What can patients do to facilitate shared decision making? A qualitative study of patients with depression or schizophrenia and psychiatrists.

PURPOSE: Patient involvement in decision making is endorsed by patients and professionals. While research has recently been conducted on how professionals can promote shared decision making (SDM), little is known about how patients can also facilitate SDM. METHODS: Seven focus groups were conducted: 3 with psychiatrists and 4 with patients with schizophrenia or depression. The focus groups were transcribed and independently coded line by line by 2 researchers. Data were analyzed using content analysis. RESULTS: Seven themes related to patient attitudes and behaviors were identified: honesty and openness with one's psychiatrist and oneself, trust in one's psychiatrist and patience with the treatment, respect and politeness, informing the psychiatrist and giving feedback, engagement/active participation during the consultation, gathering information/preparing for the consultation and implementing decisions. Barriers (e.g., avolition, lack of decisional capacity, powerlessness during involuntary treatment) and facilitators of active patient behavior were also identified. CONCLUSIONS: There are various ways in which patients can facilitate SDM/play a more active role in decision making, with patients emphasizing being open and honest and psychiatrists emphasizing being active in the consultation. Interventions to increase active patient behavior may enhance SDM in mental health care.

Managers' reactions towards employees' disclosure of psychiatric or somatic diagnoses.

AIMS: To study whether employees who disclose a psychiatric diagnosis, such as depression risk stigmatisation and discrimination at the workplace. METHODS: Randomised experimental study with 748 managers from German companies incorporating four case vignettes displaying an employee with different 'diagnoses' (depression, burnout, private crisis and thyroid dysfunction), but identical unspecific complaints. Main outcome measures were the managers' attitudes and their impact on stigmatisation with respect to job performance. RESULTS: In nearly all aspects of job performance, the diagnosis depression (psychiatric disorder) was seen as more critical than the diagnosis of a thyroid dysfunction (somatic disease). The diagnosis 'burnout' did not prove to be less stigmatising than 'depression'. Likewise 'private crisis' was rated less favourably than thyroid dysfunction. CONCLUSIONS: Therefore, employees have to evaluate if they disclose their psychiatric disorder or if they conceal it as a somatic illness.

[Understanding the term burnout in psychiatry and psychotherapy]. / Verständnis des Begriffs Burnout in Psychiatrie und Psychotherapie.

BACKGROUND: Currently there is much debate about the concept of burnout and its use as a diagnostic entity. The aim of the present survey was to present the view of mental health professionals towards the concept of burnout. METHODS: A total of 300 mental health professionals were surveyed using a structured questionnaire. RESULTS: The majority of participants see burnout as a state of exhaustion which constitutes a risk factor for later developing a mental disorder. Participants reported that from their point of view typical triggers for burnout exist while symptoms overlap to a great extent with depression. Psychotherapy as well as interventions at the workplace are regarded as promising interventions; however, in the clinical routine only a minority of participants actually contacted the patients' workplace. In the participants workplace settings most Burnout-Patients suffered from a diagnosis defined in ICD 10 but judged themselves to be suffering from burnout. DISCUSSION: Burnout-Patients in mental health settings differ from the picture currently drawn in the media, probably because Burnout-Patients reach the mental health sector only after already having developed a manifest psychiatric disorder.

Identification of an Arabidopsis solute carrier critical for intracellular transport and inter-organ allocation of molybdate.

Plants represent an important source of molybdenum in the human diet. Recently, MOT1 has been identified as a transport protein responsible for molybdate import in Arabidopsis thaliana L.; however, the function of the homologous protein MOT2 has not been resolved. Interestingly, MOT2-GFP analysis indicated a vacuolar location of this carrier protein. By site directed mutagenesis at the N-terminal end of MOT2, we identified a di-leucine motif that is essential for driving the protein into the vacuolar membrane. Molybdate quantification in isolated vacuoles showed that this organelle serves as an important molybdate store in Arabidopsis cells. When grown on soil, leaves from mot2 T-DNA mutants contained more molybdate, whereas mot2 seeds contained significantly less molybdate than corresponding wild-type (Wt) tissues. Remarkably, MOT2 mRNA accumulates in senescing leaves and mot2 leaves from plants that had finished their life cycle had 15-fold higher molybdate levels than Wt leaves. Reintroduction of the endogenous MOT2 gene led to a Wt molybdate phenotype. Thus, mot2 mutants exhibit impaired inter-organ molybdate allocation. As total concentrations of the molybdenum cofactor (Moco) and its precursor MPT correlates with leaf molybdate levels, we present novel evidence for an adjustment of Moco biosynthesis in response to cellular MoO4²â» levels. We conclude that MOT2 is important for vacuolar molybdate export, an N-terminal di-leucine motif is critical for correct subcellular localisation of MOT2 and activity of this carrier is required for accumulation of molybdate in Arabidopsis seeds. MOT2 is a novel element in inter-organ translocation of an essential metal ion.

