Impact of Coronavirus Disease 2019 (COVID-19) Pandemic on Surgical Site Infection in Patients with Inflammatory Bowel Disease-A Monocentric, Retrospective Cohort Study.

(1) Background: Surgical site infections (SSIs) are a relevant problem with a 25% incidence rate after elective laparotomy due to inflammatory bowel disease (IBD). The aim of this study was to evaluate whether stricter hygienic measures during the COVID-19 pandemic influenced the rate of SSI. (2) Methods: This is a monocentric, retrospective cohort study comparing the rate of SSI in patients with bowel resection due to IBD during COVID-19 (1 March 2020-15 December 2021) to a cohort pre-COVID-19 (1 February 2015-25 May 2018). (3) Results: The rate of SSI in IBD patients with bowel resection was 25.8% during the COVID-19 pandemic compared to 31.8% pre-COVID-19 (OR 0.94; 95% CI 0.40-2.20; p = 0.881). There were seventeen (17.5%) superficial and four (4.1%) deep incisional and organ/space SSIs, respectively, during the COVID-19 pandemic (p = 0.216). There were more postoperative intra-abdominal abscesses during COVID-19 (7.2% vs. 0.9%; p = 0.021). The strictness of hygienic measures (mild, medium, strict) had no influence on the rate of SSI (p = 0.553). (4) Conclusions: Hygienic regulations in hospitals during COVID-19 did not significantly reduce the rate of SSI in patients with bowel resection due to IBD. A ban on surgery, whereby only emergency surgery was allowed, was likely to delay surgery and exacerbate the disease, which probably contributed to more SSIs and postoperative complications.

CT-guided High-Dose-Rate Brachytherapy versus Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma.

Background CT-guided high-dose-rate (HDR) brachytherapy (hereafter, HDR brachytherapy) has been shown to be safe and effective for patients with unresectable hepatocellular carcinoma (HCC), but studies comparing this therapy with other local-regional therapies are scarce. Purpose To compare patient outcomes of HDR brachytherapy and transarterial chemoembolization (TACE) in patients with unresectable HCC. Materials and Methods This multi-institutional retrospective study included consecutive treatment-naive adult patients with unresectable HCC who underwent either HDR brachytherapy or TACE between January 2010 and December 2022. Overall survival (OS) and progression-free survival (PFS) were compared between patients matched for clinical and tumor characteristics by propensity score matching. Not all patients who underwent TACE had PFS available; thus, a different set of patients was used for PFS and OS analysis for this treatment. Hazard ratios (HRs) were calculated from Kaplan-Meier survival curves. Results After propensity matching, 150 patients who underwent HDR brachytherapy (median age, 71 years [IQR, 63-77 years]; 117 males) and 150 patients who underwent TACE (OS analysis median age, 70 years [IQR, 63-77 years]; 119 male; PFS analysis median age, 68 years [IQR: 63-76 years]; 119 male) were analyzed. Hazard of death was higher in the TACE versus HDR brachytherapy group (HR, 4.04; P < .001). Median estimated PFS was 32.8 months (95% CI: 12.5, 58.7) in the HDR brachytherapy group and 11.6 months (95% CI: 4.9, 22.7) in the TACE group. Hazard of disease progression was higher in the TACE versus HDR brachytherapy group (HR, 2.23; P < .001). Conclusion In selected treatment-naive patients with unresectable HCC, treatment with CT-guided HDR brachytherapy led to improved OS and PFS compared with TACE. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Chapiro in this issue.

Patient perspective on task shifting from general practitioners to medical practice assistants - a quantitative survey in Germany.

