Relationship between atopic dermatitis, depression and anxiety: a two-sample Mendelian randomization study.

BACKGROUND: Growing evidence suggests that atopic dermatitis (AD) is associated with an increased risk of depressive disorders and anxiety. However, existing studies were observational and may have uncovered correlations but could not easily disentangle noncausal or reverse-causal associations because these associations could be confounded and may not reflect true causal relationships. OBJECTIVES: To examine, in a two-sample Mendelian randomization study, the potential effect of AD on the risk of depressive disorders and anxiety. METHODS: Genetic instruments from the largest available genome-wide association study (GWAS) for AD (10 788 cases and 30 047 controls) were used to investigate the relationship to broad depression (170 756 cases and 329 443 controls), major depressive disorder (MDD; 30 603 cases and 143 916 controls) and anxiety (5580 cases and 11 730 controls). A set of complementary approaches were carried out to assess horizontal pleiotropy and related potential caveats occurring in MR studies. RESULTS: We observed no causal impact of AD on the risk of depressive disorders and anxiety, with close-to-zero effect estimates. The inverse weighted method revealed no associations of AD on broad depression [odds ratio (OR) 1·014; P = 0·431], probable MDD (OR 1·002; P = 0·568), International Classification of Diseases, Ninth/Tenth Revision-based MDD (OR 1·001; P = 0·466) or anxiety (OR 1·097; P = 0·180). CONCLUSIONS: This MR study does not support a causal effect of AD on depression and anxiety.

Selective, efficient modulation of activated CD4+ αßT cells by the novel humanized antibody GZ-αßTCR targeting human αßTCR.

Allograft rejection and immunosuppression are two major issues in transplantation medicine. The specific targeting of alloreactive T cells, the initiators and promoters of allograft rejection, would be a promising strategy to reduce unwanted T-cell responses and side effects of lifelong immunosuppression. The novel humanized monoclonal antibody GZ-αßTCR, specific for the human αßT-cell receptor, was tested in vitro and in vivo for its specificity and efficacy to modulate the αßT-cell compartment. GZ-αßTCR moderately induced apoptosis in resting αßT cells in vitro, an effect considerably amplified in activated T cells. A single dose of GZ-αßTCR significantly reduced human CD45(+)CD3(+) T cells in vivo, with a preferential modulation of CD4(+) αßT cells. Importantly, naive T cells, the T-cell subset from which alloreactivity emanates, were significantly reduced. Simultaneously, a significant, compensatory increase of γδ T cells was observed in vitro and in vivo in both humanized mouse models examined. GZ-αßTCR did not induce cytokines and was well tolerated. Thus, specificity and high efficacy make GZ-αßTCR a powerful tool to selectively eliminate putatively detrimental T-cell subsets, a major goal in transplantation medicine. At the same time, GZ-αßTCR spares γδ and natural killer cells, thus leaving the recipient's immune system competent for cell-mediated immunoregulation and cell-mediated immunity.

Solution NMR structure of the cold-shock protein from the hyperthermophilic bacterium Thermotoga maritima.

Cold-shock proteins (Csps) are a subgroup of the cold-induced proteins preferentially expressed in bacteria and other organisms on reduction of the growth temperature below the physiological temperature. They are related to the cold-shock domain found in eukaryotes and are some of the most conserved proteins known. Their exact function is still not known, but translational regulation, possibly via RNA chaperoning, has been discussed. Here we present the structure of a hyperthermophilic member of the Csp family. The NMR solution structure of TmCsp from Thermotoga maritima, the hyperthermophilic member of this class of proteins, was solved on the basis of 1015 conformational constraints. It contains five beta strands combined in two antiparallel beta sheets making up a beta barrel structure, in which beta strands 1-4 are arranged in a Greek-key topology. The side chain of R2, which is exclusively found in thermophilic members of the Csp family, probably participates in a peripheral ion cluster involving residues D20, R2, E47 and K63, suggesting that the thermostability of TmCsp is based on the peripheral ion cluster around the side chain of R2.

An evaluation of residential treatment for sexually aggressive youth.

This longitudinal study investigated the effectiveness of a one and one-half year long residential treatment program for 26 boys aged 11-15 with histories of sexually aggressive behavior. The clients were assessed with self-report and staff-report measures at the beginning and end of treatment and at several time points in between; also, aggressive acts were tabulated during a one-year follow-up period. There was evidence of improved functioning on 10 of the 12 measures. During the follow-up, 27% of the sample committed an aggressive act, and 8% committed a sexually aggressive act. On most of the measures, improvement occurred gradually over the course of treatment, and on some measures most of the improvement occurred late in the placement.

Measure how ACNPs impact outcomes.

Nurse leaders need a way to measure acute care nurse practitioners' (ACNPs') performance and justify their positions. An objective documentation tool can help to evaluate ACNPs' work activities and measure performance and outcomes.

