Subtypes of narcissistic personality disorder based on psychotherapy process: A longitudinal nonparametric analysis.

The present study aims at empirically exploring subtypes of narcissistic personality disorder (NPD), based on patient descriptors of the psychotherapeutic process. Subtype identification and characterization of NPD is central, in particular, to increase diagnostic precision, linking categorical and dimensional conceptualizations of psychopathology, and to individualize treatments. A total of N = 161 patients diagnosed with NPD undergoing clarification-oriented psychotherapy were included in the present reanalysis of a naturalistic pre-post process-outcome study. At three crucial time-points of the therapy (Sessions 15, 20, and 25), the patient's in-session quality of content, process, and relationship are assessed using intensive video- and audio analyses. Levels of psychopathology were assessed using self-reported questionnaires. Data were analyzed using longitudinal nonparametric analysis. Based on in-session processes across three time-points, a two-subtype solution was retained (optimal vs. suboptimal process qualities). Optimal process quality of time was linked with the intensity of narcissistic symptoms; suboptimal process quality was linked with a variety of general symptom loads and problematic personality traits. The two empirical subtypes were predicted by the quality of real-life functioning with an accuracy of more than 92% and were partially associated with outcome. NPD may be empirically differentiated between patients engaging in optimal psychotherapy process versus those who engage in suboptimal psychotherapy process. This differentiation has reliable clinical predictors at the outset of treatment. The present study has implications in terms of personalizing psychotherapy for patients presenting NPD, or pathological narcissism. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Mechanical Competence and Bone Quality Develop During Skeletal Growth.

Bone fracture risk is influenced by bone quality, which encompasses bone's composition as well as its multiscale organization and architecture. Aging and disease deteriorate bone quality, leading to reduced mechanical properties and higher fracture incidence. Largely unexplored is how bone quality and mechanical competence progress during longitudinal bone growth. Human femoral cortical bone was acquired from fetal (n = 1), infantile (n = 3), and 2- to 14-year-old cases (n = 4) at the mid-diaphysis. Bone quality was assessed in terms of bone structure, osteocyte characteristics, mineralization, and collagen orientation. The mechanical properties were investigated by measuring tensile deformation at multiple length scales via synchrotron X-ray diffraction. We find dramatic differences in mechanical resistance with age. Specifically, cortical bone in 2- to 14-year-old cases exhibits a 160% greater stiffness and 83% higher strength than fetal/infantile cases. The higher mechanical resistance of the 2- to 14-year-old cases is associated with advantageous bone quality, specifically higher bone volume fraction, better micronscale organization (woven versus lamellar), and higher mean mineralization compared with fetal/infantile cases. Our study reveals that bone quality is superior after remodeling/modeling processes convert the primary woven bone structure to lamellar bone. In this cohort of female children, the microstructural differences at the femoral diaphysis were apparent between the 1- to 2-year-old cases. Indeed, the lamellar bone in 2- to 14-year-old cases had a superior structural organization (collagen and osteocyte characteristics) and composition for resisting deformation and fracture than fetal/infantile bone. Mechanistically, the changes in bone quality during longitudinal bone growth lead to higher fracture resistance because collagen fibrils are better aligned to resist tensile forces, while elevated mean mineralization reinforces the collagen scaffold. Thus, our results reveal inherent weaknesses of the fetal/infantile skeleton signifying its inferior bone quality. These results have implications for pediatric fracture risk, as bone produced at ossification centers during children's longitudinal bone growth could display similarly weak points. © 2019 American Society for Bone and Mineral Research

Relict duck-billed dinosaurs survived into the last age of the dinosaurs in subantarctic Chile

In the dusk of the Mesozoic, advanced duck-billed dinosaurs (Hadrosauridae) were so successful that they likely outcompeted other herbivores, contributing to declines in dinosaur diversity. From Laurasia, hadrosaurids dispersed widely, colonizing Africa, South America, and, allegedly, Antarctica. Here, we present the first species of a duck-billed dinosaur from a subantarctic region, Gonkoken nanoi, of early Maastrichtian age in Magallanes, Chile. Unlike duckbills further north in Patagonia, Gonkoken descends from North American forms diverging shortly before the origin of Hadrosauridae. However, at the time, non-hadrosaurids in North America had become replaced by hadrosaurids. We propose that the ancestors of Gonkoken arrived earlier in South America and reached further south, into regions where hadrosaurids never arrived: All alleged subantarctic and Antarctic remains of hadrosaurids could belong to non-hadrosaurid duckbills like Gonkoken. Dinosaur faunas of the world underwent qualitatively different changes before the Cretaceous-Paleogene asteroid impact, which should be considered when discussing their possible vulnerability

3T3 Cell Lines Stably Expressing Pax6 or Pax6(5a) – A New Tool Used for Identification of Common and Isoform Specific Target Genes

Pax6 and Pax6(5a) are two isoforms of the evolutionary conserved Pax6 gene often co-expressed in specific stochiometric relationship in the brain and the eye during development. The Pax6(5a) protein differs from Pax6 by having a 14 amino acid insert in the paired domain, causing the two proteins to have different DNA binding specificities. Difference in functions during development is proven by the fact that mutations in the 14 amino acid insertion for Pax6(5a) give a slightly different eye phenotype than the one described for Pax6. Whereas quite many Pax6 target genes have been published during the last years, few Pax6(5a) specific target genes have been reported on. However, target genes identified by Pax6 knockout studies can probably be Pax6(5a) targets as well, since this isoform also will be affected by the knockout. In order to identify new Pax6 target genes, and to try to distinguish between genes regulated by Pax6 and Pax6(5a), we generated FlpIn-3T3 cell lines stably expressing Pax6 or Pax6(5a). RNA was harvested from these cell lines and used in gene expression microarrays where we identified a number of genes differentially regulated by Pax6 and Pax6(5a). A majority of these were associated with the extracellular region. By qPCR we verified that Ncam1, Ngef, Sphk1, Dkk3 and Crtap are Pax6(5a) specific target genes, while Tgfbi, Vegfa, EphB2, Klk8 and Edn1 were confirmed as Pax6 specific target genes. Nbl1, Ngfb and seven genes encoding different glycosyl transferases appeared to be regulated by both. Direct binding to the promoters of Crtap, Ctgf, Edn1, Dkk3, Pdgfb and Ngef was verified by ChIP. Furthermore, a change in morphology of the stably transfected Pax6 and Pax6(5a) cells was observed, and the Pax6 expressing cells were shown to have increased proliferation and migration capacities

A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0− virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A) produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0− virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein