na(+), all participants being in their electronic ground state, were studied experimentally in our laboratory using a radiofrequency-guided ion beam apparatus and covering the 0.10-10.00 eV center of mass (CM) energy range. In Na(+) + i-C3H7Br collisions the formation of [C3H6-Na](+) and [HBr-Na](+) by dehydrohalogenation was observed and quantified, as well as that of the ion-molecule adduct [Na-i-C3H7Br](+) together with its decomposition products C3H7(+) and NaBr. In Na(+) + i-C3H7OH collisions the dehydration product [H2O-Na](+) was also found, while [C3H6-Na](+) was hardly detected. Moreover, the [Na-i-C3H7OH](+) adduct formation as well as its decomposition into C3H7(+) and NaOH were also quantified. For all these processes, absolute reaction cross sections were measured as a function of the CM collision energy. From measured excitation functions, rate constants for the formation of [C3H6-Na](+), [HBr-Na](+), and [H2O-Na](+) at 303 K were obtained. Complementing the experiments, exhaustive ab initio structure calculations at the MP2 level of theory were performed, giving information on the most relevant features of the potential energy surfaces (PESs) where the dehydrohalogenation, dehydration, and decomposition reactions take place adiabatically for both collision systems. On these PESs different stationary points associated with potential energy minima and transition state barriers were characterized, and their connectivity was ensured using the intrinsic-reaction-coordinate method. The main topology features of the ab initio calculated PESs allowed a qualitative interpretation of the experimental data also exposing the role of the sodium ion as a catalyst in elimination reactions.

Benzene-hydrogen bond (C6H6-HX) interactions: the influence of the X nature on their strength and anisotropy.

The intermolecular potential energy of the C6H6-SH2 and C6H6-NH3 dimers is formulated as combination of independent electrostatic and nonelectrostatic contributions. The relevant parameters of the nonelectrostatic terms, derived from molecular polarizability components, have been proved to be useful to describe in a consistent way both size repulsion and dispersion attraction forces. The representation adopted for the electrostatic contribution asymptotically reproduces the dipole quadrupole interaction. To test the validity of the proposed potential formulation, the features of the most stable configurations of the systems predicted have been compared with the available ab initio and experimental data. Moreover, the strength of the C6H6-HX interaction has been analyzed comparing the obtained results with the corresponding ones for the C6H6-H2O and C6H6-CH4 systems, investigated previously with the same methodology. Information on the relative orientation dependence of the partners, arising from the anisotropy of the intermolecular interaction, evaluated at different intermolecular distances, has been also obtained. Such information is crucial to evaluate sterodynamics effects in bimolecular collisions.

Experimental and ab initio studies of the reactive processes in gas phase i-C3H7Br and i-C3H7OH collisions with potassium ions.

Collisions between potassium ions and neutral i-C3H7Br and i-C3H7OH, all in their electronic ground state, have been studied in the 0.10-10.00 eV center of mass (CM) collision energy range, using the radiofrequency-guided ion beam technique. In K(+) + i-C3H7Br collisions KHBr(+) formation was observed and quantified, while the analogous KH2O(+) formation in K(+) + i-C3H7OH was hardly detected. Moreover, formation of the ion-molecule adducts and their decomposition leading to C3H7(+) and either KBr or KOH, respectively, have been observed. For all these processes, absolute cross-sections were measured as a function of the CM collision energy. Ab initio structure calculations at the MP2 level have given information about the potential energy surfaces (PESs) involved. In these, different stationary points have been characterized using the reaction coordinate method, their connectivity being ensured by using the intrinsic-reaction-coordinate method. From the measured excitation function for KHBr(+) formation the corresponding thermal rate constant at 303 K has been calculated. The topology of the calculated PESs allows an interpretation of the main features of the reaction dynamics of both systems, and in particular evidence the important role played by the potential energy wells in controlling the reactivity for the different reaction channels.

A myeloid cell-binding adenovirus efficiently targets gene transfer to the lung and escapes liver tropism.