Confirmation bias: why psychiatrists stick to wrong preliminary diagnoses.

BACKGROUND: Diagnostic errors can have tremendous consequences because they can result in a fatal chain of wrong decisions. Experts assume that physicians' desire to confirm a preliminary diagnosis while failing to seek contradictory evidence is an important reason for wrong diagnoses. This tendency is called 'confirmation bias'. METHOD: To study whether psychiatrists and medical students are prone to confirmation bias and whether confirmation bias leads to poor diagnostic accuracy in psychiatry, we presented an experimental decision task to 75 psychiatrists and 75 medical students. RESULTS: A total of 13% of psychiatrists and 25% of students showed confirmation bias when searching for new information after having made a preliminary diagnosis. Participants conducting a confirmatory information search were significantly less likely to make the correct diagnosis compared to participants searching in a disconfirmatory or balanced way [multiple logistic regression: odds ratio (OR) 7.3, 95% confidence interval (CI) 2.53-21.22, p<0.001; OR 3.2, 95% CI 1.23-8.56, p=0.02]. Psychiatrists conducting a confirmatory search made a wrong diagnosis in 70% of the cases compared to 27% or 47% for a disconfirmatory or balanced information search (students: 63, 26 and 27%). Participants choosing the wrong diagnosis also prescribed different treatment options compared with participants choosing the correct diagnosis. CONCLUSIONS: Confirmatory information search harbors the risk of wrong diagnostic decisions. Psychiatrists should be aware of confirmation bias and instructed in techniques to reduce bias.

Psychiatrists' attitude to antipsychotic depot treatment in patients with first-episode schizophrenia.

OBJECTIVE: Despite good clinical evidence, depot antipsychotics are only seldom prescribed to patients with first episode schizophrenia. The present study aims at investigating psychiatrists' reasons for this reservation. METHOD: We surveyed 198 psychiatrists on their attitude toward offering depot treatment to first episode patients (FEP). Participants scored the extent of influence of individual factors on their decision on a seven-point-scale, additional data on their prescription practice and estimation of the relapse risk of FEP were collected. RESULTS: Psychiatrists reported that only three out of 12 factors were of influence. These were the limited availability of different second generation antipsychotic depot drugs, the frequent rejection of the depot offer by the patients and the patients' skepticism based on the lack in experience of a relapse. CONCLUSIONS: There is actually little specific reason for not prescribing depot to FEP according to the current survey. For those factors being reported to be of influence, psychoeducation, including profound information on depot treatment, the development of additional SGA depot drugs and the standard offer of depot treatment to all FEP in a shared-decision-making may be considered.

The role of abscisic acid and auxin in the response of poplar to abiotic stress.

The plant hormones auxin and abscisic acid may at first sight appear to be a conflicting pair of plant regulators. Abscisic acid content increases during stress and protects plant water status. The content of free auxin in the developing xylem of poplar declines during stress, while auxin conjugates increase. This indicates that specific down-regulation of a signal transduction chain is important in plant adaptation to stress. Diminished auxin content may be a factor that adapts growth and wood development of poplar during adverse environmental conditions. To allow integration of environmental signals, abscisic acid and auxin must interact. Data are accumulating that abscisic acid-auxin cross-talk exists in plants. However, knowledge of the role of plant hormones in the response of trees to stress is scarce. Our data show that differences in the localisation of ABA synthesis exist between the annual, herbaceous plant Arabidopsis and the perennial woody species, poplar.

How psychiatrists inform themselves and their patients about risks and benefits of antipsychotic treatment.

OBJECTIVE: In order to choose the best treatment option, physicians have to inform themselves and their patients about both the benefits and risks of available treatment options equally. Our study aims to investigate whether psychiatrists actually do conduct such a balanced information search and presentation. METHOD: Psychiatrists' information search and information presentation to a patient with schizophrenia were studied using two separate experiments. In both, participants were presented with hypothetical case vignettes and descriptions of fictitious antipsychotics. RESULTS: When searching for information, psychiatrists looked more for risks than benefits of antipsychotic treatment options (t = -3.4, df = 74, P = 0.001). However, when informing a patient, they named more benefits than risks (t = 17.1, df = 224, P < 0.001). CONCLUSION: The risk-biased information search presumably follows the principle of 'primum non nocere'. The benefit-biased information presentation might be motivated by the wish to persuade patients to accept the proposed therapy.