Measuring how acute care nurse practitioners affect outcomes.

Nurse-leaders need a way to measure acute care nurse practitioners' (ACNPs') performance and justify their positions. An objective documentation tool can help to evaluate ACNPs' work activities and measure performance and outcomes.

Does the elimination of ion pairs affect the thermal stability of cold shock protein from the hyperthermophilic bacterium Thermotoga maritima?

Cold shock proteins (Csps) from mesophiles and thermophiles differ widely in their stabilities, but show close structural similarity. Sequence variations involve mainly charged groups, supporting the view that ion pairs contribute significantly to the free energy of stabilization. Based on the known 3D structure of mesophilic Bacillus subtilis CspB and the modeled structure of hyperthermophilic Csp from Thermotoga maritima (TmCsp), D9 and H61 of TmCsp have been substituted by asparagine to find out whether the elimination of predicted ion pairs has a destabilizing effect. Thermal unfolding experiments show that the D9N mutant is destabilized by 9 degrees C, whereas H61N exhibits unaltered wild type behavior. The results are in agreement with preliminary NMR data which confirm the predicted structure only for the N-terminal ion pair.

Thermodynamics of the unfolding of the cold-shock protein from Thermotoga maritima.

Proteins from (hyper-)thermophiles are known to exhibit high intrinsic stabilities. Commonly, their thermodynamic characterization is impeded by irreversible side reactions of the thermal analysis or calorimetrical problems. Small single-domain proteins are suitable candidates to overcome these obstacles. Here, the thermodynamics of the thermal denaturation of the recombinant cold-shock protein (Csp) from the hyperthermophilic bacterium Thermotoga maritima (Tm) was studied by differential scanning calorimetry. The unfolding transition can be described over a broad pH range (3.5-8.5) by a reversible two-state process. Maximum stability (DeltaG (25 degrees C)=6.5 kcal/mol) was observed at pH 5-6 where Tm Csp unfolds with a melting temperature at 95 degrees C. The heat capacity difference between the native and the denatured states is 1.1(+/-0.1) kcal/(mol K). At pH 7, thermal denaturation occurs at 82 degrees C. The corresponding free energy profile has its maximum at 30 degrees C with DeltaGN-->U=4.8(+/-0.5) kcal/mol. At the optimal growth temperature of T. maritima (80 degrees C), Tm Csp in the absence of ligands is only marginally stable, with a free energy of stabilization not far beyond the thermal energy. With the known stabilizing effect of nucleic acids in mind, this suggests a highly dynamical interaction of Tm Csp with its target molecules.

Cloning, overexpression, purification, and physicochemical characterization of a cold shock protein homolog from the hyperthermophilic bacterium Thermotoga maritima.

Thermotoga maritima (Tm) expresses a 7 kDa monomeric protein whose 18 N-terminal amino acids show 81% identity to N-terminal sequences of cold shock proteins (Csps) from Bacillus caldolyticus and Bacillus stearothermophilus. There were only trace amounts of the protein in Thermotoga cells grown at 80 degrees C. Therefore, to perform physicochemical experiments, the gene was cloned in Escherichia coli. A DNA probe was produced by PCR from genomic Tm DNA with degenerated primers developed from the known N-terminus of TmCsp and the known C-terminus of CspB from Bacillus subtilis. Southern blot analysis of genomic Tm DNA allowed to produce a partial gene library, which was used as a template for PCRs with gene- and vector-specific primers to identify the complete DNA sequence. As reported for other csp genes, the 5' untranslated region of the mRNA was anomalously long; it contained the putative Shine-Dalgarno sequence. The coding part of the gene contained 198 bp, i.e., 66 amino acids. The sequence showed 61% identity to CspB from B. caldolyticus and high similarity to all other known Csps. Computer-based homology modeling allowed the conclusion that TmCsp represents a beta-barrel similar to CspB from B. subtilis and CspA from E. coli. As indicated by spectroscopic analysis, analytical gel permeation chromatography, and mass spectrometry, overexpression of the recombinant protein yielded authentic TmCsp with a molecular weight of 7,474 Da. This was in agreement with the results of analytical ultracentrifugation confirming the monomeric state of the protein. The temperature-induced equilibrium transition at 87 degrees C exceeds the maximum growth temperature of Tm and represents the maximal Tm-value reported for Csps so far.

Youth attitudes toward guns and violence: relations with sex, age, ethnic group, and firearm exposure.

Investigated relations between young people's scores on the Attitudes Toward Guns and Violence Questionnaire (AGVQ; Shapiro, Dorman, Burkey, Welker, & Clough, 1997), demographic variables, and exposure to firearms and violence. 1,164 students, Grades 3 to 12, from an urban, suburban, parochial, and private school system completed anonymous self-report questionnaires in their classrooms. Boys produced higher AGVQ scores than did girls. Scores were similar in Grades 3 and 5, were much higher in Grade 6 than in Grade 5, and were similar in Grades 6 and above. This pattern was found across sex, race, and school system. African Americans obtained higher scores than Caucasians on the AGVQ and on 2 of its 4 factors. Students in the urban public schools produced higher scores than did youth in the other school systems. Both traumatic and nontraumatic exposure to firearms were associated with high AGVQ scores. Sex, grade, and firearm exposure were associated with relatively large differences, while ethnic group and school system were associated with relatively small differences.

