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Interprofessional collaboration is a strategy to meet the challenges of increasing complexity in the health system. The basis for cooperation in professional life must already be established in the context of interprofessional education (IPE). Students’ attitude towards IPE is a crucial factor in the development of interprofessional competences.

Background: A positive effect of the effect of a 3-month oral spermidine intake on memory performance has already been demonstrated. The continuation of this study aimed to examine whether there could be observed an improvement in memory performance after one year., Method: 45 residents of the nursing home "Gepflegt Wohnen" in Hart bei Graz, Styria, Austria, were given a daily dose of 3.3 mg spermidine in their diet for one year., Results: The comparison of the MMSE test results at baseline and after one year demonstrated a significant (p < 0.001) difference. The mean improvement is 5 points., Conclusion: The new results confirm the already proven positive effect of oral spermidine intake on memory performance., (© 2023. The Author(s).)

Since December 2019 the world has been dealing with a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. The first SARS-CoV-2 vaccine was made available in Europe at the end of 2020. 202 volunteers from the vicinity of the University of Applied Sciences Wiener Neustadt took part in this study; their IgG levels recognizing the RBD of SARS-CoV-2 were determined. The aim was to evaluate the SARS-CoV-2 titer levels of vaccinated, recovered and vaccinated plus recovered persons. We could show that there is a significant difference in the antibody levels of vaccinated, vaccinated plus recovered and only recovered probands. Additionally, the highest antibody levels were found in triple vaccinated persons. Furthermore, the Moderna vaccine seems to have a higher immune response., Competing Interests: The authors have no conflict of interest to disclose., (© 2022 Published by Elsevier Inc.)

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two efflux transporters which are expressed in the apical (i.e. airway lumen-facing) membranes of lung epithelial cells. To assess the influence of P-gp and BCRP on the pulmonary disposition of inhaled drugs, we performed positron emission tomography (PET) imaging in rats after intratracheal aerosolization of two model P-gp/BCRP substrate radiotracers (i.e. [ 11 C]erlotinib and [ 11 C]tariquidar). We studied rat groups in which both transporters were active (i.e. wild-type rats), either of the two transporters was inactive (Abcb1a/b (-/-) and Abcg2 (-/-) rats) or both transporters were inactive (Abcg2 (-/-) rats in which pulmonary P-gp activity was inhibited by treatment with unlabeled tariquidar). PET-measured lung distribution data were compared with brain-to-plasma radioactivity concentration ratios measured in a gamma counter at the end of the PET scan. For [ 11 C]erlotinib, lung exposure (AUC lungs ) was moderately but not significantly increased in Abcb1a/b (-/-) rats (1.6-fold) and Abcg2 (-/-) rats (1.5-fold), and markedly (3.6-fold, p < 0.0001) increased in tariquidar-treated Abcg2 (-/-) rats, compared to wild-type rats. Similarly, the brain uptake of [ 11 C]erlotinib was substantially (4.5-fold, p < 0.0001) increased when both P-gp and BCRP activities were impaired. For [ 11 C]tariquidar, differences in AUC lungs between groups pointed into a similar direction as for [ 11 C]erlotinib, but were less pronounced and lacked statistical significance. Our study demonstrates functional P-gp and BCRP activity in vivo in the lungs and further suggests functional redundancy between P-gp and BCRP in limiting the pulmonary uptake of a model P-gp/BCRP substrate, analogous to the blood-brain barrier. Our results suggest that pulmonary efflux transporters are important for the efficacy and safety of inhaled drugs and that their modulation may be exploited in order to improve the pharmacokinetic and pharmacodynamic performance of pulmonary delivered drugs., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Several drugs approved for inhalation for the treatment of pulmonary diseases are substrates of the adenosine triphosphate-binding cassette (ABC) transporter P-glycoprotein (P-gp). P-gp is expressed in the apical membrane of pulmonary epithelial cells and could play a role in modulating the pulmonary absorption and distribution of inhaled drugs, thereby potentially contributing to variability in therapeutic response and/or systemic side effects. We developed a new in vivo experimental approach to assess the functional impact of P-gp on the pulmonary delivery of inhaled drugs in rats. By using positron emission tomography (PET) imaging, we measured the intrapulmonary pharmacokinetics of the model P-gp substrates (R)-[ 11 C]verapamil ([ 11 C]VPM) and [ 11 C]-N-desmethyl-loperamide ([ 11 C]dLOP) administered by intratracheal aerosolization in three rat groups: wild-type, Abcb1a/b (-/-) and wild-type treated with the P-gp inhibitor tariquidar. Lung exposure (AUC lung&#95;right ) to [ 11 C]VPM was 64% and 50% lower (p < 0.05) in tariquidar-treated and in Abcb1a/b (-/-) rats, respectively, compared to untreated wild-type rats. For [ 11 C]dLOP, AUC lung&#95;right was 59% and 34% lower (p < 0.05) in tariquidar-treated and in Abcb1a/b (-/-) rats, respectively. Our results show that P-gp can affect the pulmonary disposition of inhaled P-gp substrates, whereby a decrease in P-gp activity may lead to lower lung exposure and potentially to a decrease in therapeutic efficacy. Our study highlights the potential of PET imaging with intratracheally aerosolized radiotracers to assess the impact of membrane transporters on pulmonary drug delivery, in rodents and potentially also in humans., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged at the end of 2019, causing the coronavirus disease (COVID-19). The main sources of infections are infected and asymptomatic persons. One major problem of the pandemic are the diverse symptoms and the varying manifestations of the illness. In this study, the IgG level recognizing the RBD of SARS-CoV-2 was determined within 336 volunteers from the environment of the University of Applied Sciences Wiener Neustadt. The aims of this study were to identify the estimated number of undiscovered COVID-19 infections and the corresponding antibody levels. In total, 11.3% of the nonvaccinated probands had a positive IgG antibody titer against SARS-CoV-2, whereas 4.0% did not test positive for SARS-CoV-2 or had never been tested at the time of sampling. Probands in this study reported tiredness (57,5%), ageusia/anosmia (55%) and headache (47,5%) as most frequent symptoms., Competing Interests: The authors have no conflict of interest to disclose., (© 2021 The Authors. Published by Elsevier Inc.)

