Predicting Optimal Outcomes in Cognitive Therapy or Interpersonal Psychotherapy for Depressed Individuals Using the Personalized Advantage Index Approach

IntroductionAlthough psychotherapies for depression produce equivalent outcomes, individual patients respond differently to different therapies. Predictors of outcome have been identified in the context of randomized trials, but this information has not been used to predict which treatment works best for the depressed individual. In this paper, we aim to replicate a recently developed treatment selection method, using data from an RCT comparing the effects of cognitive therapy (CT) and interpersonal psychotherapy (IPT).Methods134 depressed patients completed the pre- and post-treatment BDI-II assessment. First, we identified baseline predictors and moderators. Second, individual treatment recommendations were generated by combining the identified predictors and moderators in an algorithm that produces the Personalized Advantage Index (PAI), a measure of the predicted advantage in one therapy compared to the other, using standard regression analyses and the leave-one-out cross-validation approach.ResultsWe found five predictors (gender, employment status, anxiety, personality disorder and quality of life) and six moderators (somatic complaints, cognitive problems, paranoid symptoms, interpersonal self-sacrificing, attributional style and number of life events) of treatment outcome. The mean average PAI value was 8.9 BDI points, and 63% of the sample was predicted to have a clinically meaningful advantage in one of the therapies. Those who were randomized to their predicted optimal treatment (either CT or IPT) had an observed mean end-BDI of 11.8, while those who received their predicted non-optimal treatment had an end-BDI of 17.8 (effect size for the difference = 0.51).DiscussionDepressed patients who were randomized to their predicted optimal treatment fared much better than those randomized to their predicted non-optimal treatment. The PAI provides a great opportunity for formal decision-making to improve individual patient outcomes in depression. Although the utility of the PAI approach will need to be evaluated in prospective research, this study promotes the development of a treatment selection approach that can be used in regular mental health care, advancing the goals of personalized medicine.     

Isopods as indicators of the copper content of soil and litter

Summary In two species of isopods (mainlyTracheoniscus rathkei, plus a fewOniscus asellus) total copper content as well as the amount of copper extractable with zinc-dibenzyldithiocarbamate in CCl₄ (CTC) were determined. Both copper fractions show near perfect relationship with total copper concentration of the litter collected in the isopods' habitats. Between copperrich and copper-poor sites in Tirol, Austria, mean total copper content of the isopods varies by a factor of 7, mean CTC-extracted copper by a factor of 140 (Table 2). With the exception of one, particularly impoverished, site the concentration of copper in the CTC-extracted compartment reflects the total copper concentration of the food of the animals. Both copper fractions increase with the weight of animals, but the proportionality factor of the increase is three times larger for total copper than for CTC-extracted copper.A simplified geological map of Tirol is given in which the relationship between copper content of soil and litter and of the isopods at selected sites is indicated.     

Sensitive detection of glucagon aggregation using amyloid fibril-specific antibodies

Sensitive detection of protein aggregates is important for evaluating the quality of biopharmaceuticals and detecting misfolded proteins in several neurodegenerative diseases. However, it is challenging to detect extremely low concentrations (<10 ppm) of aggregated protein in the presence of high concentrations of soluble protein. Glucagon, a peptide hormone used in the treatment of extreme hypoglycemia, is aggregation-prone and forms amyloid fibrils. Detection of glucagon fibrils using conformation-specific antibodies is an attractive approach for identifying such aggregates during process and formulation development. Therefore, we have used yeast surface display and magnetic-activated cell sorting to sort single-chain antibody libraries to identify antibody variants with high conformational specificity for glucagon fibrils. Notably, we find several high-affinity antibodies that display excellent selectivity for glucagon fibrils, and we have integrated these antibodies into a sensitive immunoassay. Surprisingly, the sensitivity of our assay—which involves direct (nonantibody mediated) glucagon immobilization in microtiter plates—can be significantly enhanced by pretreating the microtiter plates with various types of globular proteins before glucagon immobilization. Moreover, increased total concentrations of glucagon peptide also significantly improve the sensitivity of our assay, which appears to be due to the strong seeding activity of immobilized fibrils at high glucagon concentrations. Our final assay is highly sensitive (fibril detection limit of ~0.5–1 ppm) and is >20 times more sensitive than detection using a conventional, amyloid-specific fluorescent dye (Thioflavin T). We expect that this type of sensitive immunoassay can be readily integrated into the drug development process to improve the generation of safe and potent peptide therapeutics.     

Die parasympathikolytische und die Parasympathikomimetische Wirkung des Atropins auf die Chromatophoren

Zusammenfassung Atropin hat auf den physiologischen und auf den morphologischen Farbwechsel in höheren Konzentrationen eine parasympathikomimetische Wirkung, d. h. es wirkt acetylcholinartig. In geringeren Konzentrationen zeigt sich die bekannte parasympathikolytische Wirkung des Atropins, indem es die Acetylcholinwirkung hemmt.     

The Snf1‐related protein kinases SnRK2.4 and SnRK2.10 are involved in maintenance of root system architecture during salt stress

The sucrose non‐fermenting‐1‐related protein kinase 2 (SnRK2) family represents a unique family of plant‐specific protein kinases implicated in cellular signalling in response to osmotic stress. In our studies, we observed that two class 1 SnRK2 kinases, SnRK2.4 and SnRK2.10, are rapidly and transiently activated in Arabidopsis roots after exposure to salt. Under saline conditions, snrk2.4 knockout mutants had a reduced primary root length, while snrk2.10 mutants exhibited a reduction in the number of lateral roots. The reduced lateral root density was found to be a combinatory effect of a decrease in the number of lateral root primordia and an increase in the number of arrested lateral root primordia. The phenotypes were in agreement with the observed expression patterns of genomic yellow fluorescent protein (YFP) fusions of SnRK2.10 and ‐2.4, under control of their native promoter sequences. SnRK2.10 was found to be expressed in the vascular tissue at the base of a developing lateral root, whereas SnRK2.4 was expressed throughout the root, with higher expression in the vascular system. Salt stress triggered a rapid re‐localization of SnRK2.4–YFP from the cytosol to punctate structures in root epidermal cells. Differential centrifugation experiments of isolated Arabidopsis root proteins confirmed recruitment of endogenous SnRK2.4/2.10 to membranes upon exposure to salt, supporting their observed binding affinity for the phospholipid phosphatidic acid. Together, our results reveal a role for SnRK2.4 and ‐2.10 in root growth and architecture in saline conditions.     

Ein direkter Beweis für die Fähigkeit einzelner Sehzellen des Insektenauges,die Schwingungsrichtung polarisierten Lichtes zu analysieren

Summary Action potentials from single visual cells of the compound eye are lead off during illumination of the retina of Calliphora erythrocephala by means of intracellular capillary microelectrodes. The size of the monophasic and depolarizing action-potentials depends on light-intensity and on plane of polarized light. Turning the plane of polarization from maximum to minimum efficacy equals a decrease of intensity of about 50%. As the dioptric apparatus is optically isotropic, the experiments described here prove the hypothesis of Autrum and Stumpf, namely that the single visual cell responds to different planes of polarization with different states of excitation.

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Die Untersuchungen wurden von der Deutschen Forschungsgemeinschaft unterstützt.     

Centrosome‐mediated microtubule remodeling during axon formation in human iPSC‐derived neurons

Axon formation critically relies on local microtubule remodeling and marks the first step in establishing neuronal polarity. However, the function of the microtubule‐organizing centrosomes during the onset of axon formation is still under debate. Here, we demonstrate that centrosomes play an essential role in controlling axon formation in human‐induced pluripotent stem cell (iPSC)‐derived neurons. Depleting centrioles, the core components of centrosomes, in unpolarized human neuronal stem cells results in various axon developmental defects at later stages, including immature action potential firing, mislocalization of axonal microtubule‐associated Trim46 proteins, suppressed expression of growth cone proteins, and affected growth cone morphologies. Live‐cell imaging of microtubules reveals that centriole loss impairs axonal microtubule reorganization toward the unique parallel plus‐end out microtubule bundles during early development. We propose that centrosomes mediate microtubule remodeling during early axon development in human iPSC‐derived neurons, thereby laying the foundation for further axon development and function.