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Clear cell renal cell carcinoma (ccRCC) accounts for ~75% of kidney cancers. The biallelic inactivation of the von Hippel–Lindau tumor suppressor gene (VHL) is the truncal driver mutation of most cases of ccRCC. Cancer cells are metabolically reprogrammed and excrete modified nucleosides in larger amounts due to their increased RNA turnover. Modified nucleosides occur in RNAs and cannot be recycled by salvage pathways. Their potential as biomarkers has been demonstrated for breast or pancreatic cancer. To assess their suitability as biomarkers in ccRCC, we used an established murine ccRCC model, harboring Vhl, Trp53 and Rb1 (VPR) knockouts. Cell culture media of this ccRCC model and primary murine proximal tubular epithelial cells (PECs) were investigated by HPLC coupled to triple-quadrupole mass spectrometry using multiple-reaction monitoring. VPR cell lines were significantly distinguishable from PEC cell lines and excreted higher amounts of modified nucleosides such as pseudouridine, 5-methylcytidine or 2′-O-methylcytidine. The method’s reliability was confirmed in serum-starved VPR cells. RNA-sequencing revealed the upregulation of specific enzymes responsible for the formation of those modified nucleosides in the ccRCC model. These enzymes included Nsun2, Nsun5, Pus1, Pus7, Naf1 and Fbl. In this study, we identified potential biomarkers for ccRCC for validation in clinical trials.

Overactive Janus kinases (JAKs) are known to drive leukemia, making them well-suited targets for treatment. We sought to identify new JAK-activating mutations and instead found a JAK1-inactivating pseudokinase mutation, V666G. In contrast to other pseudokinase mutations that canonically lead to an active kinase, the JAK1 V666G mutation led to under-activation seen by reduced phosphorylation. To understand the functional role of JAK1 V666G in modifying kinase activity we investigated its influence on other JAK kinases and within the Interleukin-2 pathway. JAK1 V666G not only inhibited its own activity, but its presence could inhibit other JAK kinases. These findings provide new insights into the potential of JAK1 pseudokinase to modulate its own activity, as well as of other JAK kinases. Thus, the features of the JAK1 V666 region in modifying JAK kinases can be exploited to allosterically inhibit overactive JAKs.

Background To gain insight into vedolizumab (VEDO) use as a first-line biologic in Crohn′s disease (CD), this comparative, two-arm prospective real-world-evidence (RWE) study with propensity score (PS) adjustment aimed to assess, within the maintenance phase, the 2-year comparative effectiveness and persistence of VEDO vs anti-TNF therapy in biologic-naïve CD patients. Methods Between 2017-2020, 1200 consecutively enrolled biologic-naïve and biologic-experienced patients with ulcerative colitis (UC) and CD were prospectively included in the VEDOIBD study from 45 IBD-experienced centres across Germany. 260 biologic-naïve CD patients starting a new therapy with VEDO or anti-TNF were included in this RWE comparison of VEDO vs anti-TNF. The Kaplan-Meier curve was used to summarize the treatment persistence from the start of therapy through week-104. The primary outcome was two-year clinical remission (HBI ≤ 4). Patients were analysed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure). To reduce the effect of confounders, PS adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used to evaluate the effectiveness. The results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 63 VEDO and 197 anti-TNF (ADA: 58.4%, IFX: 41.6%) biologic-naïve CD-patients were evaluated. Two years after treatment initiation approximately 83% of VEDO patients were still in continuous treatment vs only 56% of anti-TNF patients (Fig. 1). In the mITT analysis (Fig. 2), there was a significantly higher clinical remission rate with VEDO when compared to anti-TNF after two years (VEDO: 64.2% vs anti-TNF: 44.7%), and a higher steroid-free remission (VEDO: 62.5% vs anti-TNF: 41.6%). Both differences were statistically significant (p Conclusion Compared to previous RCTs, this prospective two-year RWE study comparing VEDO with anti-TNF showed that, in biologic-naïve CD patients, remission rates at two years with VEDO were remarkably higher than with anti-TNF. Given the favourable side effect profile of VEDO, these findings may aid physicians’ decision-making on the choice of VEDO as a first-line biologic for CD.

Background Observational real-world evidence (RWE) studies on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are required in addition to RCTs, which are usually confined to selected patients and thus may not represent distinct treatment patterns and everyday clinical practice. For this reason, the prospective, controlled, propensity score (PS)-adjusted RUN-UC study was conducted in UC patients starting a newly initiated biologics therapy with a follow-up period of 3 years. The aim of the present analysis was to investigate the induction phase effectiveness of UST vs anti-TNF vs vedolizumab (VEDO) in UC in terms of clinical and steroid-free remission. Methods Between 2020-2022, 507 UC patients starting a new therapy with UST or other biologics were enrolled in 34 IBD-experienced centres across Germany. After exclusion of small molecules and missing outcomes, the final sample consisted of 317 patients. Response modified (reduction of partial Mayo score (pMayo) by ≥ 3 points from baseline to week-16 and a reduction of at least 30% or reaching remission at week-16), clinical remission (pMayo ≤ 1 plus a bleeding subscore=0), and steroid-free remission (pMayo ≤ 1, bleeding subscore=0 and no systemic use of steroids or oral budesonide during the last 8 weeks) were considered as outcomes. To reduce the effect of confounders, PS adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Health-related quality of life was assessed by using the self-reported visual analogue scale (EQ-VAS) of the EQ-5D. Changes in EQ-VAS from baseline to week-16 were assessed with a linear model. Results 101 UST (bio-naïve: 6), 106 anti-TNF (ADA: 24.5%, IFX: 65.1%, GOL: 10.4%) (bio-naïve: 70) and 110 VEDO (bio-naïve: 73) UC-patients were included. PS adjustment removed systematic differences between the three groups (UST/anti-TNF/VEDO: 44.9/43.8/48.1% males, 6.7/9.9/5.5% smokers, 7.9/12.5/9.3% EIM). The effectiveness of UST in terms of response, clinical and steroid-free remission was comparable to that of anti-TNF and VEDO at week 16 (Tab. 1). We observed a significant increase in EQ-VAS within all three groups (Tab. 2). The increase in the UST group was significantly higher than in the VEDO group and numerically higher than in the anti-TNF group. Conclusion In this prospective RUN-UC study, with propensity score weighted groups, UST showed similar induction phase effectiveness in comparison with anti-TNF and VEDO. Quality of life was significantly improved in the UST group vs VEDO and was numerically higher than anti-TNF after the induction phase.

