Spontaneous eye-blinks are a ubiquitous behavior. However, blink timing is not random, nor does it always follow physiological demands. Research rather suggests that blink timing, and thus the structure of blinking behavior, is influenced by cognitive processes, such as attention. Since attention is regarded a necessary precursor of media use phenomena, the present study investigates the relation between the structure of blinking behavior and the media use phenomenon of spatial presence. To this end, spontaneous eye-blinks have been observed in an experiment during the reception of a video story. The methods of T-pattern analysis, ISI distance, and IBI variability have been used to quantify stimulus-dependent blink structure, which has then been related to self-reports of spatial presence experiences. While the T-pattern analysis and ISI distance showed converging results for behavior structure, a hypothesized relation between more stimulus-dependent blink structure and stronger presence experiences was not found. On the contrary, blink data suggested a difference in attention allocation, whereas self-report data indicated no difference in presence experiences. This demonstrates that beyond self-report and the analysis of event frequencies, the analysis of behavior structure offers insights into behavior synchronization between participants, allowing for new inferences on internal processing of media stimuli.

Pythiosis is a deadly infectious disease of humans and animals living in tropical and subtropical countries. The causative agent is the oomycete Pythium insidiosum. Treatment of pythiosis is challenging. The use of antimicrobial agents usually fails in the treatment of pythiosis. Many patients undergo surgical removal of an infected organ (i.e., eye, arm, and leg). The immunotherapeutic vaccine, prepared from the crude extract of P. insidiosum, shows limited efficacy against pythiosis. The fatal outcome occurs in patients with advanced disease. There are urgent needs for an effective therapeutic modality for pythiosis. Recently, the exo-1,3-β-glucanase (Exo1) has been identified as a conserve immunoreactive protein of P. insidiosum. Exo1 was predicted to reside at the cell membrane and hydrolyze cell wall β-glucan during cell growth. An Exo1 ortholog is absent in the human genome, making it an appealing target for drug or vaccine development. We attempted to clone and express the codon-optimized exo1 gene of P. insidiosum in E. coli. To solve the inclusion body formation, expression and purification of Exo1 were achievable in the denaturing condition using SDS- and urea-based buffers. Exo1 lacked hydrolytic activity due to the absence of proper protein folding and post-translational modifications. ELISA and Western blot analyses demonstrated the immunoreactivity of Exo1 against pythiosis sera. In conclusion, we successfully expressed and purified the immunoreactive Exo1 protein of P. insidiosum. The recombinant Exo1 can be produced at an unlimited amount and could serve as an extra protein to enhance the effectiveness of the current form of the vaccine against pythiosis.

Frequent side effects of atypical antipsychotics including olanzapine are increases of appetite and body weight, elevating the risk of metabolic disorders. We found previously an increase of ghrelin levels after showing pictures with food, but not after neutral pictures in healthy subjects. Now, we tested whether this effect is changed after one week of treatment of healthy subjects with olanzapine. Furthermore the influence of this drug on ghrelin, leptin, insulin and glucose levels was investigated.

The Trier social stress test (TSST) is well established to induce psychological stress in human experiments. So far the effect of TSST, performed in the late evening, on sleep and on stress hormone secretion before sleep onset was not examined. The corticotropin releasing hormone receptor type 1 (CRH R1) gene encodes the CRHR1 receptor. This protein is essential in the activation of the stress response of the hypothalamo-pituitary-adrenocortical (HPA) system. Variants of the single nucleotide polymorphism (SNP) rs110402 of the CRHR1 gene were shown to influence the risk to develop depression after childhood maltreatment. This risk is elevated in homozyguous C carriers of this SNP, whereas TT carriers appear to be more resilient to this risk. We examined the effect of TSST on sleep and HPA hormones and whether this effect is influenced by the CRHR 1 genotype.