Conservation of rapid two-state folding in mesophilic, thermophilic and hyperthermophilic cold shock proteins.

The cold shock protein CspB from Bacillus subtilis is only marginally stable, but it folds extremely fast in a simple N reversible U two-state reaction. The corresponding cold shock proteins from the thermophile Bacillus caldolyticus and the hyperthermophile Thermotoga maritima show strongly increased conformational stabilities, but unchanged very fast two-state refolding kinetics. The absence of intermediates in the folding of B. subtilis CspB is thus not a corollary of its low stability. Rather, two-state folding and an unusually native-like activated state of folding seem to be inherent properties of these small all-beta proteins. There is no link between stability and folding rate, and numerous sequence positions exist which can be varied to modulate the stability without affecting the rate and mechanism of folding.

Development and factor analysis of a measure of youth attitudes toward guns and violence.

Administered the Attitudes Toward Guns and Violence Questionnaire (AGVQ) to 1,619 students in Grades 3, 5, 6, 7, 9, 11, and 12 from four demographically diverse school systems. Fifty-two of the 61 items exhibited satisfactory part-whole correlation and correlation with a validity criterion. Factor analysis revealed four main factors: Aggressive Response to Shame, Comfort With Aggression, Excitement, and Power/Safety. The instrument was reduced to 23 items by deleting items with high cross-loadings. Construct validity was similar for the longer and shorter versions. Youth who self-reported owning a gun produced scores 1.5 SD higher than nonowners. Low scores were associated with a 1 in 125 chance of gun ownership, and high scores were associated with a 1 in 3 chance. Congruency coefficients indicated similar factor structure for the present sample and a separate sample of 5th-, 7th- and 9th-grade students. These results indicate that the AGVQ is a reliable and valid measure of violence-related attitudes in young people.

The Youth Client Satisfaction Questionnaire: development, construct validation, and factor structure.

Developed and pilot-tested a measure of satisfaction with mental health services for young clients. One hundred fifty youth from 11 to 17 years of age who had completed services received the measure as a telephone interview. Fourteen of 17 candidate items met criteria for test-retest reliability, part-whole correlation, and correlation with a validation item, and they were retained in the instrument. Total score test-retest reliability and internal consistency were highly satisfactory. Principal components analysis revealed two factors, labeled Relationship With Therapist and Benefits of Therapy. Unexpectedly, satisfaction scores were not related to change in youth self-reported behavior problems. However, convergent validity was indicated by significant relationships with change in parent-reported behavior problems, parent satisfaction, parent ratings of treatment progress, therapist ratings of progress, and Global Assessment of Functioning change scores. These results indicate that the Youth Client Satisfaction Questionnaire is a reliable and valid measure of consumer evaluations of their treatment.

A naturalistic study of psychotherapeutic methods and client in-therapy functioning in a child community setting.

Utilized a naturalistic methodology to examine treatment responses associated with major psychotherapeutic methods in 150 youth aged 11 to 17 years old in a community mental health center. Treatment methods were not experimentally controlled but were measured retrospectively by therapist report. Treatment response was assessed by a composite of 6 measures completed by clients, parents, and therapists. Pretest/posttest comparisons indicated improved functioning in the sample as a whole. Treatment response was not related to the proportion of therapy using individual, family, or group modalities. Therapy response was positively associated with extent of use of cognitive therapy. Social skills training, behavior therapy, and family systems therapy were associated with more positive treatment response in some subgroups of clients. The number of approaches used in an individual case (technical eclecticism) was positively related to client response. Treatment response was more consistently related to level of client and parent functioning in therapy than to treatment method.

Significance of kin relations and individual preferences in the social behaviour of Cebus apella.

Captive tufted capuchins (Cebus apella) formed a group characterized by greater affiliative behaviour within matrilines. Affiliation within the matriline is dependent upon social intimacy during infancy with matriline members. Courtship and mating are not identically distributed: subordinate and subadult males participate in a larger proportion of matings than of courtships. In all these aspects of social behaviour, variability across individuals contributes to the complex dynamics of the social group.

Social relations in groups of the black-capped capuchin (Cebus apella) in captivity. Interactions of group-born infants during their second half-year of life.

During the second half-year of life, capuchin monkey infants maintain close contacts to kin-related animals. Apart from these contacts, they frequently interact with other infants and juveniles 1 year older. During this period of life the 'peer phase' begins in the life of the infants. Furthermore, gender differences, especially in respect to social play, become obvious.