Background In this two-arm prospective real-world-evidence (RWE) study with propensity score adjustment, we aimed to analyse the persistence of biologic therapy in biologic-naïve ulcerative colitis (UC) patients and to compare the 2-year effectiveness of vedolizumab (VEDO) and anti-TNF. Methods Between 2017 and 2020, 1200 consecutively enrolled biologic-naïve and biologic-experienced patients with UC and CD (Crohn’s disease) were prospectively included in the VEDOIBD study from 45 IBD-experienced centres across Germany. After the exclusion of biologic-experienced patients, CD, and missing outcomes, the final sample consisted of 314 biologic-naïve UC patients with 2-year follow-up data. In this mITT analysis switching was considered as outcome failure, and clinical remission and (steroid-free) remission rates (pMayo ≤1 plus a bleeding subscore=0 - and no systemic use of steroids or oral budesonide at two years) at two years were predefined as outcomes. To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results The two-year maintenance phase effectiveness of 182 VEDO and 132 anti-TNF (ADA: 25.8%; IFX: 58.3%; GOL 15.9%) biologic-naïve UC patients were analysed in this prospective RWE-comparison of VEDO vs anti-TNF. Significantly more patients switched to another biologic in the anti-TNF group when compared to the VEDO group up to 2 years (54% vs 29%; p Conclusion As shown previously, in the induction phase, there is comparable effectiveness for VEDO and anti-TNF, although the remission rates are relatively low and similar to the range reported in RCTs. Over one year, the effectiveness tends to improve in favour of VEDO, potentially due to better treatment persistence. After two years, the clinical remission rate in the VEDO group is statistically significantly higher than in the anti-TNF group. The higher treatment persistence of VEDO vs anti-TNF and the higher effectiveness may suggest VEDO as a first-line biologics therapy option in UC patients.

Background Since April 2020, vedolizumab (VEDO) has been available for use in IBD in intravenous (iv) and subcutaneous (sc) formulations. Due to limited data on real-world use and effectiveness, the objectives of this real-world evidence (RWE), observational, prospective study are to observe (1) the time point of conversion to VEDO sc, (2) the 6-month remission rate with VEDO sc. using data from the VEDOIBD study. Methods Between 2017-2020, 1200 consecutively enrolled patients with ulcerative colitis (UC) and Crohn’s disease (CD) were prospectively included in the VEDOIBD study from 45 IBD-experienced centers across Germany. Additionally, 74 VEDO-naïve patients were included with the goal of conversion to VEDO sc after an iv-induction period with VEDO (VEDO iv week 0, 2, 6). Effectiveness was measured by clinical remission (HBI ≤ 4) at month 6. Results A total of 180 IBD patients with a running VEDO iv therapy were converted to VEDO sc during the entire study, with at least one 6-month visit from 119 patients (UC: n=67; CD: n=52). Characteristics are shown in Table 1. 87 IBD patients (73.1%) were still receiving VEDO sc after 6 months. 32 IBD patients (26.9%) stopped VEDO sc therapy within the first 6 months. The majority of patients returned to treatment with VEDO iv (37.9%) and the others switched to other biologics: 24.1% ustekinumab, 34.5% anti-TNF (Figure 1). At the time of conversion to sc, 92 patients (77.3%) were in remission (UC: 75%; CD: 84.6%). Of those, 88% remained in remission at 6 months (UC: 89.6%; CD: 86.4%). 45.8% of patients not in remission at the time of conversion to VEDO sc were in remission at 6 months (UC: 50%; CD: 37.5%). Of the 74 patients with planned conversion to VEDO sc, 52 patients (70.3%) received VEDO sc as planned previously: 11.5% within the first 2 weeks, 42.3% after week 6, 19.2% after week 14, and 26.8% after six months or later. Conclusion IBD patients with a conversion from VEDO iv to VEDO sc show high effectiveness after 6 months; conversion usually was carried out between 6 and 14 weeks. Based on these data, VEDO sc is shown to be an effective alternative to VEDO iv in RWE and should therefore be considered an important option in treatment planning and discussion with patients.

Introduction The aim of this study was to investigate patients' preferences regarding the evolving treatment landscape in Crohn's disease (CD) and ulcerative colitis (UC) based on a discrete choice experiment. Methods Eligible patients (aged 18 years or older) had a confirmed diagnosis of CD or UC and were willing and able to participate in telephone interviews. The survey design is based on a prior literature review, a pilot study, and clinical expert discussions. Preferences related to clinical and practical features of advanced therapies, like tumor necrosis factor alpha inhibitors, anti-integrins, anti-interleukins, and Janus kinase inhibitors, were assessed. Patients were asked to choose between two different hypothetical treatment alternatives visualized in up to 11 choice scenarios. Based on these choices, the relative importance of treatment characteristics was derived from regression coefficients estimated by a conditional logit model. Results Of the 291 patients included, 219 (75%) were eligible for this analysis. Among the evaluated attributes in CD, 1-year remission rate was ranked highest, with 42.3% relevance for the overall decision. The second most important attribute was the frequency of serious adverse events (AE) (25.1%), followed by sustained remission over 2 years (17.8%). Lower importance was assigned to the administration mode (14.6%) and none to the frequency of non-serious AE (0.1%). In UC, preferences were driven by efficacy (25.3% for mucosal healing; 23.4% for corticosteroid-free remission) and the frequency of serious AE (18.3%), followed by the administration mode (18.1%). Also, non-serious AE were classified as relevant factors for decision-making (10.7%), while maintaining remission for at least 2 years showed no significant impact (4.4%). Conclusion For both indications, efficacy outcomes were rated most important, followed by the frequency of serious AE. Variations were mainly found in the evaluation of non-serious AE and sustained remission. Considering patient preferences may improve the effectiveness of available therapies for moderate to severe CD and UC.

Metabolomics has expanded from cellular to subcellular level to elucidate subcellular compartmentalization. By applying isolated mitochondria to metabolome analysis, the hallmark of mitochondrial metabolites has been unraveled, showing compartment-specific distribution and regulation of metabolites. This method was employed in this work to study a mitochondrial inner membrane protein Sym1, whose human ortholog MPV17 is related to mitochondria DNA depletion syndrome. Gas chromatography–mass spectrometry-based metabolic profiling was combined with targeted liquid chromatography–mass spectrometry analysis to cover more metabolites. Furthermore, we applied a workflow employing ultra-high performance liquid chromatography–quadrupole time of flight mass spectrometry with a powerful chemometrics platform, focusing on only significantly changed metabolites. This workflow highly reduced the complexity of acquired data without losing metabolites of interest. Consequently, forty-one novel metabolites were identified in addition to the combined method, of which two metabolites, 4-guanidinobutanal and 4-guanidinobutanoate, were identified for the first time in Saccharomyces cerevisiae. With compartment-specific metabolomics, we identified sym1Δ cells as lysine auxotroph. The highly reduced carbamoyl-aspartate and orotic acid indicate a potential role of the mitochondrial inner membrane protein Sym1 in pyrimidine metabolism.

