Metabolism: flow and contractility of the Langendorff heart

This thesis reviews current literature and describes experimental studies on the regulation and modification of coronary flow and contractility in isolated rat hearts. In chapter I and introduction is given to the problems of fatty acid toxicity and myocardial function. Coronary flow rate and pump function of the myocardium are mainly determined by the contractile status of vascular smooth muscle cells and cardiac striated muscle cells, respectively. Therefore in chapters II and III morphological and (ultra)structural aspects of both types of cells have been described. In chapters IV and V functional and metabolic aspects of coronary circulation and contractility are illustrated. In both vascular smooth and cardiac striated muscle cells: (i) the intracellular calcium concentration is the main determinant of the contractile status of actomyosin, (ii) contraction takes place after the action potentialinduced calcium-influx through the plasmamembrane and calcium release from intracellular stores (sarcoplasmic reticulum, mitochondria), (iii) relaxation is achieved after reduction of the cytoplasmic calcium level by calcium-pump systems in the plasmamembrane, sarcoplasmic reticulum and mitochondria, (iv) calcium-ions trigger the coupling between the contraction-relaxation cycle with energy metabolism since glycogenolysis and lipolysis are both stimulated by calcium

Development and validation of a clinically applicable ARM use monitor for people after stroke

Objective: To develop and validate a clinically applicable and easy-to-use accelerometry-based device to measure arm use in people after stroke; the Ac-tiv8 arm use monitor (Activ8-AUM). Design: Development and validation study. Patients: A total of 25 people at different stages of rehabilitation after stroke were included in this study. Methods: The Activ8-AUM consists of 3 single-sensor Activ8s: one on the unaffected thigh and one on each wrist. Arm use was calculated by combining movement intensity of the arms with data from body posture and movements on the leg sensor. Data were divided into 2 sets: one for determining situation-specific movement intensity thresholds for arm use, and the other to validate the Activ8-AUM using video recordings. Results: Overall agreement between the Activ8-AUM and video recordings was 75%, sensitivity was 73% and specificity was 77%. Agreement between the different categories of arm use ranged from 42% to 93% for the affected arm and from 24% to 82% for the unaffected arm. Conclusion: By combining the movement intensity threshold with body posture and movements, good agreement was reached between the Activ8-AUM and video recordings. This result, together with the easy-to-use configuration, makes the Activ8-AUM a promising device to measure arm use in people after stroke

Minimal Model for Sand Dunes

We propose a minimal model for aeolian sand dunes. It combines an analytical description of the turbulent wind velocity field above the dune with a continuum saltation model that allows for saturation transients in the sand flux. The model provides a qualitative understanding of important features of real dunes, such as their longitudinal shape and aspect ratio, the formation of a slip face, the breaking of scale invariance, and the existence of a minimum dune size.Comment: 4 pages, 4 figures, replaced with publishd versio

Effectiveness of a Self-Management Intervention to Promote an Active Lifestyle in Persons With Long-Term Spinal Cord Injury: The HABITS Randomized Clinical Trial

Background. Most people with long-term spinal cord injury (SCI) have a very inactive lifestyle. Higher activity levels have been associated with health benefits and enhanced quality of life. Consequently, encouraging an active lifestyle is important and behavioral interventions are needed to establish durable lifestyle changes. Objective. The Healthy Active Behavioral Intervention in SCI (HABITS) study was aimed to evaluate the effectiveness of a structured self-management intervention to promote an active lifestyle in inactive persons with long-term SCI. Methods. This assessor-blinded randomized controlled trial was conducted at 4 specialized SCI units in the Netherlands. Sixty-four individuals with long-term SCI (>10 years), wheelchair-user and physically inactive, were included. Participants were randomized to either a 16-week self-management intervention consisting of group meetings and individual counseling and a book, or to a control group that only received information about active lifestyle by one group meeting and a book. Measurements were performed at baseline, 16 weeks, and 42 weeks. Primary outcome measures were self-reported physical activity and minutes per day spent in wheelchair driving. Secondary outcomes included perceived behavioral control (exercise self-efficacy, proactive coping), stages of change concerning exercise, and attitude toward exercise. Results. Mixed models analyses adjusted for age, sex, level of SCI, time since injury, baseline body mass index, and location did not show significant differences between the intervention and control groups on the primary and secondary outcomes (P ≥.05). Conclusions. A structured 16-week self-management intervention was not effective to change behavior toward a more active lifestyle and to improve perceived behavioral control, stages of change, and attitude

Effect of different operationalizations of sedentary behavior in people with chronic stroke

Purpose: Sedentary behavior is common in people with stroke and has devastating impact on their health. Quantifying it is important to provide people with stroke with adequate physical behavior recommendations. Sedentary behavior can be quantified in terms of posture (sitting) or intensity (low energy expenditure). We compared the effect of different operationalizations of sedentary behavior on sedentary behavior outcomes (total time; way of accumulation) in people with stroke. Methods: Sedentary behavior was analyzed in 44 people with chronic stroke with an activity monitor that measured both body postures and movement intensity. It was operationalized as: (1) combining postural and intensity data; (2) using only postural data; (3) using only intensity data. For each operationalization, we quantified a set of outcomes. Repeated measures ANOVA and Bland–Altman plots were used to compare the operationalizations. Results: All sedentary behavior outcomes differed significantly between all operationalizations (p < 0.01). Bland–Altman plots showed large limits of agreement for all outcomes, showing large individual differences between operationalizations. Conclusions: Although it was neither possible nor our aim to investigate the validity of the two-component definition of sedentary behavior, our study shows that the type of operationalization of sedentary behavior si

Endocrinologic disorders and optic pathway gliomas in children with neurofibromatosis type 1

