[Occupational and social participation disorders in patients in office-practice medical care]. / Berufliche und soziale Partizipationsstörungen bei Patienten in der vertragsärztlichen Versorgung.

BACKGROUND: Primary care physicians play a crucial role in the assessment of restrictions in of participation, i. e. especially sick leave. In this study we investigated to which degree patients in primary care suffer from disorders of participation and how this is related to problems at the workplace and sick leave. METHOD: A total of 382 patients, aged 18-65, were investigated in primary care office practices. Self-reported disorders of participation were measured with the IMET, together with sociodemographic and work-related information. RESULTS: 27,4% of 299 patients who were at present working reported to have problems at the workplace. 19% were at present on sick leave. These patients did significantly more often report mobbing at the workplace. No differences were found with respect to quantitative or qualitative overtaxation or with respect to context variables. Restrictions in of participation were strongest related to the workplace but were also reported for the domain of family or social activities. Patients on sick leave also showed more impairment in these private areas than patients at work. The treating physicians saw psychosocial problems as a primary cause for disorders of participation at the workplace. CONCLUSION: Chronic illness does impair occupational as well as general social participation, and such patients are frequently seen in primary care. Physicians in primary health care therefore play an important role in the treatment of restrictions in of participation and especially in early intervention.

Fragmentation of ionized doped helium nanodroplets: theoretical evidence for a dopant ejection mechanism.

We report a theoretical study of the effect induced by a helium nanodroplet environment on the fragmentation dynamics of a dopant. The dopant is an ionized neon cluster Ne(n) (+) (n=4-6) surrounded by a helium nanodroplet composed of 100 atoms. A newly designed mixed quantum/classical approach is used to take into account both the large helium cluster zero-point energy due to the light mass of the helium atoms and all the nonadiabatic couplings between the Ne(n) (+) potential-energy surfaces. The results reveal that the intermediate ionic dopant can be ejected from the droplet, possibly with some helium atoms still attached, thereby reducing the cooling power of the droplet. Energy relaxation by helium atom evaporation and dissociation, the other mechanism which has been used in most interpretations of doped helium cluster dynamics, also exhibits new features. The kinetic energy distribution of the neutral monomer fragments can be fitted to the sum of two Boltzmann distributions, one with a low kinetic energy and the other with a higher kinetic energy. This indicates that cooling by helium atom evaporation is more efficient than was believed so far, as suggested by recent experiments. The results also reveal the predominance of Ne(2) (+) and He(q)Ne(2) (+) fragments and the absence of bare Ne(+) fragments, in agreement with available experimental data (obtained for larger helium nanodroplets). Moreover, the abundance in fragments with a trimeric neon core is found to increase with the increase in dopant size. Most of the fragmentation is achieved within 10 ps and the only subsequent dynamical process is the relaxation of hot intermediate He(q)Ne(2) (+) species to Ne(2) (+) by helium atom evaporation. The dependence of the ionic fragment distribution on the parent ion electronic state reached by ionization is also investigated. It reveals that He(q)Ne(+) fragments are produced only from the highest electronic state, whereas He(q)Ne(2) (+) fragments originate from all the electronic states. Surprisingly, the highest electronic states also lead to fragments that still contain the original ionic dopant species. A mechanism is conjectured to explain this fragmentation inhibition.

Modeling the fragmentation dynamics of ionic clusters inside helium nanodroplets: the case of He100Ne4+.

We present simulation results on the effect of a helium nanodroplet environment on the fragmentation dynamics of embedded molecular systems. The helium atoms are treated explicitly, with zero-point effects taken into account through an effective helium-helium interaction potential. The ionized neon tetramer is used as a model molecular system because, like all the small rare-gas clusters, it fragments extensively upon ionization. All the nonadiabatic effects between electronic states of the ionized neon cluster are taken into account. The results reveal a predominance of Ne2+ and HepNe2+ fragments and the absence of bare Ne+ fragments, in agreement with available experimental data. The neutral monomer fragments exhibit a rather wide kinetic energy distribution that can be fitted to the sum of two Boltzmann distributions, one with a low kinetic energy and the other with a higher kinetic energy. This indicates that cooling by helium atom evaporation is more efficient than was believed so far, as suggested by recent experimental results. Purely classical calculations are shown to strongly overestimate the amount of cage effect (cooling), clearly indicating the need to take into account zero-point effects.

