Structural and chemical properties of NiOx thin films: the role of oxygen vacancies in NiOOH formation in a H2O atmosphere.

NiOx films grown from 50 nm thick Ni on Si(111) were put in contact with oxygen and subsequently water vapor at elevated temperatures. Near ambient pressure (NAP)-XPS and -XAS reveal the formation of oxygen vacancies at elevated temperatures, followed by H2O dissociation and saturation of the oxygen vacancies with chemisorbing OH. Through repeated heating and cooling, OH-saturated oxygen vacancies act as precursors for the formation of thermally stable NiOOH on the sample surface. This is accompanied by a significant restructuring of the surface which increases the probability of NiOOH formation. Exposure of a thin NiOx film to H2O can lead to a partial reduction of NiOx to metallic Ni accompanied by a distinct shift of the NiOx spectra with respect to the Fermi edge. DFT calculations show that the formation of oxygen vacancies and subsequently Ni0 leads to a state within the band gap of NiO which pins the Fermi edge.

[Staffing levels and patient-related outcomes : Systematic literature review on international evidence]. / Personalbesetzung und patientenbezogene Outcomes : Systematische Literaturübersicht zur internationalen Evidenz.

The objective of this study was to systematically review the international literature with respect to significant links between staffing levels or qualification on the one hand and patient-related outcomes on the other. Of the initial 7778 abstracts identified by means of a complex search strand in PubMed and CINAHL, 51 could finally be included in a qualitative synthesis. A total of nine different patient-related outcome categories with significant associations on an at least ordinally scaled level were distinguished. None of the studies included had a (quasi-)experimental research design. Despite, in some instances, high numbers of cases at multiple sites and efforts to control obvious confounding variables by regression analysis, no evidence-based conclusions for health policy or clinical practice can be drawn from the available observational studies. There is therefore a considerable need for prospective randomized or at least quasi-experimental studies also as accompanying research on novel models of financing.

[Structural features and regional characteristics of psychiatric hospitals in Germany]. / Strukturmerkmale und regionale Besonderheiten psychiatrischer Krankenhäuser in Deutschland.

BACKGROUND: The German Law for the Development of Care and Funding for Psychiatric and Psychosomatic Services (PsychVVG) has established a new regulation for the mental healthcare system. In the future, characteristics of hospitals and catchment areas will be an elementary part of negotiations on remuneration. OBJECTIVE: The aim of this study was to identify structural and regional characteristics of psychiatric hospitals in Germany that contribute to increased average costs according to the views of clinical managers and directors. METHODS: In this study 37 guided expert interviews were conducted with business managers, financial controllers, leading medical and nursing personnel from psychiatric hospitals and the characteristics relevant for the budget and increased average costs were collated. RESULTS: Important factors with top priority were hospital infrastructure, characteristics of the catchment area and specialties of inpatient services provided. Obligatory service for a defined catchment area, increased documentation requirements and infrastructure of buildings and grounds were estimated as being associated with the highest additional financial expenditure. CONCLUSION: It is a challenge for clinics to prove increased average costs due to the respective hospital structural and regional characteristics. This study shows which characteristics should be considered as most cost-relevant from the perspective of hospital management.

[Activities without patient contact : Estimate of time costs based on telephone interviews in eight psychiatric hospitals]. / Tätigkeiten ohne Patientenkontakt : Zeitaufwandsschätzungen aus Telefoninterviews in acht psychiatrischen Kliniken.

The aim of this pilot study was to estimate the share of working time that staff in psychiatric hospitals theoretically spend on obligatory activities, such as training and further education, organizational and documentation tasks as well as statutory lecturing duties without patient contact. A total of 47 physicians, 39 nurses, 34 psychologists and 35 social workers from eight psychiatric hospitals were interviewed. The results reveal that the theoretically remaining time for direct patient contact is low. The ratio of time spent with versus time spent without patient contact was even worse for senior physicians and leading nurses as well as part-time employees; however, all activities without direct contact to patients seemed to be indispensable in terms of quality of treatment and care. Hence, employees in German psychiatric hospitals regularly have to make decisions on which of their duties they prefer to neglect, to which they are actually obligated.