Objective. To establish the prevalence of endocrinologic disorders in children with neurofibromatosis type 1 (NF1) and the relationship between these disorders and cerebral abnormalities on magnetic resonance imaging. Design. A prospective follow-up study. Setting. A multidisciplinary neurofibromatosis clinic. Patients. A total of 122 children diagnosed with NF1 according to diagnostic criteria set by the National Institutes of Health. Results. Central precocious puberty (CPP) was diagnosed in 3 children and growth hormone deficiency (GHD) in 3 children. Optic pathway gliomas were observed in 15 children; in 9 of the 15 cases, the optic chiasm was involved. Of the 3 children with CPP, only 1 showed a chiasma glioma on magnetic resonance imaging. In 1 case with GHD, an optic chiasm glioma was detected on neuroimaging. Two of the 9 children with an optic chiasm glioma presented with CPP or GHD. Conclusions. It has been suggested that CPP in children with NF1 is found exclusively in the presence of a chiasma glioma. We conclude that chiasma glioma may not be obligatory in children with NF1 and CPP or GHD. Moreover, we report a prevalence of GHD in children with NF1 of 2.5%, which has not been established earlier

Patients' and clinicians' preferences in adjuvant treatment for high-risk endometrial cancer:Implications for shared decision making

Background. Decision making regarding adjuvant therapy for high-risk endometrial cancer is complex. The aim of this study was to determine patients' and clinicians' minimally desired survival benefit to choose chemoradiotherapy over radiotherapy alone. Moreover, influencing factors and importance of positive and negative treatment effects (i.e. attribute) were investigated. Methods. Patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy and multidisciplinary gynaecologic oncology clinicians completed a trade-off questionnaire based on PORTEC-3 trial data. Results. In total, 171 patients and 63 clinicians completed the questionnaire. Median minimally desired benefit to make chemoradiotherapy worthwhile was significantly higher for patients versus clinicians (10% vs 5%, p = 0.02). Both patients and clinicians rated survival benefit most important during decision making, followed by long-term symptoms. Older patients (OR 0.92 [95%CI 0.87 & ndash;0.97]; p = 0.003) with comorbidity (OR 0.34 [95% CI 0.12 & ndash;0.89]; p = 0.035) had lower preference for chemoradiotherapy, while patients with better numeracy skills (OR 1.2 [95%CI 1.05 & ndash;1.36], p = 0.011) and chemoradiotherapy history (OR 25.0 [95%CI 8.8 & ndash;91.7]; p < 0.001) had higher preference for chemoradiotherapy. & nbsp;Conclusions. There is a considerable difference in minimally desired survival benefit of chemoradiotherapy in high-risk endometrial cancer among and between patients and clinicians. Overall, endometrial cancer patients needed higher benefits than clinicians before preferring chemoradiotherapy. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

Clinical impact of HLA class I expression in rectal cancer

Contains fulltext : 69499.pdf (publisher's version ) (Open Access)PURPOSE: To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas. EXPERIMENTAL DESIGN: Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10). RESULTS: Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with < or =50% of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression had no effect on cancer-specific survival or recurrence-free survival. CONCLUSIONS: Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors, having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates patient's prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed

EAES and SAGES 2018 consensus conference on acute diverticulitis management:evidence-based recommendations for clinical practice

Background Acute diverticulitis (AD) presents a unique diagnostic and therapeutic challenge for general surgeons. This collaborative project between EAES and SAGES aimed to summarize recent evidence and draw statements of recommendation to guide our members on comprehensive AD management. Methods Systematic reviews of the literature were conducted across six AD topics by an international steering group including experts from both societies. Topics encompassed the epidemiology, diagnosis, management of non-complicated and complicated AD as well as emergency and elective operative AD management. Consensus statements and recommendations were generated, and the quality of the evidence and recommendation strength rated with the GRADE system. Modified Delphi methodology was used to reach consensus among experts prior to surveying the EAES and SAGES membership on the recommendations and likelihood to impact their practice. Results were presented at both EAES and SAGES annual meetings with live re-voting carried out for recommendations with < 70% agreement. Results A total of 51 consensus statements and 41 recommendations across all six topics were agreed upon by the experts and submitted for members’ online voting. Based on 1004 complete surveys and over 300 live votes at the SAGES and EAES Diverticulitis Consensus Conference (DCC), consensus was achieved for 97.6% (40/41) of recommendations with 92% (38/41) agreement on the likelihood that these recommendations would change practice if not already applied. Areas of persistent disagreement included the selective use of imaging to guide AD diagnosis, recommendations against antibiotics in non-complicated AD, and routine colonic evaluation after resolution of non-complicated diverticulitis. Conclusion This joint EAES and SAGES consensus conference updates clinicians on the current evidence and provides a set of recommendations that can guide clinical AD management practice

The evolution of cyclodextrin glucanotransferase product specificity

Cyclodextrin glucanotransferases (CGTases) have attracted major interest from industry due to their unique capacity of forming large quantities of cyclic α-(1,4)-linked oligosaccharides (cyclodextrins) from starch. CGTases produce a mixture of cyclodextrins from starch consisting of 6 (α), 7 (β) and 8 (γ) glucose units. In an effort to identify the structural factors contributing to the evolutionary diversification of product specificity amongst this group of enzymes, we selected nine CGTases from both mesophilic, thermophilic and hyperthermophilic organisms for comparative product analysis. These enzymes displayed considerable variation regarding thermostability, initial rates, percentage of substrate conversion and ratio of α-, β- and γ-cyclodextrins formed from starch. Sequence comparison of these CGTases revealed that specific incorporation and/or substitution of amino acids at the substrate binding sites, during the evolutionary progression of these enzymes, resulted in diversification of cyclodextrin product specificity