Background Within the framework of the prospective real-world RUN-CD registry on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD), a total of 901 CD-patients undergoing a newly initiated biologics therapy were enrolled in 44 IBD-experienced centers from all over Germany between 2017-2020 with a follow-up of 3 years. Here, the results on the effectiveness of the maintenance therapy over 24 months are presented as a real-world evidence (RWE) comparison of CD-patients with UST vs anti-TNF. Methods After exclusion of other biologics than UST and anti-TNF and missing outcomes (HBI), the final sample consisted of 550 CD patients. Clinical remission (HBI ≤ 4) was the predefined endpoint at month 24 and additionally, switching of biologics therapy was considered as an outcome failure. Patients were analysed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure). To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Quality of life was assessed using the self-reported visual analogue scale (EQ-VAS) of the EQ-5D with changes from baseline to 2 years. Results 308 UST (naïve: 27) and 242 anti-TNF (naïve: 162) CD-patients were included (ADA: 61.2%, IFX: 38.8%). The number of switches within 24 months was significantly lower with UST than with anti-TNF (27.6% vs 37.1%; p=0.038), and especially with IFX, whereby the difference between UST and IFX (27.6% vs 46.7%; p=0.003) proves to be statistically significant (Fig. 1). Clinical remission at two years was not statistically different for the overall UST vs anti-TNF groups (51.2% vs 54.4) (numerically higher in biologic-naïve UST- vs anti-TNF-patients, without statistically significance) (Tab. 1). Remission rates were similar for UST vs ADA, while they were significantly higher for UST vs IFX (54.4% vs 37.9%; p=0.008) (Tab. 2), and also significantly higher for ADA vs. IFX (58.2% vs 37.9%; p=0.003). As a sign of an improved QoL we observed a significant increase in EQ-VAS within both treatment groups. However, a similar increase in EQ-VAS was observed with UST and anti-TNF (+14.2 vs +12.3; p=0.147). Conclusion In this prospective two-year RWE comparison clinical remission was, also due to more frequent switches within the IFX group, significantly higher with UST when compared with IFX and higher with ADA than with IFX. Considering the effectiveness results of UST and the proven favourable safety profile, UST can be considered a first-line targeted therapy for CD.

ImportanceNoninvasive stool-based screening tests (SBTs) are effective alternatives to colonoscopy. However, a positive SBT result requires timely follow-up colonoscopy (FU-CY) to complete the colorectal cancer screening paradigm.ObjectivesTo evaluate FU-CY rates after a positive SBT result and to assess the association of the early COVID-19 pandemic with FU-CY rates.Design, Setting, and ParticipantsThis mixed-methods cohort study included retrospective analysis of deidentified administrative claims and electronic health records data between June 1, 2015, and June 30, 2021, from the Optum Labs Data Warehouse and qualitative, semistructured interviews with clinicians from 5 health care organizations (HCOs). The study population included data from average-risk primary care patients aged 50 to 75 years with a positive SBT result between January 1, 2017, and June 30, 2020, at 39 HCOs.Main Outcomes and MeasuresThe primary outcome was the FU-CY rate within 1 year of a positive SBT result according to patient age, sex, race, ethnicity, insurance type, Charlson Comorbidity Index (CCI), and prior SBT use.ResultsThis cohort study included 32 769 individuals (16 929 [51.7%] female; mean [SD] age, 63.1 [7.1] years; 2092 [6.4%] of Black and 28 832 [88.0%] of White race; and 825 [2.5%] of Hispanic ethnicity). The FU-CY rates were 43.3% within 90 days of the positive SBT result, 51.4% within 180 days, and 56.1% within 360 days (n = 32 769). In interviews, clinicians were uniformly surprised by the low FU-CY rates. Rates varied by race, ethnicity, insurance type, presence of comorbidities, and SBT used. In the Cox proportional hazards regression model, the strongest positive association was with multitarget stool DNA use (hazard ratio, 1.63 [95% CI, 1.57-1.68] relative to fecal immunochemical tests; P 4 relative to 0; P Conclusions and RelevanceThis study found that FU-CY rates after a positive SBT result for colorectal cancer screening were low among an average-risk population, with the median HCO achieving a 53.4% FU-CY rate within 1 year. Socioeconomic factors and the COVID-19 pandemic were associated with lower FU-CY rates, presenting opportunities for targeted intervention by clinicians and health care systems.

Background To gain insight into vedolizumab (VDZ) use as a first-line biologic in Crohn′s Disease (CD), this real-world study aimed to assess, within the maintenance phase, the 1-year comparative effectiveness and persistence of VDZ vs anti-TNF therapy in biologic-naïve CD-patients. Methods Between 2017–2020, 1200 consecutively enrolled biologic-naïve and biologic-experienced patients with ulcerative colitis (UC) and CD were prospectively included in the VEDOIBD-Registry from 45 IBD-experienced centres across Germany. 294 biologic-naïve CD-patients starting a new therapy with VDZ or anti-TNF (adalimumab: ADA or infliximab: IFX) were included in this real-world evidence (RWE) study. The Kaplan-Meier was used to summarize the treatment persistence from the start of therapy through week-52. The primary outcome was week-52 clinical remission (HBI ≤ 4). Patients were analyzed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure) and on a per-protocol (PP) basis (excluding switchers). To reduce selection bias in the estimation of treatment effects, the inverse probability of treatment weighting propensity score (PS) was implemented. A weighted logistic regression was used to evaluate the effectiveness. The results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 71 VDZ and 223 anti-TNF (ADA: 59.6%, IFX: 40.4%) biologic-naïve CD-patients were evaluated. 52-weeks after treatment initiation approximately 94% of VDZ patients were still in continuous treatment vs 75% of ADA and 78% of IFX (Figure 1). The mITT 1-year clinical remission rate was 76.1% for VDZ vs 63.8% for anti-TNF (OR: 1.80, 95% CI: 0.86–3.76). Similar results were observed for VDZ vs IFX (Table 1). In contrast, the clinical remission was significantly higher in the VDZ group than in the ADA group (OR: 2.24, 95% CI: 1.04–4.85). The PP analysis suggested comparative effectiveness, having excluded more anti-TNF switchers. 91.7% of week-14 responders VDZ patients were in clinical remission from week 14 through 52 vs 66.1% of anti-TNF patients (OR: 5.69, 95% CI: 1.66–19.5). Similar, significant, results were observed for VDZ vs ADA and for VDZ vs IFX (Table 2). Conclusion In this real-world setting comparing VDZ and anti-TNF in biologic-naïve patients via PS weighted analysis, VDZ showed especially in week-14 responders higher clinical remission rates in comparison to anti-TNF. The higher treatment persistence observed for VDZ, perhaps due to a more favourable safety profile vs anti-TNF, may be considered the main driver for the better effectiveness of VDZ at one year. These findings may aid physicians’ decision-making on the choice of VDZ as the first-line biologic for CD.