The worldwide prevalence of dementia is estimated at 35.6 million and will rise to 115 million by 2050. There is therefore an urgent need for well-founded dementia diagnostics and well-researched therapeutic options. Previous studies have highlighted that spermidine has the ability to trigger the important process of dissolving amyloid-beta plaques by autophagy. They also confirmed that nutritional intervention with the natural polyamine spermidine can prevent memory loss in aging model organisms. This multicentric double-blind preliminary study focused on the effect of oral spermidine supplementation on older adults' cognitive performance. Memory tests were carried out on 85 subjects aged between 60 and 96 years in 6 nursing homes in Styria. Blood samples were taken for the determination of spermidine concentration and measurement of metabolic parameters. The results demonstrated a clear correlation between the intake of spermidine and the improvement in cognitive performance in subjects with mild and moderate dementia in the group treated with the higher spermidine dosage. The most substantial improvement in test performance was found in the group of subjects with mild dementia with an increase of 2.23 points (p = 0.026) in the mini mental state examination (MMSE) and 1.99 (p = 0.47) in phonematic fluidity. By comparison, the group which had a lower spermidine intake showed consistent or declining cognitive performance.

Objectives: Rubella and tick-borne encephalitis (TBE) are infectious diseases caused by viruses. Rubella is an air-borne infection. TBE, on the other hand, is transmitted by virus-infected ticks. Both diseases show specific symptoms after an incubation period of approximately 10 days. The Austrian vaccination plan recommends vaccinations against both viruses, as only these can protect against both infectious diseases. Because of both, an increase in measles infections and the high endemic rate of TBE in Austria, our goal was to evaluate the vaccination rate, antibody titre and general level of knowledge with respect to these two infections amongst adults in order to identify possible nescience regarding booster vaccination and general titre rates., Methods: One hundred ninety-nine people participated in the study of the TBE and rubella titre determination. We used indirect ELISA and asked the volunteers to complete a questionnaire., Results: The analysis of the results showed a vaccination coverage rate of over 90% for both diseases., Conclusion: Our findings lead to the conclusion that the protection through immunization is very high and the vaccines used are extremely effective, particularly as some individuals do not adhere to the recommended vaccination schedule.