Specific and efficient gene delivery to the lung has been hampered by liver sequestration of adenovirus serotype 5 (Ad5) vectors. The complexity of Ad5 liver tropism has largely been unraveled, permitting improved efficacy of Ad5 gene delivery. However, Kupffer cell (KC) scavenging and elimination of Ad5 still represent major obstacles to lung gene delivery strategies. KC uptake substantially reduces bioavailability of Ad5 for target tissues and compensatory dose escalation leads to acute hepatotoxicity and a potent innate immune response. Here, we report a novel lung-targeting strategy through redirection of Ad5 binding to the concentrated leukocyte pool within the pulmonary microvasculature. We demonstrate that this leukocyte-binding approach retargets Ad5 specifically to lung endothelial cells and prevents KC uptake and hepatocyte transduction, resulting in 165,000-fold enhanced lung targeting, compared with Ad5. In addition, myeloid cell-specific binding is preserved in single-cell lung suspensions and only Ad.MBP-coated myeloid cells achieved efficient endothelial cell transduction ex vivo. These findings demonstrate that KC sequestration of Ad5 can be prevented through more efficient uptake of virions in target tissues and suggest that endothelial transduction is achieved by leukocyte-mediated 'hand-off' of Ad.

Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations.

Hemolytic uremic syndrome (HUS) is a disease of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. About 90% of cases are secondary to infections by Escherichia coli strains producing Shiga-like toxins (STEC-HUS), while 10% are associated with mutations in genes encoding proteins of complement system (aHUS). We describe two patients with a clinical history of STEC-HUS, who developed end-stage renal disease (ESRD) soon after disease onset. They received a kidney transplant but lost the graft for HUS recurrence, a complication more commonly observed in aHUS. Before planning a second renal transplantation, the two patients underwent genetic screening for aHUS-associated mutations that revealed the presence of a heterozygous CFI mutation in patient #1 and a heterozygous MCP mutation in patient #2, and also in her mother who donated the kidney. This finding argues that the two cases originally diagnosed as STEC-HUS had indeed aHUS triggered by STEC infection on a genetic background of impaired complement regulation. Complement gene sequencing should be performed before kidney transplantation in patients who developed ESRD following STEC-HUS since they may be undiagnosed cases of aHUS, at risk of posttransplant recurrence. Furthermore, genetic analysis of donors is mandatory before living-related transplantation to exclude carriers of HUS-predisposing mutations.

Carbon dioxide clathrate hydrates: selective role of intermolecular interactions and action of the SDS catalyst.

The ability of a single sodium dodecyl sulfate (SDS) molecule to promote the formation of CO2 clathrate hydrates in water (as it does for methane) has been investigated at the microscopic level. For this purpose, the components of the related force field were carefully formulated and assembled following the procedure previously adopted for methane. The properties of the whole system (as well as those of its components) were analyzed by carrying out extended molecular dynamics calculations. Contrary to what happens for methane, the calculations singled out the propensity of CO2 (pure) water clusters to form clathrate hydrate-like structures and the disappearance of such propensity when a single SDS molecule is added to the clusters. This feature was found to be due to the strong interaction of carbon dioxide with the additive that makes the SDS molecule lose its shape together with its ability to drive water molecules to form a suitable cage.

Microsolvation of the potassium ion with aromatic rings: comparison between hexafluorobenzene and benzene.

We employ a recently developed methodology to study structural and energetic properties of the first solvation shells of the potassium ion in nonpolar environments due to aromatic rings, which is important to understand the selectivity of several biochemical phenomena. Our evolutionary algorithm is used in the global optimization study of clusters formed of K(+) solvated with hexafluorobenzene (HFBz) molecules. The global intermolecular interaction for these clusters has been decomposed in HFBz-HFBz and in K(+)-HFBz contributions, using a potential model based on different decompositions of the molecular polarizability of hexafluorobenzene. Putative global minimum structures of microsolvation clusters up to 21 hexafluorobenzene molecules were obtained and compared with the analogous K(+)-benzene clusters reported in our previous work (J. Phys. Chem. A 2012, 116, 4947-4956). We have found that both K(+)-(Bz)n and K(+)-(HFBz)n clusters show a strong magic number around the closure of the first solvation shell. Nonetheless, all K(+)-benzene clusters have essentially the same first solvation shell geometry with four solvent molecules around the ion, whereas the corresponding one for K(+)-(HFBz)n is completed with nine HFBz species, and its structural motif varies as n increases. This is attributed to the ion-solvent interaction that has a larger magnitude for K(+)-Bz than in the case of K(+)-HFBz. In addition, the ability of having more HFBz than Bz molecules around K(+) in the first solvation shell is intimately related to the inversion in the sign of the quadrupole moment of the two solvent species, which leads to a distinct ion-solvent geometry of approach.

Experimental study of the reactive processes in the gas phase K(+) + i-C3H7Cl collisions: a comparison with Li and Na ions.

