Patients with Borderline Personality Disorder Not Participating in an RCT: Are They Different?

Background: Despite the notion that randomized controlled trials are regarded as the gold standard in psychotherapy research, questions about their generalizability have been raised. This paper focuses on the differences between participants and eligible nonparticipants of a randomized controlled trial for patients with borderline personality disorder (BPD). Sampling and Methods: One hundred forty-two patients were screened, and 122 were found eligible for study participation. Out of these, 64 patients (52.5%) gave informed consent and were included in the study. Results: The 58 eligible nonparticipants showed a lower level of functioning (global assessment of functioning score), had a history of more outpatient treatment attempts and were living alone more often. Regarding acute symptoms and severity of BPD as indexed by suicide attempts, inpatient treatments, substance abuse and history of trauma, no differences between the groups could be detected. Moreover, participants showed significantly more eating disorders, whereas nonparticipants presented more affective and anxiety disorders. Conclusions: The results indicate that lower psychosocial functioning and comorbid affective and anxiety disorders decrease BPD patients' willingness to participate in an RCT. Copyright (C) 2010 S. Karger AG, Base

Step-wise assembly, maturation and dynamic behavior of the human CENP-P/O/R/Q/U kinetochore sub-complex

Kinetochores are multi-protein megadalton assemblies that are required for attachment of microtubules to centromeres and, in turn, the segregation of chromosomes in mitosis. Kinetochore assembly is a cell cycle regulated multi-step process. The initial step occurs during interphase and involves loading of the 15-subunit constitutive centromere associated complex (CCAN), which contains a 5-subunit (CENP-P/O/R/Q/U) sub-complex. Here we show using a fluorescent three-hybrid (F3H) assay and fluorescence resonance energy transfer (FRET) in living mammalian cells that CENP-P/O/R/Q/U subunits exist in a tightly packed arrangement that involves multifold protein-protein interactions. This sub-complex is, however, not pre-assembled in the cytoplasm, but rather assembled on kinetochores through the step-wise recruitment of CENP-O/P heterodimers and the CENP-P, -O, -R, -Q and -U single protein units. SNAP-tag experiments and immuno-staining indicate that these loading events occur during S-phase in a manner similar to the nucleosome binding components of the CCAN, CENP-T/W/N. Furthermore, CENP-P/O/R/Q/U binding to the CCAN is largely mediated through interactions with the CENP-N binding protein CENP-L as well as CENP-K. Once assembled, CENP-P/O/R/Q/U exchanges slowly with the free nucleoplasmic pool indicating a low off-rate for individual CENP-P/O/R/Q/U subunits. Surprisingly, we then find that during late S-phase, following the kinetochore-binding step, both CENP-Q and -U but not -R undergo oligomerization. We propose that CENP-P/O/R/Q/U self-assembles on kinetochores with varying stoichiometry and undergoes a pre-mitotic maturation step that could be important for kinetochores switching into the correct conformation necessary for microtubule-attachment

Contraception in the German-language Wikipedia: a content and quality analysis

BACKGROUND: Adolescents and adults today often obtain information about contraception from the Internet, especially from the online encyclopedia Wikipedia. This is because Google searches usually return Wikipedia entries as top hits. RESEARCH AIM: Against this background, the aim of the current study is to systematically analyze for the first time the content and quality of Wikipedia articles on contraceptive methods. Five central quality dimensions are examined: the degree of correctness (research question RQ1), completeness (RQ2), neutrality (RQ3), comprehensibility (RQ4), and currency (RQ5) of the contraceptive information – and on this basis the overall quality of the articles (RQ6). MATERIALS AND METHODS: A sample of all German-language Wikipedia articles on all contraceptive methods was formed (N = 25). These articles were analyzed by three independent, trained coders using a codebook that was developed based on the current state of the research and tested for reliability. Data analysis was performed using SPSS. The study is preregistered and all data, materials, and analysis scripts are publicly available. RESULTS: The 25 Wikipedia articles on contraceptive methods were found to vary widely in content quality. While they showed good quality on average in terms of correctness (RQ1) and neutrality (RQ3), they scored mediocre in terms of completeness (RQ2), comprehensibility (RQ4), and currency (RQ5), resulting in moderate overall quality (RQ6). DISCUSSION: More research as well as practice measures are needed to further assess and improve the quality of contraceptive information on Wikipedia and in other social media in a more targeted way