Background Observational real world studies are required in addition to RCTs which typically represent selected patients not reflecting everyday clinical practice. Between 2017–2020 patients with Crohn’s disease (CD) receiving a newly initiated biologics therapy were consecutively enrolled into the prospective, observational RUN-CD registry from 44 IBD-experienced German centres to assess effectiveness and safety of ustekinumab (UST) with a 3 years follow-up. Here, the results on the effectiveness of the maintenance therapy over 12 months are presented as a real world evidence (RWE) comparison of UST vs anti-TNF. Methods After exclusion of other biologics than UST and anti-TNF and missing outcomes, the final sample consisted of 607 CD-patients. Clinical remission (HBI ≤ 4) was the predefined endpoint at month 12. Patients were analyzed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure). To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 343 UST (naïve: 35) and 264 anti-TNF (naïve: 175) (ADA 61%, IFX 39%) CD-patients were included. PS removed systematic differences between both groups (mean of both groups: 15% perianal disease, 36% surgical resection, 41% EIM). Overall, the number of switches was lower in the UST group than in the anti-TNF group (Tab. 1). However, the number of switches within 12 months was significantly lower in the UST group only when compared to the IFX group (16.3% vs 27.2%; p=0.045) (Fig. 1). Clinical remission rates at 1 year (Tab. 2) were not statistically different for the overall UST vs. anti-TNF groups (65.8% vs 60.0%). Remission rates were similar for UST vs ADA, while these were significantly higher for UST vs. IFX (61.6% vs 41.8%; p=0.009). Looking at clinical remission in the week 16 responder group (Tab. 3), a statistically significantly higher remission rate was found in the overall group for UST (77.6%) vs anti-TNF (65.4%) (p=0.041), which was mainly driven by the higher UST remission rate in biologic-naïve CD patients (p=0.026). Conclusion This 1-year maintenance phase RWE-comparison with UST vs anti-TNF showed remarkably high clinical remission rates in both groups. Also due to a more frequent switching within the IFX group, the clinical remission rate at 1 year was significantly higher with UST than with IFX and higher with UST vs anti-TNF in the biologic-naïve groups. These results support together with the known favorable safety profile consideration of UST as a first-line targeted therapy for CD.

Background In this real-world-evidence (RWE) study we aimed to analyse the persistence of biologic therapy in biologic-naïve ulcerative colitis (UC) patients and to compare 1-year effectiveness of vedolizumab (VDZ) and anti-TNF. Methods Between 2017 and 2020, 1200 consecutively enrolled biologic-naïve and biologic- experienced patients with UC and Crohn′s disease (CD) were prospectively included in the VEDOIBD-Registry from 45 IBD-experienced centres across Germany. After exclusion of bio-experienced patients, CD and missing outcomes, the final sample consisted of 274 biologic-naïve UC-patients with 1-year follow-up data. Switchers of a drug were considered as treatment failure (modified intention-to-treat analysis; mITT) while switchers were excluded from per protocol analysis (PP). Clinical response modified (reduction of partial Mayo score (pMayo) from baseline to 1-year by >3 points or a reduction of at least 30% compared to baseline or reaching remission at 1-year) and (steroid-free) remission rates (pMayo ≤1 plus a bleeding subscore=0 (and no systemic use of steroids or budesonide at 1-year)) were predefined as outcomes. To reduce the effect of confounders, PS adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 158 VDZ and 116 anti-TNF (ADA: 27.6%, IFX: 57.8%, GOL: 14.7%) biologic-naïve UC-patients were included in this prospective RWE comparing the effectiveness of VDZ vs anti-TNF. Until week 52 significantly more patients switched to another biologic-drug in the anti-TNF group than in the VDZ group (40.5% vs 16.5%; p Conclusion The 1-year maintenance findings suggested, in line with our previous induction phase data, only moderate long-term effectiveness in both groups. However, besides the significant response data, VDZ showed numerically higher remission rates compared to anti-TNF though only borderline significant. The higher treatment persistence of VDZ vs anti-TNF, along with the higher effectiveness, may suggest VDZ as a first-line biologic therapy option in UC patients.

Summary Background Psychosocial factors significantly influence patient care in many fields of medicine, among these in the field of endocrinology. Easily applicable validated assessment tools for such psychosocial factors are lacking. Visual instruments may facilitate doctor-patient communication. This study describes the development and validation of a multidimensional visual tool for the self-assessment of health. Methods An expert panel performed the multistep development of the psychosomatic assessment health disc (PAHD). Assessment of face validity was performed by means of a focus group of medical doctors (n = 6) and patient interviews (n = 24). For determining test-retest reliability, internal consistency and construct validity, patients of an endocrine outpatient clinic in Graz, Austria, completed the PAHD and the following questionnaires: short-form 36 health survey, work ability index, Pittsburgh sleep quality index and the social life scales of the life satisfaction questionnaire. Results A numeric six-item analogue scale was developed in the form of a disc. It addresses the following aspects of health: physical well-being, social life, sexuality, mental well-being, sleep, working ability/performance. For the validation process, 177 patients (57.1% females) participated in the study. Correlation coefficients of the six items with other questionnaires ranged between r = 0.51 (social life) and r = 0.72 (sleep). Test-retest reliability was assessed among 98 patients and was ≥ 0.74 for all 6 items, while Cronbach’s alpha was 0.78. Conclusion The psychometric properties of the PAHD support its use in clinical encounters with patients suffering from endocrine disorders. Further validation studies may be required to extend its application to other fields of medicine.

There is increasing evidence for altered brain resting state functional connectivity in adolescents with disruptive behavior. While a considerable body of behavioral research points to differences between reactive and proactive aggression, it remains unknown whether these two subtypes have dissociable effects on connectivity. Additionally, callous-unemotional traits are important specifiers in subtyping aggressive behavior along the affective dimension. Accordingly, we examined associations between two aggression subtypes along with callous-unemotional traits using a seed-to-voxel approach. Six functionally relevant seeds were selected to probe the salience and the default mode network, based on their presumed role in aggression. The resting state sequence was acquired from 207 children and adolescents of both sexes [mean age (standard deviation) = 13.30 (2.60); range = 8.02–18.35] as part of a Europe-based multi-center study. One hundred eighteen individuals exhibiting disruptive behavior (conduct disorder/oppositional defiant disorder) with varying comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms were studied, together with 89 healthy controls. Proactive aggression was associated with increased left amygdala–precuneus coupling, while reactive aggression related to hyper-connectivities of the posterior cingulate cortex (PCC) to the parahippocampus, the left amygdala to the precuneus and to hypo-connectivity between the right anterior insula and the nucleus caudate. Callous-unemotional traits were linked to distinct hyper-connectivities to frontal, parietal, and cingulate areas. Additionally, compared to controls, cases demonstrated reduced connectivity of the PCC and left anterior insula to left frontal areas, the latter only when controlling for ADHD scores. Taken together, this study revealed aggression-subtype-specific patterns involving areas associated with emotion, empathy, morality, and cognitive control. Electronic supplementary material The online version of this article (10.1007/s00787-020-01601-9) contains supplementary material, which is available to authorized users.