Yawning in depression: worth looking into.

Yawning often occurs during states of increased sleep propensity. Depression is associated with sleep problems and tiredness. The aim of this paper is to review the present knowledge about possible changes of yawning during an episode of major depression (MD) and to report data on yawning from an online depression forum comprising of 450,000 postings. A literature search did not reveal any study about yawning in people with MD when compared to controls. However, there is evidence for an increased frequency of yawning under the influence of antidepressants. Analysis of the depression forum postings revealed 63 people writing about increased yawning in the context of depression. However, all but one of them were treated with antidepressants; and yawning was not reported as a symptom of depression, but in most cases (N=56) as occurring as a result of treatment with antidepressants. These findings are in agreement with a tonic hyperarousal in typical depression which is reduced by all standard antidepressants. For clinicians, it would be of interest to know whether yawning is reduced in untreated depression and whether it predicts treatment outcome.

Should men with asymptomatic non-specific urethritis be identified and treated?

There is currently a debate as to whether microscopy is necessary in asymptomatic men presenting for a sexual health screen. Arguments favouring microscopy include finding chlamydia in a significant proportion of sexual partners of men with non-specific urethritis (NSU) in studies that included symptomatic men. We aimed to investigate the proportion of partners of men with asymptomatic NSU who were diagnosed with a sexually transmitted infection. A retrospective case-note review was carried out for all men diagnosed with asymptomatic pathogen-negative NSU, and their traced sexual contacts, during a nine-month period. As a result of contact-tracing, we identified 42 partners who attended the clinic. Only one partner (2.4%) tested positive for chlamydia. A further two partners were diagnosed with a viral sexually transmitted infection (STI). The low level of chlamydia and other STIs in partners of asymptomatic men with pathogen-negative NSU does not support the routine use of microscopy to identify these patients.

Effects of N-acetylcysteine and tirilazad mesylate on intestinal functional capillary density, leukocyte adherence, mesenteric plasma extravasation and cytokine levels in experimental endotoxemia in rats.

INTRODUCTION: The study's objective was to determine the effects of the administration of N-acetylcysteine (NAC) and of tirilazad mesylate (TM) on intestinal functional capillary density, mesenteric plasma extravasation, leukocyte adherence and on cytokine release during experimental endotoxemia in rats. METHODS: In a prospective, randomized, controlled animal study, 80 male Wistar rats were examined in 2 test series. Both series were divided into 4 groups. Group 1 served as control group (CON group). Group 2 (LPS group), group 3 (NAC group) and group 4 (TM group) received endotoxin infusions (10 mg/kg over 2 h). In NAC group 150 mg/kg body weight NAC was administered after the first 30 minutes of endotoxemia intravenously. In TM group, 10 mg/kg body weight TM was administered after the first 30 minutes of endotoxemia intravenously. Animals of the series 1 underwent studies of leukocyte adherence on submucosal venular endothelium of the small bowel wall and intestinal functional capillary density (FCD) in the intestinal mucosa and the circular as well as the longitudinal muscle layer by intravital fluorescence microscopy (IVM). Plasma levels of interleukin 1beta (IL-1beta), interferone gamma (IFN-gamma) and soluble intercellular adhesion molecule1 (s-ICAM 1) as well as white blood cell count (WBC) were estimated. In the animals of the series 2 mesenteric plasma extravasation was determined by IVM and plasma levels of tumor necrosis factor alpha (TNF-alpha), IL-4, IL-6, IL-10 and malondialdehyde (MDA) were estimated. RESULTS: After LPS administration, FCD in the villi intestinales was unchanged and in the longitudinal muscularis layer it was increased. There was no effect of NAC or TM administration on FCD.Although the plasma extravasation was not significantly influenced by LPS administration, TM administration resulted in a lower plasma extravasation in the TM group compared to the other groups. After endotoxin challenge, the firmly adherence of leukocytes to vascular endothelium as a parameter of leukocyte activation in endotoxemia was increased but NAC or TM administration had no influence on leukocyte adherence. The plasma levels of IL-1beta, IL-6, IL-10, TNF-alpha, IFN-gamma and sICAM-1 were increased in the endotoxemic groups (LPS group, NAC group and TM group) and the WBC was decreased compared to controls. IL-4 levels were unchanged during observation period. Plasma MDA levels were not influenced by LPS administration compared to controls. The administration of NAC resulted in lower sICAM-1 and MDA levels compared to the LPS group. The IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma plasma levels were not influenced by NAC or TM administration. CONCLUSIONS: In this posttreatment sepsis model in rats, NAC administration resulted in lower sICAM-1 and MDA levels compared to the LPS treated animals. TM administration reduced the plasma extravasation in this model.

