Corrigendum: The quest for EEG power band correlation with ICA derived fMRI resting state networks

Contains fulltext : 136233.pdf (publisher's version ) (Open Access)[This corrects the article on p. 315 in vol. 7, PMID: 23805098.].2 p

Electrochemistry of potentially bioreductive alkylating quinones : Part 1. Electrochemical properties of relatively simple quinones, as model compounds of mitomycin- and aziridinylquinone-type antitumour agents

The influence of methyl-, hydroxy and amino substituents on the electrochemical behaviour of simple 1,4-naphtho-and 1,4-benzoquinones, model compounds of many quinoid antitumour agents, in aqueous media was studied. Significant changes in electrochemical behaviour were observed, potentially the result of a change in the electron density of the quinone moiety, pre- or post-protonation of substituents, hydrogen bond formation, tautomerization reactions and steric interactions between the quinone moiety and substituents. The information obtained was of benefit in the elucidation of the reduction mechanisms of quinoid antitumour agents such as aziridnylquinones and mitomycins

Head-to-head Comparison of Transrectal Ultrasound-guided Prostate Biopsy Versus Multiparametric Prostate Resonance Imaging with Subsequent Magnetic Resonance-guided Biopsy in Biopsy-naive Men with Elevated Prostate-specific Antigen: A Large Prospective Multicenter Clinical Study

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Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions A Prospective Multicenter Cohort Study (LIMERIC-Study)

Objective: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. Summary Background Data: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. Methods: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. Results: Of the 118 patients included (56% male, mean age 66 years, standard deviation +/- 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R-0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. Conclusions: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Genetic aspects and molecular testing in prostate cancer: a report from a Dutch multidisciplinary consensus meeting

Background: Germline and tumour genetic testing in prostate cancer (PCa) is becoming more broadly accepted, but testing indications and clinical consequences for carriers in each disease stage are not yet well defined.Objective: To determine the consensus of a Dutch multidisciplinary expert panel on the indication and application of germline and tumour genetic testing in PCa.Design, setting, and participants: The panel consisted of 39 specialists involved in PCa management. We used a modified Delphi method consisting of two voting rounds and a virtual consensus meeting.Outcome measurements and statistical analysis: Consensus was reached if >75% of the panellists chose the same option. Appropriateness was assessed by the RAND/UCLA appropriateness method.Results and limitations: Of the multiple-choice questions, 44% reached consensus. For men without PCa having a relevant family history (familial PCa/BRCA-related hered-itary cancer), follow-up by prostate-specific antigen was considered appropriate. For patients with low-risk localised PCa and a family history of PCa, active surveil-lance was considered appropriate, except in case of the patient being a BRCA2 germ -line pathogenic variant carrier. Germline and tumour genetic testing should not be done for nonmetastatic hormone-sensitive PCa in the absence of a relevant family history of cancer. Tumour genetic testing was deemed most appropriate for the identification of actionable variants, with uncertainty for germline testing. For tumour genetic testing in metastatic castration-resistant PCa, consensus was not reached for the timing and panel composition. The principal limitations are as fol-lows: (1) a number of topics discussed lack scientific evidence, and therefore the recommendations are partly opinion based, and (2) there was a small number of experts per discipline.Conclusions: The outcomes of this Dutch consensus meeting may provide further guidance on genetic counselling and molecular testing related to PCa.Patient summary: A group of Dutch specialists discussed the use of germline and tumour genetic testing in prostate cancer (PCa) patients, indication of these tests (which patients and when), and impact of these tests on the management and treatment of PCa.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).Experimentele farmacotherapi

The transcription factor myocyte enhancer factor-2 (MEF2) in cardiac hypertrophy and heart failure