Reactive collisions between alkali ions (Li(+), Na(+), and K(+)) and halogenated hydrocarbon molecules have been studied recently in our research group. In this paper, we have reported on the K(+) + i-C3H7Cl system in the 0.20-14.00 eV center-of-mass energy range using a radio frequency guided-ion beam apparatus developed in our laboratory. Aiming at increasing our knowledge about this kind of reactions, we compare our latest results for K(+) with those obtained previously for Li(+) and Na(+). While the reaction channels are the same in all three cases, their energy profiles, reactivity, measured reactive cross-section energy dependences, and even their reaction mechanisms, differ widely. By comparing experimentally measured reactive cross-sections as a function of the collision energy with the ab initio calculations for the different potential energy surfaces, a qualitative interpretation of the dynamics of the three reactive systems is presented in the present work.

Physical fitness before and after weight restoration in anorexia nervosa.

AIM: The aims of this paper were: 1) to evaluate the feasibility of test for evaluating physical fitness (PF) in patients with anorexia nervosa (AN); 2) to investigate the effects of nutritional rehabilitation in this population of patients; and 3) to compare their level of fitness scores (at baseline and after weight restoration) with an age-matched healthy control group. METHODS: PF was assessed with an adapted version of the Eurofit Physical Fitness Test Battery (EPFTB) administered to 37 consecutive female AN patients, at baseline and after weight restoration, and to 57 healthy age-matched females. RESULTS: The inpatient treatment, based on cognitive behavior therapy, was associated with a significant improvement in BMI (from 14.5±1.5 to 18.8±1.1, P<0.001) and in 5 out of 6 EPFTB tests (P<0.05) in the AN group. However, both in pre and post, AN patients showed significant lower EPFTB than the control group (all P<0.001) with the exception of the Sit-Up score. CONCLUSION: Results indicated that PF is lower in AN patients than in controls both at baseline and after weight restoration. Future studies should evaluate if the inclusion of an individualized health-enhancing physical activity program might improve the restoration of physical fitness.

Optimization of patient positioning for improved healing after corneal transplantation.

Corneal transplantation is the only solution which avoids loss of vision, when endothelial cells are dramatically lost. The surgery involves injecting gas into the anterior chamber of the eye, to create a bubble that pushes onto the donor cornea (graft), achieving sutureless adherence to the host cornea. During the postoperative period, patient positioning affects the bubble. To improve healing, we study the shape of the gas-bubble interface throughout the postoperative period, by numerically solving the equations of fluid motion. Patient-specific anterior chambers (ACs) of variable anterior chamber depths (ACD) are considered, for either phakic (with natural lens) and pseudophakic (with artificial lens) eyes. For each AC, gas-graft coverage is computed for different gas fill and patient positioning. The results show that the influence of positioning is negligible, regardless of gas filling, as long as the ACD is small. However, when the ACD value increases, patient positioning becomes important, especially for pseudophakic ACs. The difference between best and worst patient positioning over time, for each AC, is negligible for small ACD but significant for larger ACD, especially for pseudophakic eyes, where guidelines for optimal positioning become essential. Finally, mapping of the bubble position highlights the importance of patient positioning for an even gas-graft coverage.

Ion size influence on the Ar solvation shells of M(+)-C6F6 clusters (M = Na, K, Rb, Cs).

The size-specific influence of alkali metal ions in the gradual transition from cluster rearrangement to solvation dynamics is investigated by means of molecular dynamics simulations for alkali metal cation-hexafluorobenzene systems, M(+)-C(6)F(6) (M = Na, K, Rb and Cs), surrounded by Ar atoms. To analyze such transition, different small aggregates of the M(+)-C(6)F(6)-Ar(n) (n = 1, ..., 30) type and M(+)-C(6)F(6) clusters solvated by about 500 Ar atoms are considered. The Ar-C(6)F(6) interaction contribution has been described using two different formalisms, based on the interaction decomposition in atom-bond and in atom-effective atom terms, which have been applied to study the small aggregates and to investigate the Ar solvated M(+)-C(6)F(6) clusters, respectively. The selectivity of the promoted phenomena from the M(+) ion size and their dependence from the number of Ar atoms is characterized.

Competitive role of CH4-CH4 and CH-π interactions in C6H6-(CH4)n aggregates: the transition from dimer to cluster features.