INTRODUCTION: Various developments result in increasing workloads in general practices. New models of care and a restructuring of the division of tasks could provide relief. One approach is to extend the delegation of medical tasks from general practitioners (GPs) to medical practice assistants (MPAs). So far, there has been a lack of information about specific situations in which patients are willing to be treated exclusively by MPAs. METHODS: In three German federal states, patients who visited a general practice were surveyed exploratively and cross-sectionally with a self-designed, paper-based questionnaire. The data were analysed descriptively and multivariate. A mixed binary logistic regression model was calculated to account for cluster effects at practice level (random intercept model). The dependent variable was patients' acceptance of task delegation. RESULTS: A total of 1861 questionnaires from 61 general practices were included in the analysis. Regarding the current problem/request, a total of 30% of respondents could imagine being treated only by MPAs. Regarding theoretical reasons for consultation, more than half of the patients agreed to be treated by MPAs. According to the regression model, MPAs were preferred when patients were younger (10-year OR = 0.84, 95%-CI [0.75, 0.93]) or had a less complicated issue (OR = 0.44, 95%-CI [0.26, 0.8]). For four current problems/requests ("acute complaints" OR = 0.27, 95%-CI [0.17, 0.45], "routine health check" OR = 0.48, 95%-CI [0.3, 0.79], "new problem" OR = 0.13, 95%-CI [0.06, 0.28], "known problem" OR = 0.16, 95%-CI [0.1, 0.27]) patients prefer to be treated by GPs instead of MPAs. DISCUSSION: For the first time, statements could be made on patients' acceptance of task delegation in relation to current and theoretical reasons for treatment in general practices in Germany. The discrepancy in response behaviour on a theoretical and individual level could be explained by different contexts of questions and differences at practice level. Overall, patients seem to be open to increased delegation of medical tasks, depending on the reason for treatment. Selection and response biases should be considered in the interpretation. CONCLUSION: The results are not completely opposed to an extension of task delegation. Further interventional studies could provide information on the possible effects of expansion of delegable tasks.

Outcome and management of decompressive hemicraniectomy in malignant hemispheric stroke following cardiothoracic surgery.

Management of malignant hemispheric stroke (MHS) after cardiothoracic surgery (CTS) remains difficult as decision-making needs to consider severe cardiovascular comorbidities and complex coagulation management. The results of previous randomized controlled trials on decompressive surgery for MHS cannot be generally translated to this patient population and the expected outcome might be substantially worse. Here, we analyzed mortality and functional outcome in patients undergoing decompressive hemicraniectomy (DC) for MHS following CTS and assessed the impact of perioperative coagulation management on postoperative hemorrhagic and cardiovascular complications. All patients that underwent DC for MHS resulting as a complication of CTS between June 2012 and November 2021 were included in this observational cohort study. Outcome was determined according to the modified Rankin Scale (mRS) score at 1 and 3-6 months. Clinical and demographic data, anticoagulation management and postoperative hemorrhagic and thromboembolic complications were assessed. In order to evaluate a predictive association between clinical and radiological parameters and the outcome, we used a multivariate logistic regression analysis. Twenty-nine patients undergoing DC for MHS after CTS with a female-to-male ratio of 1:1.9 and a median age of 60 (IQR 49-64) years were identified out of 123 patients undergoing DC for MHS. Twenty-four patients (83%) received pre- or intraoperative substitution. At 30 days, the in-hospital mortality rate and neurological outcome corresponded to 31% and a median mRS of 5 (5-6), which remained stable at 3-6 months [Mortality: 42%, median mRS: 5 (4-6)]. Postoperatively, 15/29 patients (52%) experienced new hemorrhagic lesions and Bayesian logistic regression predicting mortality (mRS = 6) after imputing missing data demonstrated a significantly increased risk for mortality with longer aPPT (OR = 13.94, p = .038) and new or progressive hemorrhagic lesions after DC (OR = 3.03, p = .19). Notably, all but one hemorrhagic lesion occurred before discontinued anticoagulation and/or platelet inhibition was re-initiated. Despite perioperative discontinuation of anticoagulation and/or platelet inhibition, no coagulation-associated cardiovascular complications were noted. In conclusion, Cardiothoracic surgery patients suffering MHS will likely experience severe neurological disability after DC, which should remain a central aspect during counselling and decision-making. The complex coagulation situation after CTS, however, should not per se rule out the option of performing life-saving surgical decompression.