Vibrational dynamics of the hydrogen bonded complexes (CH2)2O-HF and -DF investigated by combined jet- and cell-Fourier transform infrared spectroscopy.

Fourier transform infrared spectra of the Vs stretching bands of HF and DF bonded to (CH2)2O have been recorded at 0.5 cm(-1) resolution in a cooled cell and in a supersonic expansion seeded with argon. The analysis of the congested spectra of this type of medium strength hydrogen bonded complexes exploits a combination of controlled temperature effects in the ranges 25-80 K and 200-300 K and a band contour simulation program accounting for homogeneous and inhomogeneous contributions. Significant anharmonic couplings between the donor stretch mode and three of the low frequency intermolecular modes are found to be responsible for the characteristic hot band patterns in the Vs fundamental region of cell spectra. A global analysis of sum and difference combination bands involving Vs provides reliable values of intermolecular frequencies, anharmonic coupling constants and a good estimate of the dissociation energy of the complex which compares favorably with ab initio results. The effective linewidth provides a lower bound for the predissociation lifetime of 1.5 ps for HF and 7 ps for DF containing complexes, respectively. The correlation between effective linewidths and vibrational densities of states for (CH2)2O-HF and -DF underlines the important role of intramolecular vibrational redistribution in the vibrational dynamics of these complexes while the lifetime decrease for HF (or DF) bonded to oxygenated cyclic ethers with respect to sulfured homologues might be explained by the change in the arrangement of the acid relative to the plane of the acceptor subunit.

Vibrational dynamics of medium strength hydrogen bonds: Fourier transform infrared spectra and band contour analysis of the DF stretching region of (CH2)2S-DF.

Fourier transform infrared spectra of the nu(s) band of the (CH2)(2)S-DF complex have been recorded at 0.1-0.5 cm(-1) resolution in a cooled cell and in a supersonic jet expansion seeded with argon. A sufficient density of (CH(2))(2)S-DF heterodimers is produced by a double injection nozzle device, which limits the possibility of reaction between thiirane and DF before the expansion. The observation of partially resolved PQR branch structures at cell temperatures as high as 252 K indicates relatively small effective line widths, which allow a detailed analysis of the underlying vibrational couplings and of the structural properties of the complex. The analysis of cell and free jet spectra in the temperature range 50-250 K is performed with a software package for the simulation and fitting of multiple hot band progressions in asymmetric rotors. The analysis reveals that the three low frequency hydrogen-bond modes are strongly coupled to the DF stretch with anharmonic coupling constants, which indicates a strengthening of the hydrogen bond upon vibrational excitation of DF. Rovibrational parameters and a reliable upper bound for the homogeneous line width have been extracted.

Rovibrational and dynamical properties of the hydrogen bonded complex (CH2)2S-HF: a combined free jet, cell, and neon matrix-Fourier transform infrared study.

Fourier transform infrared spectra of the nu(s) (HF stretching) band of the (CH(2))(2)S-HF complex have been recorded at 0.1-0.5 cm(-1) resolution in a cooled cell, in a supersonic jet expansion seeded with argon and in a neon matrix at 4.5 K. The combination of controlled temperature effects over a range of 40-250 K and a sophisticated band contour simulation program allows the separation of homogeneous and inhomogeneous contributions and reveals significant anharmonic couplings between intramolecular and intermolecular vibrational modes similar to our previous work on (CH(2))(2)S-DF. The sign of the coupling constants is consistent with the expected strengthening of the hydrogen bond upon vibrational excitation of HF which also explains the observed small variations of the geometrical parameters in the excited state. The analysis of sum and difference combination bands involving nu(s) provides accurate values of intermolecular harmonic frequencies and anharmonicities and a good estimate of the dissociation energy of the complex. Frequencies and coupling parameters derived from gas phase spectra compare well with results from neon matrix experiments. The effective linewidth provides a lower bound for the predissociation lifetime of 10 ps. The comparison between effective linewidths and vibrational densities of states for (CH(2))(2)S-HF and -DF complexes highlights the important role of intramolecular vibrational redistribution in the vibrational dynamics of medium strength hydrogen bonds.