Background: ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) are co-localized at the blood-brain barrier (BBB), where they restrict the brain distribution of many different drugs. Moreover, ABCB1 and possibly ABCG2 play a role in Alzheimer's disease (AD) by mediating the brain clearance of beta-amyloid (Aβ) across the BBB. This study aimed to compare the abundance and activity of ABCG2 in a commonly used β-amyloidosis mouse model (APP/PS1-21) with age-matched wild-type mice., Methods: The abundance of ABCG2 was assessed by semi-quantitative immunohistochemical analysis of brain slices of APP/PS1-21 and wild-type mice aged 6 months. Moreover, the brain distribution of two dual ABCB1/ABCG2 substrate radiotracers ([ 11 C]tariquidar and [ 11 C]erlotinib) was assessed in APP/PS1-21 and wild-type mice with positron emission tomography (PET). [ 11 C]Tariquidar PET scans were performed without and with partial inhibition of ABCG2 with Ko143, while [ 11 C]erlotinib PET scans were only performed under baseline conditions., Results: Immunohistochemical analysis revealed a significant reduction (by 29-37%) in the number of ABCG2-stained microvessels in the brains of APP/PS1-21 mice. Partial ABCG2 inhibition significantly increased the brain distribution of [ 11 C]tariquidar in APP/PS1-21 and wild-type mice, but the brain distribution of [ 11 C]tariquidar did not differ under both conditions between the two mouse strains. Similar results were obtained with [ 11 C]erlotinib., Conclusions: Despite a reduction in the abundance of cerebral ABCG2 and ABCB1 in APP/PS1-21 mice, the brain distribution of two dual ABCB1/ABCG2 substrates was unaltered. Our results suggest that the brain distribution of clinically used ABCB1/ABCG2 substrate drugs may not differ between AD patients and healthy people.

P-glycoprotein (P-gp, ABCB1) is an efflux transporter at the blood-brain barrier (BBB), which mediates clearance of beta-amyloid (Aβ) from brain into blood. We used ( R )-[ 11 C]verapamil PET in combination with partial P-gp inhibition with tariquidar to measure cerebral P-gp function in a beta-amyloidosis mouse model (APPtg) and in control mice at three different ages (50, 200 and 380 days). Following tariquidar pre-treatment (4 mg/kg), whole brain-to-plasma radioactivity concentration ratios ( K p,brain ) were significantly higher in APPtg than in wild-type mice aged 50 days, pointing to decreased cerebral P-gp function. Moreover, we found an age-dependent decrease in cerebral P-gp function in both wild-type and APPtg mice of up to -50%. Alterations in P-gp function were more pronounced in Aβ-rich brain regions (hippocampus, cortex) than in a control region with negligible Aβ load (cerebellum). PET results were confirmed by immunohistochemical staining of P-gp in brain microvessels. Our results confirm previous findings of reduced P-gp function in Alzheimer's disease mouse models and show that our PET protocol possesses adequate sensitivity to measure these functional changes in vivo. Our PET protocol may find use in clinical studies to test the efficacy of drugs to induce P-gp function at the human BBB to enhance Aβ clearance.

Previous studies have highlighted that spermidine has the ability to trigger the important process of dissolving amyloid-beta plaques by autophagy. This manuscript focuses on the correlation of serum spermidine levels between age and between performance in mini-mental state examinations. It will serve as a premise for an ongoing multicentric placebo-controlled study, which focuses on the effect of oral spermidine supplementation on memory performance. Memory tests were carried out on 80 subjects aged 60-96 years old in 6 nursing homes in Styria. Blood samples were taken for the determination of spermidine concentration. The results showed a significant correlation between the spermidine concentration and the mini-mental state examination score (p = 0.025). On the basis of the dependence demonstrated it can be concluded that spermidine might be suitable as a biomarker for the diagnosis of neurocognitive changes (senile dementia or Alzheimer's disease).

In this study, levels of inflammatory protein biomarkers in venous plasma, plasma derived from capillary blood from the earlobe, and capillary plasma stored as dried plasma spots (DPS) were compared. Samples from 12 male individuals were assessed with a panel of 92 inflammation-related proteins using multiplex proximity extension assay. Correlations between sample types varied greatly between analytes. A high correlation of ρ > 0.8 was observed between capillary plasma and DPS for 32 analytes. At this level of correlation, 13 analytes correlated between venous and capillary plasma and 5 analytes in the comparison of venous blood with DPS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients., Methods: In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke., Results: Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections., Conclusions: LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections.

Unlabelled: Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum., Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody., Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children.