Racialised identity, racism and the mental health of children and adolescents.

As a social justice issue, it is suggested that racialised identity may represent a critical moderator in the association between racism and adverse mental health. We performed a meta-moderation analysis of studies on racialised identity, racism and adverse mental health in children and adolescents. We searched Pubmed, Web of Science, SocINDEX, PsychInfo, Medline, CINAHL and EBSCO Academic Search Ultimate for peer-reviewed articles published between January 2013 and December 2022. Nine studies, encompassing 2146 Black, Moroccan, Turkish, Indigenous, South Korean, Latinx and Multi-heritage children and adolescents between the ages of 7 and 16, were included, covering depressive symptoms, substance use, internalising symptoms and externalising symptoms. A random effect meta-analysis reported a medium size positive correlation of 0.26 (95% CI = 0.20-0.32) between racism and adverse mental health. A comparison between internalising and externalising symptoms revealed a smaller positive correlation of 0.25 (95% CI = 0.09-0.41) for internalising symptoms and a slightly larger positive correlation of 0.30 (95% CI = 0.19-0.41) for externalising symptoms. A small negative moderation of -0.07 (95% CI = -0.17 to 0.02) was found for racialised identity in the association between racism and internalising symptoms, whilst no moderation was found between racism and externalising symptoms. Overall, a negligible moderation of -0.02 (95% CI = -0.08-0.05) was found for racialised identity in the association of racism to adverse mental health. These findings suggest that the effect of racism on internalising symptoms is slightly stronger for children and adolescents with lower racialised identities and slightly weaker for those with higher racialised identities.

[Medical care in GP practices during the Covid-19 pandemic: A questionnaire-based survey among general practitioners and medical practice assistants asking for their opinion about changes, needs and burdens]. / Die hausärztliche Versorgung während der COVID-19-Pandemie: eine Fragebogenerhebung unter Hausärzt*innen und Medizinischen Fachangestellten zu ihrer Perspektive auf Veränderungen, Bedarfe und Belastungen.

INTRODUCTION: The coronavirus pandemic did not only result in changes in the provision and utilization of health care services in general practice but also in an increased workload for physicians and medical practice assistants. The VeCo practice study retrospectively explores the experiences of both professional groups two years after the start of the pandemic. METHODS: In March and April 2022, general practitioners and medical practice assistants in the three German federal states of Berlin, Brandenburg and Thuringia were asked to complete a paper-based questionnaire. RESULTS: 657 general practitioners and 762 medical practice assistants completed the questionnaire. Both professional groups agreed to statements indicating a reduction in regular health care provisions. Nevertheless, 74% of the physicians and 82.9% of the medical practice assistants considered the health care provided to their patients during the pandemic as good. This was only possible through considerable additional effort and stress. While more than half of both groups reported that work was still enjoyable, three quarters of both groups stated that the challenges arising from the pandemic outstripped their capacity. Both groups would like to receive more recognition from society (medical practice assistants 93.2%, general practitioners 85.3%) and from their patients (87.7% and 69.9%, respectively). DISCUSSION: General practitioners and medical practice assistants reduced regular health care provision but were still able to maintain a good quality of care for their patients during the pandemic. It became clear that more appreciation and adequate financial compensation are necessary to ensure long-term sustainability of GP care. CONCLUSION: The subjective view of general practitioners and medical practice assistants on their health care provision shows that appreciation and adequate financial renumeration, particularly when working under most difficult conditions, are necessary to increase the attractiveness of a career in general practice, for both physicians and medical practice assistants.

Simultaneous [18F]fluoride and gadobutrol enhanced coronary positron emission tomography/magnetic resonance imaging for in vivo plaque characterization.

