Synthesis and Characterization of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering

Novel, injectable hydrogels were developed that solidify through a dual-gelation, physical and chemical, mechanism upon preparation and elevation of temperature to 37°C. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant epoxy rings and a hydrolyticallydegradable polyamidoamine-based diamine crosslinker were synthesized, characterized, and combined to produce in situ forming hydrogel constructs. Network formation through the epoxyamine reaction was shown to be rapid and facile, and the progressive incorporation of the hydrophilic polyamidoamine crosslinker into the hydrogel was shown to mitigate the often problematic tendency of thermogelling materials to undergo significant post-formation gel syneresis. The results suggest that this novel class of injectable hydrogels may be attractive substrates for tissue engineering applications due to the synthetic versatility of the component materials and beneficial hydrogel gelation kinetics and stability

Donor InSight: characteristics and representativeness of a Dutch cohort study on blood and plasma donors

BACKGROUND AND OBJECTIVES: More insight into donor health and behaviour may contribute to more efficient and focused strategies regarding donor care and management. Donor InSight (DIS) is a Dutch cohort study of blood and plasma donors. We aimed to outline the objectives and methods of DIS, describe the cohort, and compare it to the active Dutch donor population. MATERIALS AND METHODS: In 2007-2009 (DIS-I, n = 31 338) and 2012-2013 (DIS-II, 34 826, of whom 22 132 also participated in DIS-I) questionnaire data on demographics, donation, lifestyle, family composition, health and disease were collected. A second follow-up (DIS-III, n = 3046), including donors with differing haemoglobin trajectories, was completed in 2015-2016. DIS-III includes data on genetic determinants, iron and red cell indices. Representativeness of the DIS-I sample for the entire Dutch donor population was assessed by comparing characteristics of both. RESULTS: Donor InSight was initially set up because of a need for more detailed information and evidence as a basis for decision-making in blood banks. DIS-I sample is comparable to the total Dutch donor population in terms of age, body mass index, haemoglobin level, blood pressure, blood type and donation behaviour. CONCLUSION: Donor InSight is a cohort study representative of the Dutch donor population. It provides evidence to support evidence-based decision making

Associations between single nucleotide polymorphisms and erythrocyte parameters in humans:A systematic literature review

Individual variations in erythrocyte parameters are influenced by factors like sex, age, diet and season. Genetic variations have also been associated with erythrocyte parameters. The aim of this systematic review is to provide an overview of associations between single nucleotide polymorphisms (SNPs) and erythrocyte parameters in humans. A systematic review protocol was published at the international prospective register of systematic reviews (registration number CRD42016053052). Literature searches were conducted in Medline and Embase. Studies were included if: investigating a(n) causality/association/correlation; population-based; investigating a human population of Caucasian/mixed-ethnic descent; and written in English, Dutch or German. Study quality was assessed using the quality of genetic association studies tool. In total, 4385 studies were screened on title/abstract and 194 studies were screened on full text. Inclusion criteria were met by 13 candidate gene studies (n = 126–49,488) and eight genome-wide association studies (GWASes, n = 1664–116,666). One moderate and six good quality GWAS(es) identified 1237 SNPs located in/near 241 genes. SNPs in/near ten genes were found to be associated with one or more erythrocyte parameter(s) by multiple GWASes, namely HIST1H2AC, MPST, SLC17A1 and SLC17A3 with mean cell hemoglobin (MCH), HIST1H1T and KCTD17 with MCH and mean cell volume (MCV), HBS1L and MYB with MCH, MCV and red cell count (RCC), HFE with MCH, MCV and hemoglobin, and TMPRSS6 with MCH, MCV, hemoglobin and mean cell hemoglobin concentration (MCHC). Four genes were found across multiple erythrocyte parameters by one study in each parameter. Fourteen SNPs were associated with one or more erythrocyte parameter(s) in multiple cohorts, namely rs129128, rs17342717, rs228129 and rs5756504 (MCH), rs4895441, rs7775698, rs9376092 and rs9494145 (MCH, MCV, RCC), rs6569992 (MCH, RCC), rs1800562 (hemoglobin, MCH, MCV), rs130624 and rs198846 (MCH, MCV), rs4820268 and rs855791 (MCH, MCV, MCHC). Further research on these fourteen genes in erythropoiesis is recommended, especially eight whose role in erythropoiesis is unclear

The association between population density and blood lipid levels in Dutch blood donors.

BACKGROUND: In low and middle-income countries (LMIC), the total and LDL cholesterol and triglyceride levels of residents of urban areas are reported to be higher than those of rural areas. This may be due to differences in lifestyle behaviors between residents of urban areas and rural areas in LMIC. In this study, our aims were to (1) examine whether or not LDL cholesterol, total/HDL ratios and triglyceride levels of individuals in densely populated areas are higher than those of individuals living in less-densely populated areas in a high-income country (HIC) and (2) investigate the potential mediating roles of physical activity and sedentary behavior. METHODS: We used cross-sectional data from 2547 Dutch blood donors that participated in Donor InSight-III. Linear regression was used to analyze the association between population density and LDL cholesterol, total/HDL cholesterol ratio and HDL cholesterol. The mediating roles of moderate-to-vigorous physical activity (MVPA) and sedentary behavior were investigated in a subsample (n = 740) for which objectively measured MVPA/sedentary behavior data was available. Multiple mediation with linear regression analyses were performed and the product-of-coefficients method was used to calculate direct and indirect effects. RESULTS: Mean LDL cholesterol and median total cholesterol/HDL cholesterol ratio and triglyceride levels were 2.89, 3.43 and 1.29 mmol/L, respectively. Population density was not associated with LDL cholesterol [β 0.00 (- 0.01; 0.01)], log transformed total/HDL cholesterol ratio [β 1.00 (1.00; 1.00)] and triglyceride levels [β 1.00 (0.99; 1.00)]. No statistically significant direct or indirect effects were found. CONCLUSION: Contrary to previous findings in LMIC, no evidence was found that population density is associated with blood lipid levels in blood donors in the Netherlands or that MVPA and sedentary behavior mediate this association. This may be the result of socioeconomic differences and, in part, may be due to the good health of the study population and the relatively high population density in the Netherlands. Also, compared to LMIC, differences in physical activity levels in more versus less populated areas may be less pronounced in HIC