The phase delay syndrome is a rare incapacitating disorder of the circadian sleep-wake rhythm. It results in sleep period which is delayed related to the environment. No therapy is available so far. We report off label use of tasimelteon in an individual curative trial which aimed to treat this disorder. Tasimelteon is an agonist at melatonin (MT) 1 and 2 receptors. The substance is approved to treat non-24-h-sleep-wake-disorder in totally blind patients. In our trial the 62 years old patient reported a history of this disorder since his youth. Furthermore he had a history of adrenalectomy and cortisone substitution after Cushing's syndrome and of Whipple procedure due to pancreatic cancer. Before treatment his sleep onset ocurred between 06.00 and 08.00h. He awakened by 16.00h. Already after some days treatment with an oral dose of 20 mg tasimelteon his sleep period was advanced by about four hours as documented by sleep diary and actigraphy. He reported improved quality of life as his participation in daily living became possible. This effect was stable so far for more than six weeks. The substance was well tolerated. Our findings suggest that tasimelteon is capable to reentrain delayed sleep period in phase delay syndrome. Tasimelteon appears to be suited to treat circadian sleep-wake disorders also beyond non-24-h sleep-wake-disorder.

Weight gain and increased appetite are major side effects of Olanzapine. We investigated the role of Brodmann area 25 (BA25), which participates in the regulation of autonomic and endocrine systems.

Mesenchymal stromal cell (MSC) infusion could be a means to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase I study was to evaluate the feasibility, safety and tolerability of a single infusion of MSCs in liver transplant recipients.Ten liver transplant recipients under standard immunosuppression received 1.5–3 × 106/kg third-party unrelated MSCs on postoperative day 3 ± 2, and were prospectively compared to a control group of ten liver transplant recipients. As primary endpoints, MSC infusion toxicity was evaluated, and infectious and cancerous complications were prospectively recorded until month 12 in both groups. As secondary endpoints, rejection rate, month-6 graft biopsies, and peripheral blood lymphocyte phenotyping were compared. Progressive immunosuppression weaning was attempted from month 6 to 12 in MSC recipients.No variation in vital parameters or cytokine release syndrome could be detected during and after MSC infusion. No patient developed impairment of organ functions (including liver graft function) following MSC infusion. No increased rate of opportunistic infection or de novo cancer was detected. As secondary endpoints, there was no difference in overall rates of rejection or graft survival. Month-6 biopsies did not demonstrate a difference between groups in the evaluation of rejection according to the Banff criteria, in the fibrosis score or in immunohistochemistry (including Tregs). No difference in peripheral blood lymphocyte typing could be detected. The immunosuppression weaning in MSC recipients was not successful.No side effect of MSC infusion at day 3 after liver transplant could be detected, but this infusion did not promote tolerance. This study opens the way for further MSC or Treg-based trials in liver transplant recipients.Therapy with mesenchymal stromal cells (MSCs) has been proposed as a means to improve results of solid organ transplantation. One of the potential MSC role could be to induce tolerance after liver transplantation, i.e. allowing the cessation of several medications with severe side effects. This study is the first-in-man use of MSC therapy in ten liver transplant recipients. This study did not show toxicity after a single MSC infusion but it was not sufficient to allow withdrawal of immunosuppression.Clinical trial registration number: Eudract: # 2011-001822-81, ClinicalTrials.gov: # NCT 01429038.

Prior studies pointed out that lower levels of cardiac vagal control, also described as HRV, are associated with a variety of adverse health outcomes, including coronary artery disease and diabetes. Our focus was on the effect of Olanzapine on the subgenual anterior cingulate cortex (sgACC), explicitly on Brodmann Area 25 (BA 25), due to its regulatory key role in the autonomic system, specifically the HRV.

Blunted heart rate variability (HRV) both, in wake-time and in sleep, is a consistent finding in major depression [1] and in primary insomnia. As decreased HRV reflects a dysbalanced activity of the autonomous nervous system (ANS), we expected, that in major depression blunted HRV also correlates with increased subjective and objective sleep problems.