AIMS: 18F-sodium fluoride ([18F]fluoride) and gadobutrol are promising probes for positron emission tomography (PET) and magnetic resonance imaging (MRI) characterizing coronary artery disease (CAD) activity. Unlike [18F]fluoride-PET/computed tomography (CT), the potential of PET/MR using [18F]fluoride and gadobutrol simultaneously, has so far not been evaluated. This study assessed feasibility and diagnostic potential of [18F]fluoride and gadobutrol enhanced dual-probe PET/MR in patients with CAD. METHODS AND RESULTS: Twenty-one patients (age, 66.7 ± 6.7 years) with CAD scheduled for invasive coronary angiography (XCA) underwent simultaneous [18F]fluoride (mean activity/effective dose: 157.2 ± 29.7 MBq/3.77 ± 0.72 mSv) and gadobutrol enhanced PET/MR on an integrated PET/MRI (3 T) scanner. Optical coherence tomography (OCT) was used as reference. Target-to-background ratio (TBR, [18F]fluoride-PET) and contrast-to-noise ratio (CNR) values (MRI, gadobutrol) were calculated for each coronary segment. Previously suggested PET/CT-TBR thresholds for adverse coronary events were evaluated. High-risk plaques, i.e. calcified and non-calcified thin-cap fibroatheromas (TCFAs) were predominantly located in segments with a TBR >1.28 (P = 0.012). Plaques containing a lipid core on OCT, were more frequently detected in segments with a TBR >1.25 (P < 0.001). TBR values significantly correlated with maximum calcification thickness (P = 0.009), while fibrous cap thickness was significantly less in segments with a TBR >1.28 (P = 0.044). Above a TBR threshold of >1.28, CNR values significantly correlated with the presence of calcified TCFAs (P = 0.032). CONCLUSION: Simultaneous [18F]fluoride and gadobutrol dual-probe PET/MRI is feasible in clinical practice and may facilitate the identification of high-risk patients. The combination of coronary MR-derived CNR values post gadobutrol and [18F]fluoride based TBR values may improve identification of high-risk plaque features.

Mechanisms of exposure and response prevention in obsessive-compulsive disorder: effects of habituation and expectancy violation on short-term outcome in cognitive behavioral therapy.

BACKGROUND: Exposure and response prevention is effective and recommended as the first choice for treating obsessive-compulsive disorders (OCD). Its mechanisms of action are rarely studied, but two major theories make distinct assumptions: while the emotional processing theory assumes that treatment effects are associated with habituation within and between exposure sessions, the inhibitory learning approach highlights the acquisition of additional associations, implying alternative mechanisms like expectancy violation. The present study aimed to investigate whether process variables derived from both theories predict short-term outcome. METHOD: In a university outpatient unit, 110 patients (63 female) with OCD received manual-based cognitive-behavioral therapy with high standardization of the first two exposure sessions. Specifically, therapists repeated the first exposure session identically and assessed subjective units of distress as well as expectancy ratings in the course of exposure sessions. Based on these data, individual scores for habituation and distress-related expectancy violation were calculated and used for prediction of both percentage change on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and remission status after 20 therapy sessions. RESULTS: In a multiple regression model for percentage change, within-session habituation during the first exposure was a significant predictor, while in a logistic regression predicting remission status, distress-related expectancy violation during the first exposure revealed significance. A path model further supported these findings. CONCLUSIONS: The results represent first evidence for distress-related expectancy violation and confirm preliminary findings for habituation, suggesting that both processes contribute to treatment benefits of exposure in OCD, and both mechanisms appear to be independent.

Partial Measurement Invariance: Extending and Evaluating the Cluster Approach for Identifying Anchor Items.