Significance of plant sulfite oxidase.

Sulfite oxidizing activities are known since years in animals, microorganisms, and also plants. Among plants, the only enzyme well characterized on molecular and biochemical level is the molybdoenzyme sulfite oxidase (SO). It oxidizes sulfite using molecular oxygen as electron acceptor, leading to the production of sulfate and hydrogen peroxide. The latter reaction product seems to be the reason why plant SO is localized in peroxisomes, because peroxisomal catalase is able to decompose hydrogen peroxide. On the other hand, we have indications for an additional reaction taking place in peroxisomes: sulfite can be nonenzymatically oxidized by hydrogen peroxide. This will promote the detoxification of hydrogen peroxide especially in the case of high amounts of sulfite. Hence we assume that SO could possibly serve as "safety valve" for detoxifying excess amounts of sulfite and protecting the cell from sulfitolysis. Supportive evidence for this assumption comes from experiments where we fumigated transgenic poplar plants overexpressing ARABIDOPSIS SO with SO(2) gas. In this paper, we try to explain sulfite oxidation in its co-regulation with sulfate assimilation and summarize other sulfite oxidizing activities described in plants. Finally we discuss the importance of sulfite detoxification in plants.

Interaction of sulfur and nitrogen nutrition in tobacco (Nicotiana tabacum) plants: significance of nitrogen source and root nitrate reductase.

The significance of root nitrate reductase for sulfur assimilation was studied in tobacco (NICOTIANA TABACUM) plants. For this purpose, uptake, assimilation, and long-distance transport of sulfur were compared between wild-type tobacco and transformants lacking root nitrate reductase, cultivated either with nitrate or with ammonium nitrate. A recently developed empirical model of plant internal nitrogen cycling was adapted to sulfur and applied to characterise whole plant sulfur relations in wild-type tobacco and the transformant. Both transformation and nitrogen nutrition strongly affected sulfur pools and sulfur fluxes. Transformation decreased the rate of sulfate uptake in nitrate-grown plants and root sulfate and total sulfur contents in root biomass, irrespective of N nutrition. Nevertheless, glutathione levels were enhanced in the roots of transformed plants. This may be a consequence of enhanced APR activity in the leaves that also resulted in enhanced organic sulfur content in the leaves of the tranformants. The lack of nitrate reductase in the roots in the transformants caused regulatory changes in sulfur metabolism that resembled those observed under nitrogen deficiency. Nitrate nutrition reduced total sulfur content and all the major fractions analysed in the leaves, but not in the roots, compared to ammonium nitrate supply. The enhanced organic sulfur and glutathione levels in ammonium nitrate-fed plants corresponded well to elevated APR activity. But foliar sulfate contents also increased due to decreased re-allocation of sulfate into the phloem of ammonium nitrate-fed plants. Further studies will elucidate whether this decrease is achieved by downregulation of a specific sulfate transporter in vascular tissues.

Fluorescent proteins in poplar: a useful tool to study promoter function and protein localization.

The jellyfish (Aequorea victoria) green fluorescent protein (GFP) and its variants (CFP [cyan] and YFP [yellow]) were successfully used as a vital marker system for the transformation of hybrid poplar (Populus tremula x P. alba). Our results show that, in this woody plant, fluorescent proteins can be expressed: (i) transiently in protoplasts after PEG-mediated transformation, as well as in leaf cells after particle bombardment, and (ii) stably in callus cells and plants after Agrobacterium-mediated transformation. For these studies, we constructed vectors permitting easy recloning of any promoter fragments of interest. Confocal laser scanning microscopy was used both for visualization and differentiation between the different colours of the GFP variants and autofluorescence of chlorophyll and lignified xylem vessels. Peroxisomes were chosen as target organelles for GFP translocation via the peroxisomal targeting sequence PTS1 because this allowed us to concentrate the fluorochrome in the small volume of a few peroxisomes, giving a bright fluorescence over background noise.

Vectors for RNAi technology in poplar.