The type I interferon receptor: structure, function, and evolution of a family business.

Recent results indicate that coherent models of how multiple interferons (IFN) are recognized and signal selectively through a common receptor are now feasible. A proposal is made that the IFN receptor, with its subunits IFNAR-1 and IFNAR-2, presents two separate ligand binding sites, and this double structure is both necessary and sufficient to ensure that the different IFN are recognized and can act selectively. The key feature is the duplication of the extracellular domain of the IFNAR-1 subunit and the configurational geometry that this imposes on the intracellular domains of the receptor subunits and their associated tyrosine kinases.

Shared receptor components but distinct complexes for alpha and beta interferons.

The type I interferon family includes 13 alpha, one omega and one beta subtypes recognized by a complex containing the receptor subunits ifnar1 and ifnar2 and their associated Janus tyrosine kinases, Tyk2 and Jak1. To investigate the reported differences in the way that alpha and beta interferons signal through the receptor, we introduced alanine-substitutions in the ifnar2 extracellular domain, and expressed the mutants in U5A cells, lacking endogenous ifnar2. A selection, designed to recover mutants that responded preferentially to alpha or beta interferon yielded three groups: I, neutral; II, sensitive to alpha interferon, partially resistant to beta interferon; III, resistant to alpha interferon, partially sensitive to beta interferon. A mutant clone, TMK, fully resistant to alpha interferon with good sensitivity to beta interferon, was characterized in detail and compared with U5A cells complemented with wild-type ifnar2 and also with Tyk2-deficient 11.1 cells, which exhibit a similar alpha-unresponsive phenotype with a partial beta interferon response. Using anti-receptor antibodies and mutant forms of beta interferon, three distinct modes of ligand interaction could be discerned: (i) alpha interferon with ifnar1 and ifnar2; (ii) beta interferon with ifnar1 and ifnar2; (iii) beta interferon with ifnar2 alone. We conclude that alpha and beta interferons signal differently through their receptors because the two ligand subtypes interact with the receptor subunits ifnar 1 and ifnar2 in entirely different ways.

Differences in activity between alpha and beta type I interferons explored by mutational analysis.

Type I interferon (IFN) subtypes alpha and beta share a common multicomponent, cell surface receptor and elicit a similar range of biological responses, including antiviral, antiproliferative, and immunomodulatory activities. However, alpha and beta IFNs exhibit key differences in several biological properties. For example, IFN-beta, but not IFN-alpha, induces the association of tyrosine-phosphorylated receptor components ifnar1 and ifnar2, and has activity in cells lacking the IFN receptor-associated, Janus kinase tyk2. To define the structural basis for these functional differences we produced human IFN-beta with point mutations and compared them to wild-type IFN-beta in assays that distinguish alpha and beta IFN subtypes. IFN-beta mutants with charged residues (N86K, N86E, or Y92D) introduced at two positions in the C helix lost the ability to induce the association of tyrosine-phosphorylated receptor chains and had reduced activity on tyk2-deficient cells. The combination of negatively charged residues N86E and Y92D (homologous with IFN-alpha8) increased the cross-species activity of the mutant IFN-betas on bovine cells to a level comparable to that of human IFN-alphas. In contrast, point mutations in the AB loop and D helix had no significant effect on these subtype-specific activities. A subset of these latter mutations did, however, reduce activity in a manner analogous to IFN-alpha mutations. The effects of these mutations on IFN-beta activity are discussed in the context of a family of related ligands acting through a common receptor and signaling pathway.