When measurement invariance does not hold, researchers aim for partial measurement invariance by identifying anchor items that are assumed to be measurement invariant. In this paper, we build on Bechger and Maris's approach for identification of anchor items. Instead of identifying differential item functioning (DIF)-free items, they propose to identify different sets of items that are invariant in item parameters within the same item set. We extend their approach by an additional step in order to allow for identification of homogeneously functioning item sets. We evaluate the performance of the extended cluster approach under various conditions and compare its performance to that of previous approaches, that are the equal-mean difficulty (EMD) approach and the iterative forward approach. We show that the EMD and the iterative forward approaches perform well in conditions with balanced DIF or when DIF is small. In conditions with large and unbalanced DIF, they fail to recover the true group mean differences. With appropriate threshold settings, the cluster approach identified a cluster that resulted in unbiased mean difference estimates in all conditions. Compared to previous approaches, the cluster approach allows for a variety of different assumptions as well as for depicting the uncertainty in the results that stem from the choice of the assumption. Using a real data set, we illustrate how the assumptions of the previous approaches may be incorporated in the cluster approach and how the chosen assumption impacts the results.

Clinical Utility of the 6-Item CTS, Boston-CTS, and Hand-Diagram for Carpal Tunnel Syndrome.

Background: Self-reported measures are often used in research and clinical practice to diagnose carpal tunnel syndrome (CTS) and guide therapeutic choices. We aimed to assess the clinical utility of the Norwegian versions of two self-reported outcome measures for symptom severity assessment, the 6-item CTS (CTS-6), and Boston-CTS (BCTQ), and of one diagnostic measure, the hand-diagram, by evaluating measurement properties including discriminative ability for severity assessment (CTS-6, BCTQ), and diagnosis of CTS (hand-diagram). Methods: We performed forward and backward translation and cultural adaptation of the Norwegian CTS-6 and BCTQ. Following COSMIN guidelines, we investigated internal consistency, reliability, construct validity, and discriminative ability for distinguishing between severity levels of CTS in patients with confirmed CTS for the CTS-6 and BCTQ and reliability and discriminative ability for diagnosing CTS for the hand-diagram. Results: Two hundred and fifty-one patients referred for diagnostic work-up for CTS with nerve conduction studies (NCS) participated. The CTS-6 and BCTQ had acceptable internal consistency (Crohnbach's α = 0.82 and 0.86, respectively), reliability (ICC = 0.86 and 0.90; SEM = 0.24 and 0.20; SDC95% = 0.68 and 0.55, respectively), construct validity (all eight pre-defined hypotheses confirmed) and discriminative ability to distinguish between severity levels of CTS [Area under the curve (AUC) = 0.75, 95% CI 0.64-0.85]. The hand-diagram had acceptable reliability (Cohen's kappa = 0.69) and discriminative ability to diagnose CTS (sensitivity = 0.72, specificity = 0.90). Conclusion: Our findings support the clinical utility of the CTS-6 and BCTQ for symptom severity assessment and of the hand-diagram for diagnostic screening.

Comparison of diagnostic value of 68 Ga-DOTATOC PET/MRI and standalone MRI for the detection of intracranial meningiomas.

To evaluate the diagnostic performance of magnetic resonance imaging (MRI) alone in comparison to positron emission tomography/ magnetic resonance imaging (PET/MRI) in patients with meningiomas. 57 patients with a total of 112 meningiomas of the brain were included. PET/MRI, including a fully diagnostic contrast enhanced MRI and PET, were acquired. PET/MRI was used as reference standard. The size and location of meningiomas was recorded. Likelihood-ratio chi-square tests were used to calculate p-values within logistic regression in order to compare different models. A multi-level logistic regression was applied to comply the hierarchical data structure. Multi-level regression adjusts for clustering in data was performed. The majority (n = 103) of meningiomas could be identified based on standard MRI sequences compared to PET/MRI. MRI alone achieved a sensitivity of 95% (95% CI 0.78, 0.99) and specificity of 88% (95% CI 0.58, 0.98). Based on intensity of contrast medium uptake, 97 meningiomas could be diagnosed with intense uptake (93.75%). Sensitivity was lowest with 74% for meningiomas < 0.5 cm3, high with 95% for meningiomas > 2cm3 and highest with 100% for meningiomas 0.5-1.0 cm3. Petroclival meningiomas showed lowest sensitivity with 88% compared to sphenoidal meningiomas with 94% and orbital meningiomas with 100%. Specificity of meningioma diagnostic with MRI was high with 100% for sphenoidal and hemispherical-dural meningiomas and meningiomas with 0.5-1.0 and 1.0-2.0 cm3. Overall MRI enables reliable detection of meningiomas compared to PET/MRI. PET/MRI imaging offers highest sensitivity and specificity for small or difficult located meningiomas.

