Recommendations for a Dutch Sustainable Biobanking Environment

Biobanks and their collections are considered essential for contemporary biomedical research and a critical resource toward personalized medicine. However, they need to operate in a sustainable manner to prevent research waste and maximize impact. Sustainability is the capacity of a biobank to remain operative, effective, and competitive over its expected lifetime. This remains a challenge given a biobank's position at the interplay of ethical, societal, scientific, and commercial values and the difficulties in finding continuous funding. In the end, biobanks are responsible for their own sustainability. Still, biobanks also depend on their surrounding environment, which contains overarching legislative, policy, financial, and other factors that can either impede or promote sustainability. The Biobanking and Biomolecular Research Infrastructure for The Netherlands (BBMRI.nl) has worked on improving the national environment for sustainable biobanking. In this article, we present the final outcomes of this BBMRI.nl project. First, we summarize the current overarching challenges of the Dutch biobanking landscape. These challenges were gathered during workshops and focus groups with Dutch biobanks and their users, for which the full results are described in separate reports. The main overarching challenges relate to sample and data quality, funding, use and reuse, findability and accessibility, and the general image of biobanks. Second, we propose a package of recommendations—across nine themes—toward creating overarching conditions that stimulate and enable sustainable biobanking. These recommendations serve as a guideline for the Dutch biobanking community and their stakeholders to jointly work toward practical implementation and a better biobanking environment. There are undoubtedly parallels between the Dutch situation and the challenges found in other countries. We hope that sharing our project's approach, outcomes, and recommendations will support other countries in their efforts toward sustainable biobanking

An Inquiry into the Practice of Proving in Low-Dimensional Topology

The aim of this article is to investigate specific aspects connected with visualization in the practice of a mathematical subfield: low-dimensional topology. Through a case study, it will be established that visualization can play an epistemic role. The background assumption is that the consideration of the actual practice of mathematics is relevant to address epistemological issues. It will be shown that in low-dimensional topology, justifications can be based on sequences of pictures. Three theses will be defended. First, the representations used in the practice are an integral part of the mathematical reasoning. As a matter of fact, they convey in a material form the relevant transitions and thus allow experts to draw inferential connections. Second, in low-dimensional topology experts exploit a particular type of manipulative imagination which is connected to intuition of two- and three-dimensional space and motor agency. This imagination allows recognizing the transformations which connect different pictures in an argument. Third, the epistemic—and inferential—actions performed are permissible only within a specific practice: this form of reasoning is subject-matter dependent. Local criteria of validity are established to assure the soundness of representationally heterogeneous arguments in low-dimensional topology

Both resistance- and endurance-type exercise reduce the prevalence of hyperglycaemia in individuals with impaired glucose tolerance and in insulin-treated and non-insulin-treated type 2 diabetic patients

Aims/hypothesis The present study compares the impact of endurance- vs resistance-type exercise on subsequent 24 h blood glucose homeostasis in individuals with impaired glucose tolerance (IGT) and type 2 diabetes. Methods Fifteen individuals with IGT, 15 type 2 diabetic patients treated with exogenous insulin (INS), and 15 type 2 diabetic patients treated with oral glucose-lowering medication (OGLM) participated in a randomised crossover experiment. Participants were studied on three occasions for 3 days under strict dietary standardisation, but otherwise free-living conditions. Blood glucose homeostasis was assessed by ambulatory continuous glucose monitoring over the 24 h period following a 45 min session of resistance-type exercise (75% one repetition maximum), endurance-type exercise (50% maximum workload capacity) or no exercise at all. Results Average 24 h blood glucose concentrations were reduced from 7.4±0.2, 9.6±0.5 and 9.2±0.7 mmol/l during the control experiment to 6.9±0.2, 8.6±0.4 and 8.1±0.5 mmol/l (resistance-type exercise) and 6.8±0.2, 8.6±0.5 and 8.5±0.5 mmol/l (endurance-type exercise) over the 24 h period following a single bout of exercise in the IGT, OGLM and INS groups, respectively (p 10 mmol/l) was reduced by 35±7 and 33±11% over the 24 h period following a single session of resistanceand endurance-type exercise, respectively (p< 0.001 for both treatments). Conclusions/interpretation A single session of resistanceor endurance-type exercise substantially reduces the prevalence of hyperglycaemia during the subsequent 24 h period in individuals with IGT, and in insulin-treated and non-insulin-treated type 2 diabetic patients. Both resistance- and endurance-type exercise can be integrated in exercise intervention programmes designed to improve glycaemic control. Trial registration: Clinicaltrials.gov NCT00945165 Funding: The Netherlands Organization for Health Research and Development (ZonMw, the Netherlands). © 2011 The Author(s)

Consumption of New Zealand blackcurrant extract improves recovery from exercise-induced muscle damage in non-resistance trained men and women: A double-blind randomised trial