Background Physicians are exposed to workplace factors that may result in acute or chronic stress resulting in burnout. This may impact the productivity and result in suboptimal patient care practices. Methods We surveyed pediatric cardiology attending physicians at our institution to assess their perception of burnout and work-life balance using the Maslach Burnout Inventory and the Areas of Work-Life Survey. Results Forty-five out of the 50 pediatric cardiology attendings responded to the survey. They were divided into 4 groups: Interventional/Electrophysiology [n = 3], Cardiac Intensive Care/Inpatient [n = 8], Non-Invasive Imaging [n = 6], and Outpatient [n = 28]. The Maslach Burnout Inventory demonstrated group-specific scores in the areas of emotional exhaustion, depersonalization, and personal accomplishment that were all significantly better than the general population. However, group-specific Areas of Work-Life Survey results demonstrated concerning findings with respect to the perception of work-life balance. Conclusions Although the Maslach Burnout Inventory did not demonstrate significant burnout among the attending physicians, the Areas of Work-Life Survey results demonstrated reduced work engagement, which can impact patient care and lead to burnout in the future. Based on these results, we plan to implement strategies to help increase work engagement and improve overall organizational effectiveness.

Clinical hypnosis for improving learning has been advocated by scholars dating back to the late 19th century. Empirical research seeking to validate its use has been supported particularly for real life applications, though less so in laboratory memory experiments. Suggestions for the use of waking/alert hypnosis suggestion for both highly suggestible students who experience more advanced and compelling phenomena associated with hypnosis, and students in general are offered. Suggestions for future research are also provided.

In this study, we identified a novel pyrazole-based derivative (P3C) that displayed potent cytotoxicity against 27 human cancer cell lines derived from different tissue origins with 50% cytotoxic concentrations (CC50) in the low micromolar and nanomolar range, particularly in two triple-negative breast cancer (TNBC) cell lines (from 0.25 to 0.49 µM). In vitro assays revealed that P3C induces reactive oxygen species (ROS) accumulation leading to mitochondrial depolarization and caspase-3/7 and -8 activation, suggesting the participation of both the intrinsic and extrinsic apoptotic pathways. P3C caused microtubule disruption, phosphatidylserine externalization, PARP cleavage, DNA fragmentation, and cell cycle arrest on TNBC cells. In addition, P3C triggered dephosphorylation of CREB, p38, ERK, STAT3, and Fyn, and hyperphosphorylation of JNK and NF-kB in TNBC cells, indicating the inactivation of both p38MAPK/STAT3 and ERK1/2/CREB signaling pathways. In support of our in vitro assays, transcriptome analyses of two distinct TNBC cell lines (MDA-MB-231 and MDA-MB-468 cells) treated with P3C revealed 28 genes similarly affected by the treatment implicated in apoptosis, oxidative stress, protein kinase modulation, and microtubule stability.

Background Prospective, observational real world studies on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD) are required in addition to RCTs, usually confined to selected patients, which may not represent special treatment patterns and everyday clinical practice. The aim of the present 3-year RUN-CD study was to investigate the induction phase effectiveness of UST vs. other biologics (OB) in CD in terms of clinical and steroid-free remission at week 16. To the best of our knowledge, RUN-CD is currently the largest prospective real world evidence (RWE) study with UST in CD using propensity score adjustment. Methods Between 2017–2020, 901 CD-patients starting a new therapy with UST or OB, were enrolled in 44 IBD-experienced centers across Germany. After exclusion of missing outcomes, the final sample consisted of 657 patients. Clinical remission (HBI ≤ 4), and steroid-free remission (HBI ≤ 4 and no systemic use of steroids or budesonide during the last 8 weeks) were considered as outcomes at week 16. To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 339 UST (naïve: 34) and 318 OB CD-patients were included (ADA: 50.3%, IFX: 37.4%, VDZ: 12.3%) (naïve: 203). PS removed systematic differences between both groups (30.8% smokers, 15.1% perianal disease, 36.2% surgical resection, 40.5% EIM). The effectiveness of UST for clinical and steroid-free remission was comparable to that of OB at week 16. Besides, in bio-naïve patients, clinical remission was numerically, though not significantly, higher in UST vs OB (Table 1). Similar results were observed in the bio-experienced UST vs. OB groups [remission: 59.3% vs 55.4%; OR: 1.17 (0.73–1.90)]. For both the remission rates were higher in the bio-naïve than in the bio-experienced groups (p Conclusion In this prospective RUN-CD study, with propensity score weighted groups, UST showed similar induction effectiveness in comparison with OB therapies. Remarkably higher remission rates were observed in this RWE study than in prior RCTs. An additional favorable safety profile supports consideration of UST as a first-line targeted therapy for CD.

This investigation combined the data from two studies that used modified scoring of the Harvard Group Scale of Hypnotic Susceptibility (ShorOrne, 1962) to evaluate deliberate, volitional responses to suggestions. One study also employed subjective ratings of each item of the Harvard Scale, with comparisons of nonvolitional, volitional, and non-responses. Based on the assumption that participants would have marked volitional responses as positive responses using the traditional scale, the traditional scoring method was found to inflate mean hypnotic responsiveness by nearly one point. Two hypothesized correlates of hypnotic performance, rapport with the hypnotist and a phenomenological measure of hypnosis, increased significantly when volitional responses were taken into account. The way in which participants were recruited did not predict volitional responses, but individuals who reported deliberate responses to suggestions from the Harvard Scale were less likely to express willingness to participate in future studies. Some of the volitional responses to the items were rated as subjectively more real compared to no responses, though nonvolitional responses were rated as the most real compared with compliance responses and no responses for all items. More difficult items were more likely to be performed volitionally than easier items. It is suggested that future studies using hypnotic inventories account for volitional responses. The nature of deliberately produced responses should also be examined using qualitative and quantitative data, especially with respect to how a given suggestion may affect the execution of the volitional behavior.

Epigenetic aberrations are prominent in bladder cancer (BC) and contribute to disease pathogenesis. We characterized histone deacetylase (HDAC) expression, a family of deacetylation enzymes, in both in vitro and in vivo BC model systems and analyzed expression data from The Cancer Genome Atlas (TCGA). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis was used to determine the expression status of Class I and II HDACs in ten human BC cell lines, while qRT-PCR was used to determine HDAC expression in 24 human tumor specimens. The TCGA cohort consists of 408 muscle invasive BC (MIBC) clinical samples and analysis of this data set identified expression of HDAC4 and -9 as being associated with basal&ndash, squamous disease. These findings agree with qRT-PCR results identifying increased expression of HDAC4, -7, and -9 in basal BC cell lines (p &lt, 0.05, Kruskal&ndash, Wallis test) and in clinical specimens with invasive bladder cancer (not statistically significant). We also observed increased expression in Hdac4, -7, and -9 in commonly used BC mouse models. Here, we identify suitable preclinical model systems for the study of HDACs, and show increased expression of Class IIa HDACs, specifically HDAC4 and HDAC9, in basal BC cell lines and in invasive clinical specimens. These results suggest this class of HDACs may be best suited for targeted inhibition in patients with basal BC.