The heart responds to stress signals by hypertrophic growth, which is the first step towards heart failure (HF). The genetic pattern underlying HF remains largely elusive. Although the transcription factor Myocyte Enhancer Factor-2 (MEF2) is known to be a common endpoint for several hypertrophic signaling pathways, its precise role in myocardial remodeling is unknown. To this end, we pursued comprehensive gain- and loss-of-function approaches for MEF2 transcriptional activity in heart muscle in vitro and in vivo. We generated transgenic mice overexpressing MEF2 in the heart, which resulted in HF. In line, adenoviral delivery of MEF2 to cultured cardiomyocytes induced myocyte elongation, myofibril degeneration, and redistribution of focal adhesions, as seen in failing hearts. We also generated mice expressing a dominant negative form of MEF2 and crossed these mice with calcineurin transgenic mice, a model for cardiac hypertrophy and heart failure. This did not prevent cardiac hypertrophy, but protected the mice from HF. To identify MEF2 target genes, we generated inducible stable cardiac cell lines, expressing the active form of MEF2, and performed microarray analysis. Functional clustering of MEF2 target genes revealed an overrepresentation of genes involved in cytoskeletal remodeling and cell-matrix adhesion. We describe myotonic dystrophy protein kinase (DMPK) as a direct transcriptional target for MEF2. By siRNA-mediated knockdown of DMPK expression, we demonstrate the involvement of this gene in the pathological aspects of MEF2 induced cardiomyocyte remodeling. Given the resemblance between MEF2 induced cardiac remodeling and the cardiac phenotype of mice lacking Muscle LIM Protein (MLP), an established mouse model for inherited dilated cardiomyopathy, we analyzed MEF2 transcription factor activity in MLP knockout mice by genetic crossbreeding with MEF2 reporter mice. Following confirmation that MEF2 activity was severely upregulated, we used conditional transgenesis to express a dominant-negative form of MEF2 (DNMEF2) in the murine MLP deficient heart and combined this with echocardiographic analysis to examine the effect on cardiac remodeling. Surprisingly, histological and functional analyses indicated that MEF2 inhibition in MLP knockout mice did not effect the genesis of dilated cardiomyopathy. Finally, the significance of MEF2 transcriptional activity was assessed in the setting of a more physiological model of biomechanical stress in the form of chronic murine pressure overload using conditional transgenesis to express a dominant-negative form of MEF2 (DNMEF2) in the postnatal heart. Surprisingly, echocardiography indicated that MEF2 inhibition did not improve end-diastolic and end-systolic ventricular dimensions and contractility as observed in calcineurin transgenic hearts with conditional MEF2 inhibition. In fact, cardiac function was significantly worsened in the setting of MEF2 inhibition, which could be correlated with specific defects in mitochondrial adaptation during pressure overload. Taken together, in this thesis we demonstrate that MEF2 activation in the heart does not evoke the classic hypertrophic response, yet promotes a gene program primarily involved in processes associated with dilated cardiomyopathy. Although MEF2 activation is required for maladaptive cardiac remodeling downstream of calcineurin signaling, its activity is not the sole trigger in certain forms of dilated cardiomyopathy, and is even necessary for the adaptive response of the heart during pressure overload

Blood-based and urinary prostate cancer biomarkers: a review and comparison of novel biomarkers for detection and treatment decisions

BACKGROUND: The diagnosis of prostate cancer (PCa) is currently based on serum PSA testing and/or abnormal digital rectal examination and histopathologic evaluation of prostate biopsies. The main drawback of PSA testing is the lack of specificity for PCa. To improve early detection of PCa more specific biomarkers are needed. In the past few years, many new promising biomarkers have been identified; however, to date, only a few have reached clinical practice. METHODS: In this review, we discuss new blood-based and urinary biomarker models that are promising for usage in PCa detection, follow-up and treatment decision-making. These include Prostate Health Index (PHI), prostate cancer antigen 3 (PCA3), four-kallikrein panel (4K), transmembrane protease serine 2-ERG (TMPRSS2-ERG), ExoDx Prostate Intelliscore, SelectMDx and the Mi-Prostate score. Only few head-to-head studies are available for these new fluid-based biomarkers and/or models. The blood-based PHI and urinary PCA3 are two US Food and Drug Administration-approved biomarkers for diagnosis of PCa. In the second part of this review, we give an overview of published studies comparing these two available biomarkers for prediction of (1) PCa upon prostate biopsy, (2) pathological features in radical prostatectomy specimen and (3) significant PCa in patients eligible for active surveillance. RESULTS: Studies show opposing results in comparison of PHI with PCA3 for prediction of PCa upon initial and repeat prostate biopsy. PHI and PCA3 are able to predict pathological findings on radical prostatectomy specimen, such as tumor volume and Gleason score. Only PHI could predict seminal vesicle invasion and only PCA3 could predict multifocality. There is some evidence that PHI outperforms PCA3 in predicting significant PCa in an active surveillance population. CONCLUSIONS: Future research should focus on independent validation of promising fluid-based biomarkers/models, and prospective comparison of biomarkers with each other

Preferences for first and last mile shared mobility between stops and activity locations: A case study of local public transport users in Utrecht, the Netherlands

Shared transport modes can potentially contribute to first and last mile connections of public transport (PT) trips but this remains quite underexplored in the literature. Our study explores the user preferences for shared modes as first and last mile option to connect activity locations. We have focussed on local public transport in the Utrecht province, The Netherlands, which includes bus and tram lines. Its diversity in land use and PT network density, the overall high bicycle usage, as well as the increased proliferation of shared mobility concepts yield promising information which can be a harbinger for future PT integration worldwide. For both the urban and suburban areas of the province, we have designed and conducted a stated choice experiment. Respondents were able to choose from shared bicycles, e-bikes, e-scooters, and e-mopeds to reach their urban destination from a PT stop. For suburban destinations, we also included light-electric vehicles (LEVs), e-cars, and demand-responsive taxi services. Such a complete list of possibilities to travel by shared modes allows comparing the different options and producing trade-offs not available yet in the literature. A sample of 499 respondents (285 urban and 214 suburban PT travellers) considered their first and last mile mode choice of a recent PT trip in light of the new options. Results show that shared (electric-)bicycles and e-scooters are generally preferred over other shared mobility options. The latter specifically targets younger people (<26 years) and travellers towards suburban destinations. Still, a majority of PT users prefers not to use shared modes in the first and last mile. We found that age, current cycling behaviour and weekday/weekend travelling are the most important factors which determine these preferences. We argue that shared bicycles and e-bikes are the most capable modes in providing benefits to PT travellers in this context and, given the relatively low travel time sensitivity, can best be distributed around the most important PT stops.Transport and Plannin