The potential of double-stranded RNA interference (RNAi) technology was studied for down-regulation of gene expression in poplar. A set of vectors was constructed generating RNAs capable of duplex formation of sequences specific for the beta-glucuronidase (GUS) reporter gene system. These gene cassettes are driven by the CaMV-35S promoter. To address the question of gene silencing, we tested the functionality of these vectors, both in transient assays by transforming protoplasts with the RNAi constructs, and in stably transformed GUSexpressing poplar plants. Agrobacterium-mediated transformation of those GUS-expressing plants with a GUS-specific RNAi construct showed a strong down-regulation of the reporter gene. From these results we conclude that RNAi is also functional in poplar.

Identification and biochemical characterization of Arabidopsis thaliana sulfite oxidase. A new player in plant sulfur metabolism.

In mammals and birds, sulfite oxidase (SO) is a homodimeric molybdenum enzyme consisting of an N-terminal heme domain and a C-terminal molybdenum domain (EC ). In plants, the existence of SO has not yet been demonstrated, while sulfite reductase as part of sulfur assimilation is well characterized. Here we report the cloning of a plant sulfite oxidase gene from Arabidopsis thaliana and the biochemical characterization of the encoded protein (At-SO). At-SO is a molybdenum enzyme with molybdopterin as an organic component of the molybdenum cofactor. In contrast to homologous animal enzymes, At-SO lacks the heme domain, which is evident both from the amino acid sequence and from its enzymological and spectral properties. Thus, among eukaryotes, At-SO is the only molybdenum enzyme yet described possessing no redox-active centers other than the molybdenum. UV-visible and EPR spectra as well as apparent K(m) values are presented and compared with the hepatic enzyme. Subcellular analysis of crude cell extracts showed that SO was mostly found in the peroxisomal fraction. In molybdenum cofactor mutants, the activity of SO was strongly reduced. Using antibodies directed against At-SO, we show that a cross-reacting protein of similar size occurs in a wide range of plant species, including both herbacious and woody plants.

Crystal structures of human gephyrin and plant Cnx1 G domains: comparative analysis and functional implications.

The molybdenum cofactor (Moco) consists of a unique and conserved pterin derivative, usually referred to as molybdopterin (MPT), which coordinates the essential transition metal molybdenum (Mo). Moco is required for the enzymatic activities of all Mo-enzymes, with the exception of nitrogenase and is synthesized by an evolutionary old multi-step pathway that is dependent on the activities of at least six gene products. In eukaryotes, the final step of Moco biosynthesis, i.e. transfer and insertion of Mo into MPT, is catalyzed by the two-domain proteins Cnx1 in plants and gephyrin in mammals. Gephyrin is ubiquitously expressed, and was initially found in the central nervous system, where it is essential for clustering of inhibitory neuroreceptors in the postsynaptic membrane. Gephyrin and Cnx1 contain at least two functional domains (E and G) that are homologous to the Escherichia coli proteins MoeA and MogA, the atomic structures of which have been solved recently. Here, we present the crystal structures of the N-terminal human gephyrin G domain (Geph-G) and the C-terminal Arabidopsis thaliana Cnx1 G domain (Cnx1-G) at 1.7 and 2.6 A resolution, respectively. These structures are highly similar and compared to MogA reveal four major differences in their three-dimensional structures: (1) In Geph-G and Cnx1-G an additional alpha-helix is present between the first beta-strand and alpha-helix of MogA. (2) The loop between alpha 2 and beta 2 undergoes conformational changes in all three structures. (3) A beta-hairpin loop found in MogA is absent from Geph-G and Cnx1-G. (4) The C terminus of Geph-G follows a different path from that in MogA. Based on the structures of the eukaryotic proteins and their comparisons with E. coli MogA, the predicted binding site for MPT has been further refined. In addition, the characterized alternative splice variants of gephyrin are analyzed in the context of the three-dimensional structure of Geph-G.

ABA3 is a molybdenum cofactor sulfurase required for activation of aldehyde oxidase and xanthine dehydrogenase in Arabidopsis thaliana.