Assessment of the hepatic tumor extracellular matrix using elastin-specific molecular magnetic resonance imaging in an experimental rabbit cancer model.

To investigate the imaging performance of an elastin-specific molecular magnetic resonance imaging (MRI) probe with respect to the extracellular matrix (ECM) in an experimental hepatic cancer model. Twelve rabbits with hepatic VX2 tumors were examined using 3 T MRI 14, 21, and 28 days after tumor implantation for two subsequent days (gadobutrol, day 1; elastin-specific probe, day 2). The relative enhancement (RE) of segmented tumor regions (central and margin) and the peritumoral matrix was calculated using pre-contrast and delayed-phase T1w sequences. MRI measurements were correlated to histopathology and element-specific and spatially resolved mass spectrometry (MS). Mixed-model analysis was performed to assess the performance of the elastin-specific probe. In comparison to gadobutrol, the elastin probe showed significantly stronger RE, which was pronounced in the tumor margin (day 14-28: P ≤ 0.007). In addition, the elastin probe was superior in discriminating between tumor regions (χ2(4) = 65.87; P < 0.001). MRI-based measurements of the elastin probe significantly correlated with the ex vivo elastinstain (R = .84; P <0 .001) and absolute gadolinium concentrations (ICP-MS: R = .73, P <0 .01). LA-ICP-MS imaging confirmed the colocalization of the elastin-specific probe with elastic fibers. Elastin-specific molecular MRI is superior to non-specific gadolinium-based contrast agents in imaging the ECM of hepatic tumors and the peritumoral tissue.

Photoisomerization Neutralizes Vasoconstrictive Activity of a Heme Degradation Product.

Delayed cerebral ischemia (DCI) caused by cerebral vasospasm is the leading determinant of poor outcome and mortality in subarachnoid hemorrhage (SAH) patients, but current treatment options lack effective prevention and therapy. Two substance families of heme degradation products (HDPs), bilirubin oxidation end products (BOXes) and propentdyopents (PDPs), are elicitors of pathologic cerebral hypoperfusion after SAH. Z-configured HDPs can be photoconverted into the corresponding E-isomers. We hypothesize that photoconversion is a detoxification mechanism to prevent and treat DCI. We irradiated purified Z-BOXes and Z-PDPs with UV/Vis light and documented the Z-E photoconversion. E-BOX A slowly reisomerizes to the thermodynamically favored Z-configuration in protein-containing media. In contrast to vasoconstrictive Z-BOX A, E-BOX A does not cause vasoconstriction in cerebral arterioles in vitro and in vivo in wild-type mice. Our results enable a critical assessment of light-induced intrathecal photoconversion and suggest the use of phototherapy to prevent and cure HDP-mediated cerebral vasospasms.

Pyrrolic and Dipyrrolic Chlorophyll Degradation Products in Plants and Herbivores.

The degradation of chlorophyll, the omnipresent green pigment, has been investigated intensively over the last 30 years resulting in many elucidated tetrapyrrolic degradation products. With a comparison to the degradation of the structurally similar heme, we hereby propose a novel additional chlorophyll degradation mechanism to mono- and dipyrrolic products. This is the first proof of the occurrence of a family of mono- and dipyrrols in leaves that are previously only known as heme degradation products. This product family is also found in spit and feces of herbivores with specific metabolomic patterns reflecting the origin of the samples. Based on chromatographic and mass spectrometric evidence as well as on mechanistic considerations we also suggest several tentative new degradation products. One of them, dihydro BOX A, was fully confirmed as a novel natural product by synthesis and comparison of its spectroscopic data.