Introduction Acute neuromuscular respiratory failure is a source of morbidity and mortality in neurological diseases, including acute inflammatory demyelinating polyneuropathy (AIDP), also known as Guillain-Barré syndrome. It is important for health care providers to recognize this condition and provide early ventilatory support. In this simulation, learners must assess and treat a standardized patient with acute respiratory complications related to AIDP. Methods This is a single-session simulation that can be run in a standard simulation center using a live standardized patient. The simulation scenario is followed by a facilitated debriefing session. Details about the simulation scenario, critical action checklist, environment preparation, actors/roles, and debriefing session are outlined. Results A total of 14 neurology residents participated in this simulation. A postsimulation survey revealed that participants thought the simulation achieved its stated objectives, was useful, and would impact their future practice. Discussion We designed this simulation to assess a learner's ability to identify acute neuromuscular respiratory weakness in a patient with AIDP and initiate treatment with ventilatory support. This simulation can easily be incorporated into an existing curriculum for neurology residents or for trainees in other specialties.

Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process.

Background and Aims: Azathioprine [AZA] is recommended for maintenance of steroid-free remission in inflammatory bowel disease IBD. The aim of this study has been to establish the incidence and severity of AZA-induced pancreatitis, an idiosyncratic and major side effect, and to identify specific risk factors. Methods: We studied 510 IBD patients [338 Crohn’s disease, 157 ulcerative colitis, 15 indeterminate colitis] with initiation of AZA treatment in a prospective multicentre registry study. Acute pancreatitis was diagnosed in accordance with international guidelines. Results: AZA was continued by 324 [63.5%] and stopped by 186 [36.5%] patients. The most common cause of discontinuation was nausea [12.2%]. AZA-induced pancreatitis occurred in 37 patients [7.3%]. Of these: 43% were hospitalised with a median inpatient time period of 5 days; 10% had peripancreatic fluid collections; 24% had vomiting; and 14% had fever. No patient had to undergo nonsurgical or surgical interventions. Smoking was the strongest risk factor for AZA-induced acute pancreatitis [p < 0.0002] in univariate and multivariate analyses. Conclusions: AZA-induced acute pancreatitis is a common adverse event in IBD patients, but in this study had a mild course in all patients. Smoking is the most important risk factor.

Background Currently available, pneumatic-based medical devices are operated using closed-loop pulsatile or open continuous systems. Medical devices utilizing gases with a low atomic number in a continuous closed loop stream have not been documented to date. This work presents the construction of a portable helium circulation addressing the need for actuating a novel, pneumatically operated catheter pump. The design of its control system puts emphasis on the performance, safety and low running cost of the catheter pump. Methods and results Static and dynamic characteristics of individual elements in the circulation are analyzed to ensure a proper operation of the system. The pneumatic circulation maximizes the working range of the drive unit inside the catheter pump while reducing the total size and noise production. Separate flow and pressure controllers position the turbine's working point into the stable region of the pressure creation element. A subsystem for rapid gas evacuation significantly decreases the duration of helium removal after a leak, reaching subatmospheric pressure in the intracorporeal catheter within several milliseconds. Conclusions The system presented in the study offers an easy control of helium mass flow while ensuring stable behavior of its internal components.

Background The VEDOibd I study is an investigator initiated, ongoing, non-interventional trial on biologics in IBD-patients (Crohn′s disease (CD) and ulcerative colitis (UC)) in Germany with consecutive recruitment and prospective documentation of effectiveness in induction and maintenance therapy of biologics, especially vedolizumab (VEDO). The aim of this analysis was to compare steroid-free remission rates in CD- and UC-patients after a 14-week-long induction phase of VEDO (bio-naïve and bio-experienced) vs. other biologics (infliximab (IFX), adalimumab (ADA), Golimumab (GLM), Ustekinumab (UST)) in bio-naïve patients. Methods From 10/2017 to 07/2019 750 IBD-patients (CD: 414; UC: 336) from 45 gastroenterology practices and hospitals with IBD-experience from all over Germany were recruited in the VEDOibd I study of whom 232 CD- and 184 UC-patients completed induction phase (week 14) in this interim analysis. At week 14 we compared clinical response (CD: reduction of Harvey Bradshaw Index [HBI] from baseline to week 14 by >3 points or HBI < 4 in week 14; UC: reduction of partial Mayo score [pMayo] from baseline to week 14 by >3 points or a reduction of at least 30% compared with baseline) and steroid-free remission rates (CD: HBI < 4 and no systemic use of steroids or budesonide at week 14; UC: pMayo ≤1 plus a bleeding subscore = 0 and no systemic use of steroids or budesonide at week 14) in patients with VEDO vs. other biologics. Results Ninety-two CD- and 111 UC-patients started a first-time VEDO therapy; of these 40 CD- (43%) and 57 UC-patients (51%) were bio-naïve. Furthermore 140 CD-patients (IFX 48.6%; ADA 47.1%; UST 4.3%) and 73 UC-patients (IFX 58.9%; ADA 24.7%; GLM 16.4%) started treatment with another biologic than VEDO and all of these were bio-naïve. Baseline characteristics were well balanced between both naïve groups (VEDO/other biologics; p > 0.05): males [%]: CD 38/41, UC 37/51; age [years]: CD 46 ± 15/42 ± 15, UC 43 ± 19/39 ± 15; disease duration [years]: CD 15 ± 11/9 ± 11, UC 9 ± 9/6 ± 7; extraintestinal manifestations [%]: CD 23/20, UC 7/15. Response/steroid-free remission rates after induction phase in biologic-naïve patients with VEDO and other biologics were 74.4%/57.5% vs. 78.4%/64.3% in CD (p>0.05) and 60.0%/21.1% vs. 56.0%/13.7% in UC (p>0.05), respectively. Conclusion In this real-world setting we could show that in CD the effectiveness of VEDO vs. other biologics was very similar in bio-naïve patients and that in UC patients, VEDO treatment tended to be numerically superior to other biologics with respect to response and steroid-free remission rates. Further follow-up data of this interim-analysis including the whole planned study population of 1.200 IBD-patients will be shown in the near future.

Understanding how arthropod pests and their natural enemies interact in complex agroecosystems is essential for pest management programmes. Theory predicts that prey sharing a predator, such as a biological control agent, can indirectly reduce each other's density at equilibrium (apparent competition). From this premise, we (i) discuss the complexity of indirect interactions among pests in agroecosystems and highlight the importance of natural enemy-mediated indirect interactions other than apparent competition, (ii) outline factors that affect the nature of enemy-mediated indirect interactions in the field and (iii) identify the way to manipulate enemy-mediated interactions for biological control. We argue that there is a need to increase the link between community ecology theory and biological control to develop better agroecological methods of crop protection via conservation biological control. In conclusion, we identify (i) interventions to be chosen depending on agroecosystem characteristics and (ii) several lines of research that will improve the potential for enemy-mediated indirect interactions to be applied to biological control.