The association between population density and blood lipid levels in Dutch blood donors

Background: In low and middle-income countries (LMIC), the total and LDL cholesterol and triglyceride levels of residents of urban areas are reported to be higher than those of rural areas. This may be due to differences in lifestyle behaviors between residents of urban areas and rural areas in LMIC. In this study, our aims were to (1) examine whether or not LDL cholesterol, total/HDL ratios and triglyceride levels of individuals in densely populated areas are higher than those of individuals living in less-densely populated areas in a high-income country (HIC) and (2) investigate the potential mediating roles of physical activity and sedentary behavior. Methods: We used cross-sectional data from 2547 Dutch blood donors that participated in Donor InSight-III. Linear regression was used to analyze the association between population density and LDL cholesterol, total/HDL cholesterol ratio and HDL cholesterol. The mediating roles of moderate-to-vigorous physical activity (MVPA) and sedentary behavior were investigated in a subsample (n = 740) for which objectively measured MVPA/sedentary behavior data was available. Multiple mediation with linear regression analyses were performed and the product-of-coefficients method was used to calculate direct and indirect effects. Results: Mean LDL cholesterol and median total cholesterol/HDL cholesterol ratio and triglyceride levels were 2.89, 3.43 and 1.29 mmol/L, respectively. Population density was not associated with LDL cholesterol [β 0.00 (- 0.01; 0.01)], log transformed total/HDL cholesterol ratio [β 1.00 (1.00; 1.00)] and triglyceride levels [β 1.00 (0.99; 1.00)]. No statistically significant direct or indirect effects were found. Conclusion: Contrary to previous findings in LMIC, no evidence was found that population density is associated with blood lipid levels in blood donors in the Netherlands or that MVPA and sedentary behavior mediate this association. This may be the result of socioeconomic differences and, in part, may be due to the good health of the study population and the relatively high population density in the Netherlands. Also, compared to LMIC, differences in physical activity levels in more versus less populated areas may be less pronounced in HIC

Dietary intake of heme iron is associated with ferritin and hemoglobin levels in Dutch blood donors: results from Donor InSight.

Whole blood donors, especially frequently donating donors, have a risk of iron deficiency and low hemoglobin (Hb) levels, which may affect their health and eligibility to donate. Lifestyle behaviors, such as dietary iron intake and physical activity, may influence iron stores and thereby Hb levels. We aimed to investigate whether dietary iron intake and questionnaire-based moderate-to-vigorous physical activity (MVPA) were associated with Hb levels, and whether ferritin levels mediated these associations. In Donor InSight-III, a Dutch cohort study of blood and plasma donors, data on heme and non-heme iron intake (mg/day), MVPA (10 minutes/day), Hb levels (mmol/L) and ferritin levels (mg/L) were available in 2,323 donors (1,074 male). Donors with higher heme iron intakes [regression coefficients (β) in men and women: 0.160 and 0.065 mmol/L higher Hb per 1 mg of heme iron, respectively] and lower nonheme iron intakes (β: -0.014 and -0.017, respectively) had higher Hb levels, adjusted for relevant confounders. Ferritin levels mediated these associations [indirect effect (95% confidence interval) in men and women, respectively: 0.074 (0.045; 0.111) and 0.061 (0.030; 0.096) for heme and -0.003 (-0.008;0.001) and -0.008 (-0.013;-0.003) for non-heme]. MVPA was negatively associated with Hb levels in men only (β: -0.005), but not mediated by ferritin levels. In conclusion, higher heme and lower non-heme iron intake were associated with higher Hb levels in donors, via higher ferritin levels. This indicates that donors with high heme iron intake may be more capable of maintaining iron stores to recover Hb levels after blood donation

Development and validation of a universal blood donor genotyping platform: a multinational prospective study.

Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non-self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates. This DNA-based test is capable of simultaneously typing most clinically relevant red blood cell (RBC), human platelet (HPA), and human leukocyte (HLA) antigens. Validation was performed, using samples from 7927 European, 27 South Asian, 21 East Asian, and 9 African blood donors enrolled in 2 national biobanks. We illustrated the usefulness of the platform by analyzing antibody data from patients sensitized with multiple RBC alloantibodies. Genotyping results demonstrated concordance of 99.91%, 99.97%, and 99.03% with RBC, HPA, and HLA clinically validated typing results in 89 371, 3016, and 9289 comparisons, respectively. Genotyping increased the total number of antigen typing results available from 110 980 to >1 200 000. Dense donor typing allowed identification of 2 to 6 times more compatible donors to serve 3146 patients with multiple RBC alloantibodies, providing at least 1 match for 176 individuals for whom previously no blood could be found among the same donors. This genotyping technology is already being used to type thousands of donors taking part in national genotyping studies. Extraction of dense antigen-typing data from these cohorts provides blood supply organizations with the opportunity to implement a policy of genomics-based precision matching of blood.NHS Blood and Transplant, National Institute for Health Research, Health Data Research UK and Sanquin