Enhancing the Silanization Reaction of the Silica-Silane System by Different Amines in Model and Practical Silica-Filled Natural Rubber Compounds.

Diphenyl guanidine (DPG) is an essential ingredient in silica-reinforced rubber compounds for low rolling resistance tires, as it not only acts as a secondary accelerator, but also as a catalyst for the silanization reaction. However, because of concern over the toxicity of DPG that liberates aniline during high-temperature processing, safe alternatives are required. The present work studies several amines as potential alternatives for DPG. Different amines (i.e., hexylamine, decylamine, octadecylamine, cyclohexylamine, dicyclohexylamine, and quinuclidine) are investigated in a model system, as well as in a practical rubber compound by taking the ones with DPG and without amine as references. The kinetics of the silanization reaction of the silica/silane mixtures are evaluated using model compounds. The mixtures with amines show up to 3.7 times higher rate constants of the primary silanization reaction compared to the compound without amine. Linear aliphatic amines promote the rate constant of the primary silanization reaction to a greater extent compared to amines with a cyclic structure. The amines with short-alkyl chains that provide better accessibility towards the silica surface, enhance the primary silanization reaction more than the ones with long-alkyl chains. The different amines have no significant influence on the rate constant of the secondary silanization reaction. The amine types that give a higher primary silanization reaction rate constant show a lower flocculation rate in the practical compounds. For the systems with a bit lower primary silanization reaction rate, but higher extent of shielding or physical adsorption that still promotes higher interfacial compatibility between the elastomer and the filler surface, the rubber compounds show a lower Payne effect which would indicate lower filler-filler interaction. However, the flocculation rate constant remained high.

Epidermal growth factor inhibits transiently the progression from G2-phase to mitosis: a receptor-mediated phenomenon in various cells.

An immediate effect of epidermal growth factor (EGF) on the cell cycle is described. EGF, when given to replicating cells such as HeLa, A431, and D HER 14, very rapidly inhibits the transition from G2 phase to mitosis (M) in a transient fashion. The influence of EGF (10(-10) to 10(-7) M concentrations) on the G2-M transition of individual cells has been analyzed by time-lapse photography in cell lines carrying intact, mutated, or no EGF receptor. The G2-M transition of cells devoid of EGF receptor or carrying an EGF receptor devoid of most of the cytoplasmic domain was not influenced by EGF. In cells carrying intact EGF receptor, EGF caused a transient and dose-dependent delay in G2 phase which could last for greater than 2 h. Cells were inhibited in G2 within less than 10-20 min prior to prophase. A parasynchronous recovery from G2 inhibition was observed at large EGF concentrations; the G2-M transition rate exceeded that of the controls. The system described may represent a model for the mechanistic analysis of a ligand-induced transient restriction of the cell cycle, particularly at the G2-M border.

Identification of an allosteric binding site on the transcription factor p53 using a phage-displayed peptide library.

Monoclonal antibody PAb1620 recognizes a conformational epitope on the transcription factor p53 and, upon binding, allosterically inhibits p53 binding to DNA. A highly diverse (1.5 x 10(10) members) phage-displayed library of peptides containing 40 random amino acids was used to identify the PAb1620 binding site on p53. Panning this library against PAb1620 resulted in three unique peptides which have statistically significant sequence identities with p53 sufficient to identify the binding site as being composed of amino acids 106-113 and 146-156. Based on these results, we propose a mechanism by which PAb1620 can allosterically inhibit p53 binding to DNA through an indirect interaction between the antibody binding site and the L1 loop (amino acids 112-124) of p53, which is a component of the DNA binding region.

A comparative study of the phase transitions of phospholipid bilayers and monolayers.