The relationship between hypnotizability, personality style, and attachment was examined according to sex in 99 student participants. No specific differences for personality and hypnotizability were found in the highly hypnotizable participants according to sex. Similarly, no differences were found between high, medium, and low hypnotizable females, though differences were found among males. For males, the best predictor of hypnotizability was the unselfish/self-sacrificing personality style, which explained 40% of variance. This was in contrast to low hypnotizable males, who were less spontaneous/borderline, self-critical/avoidant, unselfish/self-sacrificing, but more assertive/antisocial. In comparison with females, low hypnotizable males were less intuitive/schizotypal and less loyal/dependent. Within the whole sample and among securely attached high hypnotizables, two peaks were observed for charming/histrionic and optimistic/rhapsodic styles, which suggests a "prone to hypnosis" personality style. Such people are optimistic and charming, and tend to be securely attached. This may suggest a high self-selection bias in hypnosis experiments and potentially creates confounds for the majority of such studies.

A tanulmany a kockazatnak es a kockazatok felmeresenek az eves beszamolok (penzugyi kimutatasok) konyvvizsgalatban betoltott szerepevel foglalkozik. A modern konyvvizsgalat – belső es kulső korlatainal fogva – nem letezhet a vizsgalt vallalkozas uzleti kockazatainak felmerese nelkul. Olyannyira igaz ez, hogy a szakma alapvető szabalyait lefektető nemzeti es nemzetkozi standardok is kotelező jelleggel előirjak az ugyfelek uzleti kockazatainak megismereset. Mindez nem oncelu tevekenyseg, hanem eppen ez jelenti a konyvvizsgalat kiindulo magjat: a kockazatbecsles – a tervezes reszekent – az audit vegrehajtasanak alapja, es egyben vezerfonala. A szerző előszor bemutatja a konyvvizsgalat es a kockazat kapcsolatanak alapvonasait, azt, hogy mikent jelenik meg egyaltalan a kockazat problemaja a konyvvizsgalatban. Ezt kovetően a kulonfele kockazatalapu megkozeliteseket targyalja, majd nehany főbb elem kiragadasaval abrazolja a kockazatkoncepcio beagyazodasat a szakmai szabalyozasba. Vegul – mintegy az elmelet tesztjekent – bemutatja a kockazatmodell gyakorlati alkalmazasanak nehany aspektusat. ______ The study examines the role of risk and the assessment of risks in the external audit of financial statements. A modern audit – due to its internal and external limitations – cannot exist without the assessment of the business risk of the entity being audited. This is not a l’art pour l’art activity but rather the very core of the audit. It is – as part of the planning of the audit – a guideline to the whole auditing process. This study has three main sections. The first one explains the connection between audit and risk, the second discusses the different risk based approaches to auditing and the embeddedness of the risk concept into professional regulation. Finally – as a test of theory – some practical aspects of the risk model are discussed through the lens of former empirical research carried out mostly in the US. The conclusion of the study is that though risk based models of auditing have many weaknesses they still result in the most effective and efficient high quality audits.

Introduction: The present investigation was based on a survey in 2005, in which the authors found pulmonary function abnormalities in survivors of childhood cancer, who were treated with anticancer therapy. Aim: The purpose of the present study was to follow-up childhood cancer survivors and detect late pulmonary toxicity. Patients and methods: Lung function test was performed with spirometry in 26 survivors participated in this study (10 females and 16 males; mean age, 19.4 years at the time of the second follow-up evaluation). The average time periods from treatment until the first and second follow-up evaluation were 4.5 and 10 years, respectively. Results: The authors found 14 patients with pathological pulmonary function tests results at the time of the first follow-up evaluation, from which 7 patients had obstructive, 5 patients had mixed and 2 patients had restrictive abnormalities. However, there were only 6 patients who had abnormal pulmonary function at the time of the second follow-up evaluation (2 patients with obstructive and 4 patients with restrictive pulmonary function tests (p

This study investigates whether data available at the time of residency application can be used to predict more accurately future problems of performance, both during and after residency.The authors identified all residents with reported problematic behavior across 20 years (1987-2007) at a single residency program and created a set of matched controls. Problems were further divided into "major" (leading to significant disruptions of performance and disciplinary action) and "minor" (remediable and resolved). Application materials were then reviewed for United States Medical Licensing Examination (USMLE) scores, evidence of academic failures, interviewer ratings, negative interviewer comments, negative comments in the dean's letter, and negative comments in letters of recommendation.The presence of any negative comments in the dean's letter yielded significant correlations with future problems. Further, those applicants with future major problems had significantly more negative comments in the dean's letter than did those with future minor problems. Other factors such as USMLE scores, failed courses, letters of recommendation, and interviewer ratings and comments did not predict future problems.Most of the factors the authors assessed in prospective applicants did not predict future problems, with the exception of negative (even mildly so) comments in the dean's letter. The authors suggest that more attention should be paid to the use of the dean's letter to assess risk among applicants, and prospective study of this assessment should be performed.

What makes the uniqueness of scientific achievements and what are the premises of an outstanding career? We used the bibliography and the citation analysis of the chief of the Department of Cardiothoracic Surgery of the Medical University of Vienna over a period of thirty years and matched them with potential influencing parameters including the research environment and analyzed them with significant qualities proposed by Toledo Pereira as CDFI (commitment, determination, focus and innovation). 698 items were found in a scientific citation index expanded search over this period. The number of citations above 50 was matched with the career of the first authors and related to the scientific environment of the individuals. Compared to other areas of scientific achievements cardiosurgical research of our department seems to be highly influential in certain areas especially in the analysis of surgical and pathophysiologic problems the application of innovative procedures setting standards in many important areas in cardiovascular disciplines. It can be speculated that cardiosurgical as well as translational research can be developed from a niche player into a successful international center of excellence during the era of one single leader.

A departmental history is mirrored by its members and their scientific and clinical output. In honour of Prof. Ernst Wolners retirement the authors were invited to summarize various aspects of basic and applied research performed at the Department of Cardiothoracic Surgery in Vienna within the last decade. This free communications suffices to present a short introduction of work performed by four independent laboratories headed by staff surgeons.

Background. Unhealthy nutritional habits are a major cause of morbidity and mortality in the US. Research indicates that regular physical activity can influence dietary habits of adults. Purpose. The purpose of this study was to examine whether university students’ involvement in healthy eating differed based on current exercise status and reported reasons for exercising. Methods. A sample of 204 university students completed a 22-item survey on healthy eating and physical activity. Results. Less than 10% met all Food Guide recommendations. The leading barriers to healthy eating were time, convenience and healthy food availability. Less than half exercised on four or more days each week. The leading reasons for exercising were to improve appearance, improve health and lose weight. Being physically active did not have a significant effect on healthy eating, nor did specific reason for exercising. Discussion. Most students did not eat healthy and their physical activity levels did not significantly affect their nutritional habits. Increased awareness campaigns are warranted. Conclusions. Strategies other than physical activity promotion are needed to positively impact students’ healthy eating behaviors. Students should continue to be educated about healthy nutrition and ways to reduce perceived barriers to healthy eating.

