Keeping up with a healthy milk fatty acid profile requires selection

The effect of various fatty acids and fatty acid groups on human health is under discussion, and results are not unambiguously. However, current knowledge shows that a health-promoting milk fat profile is likely to be obtained by increasing the content of unsaturated fatty acids and reducing the proportion of palmitic acid. From a milk product point of view this would contribute to butter with a softer texture which is easier to spread. The objective of this study was to investigate the genetic impact on the milk fatty acid profile measured as g/100 g total fat for 7 FA fractions and 4 individual FA. Milk samples from all cows in the Danish herd testing scheme were collected from May 2015 to December 2017 and analyzed at a certified laboratory using MilkScanTM FT+/FT600 equipped with special software for predicting 7 FA fractions: saturated FA (SFA), Mono-unsaturated FA (MUFA), Poly-unsaturated FA (PUFA), short chain FA (SCFA), medium chain FA (MCFA), long chain FA (LCFA), and transFA; and 4 individual FA: C14:0, C16:0, C18:0, and C18:1. Heritabilities for test day measurement of the different fractions and individual FA were at the same level (0.08 to 0.16) as heritability for overall fat yield for both Danish Holstein and Danish Jersey. Genetic correlations between the fraction of unsaturated FA and total fat yield were however unfavorable indicating an unfavorable trend for the healthy FA contents unless selected for. Correlations between breeding values for FA (groups and individuals) and the different traits in the Nordic Total merit index were in general below 0.15 for both Holstein and Jersey. This suggest that selection for FA (groups and individual FA) can be carried out without harming other traits in the breeding goal. It is therefore proposed to substitute the present Fat index in the total merit index with and index composed of the FA’s weighed together based on their health promoting values and their values in relation to product quality

Environmental toxicants in breast milk of Norwegian mothers and gut bacteria composition and metabolites in their infants at 1 month.

BACKGROUND:Early disruption of the microbial community may influence life-long health. Environmental toxicants can contaminate breast milk and the developing infant gut microbiome is directly exposed. We investigated whether environmental toxicants in breastmilk affect the composition and function of the infant gut microbiome at 1 month. We measured environmental toxicants in breastmilk, fecal short-chain fatty acids (SCFAs), and gut microbial composition from 16S rRNA gene amplicon sequencing using samples from 267 mother-child pairs in the Norwegian Microbiota Cohort (NoMIC). We tested 28 chemical exposures: polychlorinated biphenyls (PCBs), polybrominated flame retardants (PBDEs), per- and polyfluoroalkyl substances (PFASs), and organochlorine pesticides. We assessed chemical exposure and alpha diversity/SCFAs using elastic net regression modeling and generalized linear models, adjusting for confounders, and variation in beta diversity (UniFrac), taxa abundance (ANCOM), and predicted metagenomes (PiCRUSt) in low, medium, and high exposed groups. RESULTS:PBDE-28 and the surfactant perfluorooctanesulfonic acid (PFOS) were associated with less microbiome diversity. Some sub-OTUs of Lactobacillus, an important genus in early life, were lower in abundance in samples from infants with relative "high" (> 80th percentile) vs. "low" (< 20th percentile) toxicant exposure in this cohort. Moreover, breast milk toxicants were associated with microbiome functionality, explaining up to 34% of variance in acetic and propionic SCFAs, essential signaling molecules. Per one standard deviation of exposure, PBDE-28 was associated with less propionic acid (- 24% [95% CI - 35% to - 14%] relative to the mean), and PCB-209 with less acetic acid (- 15% [95% CI - 29% to - 0.4%]). Conversely, PFOA and dioxin-like PCB-167 were associated with 61% (95% CI 35% to 87%) and 22% (95% CI 8% to 35%) more propionic and acetic acid, respectively. CONCLUSIONS:Environmental toxicant exposure may influence infant gut microbial function during a critical developmental window. Future studies are needed to replicate these novel findings and investigate whether this has any impact on child health

Generation of helper virus-free adeno-associated viral vector packaging/producer cell lines based on a human suspension cell line