Phase transitions in bilayers and monolayers of various synthetic phospholipids with different chain lengths as well as different polar head groups were studied by differential scanning calorimetry or with the film balance technique, respectively. With the film balance, area versus temperature curves (isobars) were recorded at different surface pressures. The monolayer phase transition from the fluid-condensed to the fluid-expanded phase is shifted towards higher temperature when the lateral pressure in the monolayer is increased. The temperature dependence of the equilibrium pressure as well as the magnitude of the area change at the transition depends only on the nature of the phospholipid head group and not on the chain length of the hydrocarbon chains of the lipid. Phospholipids with strong intermolecular attractive interactions between the head groups show low values for dpi/dTm and for the area change, deltaf, whereas phospholipids with negatively charged head groups without intermolecular attractive forces exhibit higher values for dpi/dTm and deltaf. The shift of the monolayer phase transition temperature when increasing the chain length of the lipid is almost identical to the shift in Tm observed for the bilayer system of the same phospholipids. A comparison of monolayer and bilayer systems on the basis of the absolute value of the molecular area of the phospholipid in the bilayer gel phase and the change in area at the bilayer and monolayer transition leads to the following conclusions. The behaviour of the bilayer system is very similar to that of the respective monolayer system at a lateral pressure of approx. 30 dyne/cm, because at this pressure the absolute area and the area change in both systems are the same. Further support for this conclusion comes from the experimental finding that a lateral pressure of 30 dyne/cm the shift in Tm due to the increase in charge when the methyl ester of phosphatidic acid is investigated is the same for the bilayer and the monolayer system.

FTIR spectroscopic analysis of the amide and acid bands of ganglioside GM1, in pure form and in mixtures with DMPC.

The amide I bands of sphingolipids show complicated patterns due to intra- and intermolecular interactions via hydrogen bonds. In order to assign the amide I absorption bands of the ganglioside GM1 to the different amide groups in the headgroup and back bone, the compounds N-acetylgalactosamine, N-acetylneuraminic acid, glucocerebroside and ceramide III were examined as reference systems. The frequencies of the COOH and COO- bands of the sialic acid residue of GM1 were determined by pH-titration and were found to absorb at 1729 cm-1 and 1605 cm-1, respectively. In D2O the three amide groups of GM1 give one broad absorption band at 1627 cm-1, whereas in the glucocerebroside intra- and intermolecular interactions of the amide group give rise to three distinct amide I bands. For a solid sample of GM1 in KBr also one broad band was observed in the amide I region. We also studied the influence of the ganglioside GM1 on model membranes of DMPC as host lipid. The change of the CH2 stretching vibrational absorption bands as a function of temperature reveal that addition of GM1 to DMPC leads to increased phase transition temperatures Tm with increasing ganglioside content. No Ca2+ binding to the COO- group of GM1 was observed.

Miscibility of phospholipids with identical headgroups and acyl chain lengths differing by two methylene units: effects of headgroup structure and headgroup charge.

We have investigated the influence of the chemical structure and charge of the hydrophillic headgroup on the miscibility of saturated phospholipids with acyl chain lengths differing by two methylene units, namely DMPA/DPPA, DMPC/DPPC, DMPE/DPPE and DMPG/DPPG (0.1 M NaCl). All four mixtures were analysed by DSC at pH 7. To study the influence of a change in headgroup charge, we additionally investigated DMPA/DPPA mixtures at pH 4 and 12, and DMPG/DPPG mixtures at pH 2. The experimental DSC thermograms were fitted using methods described before [Johann et al., Biophys. J. 71 (1996), 3215-3228] to obtain the temperatures of onset and end of melting and first approximations for the non-ideality parameters as a function of composition. The resulting phase diagrams were then fitted using a four non-ideality parameter model for non-ideal, non-symmetric mixing in both phases. The phase diagram of the system DMPG/DPPG has a lens-like shape, the non-ideality parameters rhog and rhol for the gel and the liquid-crystalline phase, respectively, are zero, indicating ideal mixing in both phases. For the other mixtures, differences in miscibility are observed depending on the structure of the headgroup. At pH 7, rhog > rhol, i.e., the miscibility in the liquid-crystalline phase is more ideal than in the gel state. All rhog values are positive and the sequence for rhog observed is PA>PE>PC>PG. Partial protonation of PA at pH 4 or complete deprotonation at pH 12 leads to negative non-ideality parameters for both phases, indicating a preference for mixed pair formation. Protonation of PG in DMPG/DPPG mixtures at pH 2 leads to positive non-ideality parameters for both phases, indicating a tendency for demixing. The results show, that the miscibility of phospholipids with identical headgroups but chain lengths differing by two methylene groups is dependent on headgroup structure and on headgroup charge.