Impact of technical variations on the ring-finger test for carpal tunnel syndrome.

OBJECTIVE: To assess if recording the sensory latencies of the median and ulnar nerves one-by-one (consecutive) or at the same time (simultaneous) in the ring-finger test for carpal tunnel syndrome (CTS) will show equivalent results or if it will lead to a different clinical classification of patients. METHODS: We assessed the limits of agreement between the simultaneous and the consecutive method based on the median- ulnar sensory latency difference derived by both methods in 80 subjects and compared the number of minimal CTS cases identified by the two methods. RESULTS: Limits of agreement ranged from -0.23 to 0.29 ms. A significantly higher proportion of subjects with minimal CTS (only detectable by using the comparison test) was found using the simultaneous method (n = 8 and 2, respectively; p = 0.03). CONCLUSION: The two methods have a poor to moderate agreement as indicated by the range of the limits of agreement (0.5 ms). SIGNIFICANCE: Even small methodological changes to the ring-finger test can lead to results with different clinical meaning in the same individual and one should be aware of which method was used when interpreting results.

Total syntheses of the bilirubin oxidation end product Z-BOX C and its isomeric form Z-BOX D.

Oxidative degradation products of bilirubin (BOXes) are biologically highly active and certain BOXes cause long-lasting narrowing of cerebral blood vessels presumably with a significant role in subarachnoid hemorrhage. Due to the fact that mode of action as well as fate of these BOXes is widely unknown, larger amounts of these bilirubin degradation end products are required. The total synthesis of colorless (Z)-3-(5-(2-amino-2-oxoethylidene)-4-methyl-2-oxo-2,5-dihydro-1H-pyrrol-3-yl)propanoic acid (BOX C) succeeds via a seven-step procedure with a total yield of 20%. Its isomeric form (Z)-3-(2-(2-amino-2-oxoethylidene)-4-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl)propanoic acid (BOX D) can be prepared via a five-step protocol with a yield of 30%. NMR and crystallographic studies reveal that charge delocalization within the conjugated π-systems of BOXes C and D is negligible. Exposure of solutions of Z-BOX C and Z-BOX D to bright sunlight leads to Z/E-isomerization and mixtures of the respective E/Z-BOXes C and D.

Comparative organizational research starts with sound measurement: Validity and invariance of Turker's corporate social responsibility scale in five cross-cultural samples.

As organizational research turned its focus to Corporate Social Responsibility (CSR), interest also grew in the individual's perspective on CSR. When looking for cross-cultural comparisons of the effects of CSR, measurement invariance is of utter importance as a questionnaire might not be equivalent in all investigated samples and thus bias results. We examined a previously published questionnaire assessing different aspects of personal CSR ratings. Factorial validity and measurement invariance was tested by means of confirmatory factor analysis and Bayesian structural equation modeling in five samples (total N = 1120): 2 US-American, 2 German, and 1 English-speaking Indian sample. In an exploratory-confirmatory approach, the originally proposed factor structure was altered to finally comprise four facets of CSR: employee-related CSR, environmental CSR, philanthropy and customer-related CSR. Measurement invariance tests showed evidence for small differences of the English and German version as well as significant divergences of the measurement model in the Indian sample. In conclusion, we show the validity of the questionnaire for a circumscribed Western context but are hesitant about further transfers. Future research on perception of CSR in non-western contexts might depend on new and tailored questionnaires.

Positive organizational behavior: Longitudinal effects on subjective well-being.