Background: To evaluate if plasma levels of midregional pro-adrenomedullin (MR-proADM) improve prediction of functional outcome in ischemic stroke., Methods: In 168 consecutive ischemic stroke patients, plasma levels of MR-proADM were measured within 24 hours from symptom onset. Functional outcome was assessed by the modified Rankin Scale (mRS) at 90 days following stroke. Logistic regression, receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), and Kaplan-Meier survival analysis were applied., Results: Plasma MR-proADM levels were found significantly higher in patients with unfavourable (mRS 3-6) compared to favourable (mRS 0-2) outcomes. MR-proADM levels were entered into a predictive model including the patients' age, National Institutes of Health Stroke Scale (NIHSS), and the use of recanalization therapy. The area under the ROC curve did not increase significantly. However, category-free NRI of 0.577 (p<0.001) indicated a significant improvement in reclassification of patients. Furthermore, MR-proADM levels significantly improved reclassification of patients in the prediction of outcome by the Stroke Prognostication using Age and NIHSS-100 (SPAN-100; NRI = 0.175; p = 0.04). Kaplan-Meier survival analysis showed a rising risk of death with increasing MR-proADM quintiles., Conclusions: Plasma MR-proADM levels improve prediction of functional outcome in ischemic stroke when added to the patients' age, NIHSS on admission, and the use of recanalization therapy. Levels of MR-proADM in peripheral blood improve reclassification of patients when the SPAN-100 is used to predict the patients' functional outcome.

Memory formation is thought to be mediated by dendritic-spine growth and restructuring. Myocyte enhancer factor 2 (MEF2) restricts spine growth in vitro, suggesting that this transcription factor negatively regulates the spine remodeling necessary for memory formation. Here we show that memory formation in adult mice was associated with changes in endogenous MEF2 levels and function. Locally and acutely increasing MEF2 function in the dentate gyrus blocked both learning-induced increases in spine density and spatial-memory formation. Increasing MEF2 function in amygdala disrupted fear-memory formation. We rescued MEF2-induced memory disruption by interfering with AMPA receptor endocytosis, suggesting that AMPA receptor trafficking is a key mechanism underlying the effects of MEF2. In contrast, decreasing MEF2 function in dentate gyrus and amygdala facilitated the formation of spatial and fear memory, respectively. These bidirectional effects indicate that MEF2 is a key regulator of plasticity and that relieving the suppressive effects of MEF2-mediated transcription permits memory formation.

Objectives: Previous data suggest that Dickkopf-1 (Dkk-1), an inhibitor of the canonical/β-catenin cascade of the Wnt pathway, is upregulated in carotid atherosclerosis and acute myocardial ischemia. It is currently unclear if such upregulation also occurs in cerebral ischemia., Methods: We measured plasma levels of Dkk-1 in patients with acute ischemic stroke (n=57) within 24h from symptom onset, in patients with clinically stable cerebrovascular disease (n=29) and in healthy controls (n=29). Stroke severity on admission was determined by the National Institutes of Stroke Scale (NIHSS). The modified Rankin Scale (mRS) served to define outcome at day 90. Ischemic stroke subtype and cause was determined by the Oxfordshire Community Stroke Project (OCSP) criteria and the Causative Classification of Stroke System (CCS)., Results: Dkk-1 plasma levels were significantly higher in acute stroke patients (median 727.1 pg/ml) as compared to patients with stable cerebrovascular disease (median 534.2 pg/ml; p=0.017) or healthy controls (median 371.3 pg/ml; p<0.001). The difference of Dkk-1 levels between patients with stable cerebrovascular disease and healthy controls was also significant (p=0.005). No significant differences in Dkk-1 plasma levels were found between different causes or subtypes of ischemic stroke. No correlation of Dkk-1 levels was found with stroke severity on admission and outcome at day 90., Conclusion: Our study provides for the first time evidence for a release of Dkk-1 into the circulation in patients with acute ischemic stroke and also in patients with clinically stable cerebrovascular disease., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Multiple recent human imaging studies have suggested that the structure of the brain can change with learning. To investigate the mechanism behind such structural plasticity, we sought to determine whether maze learning in mice induces brain shape changes that are detectable by MRI and whether such changes are specific to the type of learning. Here we trained inbred mice for 5 days on one of three different versions of the Morris water maze and, using high-resolution MRI, revealed specific growth in the hippocampus of mice trained on a spatial variant of the maze, whereas mice trained on the cued version were found to have growth in the striatum. The structure-specific growth found furthermore correlated with GAP-43 staining, a marker of neuronal process remodelling, but not with neurogenesis nor neuron or astrocyte numbers or sizes. Our findings provide evidence that brain morphology changes rapidly at a scale detectable by MRI and furthermore demonstrate that specific brain regions grow or shrink in response to the changing environmental demands. The data presented herein have implications for both human imaging as well as rodent structural plasticity research, in that it provides a tool to screen for neuronal plasticity across the whole brain in the mouse while also providing a direct link between human and mouse studies., (Copyright © 2010 Elsevier Inc. All rights reserved.)