The influence of charge on phosphatidic acid bilayer membranes.

A complete titration of phosphatidic acid bilayer membranes was possible for the first time by the introduction of a new anaologue, 1,2-dihexadecyl-sn-glycerol-3-phosphoric acid, which has the advantage of a high chemical stability at extreme pH values. The synthesis of the phosphatidic acid is described and the phase transition behaviour in aqueous dispersions is compared with that of three ester phosphatidic acids; 1,2-dimyristoyl-sn-glycerol-3-phosphoric acid, 1,3-dimyristoylglycerol-2-phosphoric acid and 1,2-dipalmitoyl-sn-glycerol-3-phosphoric acid. The phase transition temperatures (Tt) of aqueous phosphatidic acid dispersions at different degrees of dissociation were measured using fluorescence spectroscopy and 90 degrees light scattering. The Tt values are comparable to the melting points of the solid phosphatidic acids in the fully protonated states, but large differences exist for the charged states. The Tt vs. pH diagrams of the four phosphatidic acids are quite similar and of a characteristic shape. Increasing ionisation results in a maximum value for the transition temperatures at pH 3.5 (pK1). The regions between the first and the second pK of the phosphatidic acids are characterised by only small variations in the transition temperatures (extended plateau) in spite of the large changes occurring in the surface charge of the membranes. The slope of the plateau is very shallow with increasing ionisation. A further decrease in the H+ concentration results in an abrupt change of the transition temperature. The slope of the Tt vs. pH diagram beyond pK2 becomes very steep. This is the result of reduced hydrocarbon interaction energy, which was demonstrated by differential scanning calorimetry (Blume, A. and Eibl, H., unpublished data).

The influence of charge on bilayer membranes. Calorimetric investigations of phosphatidic acid bilayers.

The pH-dependence of the phase transition of dimyristoyl phosphatidic acid and dihexadecyl phosphatidic acid has been investigated using differential scanning calorimetry. Varying the pH induces different degrees of ionization of the polar head group. The changes in transition temperature with pH as observed by calorimetry are in good agreement with those obtained by measuring the changes in light scattering, whereas the transition temperatures reported by the fluorescent probe N-phenylnaphthylamine do not always coincide with those determined from calorimetry [1]. The observed maximum of the transition temperature at pH 3.5 corresponds to a minimum in the transition enthalpy vs. pH diagram. At this pH a particular stable bilayer phase is formed. Full protonation of phosphatidic acids leads to suspensions of mycrocrystals. The transition enthalpy approaches the value of the melting enthalpy of crystalline anhydrous phosphatidic acid. The decrease in the transition enthalpy at high pH values is due to a change in the hydrocarbon chain interactions induced by the doubly charged head groups. The cooperativity of the transition varies with the degree of ionization of the head group, being lower for doubly charged phosphatidic acids.

A calorimetric study of the thermotropic behaviour of 1,2-dipentadecylmethylidene phospholipids.

Differential scanning calorimetry was used to study the thermotropic behaviour of 1,2-dipentadecylmethylidene phospholipids with various head groups. The structural variation in the glycerol backbone region leads to a strong restriction of conformational freedom for the first two methylene segments of the chains, so that dipentadecylmethylidene phospholipids show lower transition temperatures, lower enthalpies and lower cooperativity of the transition from the gel to the liquid crystalline phase. The extreme chemical stability of these lipids in the alkaline pH region enables investigations of phosphatidylethanolamine and phosphatidic acid dispersions at high pH values. Both phospholipids show a decrease in the transition temperature and in the transition enthalpy as they become singly and doubly charged, respectively. A complex behaviour of the transition enthalpy of doubly charged 1,2-dipentadecylmethylidene phosphatidic acid was observed when the NaCl concentration of the dispersion was increased.