The intermolecular methane-methane and benzene (Bz)-methane interactions formulated in this paper are suitable to investigate systems of increasing complexity. The proposed CH(4)-CH(4) and Bz-CH(4) potential energy functions are indeed applied to study some macroscopic properties of methane and important features of both small Bz-(CH(4))(n) (n > 1-10) clusters and Bz surrounded by several CH(4) molecules. Relevant parameters of the interaction, derived from molecular polarizability components, have been proved to be useful to describe in a consistent way both size repulsion and dispersion attraction forces. The proposed potential model also allows one to isolate the role of the different intermolecular energy contributions. The spatial distribution of the CH(4) molecules in the clusters is investigated by means of molecular dynamics simulations under various conditions, even when methane phase transition from liquid to gas is likely to occur. In addition, several properties, such as radial distribution functions, density values, and mean diffusion coefficients, are analyzed in detail.

Alkali-ion microsolvation with benzene molecules.

The target of this investigation is to characterize by a recently developed methodology, the main features of the first solvation shells of alkaline ions in nonpolar environments due to aromatic rings, which is of crucial relevance to understand the selectivity of several biochemical phenomena. We employ an evolutionary algorithm to obtain putative global minima of clusters formed with alkali-ions (M(+)) solvated with n benzene (Bz) molecules, i.e., M(+)-(Bz)(n). The global intermolecular interaction has been decomposed in Bz-Bz and in M(+)-Bz contributions, using a potential model based on different decompositions of the molecular polarizability of benzene. Specifically, we have studied the microsolvation of Na(+), K(+), and Cs(+) with benzene molecules. Microsolvation clusters up to n = 21 benzene molecules are involved in this work and the achieved global minimum structures are reported and discussed in detail. We observe that the number of benzene molecules allocated in the first solvation shell increases with the size of the cation, showing three molecules for Na(+) and four for both K(+) and Cs(+). The structure of this solvation shell keeps approximately unchanged as more benzene molecules are added to the cluster, which is independent of the ion. Particularly stable structures, so-called "magic numbers", arise for various nuclearities of the three alkali-ions. Strong "magic numbers" appear at n = 2, 3, and 4 for Na(+), K(+), and Cs(+), respectively. In addition, another set of weaker "magic numbers" (three per alkali-ion) are reported for larger nuclearities.

Crossed molecular beams study of inelastic non-adiabatic processes in gas phase collisions between sodium ions and ZnBr2 molecules in the 0.10-3.50 keV energy range.

Inelastic electronically non-adiabatic reactions between Na(+) ions and neutral ZnBr(2) molecules, both in their electronic ground state, have been studied using crossed beams techniques and measuring the decaying emission radiation of the excited species produced. The fluorescent emission corresponding to Na(3 (2)P) produced by a charge transfer reaction was observed, as well as that corresponding to the decay of Zn(4s 5s (3)S), generated by dissociation of the neutral target molecule, to Zn(4s 4p (3)P). The phosphorescent decaying emission of Zn*(4s 4p (3)P) to the zinc ground state was also observed. For each emission process, the cross section energy dependences have been measured in the 0.10-3.50 keV energy range in the laboratory system. The ground electronic state of the (NaZnBr(2))(+) collision system has been characterized by ab initio chemical structure calculations at the second order Möller-Plesset perturbation level of theory using pseudo-potentials. By performing restricted open shell Hartree-Fock calculations for C(2v) geometries, four singlet and four triplet potential energy surfaces of the system have been calculated and used to interpret qualitatively the observed reactions. A simple two-state dynamical model is presented that allows an estimation of the maximum values for measured cross sections at high collision energies to be made.

A portable intermolecular potential for molecular dynamics studies of NMA-NMA and NMA-H2O aggregates.

A recently formulated intermolecular potential has been adapted to describe the interaction of the N-methylacetamide (NMA) dimer and of the NMA-H(2)O adduct. The pure electrostatic component of the intermolecular potential functional representation is as usual expressed in terms of a set of punctual charges distributed over the molecular frames, consistently with the permanent molecular dipole values. In contrast, the remainder of the intermolecular potential is expressed in terms of Improved Lennard Jones effective pair potential functions, referred to multiple interaction centers (or sites) placed on the N-methylacetamide molecule and to a single interaction center placed on the water molecule. The characteristic of this pair potential relies on a mix of transferable and non-transferable descriptions of the parameters. The first set of parameters has a structural connotation bearing a site-site interaction nature and exploiting the molecular polarizability decomposability. The second one, depending on the particles clustering and charge distribution and transfer, bears a delocalized and ambient bulk nature. This choice has been tested against ab initio calculations and molecular dynamics simulations. The results show that the model potential is appropriate for describing the energetic of the various stable configurations of NMA-NMA and NMA-H(2)O weakly interacting aggregates, including the formation of hydrogen bonds.