A Reliability Generalization Meta-analysis of the Dimensional Obsessive-Compulsive Scale.

BACKGROUND: The Dimensional Obsessive-Compulsive Scale (DOCS) is a well-established tool for assessing obsessive-compulsive symptomatology. A reliability generalization meta-analysis was conducted to estimate the average reliability of DOCS scores and how reliability estimates vary according to the composition and variability of samples, to identify study characteristics that can explain its variability, and to estimate the reliability induction rate. METHOD: A literature search produced 86 studies that met the inclusion criteria. RESULTS: For the DOCS total scores, an average alpha coefficient of .925 was found (95% CI [.920,.931]), as well as mean alphas of .881, .905, .913, and .914 for Contamination, Responsibility, Unacceptable Thoughts, and Symmetry subscales, respectively. Moderator analysis showed that internal consistency fell significantly the more clinical and subclinical participants there were in the sample, and the larger the mean score in the sample for the total scores. The most important moderator variables for the subscales were the standard deviation and the mean of the scores. CONCLUSIONS: The DOCS scores exhibited excellent internal consistency reliability for both total score and subscale scores and DOCS is suitable both for research and clinical purposes.

Improving the reporting quality of reliability generalization meta-analyses: The REGEMA checklist.

Reliability generalization (RG) is a meta-analytic approach that aims to characterize how reliability estimates from the same test vary across different applications of the instrument. With this purpose RG meta-analyses typically focus on a particular test and intend to obtain an overall reliability of test scores and to investigate how the composition and variability of the samples affect reliability. Although several guidelines have been proposed in the meta-analytic literature to help authors improve the reporting quality of meta-analyses, none of them were devised for RG meta-analyses. The purpose of this investigation was to develop REGEMA (REliability GEneralization Meta-Analysis), a 30-item checklist (plus a flow chart) adapted to the specific issues that the reporting of an RG meta-analysis must take into account. Based on previous checklists and guidelines proposed in the meta-analytic arena, a first version was elaborated by applying the nominal group methodology. The resulting instrument was submitted to a list of independent meta-analysis experts and, after discussion, the final version of the REGEMA checklist was reached. In a pilot study, four pairs of coders applied REGEMA to a random sample of 40 RG meta-analyses in Psychology, and results showed satisfactory inter-coder reliability. REGEMA can be used by: (a) meta-analysts conducting or reporting an RG meta-analysis and aiming to improve its reporting quality; (b) consumers of RG meta-analyses who want to make informed critical appraisals of their reporting quality, and (c) reviewers and editors of journals who are considering submissions where an RG meta-analysis was reported for potential publication.

Kidney-specific genetic deletion of both AMPK α-subunits causes salt and water wasting.

AMP-activated kinase (AMPK) controls cell energy homeostasis by modulating ATP synthesis and expenditure. In vitro studies have suggested AMPK may also control key elements of renal epithelial electrolyte transport but in vivo physiological confirmation is still insufficient. We studied sodium renal handling and extracellular volume regulation in mice with genetic deletion of AMPK catalytic subunits. AMPKα1 knockout (KO) mice exhibit normal renal sodium handling and a moderate antidiuretic state. This is accompanied by higher urinary aldosterone excretion rates and reduced blood pressure. Plasma volume, however, was found to be increased compared with wild-type mice. Thus blood volume is preserved despite a significantly lower hematocrit. The lack of a defect in renal function in AMPKα1 KO mice could be explained by a compensatory upregulation in AMPK α2-subunit. Therefore, we used the Cre-loxP system to knock down AMPKα2 expression in renal epithelial cells. Combining this approach with the systemic deletion of AMPKα1 we achieved reduced renal AMPK activity, accompanied by a shift to a moderate water- and salt-wasting phenotype. Thus we confirm the physiologically relevant role of AMPK in the kidney. Furthermore, our results indicate that in vivo AMPK activity stimulates renal sodium and water reabsorption.

Modeling Hedgehog Signaling Through Flux-Saturated Mechanisms.

Hedgehog (Hh) molecules act as morphogens directing cell fate during development by activating various target genes in a concentration dependent manner. Hitherto, modeling morphogen gradient formation in multicellular systems has employed linear diffusion, which is very far from physical reality and needs to be replaced by a deeper understanding of nonlinearities. We have developed a novel mathematical approach by applying flux-limited spreading (FLS) to Hh morphogenetic actions. In the new model, the characteristic velocity of propagation of each morphogen is a new key biological parameter. Unlike in linear diffusion models, FLS modeling predicts concentration fronts and correct patterns and cellular responses over time. In addition, FLS considers not only extracellular binding partners influence, but also channels or bridges of information transfer, such as specialized filopodia or cytonemes as a mechanism of Hh transport. We detect and measure morphogen particle velocity in cytonemes in the Drosophila wing imaginal disc. Indeed, this novel approach to morphogen gradient formation can contribute to future research in the field.

Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion.

The Hedgehog signalling pathway is crucial for development, adult stem cell maintenance, cell migration and axon guidance in a wide range of organisms. During development, the Hh morphogen directs tissue patterning according to a concentration gradient. Lipid modifications on Hh are needed to achieve graded distribution, leading to debate about how Hh is transported to target cells despite being membrane-tethered. Cytonemes in the region of Hh signalling have been shown to be essential for gradient formation, but the carrier of the morphogen is yet to be defined. Here we show that Hh and its co-receptor Ihog are in exovesicles transported via cytonemes. These exovesicles present protein markers and other features of exosomes. Moreover, the cell machinery for exosome formation is necessary for normal Hh secretion and graded signalling. We propose Hh transport via exosomes along cytonemes as a significant mechanism for the restricted distribution of a lipid-modified morphogen.

Balancing Hedgehog, a retention and release equilibrium given by Dally, Ihog, Boi and shifted/DmWif.

Hedgehog can signal both at a short and long-range, and acts as a morphogen during development in various systems. We studied the mechanisms of Hh release and spread using the Drosophila wing imaginal disc as a model system for polarized epithelium. We analyzed the cooperative role of the glypican Dally, the extracellular factor Shifted (Shf, also known as DmWif), and the Immunoglobulin-like (Ig-like) and Fibronectin III (FNNIII) domain-containing transmembrane proteins, Interference hedgehog (Ihog) and its related protein Brother of Ihog (Boi), in the stability, release and spread of Hh. We show that Dally and Boi are required to prevent apical dispersion of Hh; they also aid Hh recycling for its release along the basolateral part of the epithelium to form a long-range gradient. Shf/DmWif on the other hand facilitates Hh movement restrained by Ihog, Boi and Dally, establishing equilibrium between membrane attachment and release of Hh. Furthermore, this protein complex is part of thin filopodia-like structures or cytonemes, suggesting that the interaction between Dally, Ihog, Boi and Shf/DmWif is required for cytoneme-mediated Hh distribution during gradient formation.

Secreted frizzled-related proteins are required for Wnt/ß-catenin signalling activation in the vertebrate optic cup.

Secreted frizzled-related proteins (Sfrps) are considered Wnt signalling antagonists but recent studies have shown that specific family members enhance Wnt diffusion and thus positively modulate Wnt signalling. Whether this is a general and physiological property of all Sfrps remains unexplored. It is equally unclear whether disruption of Sfrp expression interferes with developmental events mediated by Wnt signalling activation. Here, we have addressed these questions by investigating the functional consequences of Sfrp disruption in the canonical Wnt signalling-dependent specification of the mouse optic cup periphery. We show that compound genetic inactivation of Sfrp1 and Sfrp2 prevents Wnt/ß-catenin signalling activation in this structure, which fails to be specified and acquires neural retina characteristics. Consistent with a positive role of Sfrps in signalling activation, Wnt spreading is impaired in the retina of Sfrp1(-/-);Sfrp2(-/-) mice. Conversely, forced expression of Sfrp1 in the wing imaginal disc of Drosophila, the only species in which the endogenous Wnt distribution can be detected, flattens the Wg gradient, suppresses the expression of high-Wg target genes but expands those typically activated by low Wg concentrations. Collectively, these data demonstrate that, in vivo, the levels of Wnt signalling activation strongly depend on the tissue distribution of Sfrps, which should be viewed as multifunctional regulators of Wnt signalling.

Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium.

Hedgehog (Hh) moves from the producing cells to regulate the growth and development of distant cells in a variety of tissues. Here, we have investigated the mechanism of Hh release from the producing cells to form a morphogenetic gradient in the Drosophila wing imaginal disk epithelium. We describe that Hh reaches both apical and basolateral plasma membranes, but the apical Hh is subsequently internalized in the producing cells and routed to the basolateral surface, where Hh is released to form a long-range gradient. Functional analysis of the 12-transmembrane protein Dispatched, the glypican Dally-like (Dlp) protein, and the Ig-like and FNNIII domains of protein Interference Hh (Ihog) revealed that Dispatched could be involved in the regulation of vesicular trafficking necessary for basolateral release of Hh, Dlp, and Ihog. We also show that Dlp is needed in Hh-producing cells to allow for Hh release and that Ihog, which has been previously described as an Hh coreceptor, anchors Hh to the basolateral part of the disk epithelium.