Effect of the lipid phase transition on the kinetics of H+/OH- diffusion across phosphatidic acid bilayers.

The kinetics of H+/OH- diffusion across dimyristoyl phosphatidic acid bilayer membranes was measured by following the absorbance of the pH-sensitive indicator Cresol red (o-cresolsulfonphthalein) entrapped in single lamellar vesicles after rapidly changing the external pH in a stopped-flow apparatus. The H+/OH- permeability coefficient was found to be in the 10(-5) to 10(-3) cm . s-1 range. The lipid phase transition has a strong influence on the permeation kinetics as the permeability coefficients in the liquid-crystalline phase are drastically higher. The permeability shows no maximum at the phase transition temperature as is the case for other ions, but displays a similar temperature dependence as water permeation. This is also reflected in the high activation energy of approx. 20 kcal/mol and supports the hypothesis (Nichols, J.W. and Deamer, D.W. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 2038-2042) of H+/OH- permeation via hydrogen bonded water molecules. A second slower kinetic phase is also observed, where the permeation is obviously controlled by counterion diffusion. The temperature dependence of this slow process displays the for ion diffusion characteristic maximum in the permeability at the phase-transition temperature.

A Fourier transform infrared spectroscopic study of the interaction of alkaline earth cations with the negatively charged phospholipid 1, 2-dimyristoyl-sn-glycero-3-phosphoglycerol.

The interaction of aqueous phospholipid dispersions of negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol, sodium salt (DMPG) with the divalent cations Mg(2+), Ca(2+) and Sr(2+) at equimolar ratios in 100 mM NaCl at pH 7 was investigated by Fourier transform infrared spectroscopy. The binding of the three cations induces a crystalline-like gel phase with highly ordered and rigid all-trans acyl chains. These features are observed after storage below room temperature for 24 h. When the gel phase is heated after prolonged incubation at low temperature phase transitions into the liquid crystalline phase are observed at 58 degrees C for the DMPG:Sr(2+), 65 degrees C for the DMPG:Mg(2+), and 80 degrees C for the DMPG:Ca(2+) complex. By subsequent cooling from temperatures above T(m) these complexes retain the features of a liquid crystalline phase with disordered acyl chains until a metastable gel phase is formed at temperatures between 38 and 32 degrees C. This phase is characterized by predominantly all-trans acyl chains, arranged in a loosely packed hexagonal or distorted hexagonal subcell lattice. Reheating the DMPG:Sr(2+) samples after a storage time of 2 h at 4 degrees C results in the transition of the metastable gel to the liquid crystalline phase at 35 degrees C. This phase transition into the liquid crystalline state at 35 degrees C is also observed for the Mg(2+) complex. However, for DMPG:Mg(2+) at higher temperatures, a partial recrystallization of the acyl chains occurs and the high temperature phase transition at 65 degrees C is also detected. In contrast, DMPG:Ca(2+) exhibits only the phase transition at 80 degrees C from the crystalline gel into the fluid state upon reheating. Below 20 degrees C, the rate of conversion from the metastable gel to a thermodynamically stable, crystalline-like gel phase decreases in the order Ca(2+)&z. Gt;Mg(2+)>Sr(2+). This conversion into the crystalline gel phase is accompanied by a complete dehydration of the phosphate groups in DMPG:Mg(2+) and by a reorientation of the polar lipid head groups in DMPG:Ca(2+) and in DMPG:Sr(2+). The primary binding sites of the cations are the PO(2)(-) groups of the phosphodiester moiety. Our infrared spectroscopic results suggest a deep penetration of the divalent cations into the polar head group region of DMPG bilayers, whereby the ester carbonyl groups, located in the interfacial region of the bilayers, are indirectly affected by strong hydrogen bonding of immobilized water molecules. In the liquid crystalline phase, the interaction of all three cations with DMPG is weak, but still observable in the infrared spectra of the DMPG:Ca(2+) complex by a slight ordering effect induced in the acyl chains, when compared to pure DMPG liposomes.