Background Recent reports on facilitated reperfusion therapy re-address interests in coronary sinus interventions (CSI). Patients in whom short time results have been reported earlier were re-evaluated, with the aim of gathering the long-term results of pressure-controlled intermittent coronary sinus occlusion (PICSO) generated in patients with acute myocardial infarction (MI) and revascularization. Methods and Results Thirty-four patients with ST elevated MI, in whom complete revascularization was achieved, underwent primary thrombolysis with or without PICSO. Follow-up data from these patients were collected for at least 48 months. Immediate perioperative differences were observed for time to peak creatine kinase (CK), as well as cumulative CK. In addition, the time until reperfusion was considerably less than for the control group (p=0.014). Long-term data showed significant differences in reinfarction (p=0.015), as well as in major adverse cardiovascular events, between the 2 groups (p

This article critiques two studies conducted by Jacobson and colleagues whose findings indicated that hypnosis hinders encoding and might not be useful in education. While their findings provide important information about hypnosis and its possible uses in teaching and learning, there are several important methodological and interpretive shortcomings that limit the applicability of the study. It is argued that the authors conflated some components of hypnotic phenomenology, as measured by the Phenomenology of Consciousness Inventory, and consequently failed to assess the hypnotic experience properly. This article argues that the encoding deficits produced by hypnosis may have resulted from the way hypnosis was used and other contextual factors, and highlights some additional concerns with the statistical analyses. This article suggests some more effective uses of hypnosis and suggestion in improving the learning process in light of prior research, and offers some ideas for future research.

This article is an exploratory study investigating the relationship between hypnotizability, personality style, and attachment. Data were collected from 99 students by means of the Harvard Group Scale of Hypnotic Susceptibility, Form A; Personality Styles and Disorders Inventory; and Relationship Scale Questionnaire. Results suggest that individual personality styles accounted for a significant amount of variance in hypnotizability in: (a) the whole sample, (b) the securely attached, and (c) the insecurely attached. High hypnotizables among both the whole sample and securely attached individuals shared the unselfish/self-sacrificing personality style as a main predictor of hypnotizability and displayed elevated scores for the charming/histrionic and the optimistic/rhapsodic personality style. Furthermore, two groups were identified among the high hypnotizables that differed mainly according to attachment style: one consists of securely attached, charming/histrionic, and optimistic/rhapsodic people, who are best described by socio-cognitive theories. The other is composed of insecurely attached intuitive/schizotypal people, who are better depicted by dissociation theories.

Tristearin implants containing polyethylene glycol 6000 (PEG) were shown to be a promising platform for the delivery of pharmaceutical proteins for periods up to 1 month. The objective of this study was to investigate the storage stability of the lipid devices, as long-term storage stability ensuring acceptable shelf-life can be considered the most important parameter for commercially viable sustained-release dosage forms. Rh-Interferon alpha-2a was stabilized by a lyophilization process using either trehalose or hydroxypropyl-beta-cyclodextrin as stabilizer. Tristearin implants containing the lyophilized protein material and 10% PEG were stored over 3 months and 6 months, both at 4 degrees C and room temperature, before release studies were initiated. Data from stored implants demonstrated trehalose not to be effective to provide full protein stabilization during long-term storage of the lipid matrices, this was apparent from both the reduced total drug level liberated and the release of aggregated specimen compared to the situation immediately after implant manufacture. In contrast, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) exhibited a high potential for protein stabilization within the matrices during both storage and release. Generally, 95% of the incorporated protein was delivered continuously within 1 month in monomeric form, even after 6 months' storage of the implants at room temperature.

The change in hospital funding with diagnosis related groups (DRG), medical advances as well as demographic changes will call for new quantitative and qualitative standards imposed on German hospitals. Increasing costs and competition in the health care sector requires new and innovative strategies for resource management. Today's policy is mainly defined by rationing and intensified workload. The introduction of DRGs will presumably further constrict management perspectives on pure financial aspects. However, to ensure future development, compassionate services and continued existence of hospitals, a balance of seemingly conflicting perspectives, such as finance, customer, process, learning and growth are of utmost importance. Herein doctors and nurses in leading positions should play a key role in changing management practice. For several years the balanced scorecard has been successfully used as a strategic management concept in non-profit organizations, even in the health care sector. This concept complies with the multidimensional purposes of hospitals and focuses on policy deployment. Finally it gives the opportunity to involve all employees in the original development, communication and execution of a balanced scorecard approach.

Despite advances in primary percutaneous interventions (PPCI), management of microvascular obstructions in reperfused myocardial tissue remains challenging and is a high-risk procedure. This has led to renewed interest in the coronary venous system as an alternative route of access to the myocardium. This article reviews historical data describing therapeutic options via cardiac veins as well as discussing the clinical potential and limitations of a catheter intervention: pressure controlled intermittent coronary sinus occlusion (PICSO). Collected experimental and clinical information suggest that PICSO also offers the potential for tissue regeneration beyond myocardial salvage. A meta-analysis of observer controlled pICSO application in animal studies showed a dose dependent reduction in infarct size of 29.3% (p < 0.001). Additionally, a 4-fold increase of hemeoxygenase-1 gene expression (p < 0.001) in the center of infarction and a 2.5 fold increase of vascular endothelial growth factor (VEGF) (p < 0.002) in border zones suggest that molecular pathways are initiating structural maintenance. Early clinical evidence confirmed significant salvage and event free survival in patients with acute myocardial infarction and risk reduction for event free survival 5 years after the acute event (p < 0.0001). This experimental and clinical evidence was recently corroborated using modern PICSO technology in PPCI showing a significant reduction of infarct size, when compared to matched controls (p < 0.04). PICSO enhances redistribution of flow towards deprived zones, clearing microvascular obstruction and leading to myocardial protection. Beyond salvage, augmentation of molecular regenerative networks suggests a second mechanism of PICSO involving the activation of vascular cells in cardiac veins, thus enhancing structural integrity and recovery.

Further developments of antibacterial coatings based on photocatalytic nanomaterials could be a promising route towards potential environmentally friendly applications in households, public buildings and health care facilities. Hereby we describe a simple chemical approach to synthesize photocatalytic nanomaterial-embedded coatings using gypsum as a binder. Various types of TiO2 nanofiber-based photocatalytic materials (nitrogen-doped and/or palladium nanoparticle decorated) and their composites with gypsum were characterized by means of scanning (SEM) and transmission (TEM) electron microscopy as well as electron and X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDX) techniques. These gypsum-based composites can be directly applied as commercially available paints on indoor walls. Herein we report that surfaces coated with photocatalytic composites exhibit excellent antimicrobial properties by killing both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) under blue light. In the case of MSSA cells, the palladium nanoparticle-decorated and nitrogen-doped TiO2 composites demonstrated the highest antimicrobial activity. For the MRSA strain even pure gypsum samples were proven to be efficient in eradicating Gram-positive human pathogens. The cytotoxicity of freestanding TiO2 nanofibers was revealed by analyzing the viability of HeLa cells using MTT and fluorescent cell assays.

Werner Mohl and coauthors present their Viewpoint examining pressure-controlled intermittent coronary sinus occlusion (PICSO). Here they postulate that PICSO should be introduced into the clinic as a valuable technique for activation of venous endothelium to initiate myocardial recovery and induce regeneration.