The xanthine oxidase class of molybdenum enzyzmes requires a terminal sulfur ligand at the active site. It has been proposed that a special sulfurase catalyzes the insertion of this ligand thereby activating the enzymes. Previous analyses of mutants in plants indicated that the genetic locus aba3 is involved in this step leading to activation of the molybdenum enzymes aldehyde oxidase and xanthine dehydrogenase. Here we report the cloning of the aba3 gene from Arabidopsis thaliana and the biochemical characterization of the purified protein. ABA3 is a two-domain protein with a N-terminal NifS-like sulfurase domain and a C-terminal domain that might be involved in recognizing the target enzymes. Molecular analysis of three aba3 mutants identified mutations in both domains. ABA3 contains highly conserved binding motifs for pyridoxal phosphate and for a persulfide. The purified recombinant protein possesses a cysteine desulfurase activity, is yellow in color, and shows a NifS-like change in absorbance in the presence of L-cysteine. Pretreatment of ABA3 with a thiol-specific alkylating reagent inhibited its desulfurase activity. These data indicate a transsulfuration reaction similar to bacterial NifS. In a fully defined in vitro system, the purified protein was able to activate aldehyde oxidase by using L-cysteine as sulfur donor. Finally, we show that the expression of the aba3 gene is inducible by drought-stress.

Characterisation of the mob locus of Rhodobacter sphaeroides WS8: mobA is the only gene required for molybdopterin guanine dinucleotide synthesis.

The mob genes of several bacteria have been implicated in the conversion of molybdopterin to molybdopterin guanine dinucleotide. The mob locus of Rhodobacter sphaeroides WS8 comprises three genes, mobABC. Chromosomal in-frame deletions in each of the mob genes have been constructed. The mobA mutant strain has inactive DMSO reductase and periplasmic nitrate reductase activities (both molybdopterin guanine dinucleotide-requiring enzymes), but the activity of xanthine dehydrogenase, a molybdopterin enzyme, is unaffected. The inability of a mobA mutant to synthesise molybdopterin guanine dinucleotide is confirmed by analysis of cell extracts of the mobA strain for molybdenum cofactor forms following iodine oxidation. Mutations in mobB and mobC are not impaired for molybdoenzyme activities and accumulate wild-type levels of molybdopterin and molybdopterin guanine dinucleotide, indicating they are not compromised in molybdenum cofactor synthesis. In the mobA mutant strain, the inactive DMSO reductase is found in the periplasm, suggesting that molybdenum cofactor insertion is not necessarily a pre-requisite for export.

Tobacco plants that lack expression of functional nitrate reductase in roots show changes in growth rates and metabolite accumulation.

When tobacco is provided with a high nitrate supply, only a small amount of the nitrate taken up by the roots is immediately assimilated inside the roots, while the majority is transported to the leaves where it is reduced to ammonium. To elucidate the importance of root nitrate assimilation, tobacco plants have been engineered that showed no detectable nitrate reductase activity in the roots. These plants expressed the nitrate reductase structural gene nia2 under control of the leaf-specific potato promoter ST-LS1 in the nitrate reductase-mutant Nia30 of Nicotiana tabacum. Homozygous T2-transformants grown in sand or hydroponics with 5.1 mM nitrate had approximately 55-70% of wild-type nitrate reductase acivity in leaves, but lacked nitrate reductase acivity in roots. These plants showed a retarded growth as compared with wild-type plants. The activation state of nitrate reductase was unchanged; however, diurnal variation of nitrate reductase acivity was not as pronounced as in wild-type plants. The transformants had higher levels of nitrate in the leaves and reduced amounts of glutamine both in leaves and roots, while roots showed higher levels of hexoses (3-fold) and sucrose (10-fold). It may be concluded that the loss of nitrate reductase acivity in the roots changes the allocation of reduced nitrogen compounds and sugars in the plant. These plants will be a useful tool for laboratories studying nitrate assimilation and its interactions with carbon metabolism.

Discordant prevalence of chlamydia trachomatis in asymptomatic couples screened using urine ligase chain reaction.

The following study was conducted to determine whether there would be an effect on the prevalence of Chlamydia trachomatis if both partners in a sexual relationship, rather than only one, underwent screening. First-void urine samples were collected from 1,690 asymptomatic women (mean age, 30 years; range, 15-70 years) and their male sex partners (mean age, 33 years; range, 16-71 years). The duration of sexual partnership for these subjects ranged from 2 months to more than 10 years.. At the time of testing, 687 of the women were pregnant. Ligase chain reaction testing revealed that 42 (2.5%) female and 63 (3.7%) male urine samples were positive. Detection rates for Chlamydia trachomatis differed for males and females, a difference that was found to be significant (P<0.0046, McNemar chi-square). Both partners tested positive in 27 (1.6%) couples, whereas at least one partner tested positive in 78 (4.6%) couples. Thus, screening males for Chlamydia trachomatis would have identified 63 (81%) of these 78 couples compared with only 42 (54%) couples had females been screened exclusively. In standard clinical practice, women most often undergo screening. The results of this study underscore the need to screen both males and females for Chlamydia trachomatis.