Increasing individual subjective well-being has various positive outcomes, knowledge about its antecedents and the mediators of this relationship can therefore help to increase subjective well-being and the accompanying positive effects. The more future oriented facets of psychological capital, i.e. optimism, hope and self-efficacy have been shown in several studies to be positively related to subjective well-being and negatively to ill-being. Furthermore, recent studies suggest coping strategies as mediators for these relationships. In our study, we examined the longitudinal relation of optimism, hope and self-efficacy with subjective well-being and ill-being in a German panel dataset and tested the mediating effect of flexible goal adjustment in a path model. Our results show a statistically significant positive effect of self-efficacy and optimism on subjective well-being as well as a statistically significant negative effect of optimism on depression over three years. All three predictors show a statistically significant relation with flexible goal adjustment, but flexible goal adjustment did not mediate the effect on subjective well-being or depression.

Getting it just right: A reevaluation of OCD symptom dimensions integrating traditional and Bayesian approaches.

Previous research using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) suggests that the heterogeneous symptoms of obsessive-compulsive disorder (OCD) may reflect four underlying dimensions. However, past results vary substantially, which may be due to (a) the reliance on aggregated scores, (b) the common use of exploratory factor analyses, and (c) the exclusion of several symptoms. The present study tested the homogeneity of the original Y-BOCS categories using confirmatory factor analysis and modified categories where necessary. To test multidimensional models, data were further analyzed with Bayesian structural equation models, which better capture item heterogeneity in contrast to ordinary factor analysis. All analyses were run with two samples of patients with OCD allowing for cross-validation. Only a minority of the original Y-BOCS categories proved to be homogeneous. Modification yielded 10 homogeneous first-order factors, which can be reduced to four second-order factors: Incompleteness, Taboo Thoughts, Responsibility, and Contamination. This two-level factor model outperformed competing factor structures. The results corroborate the notion of four broader symptom dimensions in OCD, although the specific factor structure deviates from previous research. Differences presumably derive from using the full range of OCD symptoms and the combined exploratory and confirmatory approach with BSEM as a theoretically more appropriate analytical framework.

Anti-tumor effects of fibroblast growth factor-binding protein (FGF-BP) knockdown in colon carcinoma.

BACKGROUND: Fibroblast growth factors FGF-1 and FGF-2 are often upregulated in tumors, but tightly bound to heparan sulphate proteoglycans of the extracellular matrix (ECM). One mechanism of their bioactivation relies on the FGF-binding protein (FGF-BP) which, upon reversible binding to FGF-1 or -2, leads to their release from the ECM. FGF-BP increases tumorigenicity and is highly expressed in tumors like colon carcinoma. In this paper, we analyse cellular and molecular consequences of RNAi-mediated FGF-BP knockdown in colon carcinoma, and explore the therapeutic effects of the nanoparticle-mediated delivery of small interfering RNAs (siRNAs) for FGF-BP targeting. RESULTS: Employing stable RNAi cells, we establish a dose-dependence of cell proliferation on FGF-BP expression levels. Decreased proliferation is mirrored by alterations in cell cycle distribution and upregulation of p21, which is relevant for mediating FGF-BP effects. While inhibition of proliferation is mainly associated with reduced Akt and increased GSK3ß activation, antibody array-based analyses also reveal other alterations in MAPK signalling. Additionally, we demonstrate induction of apoptosis, mediated through caspase-3/7 activation, and alterations in redox status upon FGF-BP knockdown. These effects are based on the upregulation of Bad, Bax and HIF-1α, and the downregulation of catalase. In a therapeutic FGF-BP knockdown approach based on RNAi, we employ polymer-based nanoparticles for the in vivo delivery of siRNAs into established wildtype colon carcinoma xenografts. We show that the systemic treatment of mice leads to the inhibition of tumor growth based on FGF-BP knockdown. CONCLUSIONS: FGF-BP is integrated in a complex network of cytoprotective effects, and represents a promising therapeutic target for RNAi-based knockdown approaches.