SFRPs act as negative modulators of ADAM10 to regulate retinal neurogenesis.

It is well established that retinal neurogenesis in mouse embryos requires the activation of Notch signaling, but is independent of the Wnt signaling pathway. We found that genetic inactivation of Sfrp1 and Sfrp2, two postulated Wnt antagonists, perturbs retinal neurogenesis. In retinas from Sfrp1(-/-); Sfrp2(-/-) embryos, Notch signaling was transiently upregulated because Sfrps bind ADAM10 metalloprotease and downregulate its activity, an important step in Notch activation. The proteolysis of other ADAM10 substrates, including APP, was consistently altered in Sfrp mutants, whereas pharmacological inhibition of ADAM10 partially rescued the Sfrp1(-/-); Sfrp2(-/-) retinal phenotype. Conversely, ectopic Sfrp1 expression in the Drosophila wing imaginal disc prevented the expression of Notch targets, and this was restored by the coexpression of Kuzbanian, the Drosophila ADAM10 homolog. Together, these data indicate that Sfrps inhibit the ADAM10 metalloprotease, which might have important implications in pathological events, including cancer and Alzheimer's disease.

Violencia, pulsión de muerte y cultura -- o el sujeto/subjetividad violentado/a / Violence, death instinct and culture or violence to the subject/subjectivity

Los autores parten de una opción definitoria respecto a los conceptos de "violencia", "pulsión de muerte" y "cultura" para derivar hacia dos propuestas: 1) denominar a los fenómenos grupales destructivos como anticulturales desde un punto de vista psicoanalítico; 2) los individuos involucrados en ellos, al menos como agresores, manifiestan un fracaso de su propia subjetividad. Después recuerdan algunos conceptos de S. Freud, D. Winnicott, P. Aulagnier y A. Green como particularmente útiles para la teorización del fracaso de la construcción psíquica de la subjetividad. Finalmente, intentan comprender a partir de todo ello la situación psíquica de un paciente límite que está pulsando sus posibilidades de análisis (AU)

The authors asume a defining option regarding the concepts of violence, death instinct and culture, in order to make two proposals: 1) desctructive group phenomena are considered anti-cutural, from a psycgiabakutuc point of view; 2) the individuals involved in them, at least as aggressors, express a failure of their own subjectivity. Some concepts used by Freud, Winnicott, Aulagnier and Green are considered particularly useful in order to theorize on the failure of the psychic construction of subjectivity. Finally, the authors attempt to understand the psychic situation of a border-line patient using all of the above considerations (AU)

The Drosophila ortholog of the human Wnt inhibitor factor Shifted controls the diffusion of lipid-modified Hedgehog.

The Hedgehog (Hh) family of morphogenetic proteins has important instructional roles in metazoan development and human diseases. Lipid modified Hh is able to migrate to and program cells far away from its site of production despite being associated with membranes. To investigate the Hh spreading mechanism, we characterized Shifted (Shf) as a component in the Drosophila Hh pathway. We show that Shf is the ortholog of the human Wnt inhibitory factor (WIF), a secreted antagonist of the Wingless pathway. In contrast, Shf is required for Hh stability and for lipid-modified Hh diffusion. Shf colocalizes with Hh in the extracellular matrix and interacts with the heparan sulfate proteoglycans (HSPG), leading us to suggest that Shf could provide HSPG specificity for Hh. We also show that human WIF inhibits Wg signaling in Drosophila without affecting the Hh pathway, indicating that different WIF family members might have divergent functions in each pathway.

Morbilidad psiquiátrica en un hospital general / Psychiatry morbidity in a general hospital

Ciento treinta y dos pacientes hospitalizados en el Hospital Clínico de la Universidad de Chile, 70 hombres y 62 mujeres, fueron entrevistadas a través del cuestionario de salud general de Golberg (G.H.Q), en su versión de 30 ítems. Se encontró una prevalencia de trastornos psiquiátricos de 36,4 por ciento en pacientes hospitalizados por enfermedad física. La prevalencia fue significativamente mayor en mujeres que en hombres (45,2 por ciento vs 28,6 por ciento p<0,05). Los diagnósticos más frecuentes, fueron los trastornos depresivos (33,3 por ciento) y los trastornos por ansiedad (27,1 por ciento) según los criterios del DSM-III-R