Background: Blackcurrant is rich in anthocyanins that may protect against exercise-induced muscle damage (EIMD) and facilitate a faster recovery of muscle function. We examined the effects of New Zealand blackcurrant (NZBC) extract on indices of muscle damage and recovery following a bout of strenuous isokinetic resistance exercise. Methods: Using a double-blind, randomised, placebo controlled, parallel design, twenty-seven healthy participants received either a 3 g·day−1 NZBC extract (n = 14) or the placebo (PLA) (n = 13) for 8 days prior to and 4 days following 60 strenuous concentric and eccentric contractions of the biceps brachii muscle on an isokinetic dynamometer. Muscle soreness (using a visual analogue scale), maximal voluntary contraction (MVC), range of motion (ROM) and blood creatine kinase (CK) were assessed before (0 h) and after (24, 48, 72 and 96 h) exercise. Results: Consumption of NZBC extract resulted in faster recovery of baseline MVC (p = 0.04), attenuated muscle soreness at 24 h (NZBC: 21 ± 10 mm vs. PLA: 40 ± 23 mm, p = 0.02) and 48 h (NZBC: 22 ± 17 vs. PLA: 44 ± 26 mm, p = 0.03) and serum CK concentration at 96 h (NZBC: 635 ± 921 UL vs. PLA: 4021 ± 4319 UL, p = 0.04) following EIMD. Conclusions: Consumption of NZBC extract prior to and following a bout of eccentric exercise attenuates muscle damage and improves functional recovery. These findings are of practical importance in recreationally active and potentially athletic populations, who may benefit from accelerated recovery following EIMD

Characterization of heterozygous and homozygous mouse models with the most common hypertrophic cardiomyopathy mutation MYBPC3 c.2373InsG in the Netherlands.

Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in the cardiac myosin binding protein-C (cMyBP-C) encoding gene MYBPC3. In the Netherlands, approximately 25% of patients carry the MYBPC3 c.2373InsG founder mutation. Most patients are heterozygous (MYBPC3 +/InsG) and have highly variable phenotypic expression, whereas homozygous (MYBPC3 InsG/InsG) patients have severe HCM at a young age. To improve understanding of disease progression and genotype-phenotype relationship based on the hallmarks of human HCM, we characterized mice with CRISPR/Cas9-induced heterozygous and homozygous mutations. At 18-28 weeks of age, we assessed the cardiac phenotype of Mybpc3 +/InsG and Mybpc3 InsG/InsG mice with echocardiography, and performed histological analyses. Cytoskeletal proteins and cardiomyocyte contractility of 3-4 week old and 18-28 week old Mybpc3 c.2373InsG mice were compared to wild-type (WT) mice. Expectedly, knock-in of Mybpc3 c.2373InsG resulted in the absence of cMyBP-C and our 18-28 week old homozygous Mybpc3 c.2373InsG model developed cardiac hypertrophy and severe left ventricular systolic and diastolic dysfunction, whereas HCM was not evident in Mybpc3 +/InsG mice. Mybpc3 InsG/InsG cardiomyocytes also presented with slowed contraction-relaxation kinetics, to a greater extent in 18-28 week old mice, partially due to increased levels of detyrosinated tubulin and desmin, and reduced cardiac troponin I (cTnI) phosphorylation. Impaired cardiomyocyte contraction-relaxation kinetics were successfully normalized in 18-28 week old Mybpc3 InsG/InsG cardiomyocytes by combining detyrosination inhibitor parthenolide and β-adrenergic receptor agonist isoproterenol. Both the 3-4 week old and 18-28 week old Mybpc3 InsG/InsG models recapitulate HCM, with a severe phenotype present in the 18-28 week old model

Glycemic Control for Colorectal Cancer Survivors Compared to Those without Cancer in the Dutch Primary Care for Type 2 Diabetes:A Prospective Cohort Study

SIMPLE SUMMARY: A growing number of colorectal cancer survivors live with type 2 diabetes, as a result of improved cancer diagnosis and treatment. These patients might have worse glycemic control after their cancer diagnosis, which may increase the risk of cardiovascular diseases. This prospective cohort study evaluated the quality of glycemic control for colorectal cancer survivors, as compared to those without cancer in Dutch primary care for diabetes. During a 10-year follow-up for 57,330 patients, there were 705 patients diagnosed with colorectal cancer. No clinically relevant difference on the probability of reaching the target HbA1c was observed between colorectal cancer survivors and patients with no history of cancer. These results showed a robust diabetes care system, implying that the glycemic control for colorectal cancer survivors can be delegated to the primary care professionals. ABSTRACT: Cancer survivors with diabetes tend to have worse glycemic control after their cancer diagnosis, which may increase the risk of cardiovascular diseases. We aimed to investigate whether glycemic control differs between colorectal cancer (CRC) survivors and those without cancer, among patients with type 2 diabetes being treated in the Dutch primary care. The Zwolle Outpatient Diabetes project Integrating Available Care database was linked with the Dutch Cancer Registry (n = 71,648, 1998–2014). The cases were those with stage 0–III CRC, and the controls were those without cancer history. The primary and secondary outcomes were the probability of reaching the glycated hemoglobin (HbA1c) target and the mean of HbA1c during follow-up, respectively. Mixed linear modeling was applied, where the status of CRC was a time-varying variable. Among the 57,330 patients included, 705 developed CRC during follow-up. The mean probability of reaching the HbA1c target during follow-up was 73% versus 74% (p = 0.157) for CRC survivors versus those without cancer, respectively. The mean HbA1c was 51.1 versus 50.8 mmol/mol (p = 0.045) among CRC survivors versus those without cancer, respectively. We observed a clinically comparable glycemic control among the CRC survivors without cancer, indicating that glycemic control for CRC survivors can be delegated to primary care professionals