An electrophysiological endophenotype of hypomanic and hyperthymic personality

BACKGROUND: Hyperthymic Temperament (HYT) and a closely related trait, Hypomanic Personality (HYP), have both been related to bipolar affective disorder (BAD). Intensity dependence of auditory evoked potentials (IAEP) is a suggested inverse indicator of serotonergic neurotransmission and has been found to be elevated in BAD. Therefore the present study explored for the first time whether subclinical variance of HYT/HYP is also associated with IAEP in a healthy sample. As several traits from biological personality research are correlated with HYT/HYP and also with BAD, the specificity of results against these traits was further analyzed by calculating multiple regression analyses. METHODS: Evoked potentials were recorded from a sample (N=87) homogenous for confounding variables influencing IAEP. For this reason, only 19 to 27-year-old non-smoker psychiatrically healthy male students were included. RESULTS: Significant correlations were found between IAEP and both HYP and HYT. Including Sensation or Novelty Seeking and Extraversion in Regression Analyses did not weaken the associations of HYP with IAEP much, but did affect those of HYT. However, these competing biological personality traits were hardly able to predict IAEP themselves. Impulsivity, though, was able to reduce the predictive power of HYP and HYT and to explain unique IAEP-variance. This was even more the case for Behavioral-Activation-System-Sensitivity (BAS) subscale Fun Seeking clearly dominating all regression analyses. LIMITATIONS: Homogeneity of sample. CONCLUSIONS: The impact of BAS is in agreement with the assumption that heightened BAS-sensitivity is an underlying biological cause for HYP/HYT and for BAD. Future studies on BAD should include BAS and Impulsivity besides HYP/HYT to further explore uniqueness of the latter and to develop questionnaires based on those items of a hyperthymic-hypomanic-impulsive-funseeking item pool, which possess the most external validity.     

Molecular diagnosis of kidney transplant failure based on urine

In light of the organ shortage, there is a great responsibility to assess postmortal organs for which procurement has been consented and to increase the life span of transplanted organs. The former responsibility has moved many centers to accept extended criteria organs. The latter responsibility requires an exact diagnosis and, if possible, omission of the harmful influence on the transplant. We report the course of a kidney transplant that showed a steady decline of function over a decade, displaying numerous cysts of different sizes. Clinical workup excluded the most frequent causes of chronic transplant failure. The filed allocation documents mentioned the donor’s disease of oral‐facial‐digital syndrome, a rare ciliopathy, which can also affect the kidney. Molecular diagnosis was performed by culturing donor tubular cells from the recipient´s urine more than 10 years after transplantation. Next‐generation panel sequencing with DNA from tubular urinary cells revealed a novel truncating mutation in OFD1, which sufficiently explains the features of the kidney transplants, also found in the second kidney allograft. Despite this severe donor disease, lifesaving transplantation with good long‐term outcome was enabled for 5 recipients.     

COVID-19 in solid organ transplant recipients: a single-center experience

Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney-after-heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty-three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.     

Recurrence of primary sclerosing cholangitis after liver transplantation is associated with specific changes in the gut microbiome pretransplant – a pilot study

Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation (LT). Up to 25% of patients experience recurrence of PSC (rPSC) after LT, which is associated with significant morbidity and mortality. To date, it is not possible to predict which patients are at risk for rPSC. The aetiology of PSC is complex and is speculated to involve translocation of intestinal bacteria to the liver, because of its frequent co-occurrence with inflammatory bowel diseases (IBD). Here, we investigate whether the mucosal intestinal microbiome of PSC patients (n = 97) at time of first LT can identify those patients who will develop rPSC. 16S gene sequencing of bacterial DNA isolated from formalin-fixed paraffin-embedded biopsies showed that PSC patients with Crohn’s disease (n = 15) have a reduced microbial diversity and that inflammation of the mucosa is associated with beta-diversity changes and feature differences. No differences in alpha- or beta diversity were observed between patients with rPSC (n = 14) and without rPSC (n = 83). However, many over-represented bacterial features were detected in patients with rPSC, while surprisingly, those without recurrence of disease were characterized by an increased presence of the Gammaproteobacteria Shigella. This pilot study warrants further investigation into bacterial differences between rPSC and non-rPSC patients.     

Mechanistic analysis of metabolomics patterns in rat plasma during administration of direct thyroid hormone synthesis inhibitors or compounds increasing thyroid hormone clearance

For identification of toxicological modes of action (MoAs) a database (MetaMap^®Tox) was established containing plasma metabolome consisting of approximately 300 endogenous metabolites. Each five male and female Wistar rats per groups were treated with >500 reference compounds over a period of 28 days. More than 120 specific toxicity patterns of common metabolite changes associated with unique MoAs were established.     

In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.     

Research on the psychomotor performance of patients with vertebral syndromes at spas

The influence of radon balneotherapy on the psychomotor performance of 169 male and female patients with vertebral syndromes was investigated. The speed and skill of motor response to various stimuli was measured by the Schoppe apparatus and the Viennese determination apparatus. The analysis of "steadiness" brought no results, whereas all the other parameters tested by the Schoppe and the Viennese devices showed highly significant improvements in the course of spa treatment. It was not possible to differentiate to which specific factors of spa treatment this positive influence can be ascribed.