Reliability and validity of the German version of the Structured Interview of Personality Organization (STIPO)

Background: The assessment of personality organization and its observable behavioral manifestations, i.e. personality functioning, has a long tradition in psychodynamic psychiatry. Recently, the DSM-5 Levels of Personality Functioning Scale has moved it into the focus of psychiatric diagnostics. Based on Kernberg's concept of personality organization the Structured Interview of Personality Organization (STIPO) was developed for diagnosing personality functioning. The STIPO covers seven dimensions: (1) identity, (2) object relations, (3) primitive defenses, (4) coping/rigidity, (5) aggression, (6) moral values, and (7) reality testing and perceptual distortions. The English version of the STIPO has previously revealed satisfying psychometric properties. Methods: Validity and reliability of the German version of the 100-item instrument have been evaluated in 122 psychiatric patients. All patients were diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) and were assessed by means of the STIPO. Moreover, all patients completed eight questionnaires that served as criteria for external validity of the STIPO. Results: Interrater reliability varied between intraclass correlations of .89 and 1.0, Crohnbach's a for the seven dimensions was .69 to .93. All a priori selected questionnaire scales correlated significantly with the corresponding STIPO dimensions. Patients with personality disorder (PD) revealed significantly higher STIPO scores (i.e. worse personality functioning) than patients without PD; patients cluster B PD showed significantly higher STIPO scores than patients with cluster C PD. Conclusions: Interrater reliability, Crohnbach's a, concurrent validity, and differential validity of the STIPO are satisfying. The STIPO represents an appropriate instrument for the assessment of personality functioning in clinical and research settings

Reliability and validity of the German version of the Structured Interview of Personality Organization (STIPO)

Background: The assessment of personality organization and its observable behavioral manifestations, i.e. personality functioning, has a long tradition in psychodynamic psychiatry. Recently, the DSM-5 Levels of Personality Functioning Scale has moved it into the focus of psychiatric diagnostics. Based on Kernberg's concept of personality organization the Structured Interview of Personality Organization (STIPO) was developed for diagnosing personality functioning. The STIPO covers seven dimensions: (1) identity, (2) object relations, (3) primitive defenses, (4) coping/rigidity, (5) aggression, (6) moral values, and (7) reality testing and perceptual distortions. The English version of the STIPO has previously revealed satisfying psychometric properties. Methods: Validity and reliability of the German version of the 100-item instrument have been evaluated in 122 psychiatric patients. All patients were diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) and were assessed by means of the STIPO. Moreover, all patients completed eight questionnaires that served as criteria for external validity of the STIPO. Results: Interrater reliability varied between intraclass correlations of .89 and 1.0, Crohnbach's a for the seven dimensions was .69 to .93. All a priori selected questionnaire scales correlated significantly with the corresponding STIPO dimensions. Patients with personality disorder (PD) revealed significantly higher STIPO scores (i.e. worse personality functioning) than patients without PD; patients cluster B PD showed significantly higher STIPO scores than patients with cluster C PD. Conclusions: Interrater reliability, Crohnbach's a, concurrent validity, and differential validity of the STIPO are satisfying. The STIPO represents an appropriate instrument for the assessment of personality functioning in clinical and research settings

Extended interaction networks with HCV protease NS3-4A substrates explain the lack of adaptive capability against protease inhibitors

Inhibitors against the NS3-4A protease of hepatitis C virus (HCV) have proven to be useful drugs in the treatment of HCV infection. Although variants have been identified with mutations that confer resistance to these inhibitors, the mutations do not restore replicative fitness and no secondary mutations that rescue fitness have been found. To gain insight into the molecular mechanisms underlying the lack of fitness compensation, we screened known resistance mutations in infectious HCV cell culture with different genomic backgrounds. We observed that the Q41R mutation of NS3-4A efficiently rescues the replicative fitness in cell culture for virus variants containing mutations at NS3-Asp(168). To understand how the Q41R mutation rescues activity, we performed protease activity assays complemented by molecular dynamics simulations, which showed that protease-peptide interactions far outside the targeted peptide cleavage sites mediate substrate recognition by NS3-4A and support protease cleavage kinetics. These interactions shed new light on the mechanisms by which NS3-4A cleaves its substrates, viral polyproteins and a prime cellular antiviral adaptor protein, the mitochondrial antiviral signaling protein MAVS. Peptide binding is mediated by an extended hydrogen-bond network in NS3-4A that was effectively optimized for protease-MAVS binding in Asp(168)variants with rescued replicative fitness from NS3-Q41R. In the protease harboring NS3-Q41R, the N-terminal cleavage products of MAVS retained high affinity to the active site, rendering the protease susceptible for potential product inhibition. Our findings reveal delicately balanced protease-peptide interactions in viral replication and immune escape that likely restrict the protease adaptive capability and narrow the virus evolutionary space

Distinct Pathogenesis of Pancreatic Cancer Microvesicle-Associated Venous Thrombosis Identifies New Antithrombotic Targets In Vivo

Objective Cancer patients are at high risk of developing deep venous thrombosis (DVT) and venous thromboembolism, a leading cause of mortality in this population. However, it is largely unclear how malignant tumors drive the prothrombotic cascade culminating in DVT. Approach and Results Here, we addressed the pathophysiology of malignant DVT compared with nonmalignant DVT and focused on the role of tumor microvesicles as potential targets to prevent cancer-associated DVT. We show that microvesicles released by pancreatic adenocarcinoma cells (pancreatic tumor-derived microvesicles [pcMV]) boost thrombus formation in a model of flow restriction of the mouse vena cava. This depends on the synergistic activation of coagulation by pcMV and host tissue factor. Unlike nonmalignant DVT, which is initiated and propagated by innate immune cells, thrombosis triggered by pcMV was largely independent of myeloid leukocytes or platelets. Instead, we identified externalization of the phospholipid phosphatidylethanolamine as a major mechanism controlling the prothrombotic activity of pcMV. Disrupting phosphatidylethanolamine-dependent activation of factor X suppressed pcMV-induced DVT without causing changes in hemostasis. Conclusions Together, we show here that the pathophysiology of pcMV-associated experimental DVT differs markedly from innate immune cell-promoted nonmalignant DVT and is therefore amenable to distinct antithrombotic strategies. Targeting phosphatidylethanolamine on tumor microvesicles could be a new strategy for prevention of cancer-associated DVT without causing bleeding complications