Can communication technologies reduce loneliness and social isolation in older people?: a scoping review of reviews

Background: Loneliness and social isolation in older age are considered major public health concerns and research on technology-based solutions is growing rapidly. This scoping review of reviews aims to summarize the communication technologies (CTs) (review question RQ1), theoretical frameworks (RQ2), study designs (RQ3), and positive effects of technology use (RQ4) present in the research field. Methods: A comprehensive multi-disciplinary, multi-database literature search was conducted. Identified reviews were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. A total of N = 28 research reviews that cover 248 primary studies spanning 50 years were included. Results: The majority of the included reviews addressed general internet and computer use (82% each) (RQ1). Of the 28 reviews, only one (4%) worked with a theoretical framework (RQ2) and 26 (93%) covered primary studies with quantitative-experimental designs (RQ3). The positive effects of technology use were shown in 55% of the outcome measures for loneliness and 44% of the outcome measures for social isolation (RQ4). Conclusion: While research reviews show that CTs can reduce loneliness and social isolation in older people, causal evidence is limited and insights on innovative technologies such as augmented reality systems are scarce

NirA is an alternative nitrite reductase from Pseudomonas aeruginosa with potential as an antivirulence target

The opportunistic pathogen Pseudomonas aeruginosa produces an arsenal of virulence factors causing a wide range of diseases in multiple hosts and is difficult to eradicate due to its intrinsic resistance to antibiotics. With the antibacterial pipeline drying up, antivirulence therapy has become an attractive alternative strategy to the traditional use of antibiotics to treat P. aeruginosa infections. To identify P. aeruginosa genes required for virulence in multiple hosts, a random library of Tn5 mutants in strain PAO1-L was previously screened in vitro for those showing pleiotropic effects in the production of virulence phenotypes. Using this strategy, we identified a Tn5 mutant with an insertion in PA4130 showing reduced levels of a number of virulence traits in vitro. Construction of an isogenic mutant in this gene presented results similar to those for the Tn5 mutant. Furthermore, the PA4130 isogenic mutant showed substantial attenuation in disease models of Drosophila melanogaster and Caenorhabditis elegans as well as reduced toxicity in human cell lines. Mice infected with this mutant demonstrated an 80% increased survival rate in acute and agar bead lung infection models. PA4130 codes for a protein with homology to nitrite and sulfite reductases. Overexpression of PA4130 in the presence of the siroheme synthase CysG enabled its purification as a soluble protein. Methyl viologen oxidation assays with purified PA4130 showed that this enzyme is a nitrite reductase operating in a ferredoxin-dependent manner. The preference for nitrite and production of ammonium revealed that PA4130 is an ammonia:ferredoxin nitrite reductase and hence was named NirA. IMPORTANCE The emergence of widespread antimicrobial resistance has led to the need for development of novel therapeutic interventions. Antivirulence strategies are an attractive alternative to classic antimicrobial therapy; however, they require identification of new specific targets which can be exploited in drug discovery programs. The host-specific nature of P. aeruginosa virulence adds complexity to the discovery of these types of targets. Using a sequence of in vitro assays and phylogenetically diverse in vivo disease models, we have identified a PA4130 mutant with reduced production in a number of virulence traits and severe attenuation across all infection models tested. Characterization of PA4130 revealed that it is a ferredoxin-nitrite reductase and hence was named NirA. These results, together with attenuation of nirA mutants in different clinical isolates, high level conservation of its gene product in P. aeruginosa genomes, and the lack of orthologues in human genomes, make NirA an attractive antivirulence target

The “Hidden Urbanization”: Trends of Impervious Surface in Low-Density Housing Developments and Resulting Impacts on the Water Balance

Impervious surface is an important factor for the ecological performance of the built environment, in particular for the water balance. Therefore, the rainwater drainage infrastructure of new housing developments is planned according to the expected amount of impervious surface and the resulting surface runoff. Drainage infrastructure could be overwhelmed, however, due to small, dispersed, and often overlooked increases in impervious surface cover, a process we refer to as “hidden urbanization.” There is some evidence that impervious surface cover in housing areas has increased significantly over decades, but is there also a gap between planning and implementation? In order to find out, we compared eight development plans (i.e., the legally binding documents that steer building in Germany) of low-density (single-family) housing with the actual status-quo extracted from 2016 orthophotos. All sites are located in Lower Saxony, Germany; four are close to major urban centers and four are in small municipalities. We then modeled the local water balance for the plans and status-quo and compared results. All sites but one showed a relative increase between 8 and 56% of impervious surface, comparing plans with status-quo. For all sites with an increase of impervious cover, infiltration rates decreased by 4–19%, evaporation rates increased by 0.2–1% and surface runoff increased by 4–18%. In general, the more impervious surface, the stronger the effect. Our results point to a gap between planning and implementation and they underline the environmental consequences, illustrated by effects on the water balance. In order to prevent “hidden urbanization,” we suggest that more emphasis should be put on integrated design of housing areas and monitoring of impervious surface cover

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

NirA Is an Alternative Nitrite Reductase from Pseudomonas aeruginosa with Potential as an Antivirulence Target

The opportunistic pathogen Pseudomonas aeruginosa produces an arsenal of virulence factors causing a wide range of diseases in multiple hosts and is difficult to eradicate due to its intrinsic resistance to antibiotics. With the antibacterial pipeline drying up, antivirulence therapy has become an attractive alternative strategy to the traditional use of antibiotics to treat P. aeruginosa infections. To identify P. aeruginosa genes required for virulence in multiple hosts, a random library of Tn5 mutants in strain PAO1-L was previously screened in vitro for those showing pleiotropic effects in the production of virulence phenotypes. Using this strategy, we identified a Tn5 mutant with an insertion in PA4130 showing reduced levels of a number of virulence traits in vitro. Construction of an isogenic mutant in this gene presented results similar to those for the Tn5 mutant. Furthermore, the PA4130 isogenic mutant showed substantial attenuation in disease models of Drosophila melanogaster and Caenorhabditis elegans as well as reduced toxicity in human cell lines. Mice infected with this mutant demonstrated an 80% increased survival rate in acute and agar bead lung infection models. PA4130 codes for a protein with homology to nitrite and sulfite reductases. Overexpression of PA4130 in the presence of the siroheme synthase CysG enabled its purification as a soluble protein. Methyl viologen oxidation assays with purified PA4130 showed that this enzyme is a nitrite reductase operating in a ferredoxin-dependent manner. The preference for nitrite and production of ammonium revealed that PA4130 is an ammonia:ferredoxin nitrite reductase and hence was named NirA

Comparison between a linear versus a macrocyclic contrast agent for whole body MR angiography in a clinical routine setting

<p>Abstract</p> <p>Background</p> <p>Previous experiences of whole body MR angiography are predominantly available in linear 0.5 M gadolinium-containing contrast agents. The aim of this study was to compare image quality on a four-point scale (range 1–4) and diagnostic accuracy of a 1.0 M macrocyclic contrast agent (gadobutrol, n = 80 patients) with a 0.5 M linear contrast agent (gadopentetate dimeglumine, n = 85 patients) on a 1.5 T whole body MR system. Digital subtraction angiography served as standard of reference.</p> <p>Results</p> <p>All examinations yielded diagnostic image quality. There was no significant difference in image quality (3.76 ± 0.3 versus 3.78 ± 0.3, p = n.s.) and diagnostic accuracy observed. Sensitivity and specificity of the detection of hemodynamically relevant stenoses was 93%/95% in the gadopentetate dimeglumine group and 94%/94% in the gadobutrol group, respectively.</p> <p>Conclusion</p> <p>The high diagnostic accuracy of gadobutrol in the clinical routine setting is of high interest as medical authorities (e.g. the European Agency for the Evaluation of Medicinal Products) recommend macrocyclic contrast agents especially to be used in patients with renal failure or dialysis.</p