The emerging number of clinical trials in the gene therapy field poses the challenge to the industry to produce viral vectors in a scalable, reproducible and cost-efficient manner. To address this issue, our CAP-GT platform comprises high density, serum free suspension cell lines that enable reproducible, scalable transfection and high titer production of viral vectors. An adeno-associated virus (AAV) based vector was the first approved gene therapy product in clinical applications. Attractive features of AAV as a gene therapy vector are e.g. its lack of pathogenicity and its ability to transduce dividing and non-dividing cells. Moving away from mainly targeting ultra-rare diseases and taking more common indications into focus will need to see significant improvements concerning productivity and consistent quality of AAV vector production in order to ensure supply. For this purpose, we are developing a helper virus-free packaging cell line that can easily be turned into a producer cell line by only one additional step of cell line development. Base of this packing cell line is the generation of a cell line with stable Tet-inducible expression of Rep proteins. Extensive screening of Rep expressing single cell clones resulted in clonal cell lines which produced high AAV titers upon induction and transfection of the missing components. In a next step, the adenoviral helper functions E2A and E4orf6 are introduced, due to their toxicity also under the control of a Tet-inducible promoter. In addition, the VA RNA is encoded by the same construct. Finally, a Tet-inducible capsid function and GFP as transgene flanked by the ITRs combined on one construct will be stably integrated resulting in a proof of principle producer cell line. This approach should enable a consistent quality production of AAV vectors that abolishes the drawbacks of transient transfection concerning reproducibility, consistency and high costs for GMP-grade DNA. Process optimization in regard to process duration, feeding strategy etc. is currently ongoing for further improving the vector yields

Recurrence-Free Survival Prediction for Anal Squamous Cell Carcinoma Chemoradiotherapy using Planning CT-based Radiomics Model

Objectives: Approximately 30% of non-metastatic anal squamous cell carcinoma (ASCC) patients will experience recurrence after chemoradiotherapy (CRT), and currently available clinical variables are poor predictors of treatment response. We aimed to develop a model leveraging information extracted from radiation pretreatment planning CT to predict recurrence-free survival (RFS) in ASCC patients after CRT. Methods: Radiomics features were extracted from planning CT images of 96 ASCC patients. Following pre-feature selection, the optimal feature set was selected via step-forward feature selection with a multivariate Cox proportional hazard model. The RFS prediction was generated from a radiomics-clinical combined model based on an optimal feature set with five repeats of five-fold cross validation. The risk stratification ability of the proposed model was evaluated with Kaplan-Meier analysis. Results: Shape- and texture-based radiomics features significantly predicted RFS. Compared to a clinical-only model, radiomics-clinical combined model achieves better performance in the testing cohort with higher C-index (0.80 vs 0.73) and AUC (0.84 vs 0.79 for 1-year RFS, 0.84 vs 0.78 for 2-year RFS, and 0.86 vs 0.83 for 3-year RFS), leading to distinctive high- and low-risk of recurrence groups (p<0.001). Conclusions: A treatment planning CT based radiomics and clinical combined model had improved prognostic performance in predicting RFS for ASCC patients treated with CRT as compared to a model using clinical features only

Smartwatches : accessory or tool? The driving force of visibility and usefulness

Although still in the early stages of diffusion, smartwatches represent the most popular type of wearable devices. Yet, little is known why some people are more likely to adopt smartwatches than others. To deepen the understanding of underlying factors prompting adoption behavior, the authors develop a theoretical model grounded in technology acceptance and social psychology literature. Empirical results reveal perceived usefulness and visibility as important factors that drive intention. The magnitude of these antecedents is influenced by an individual’s perception of viewing smartwatches as a technology and/or as a fashion accessory. Theoretical and managerial implications are discussed

Detailed milk fatty acid profiling of the Danish dairy cattle population

Abstract Milk fatty acid (FA) composition can be manipulated through feeding, and especially effects of grazing have been shown to promote a healthier milk FA profile due to increasing contents of beneficial FAs, like conjugated linoleic acid (CLA) and α-linolenic acid (C18:3, the main n3 FA in milk). In addition to diet-based manipulations, selective breeding for specific FA could also be a strategy for altering the FA profile as milk FA display low to moderate heritabilites (0.07-0.34 in Danish Holstein). Since 2015, milk samples from all Danish dairy cows under yield control have been analyzed using mid infrared spectroscopy. The FOSS Application Note 64 has subsequently been used to predict content of seven FA groups (short-chain FA (SCFA), medium-chain FA (MCFA), long-chain FA (LCFA), saturated FA (SFA), mono-unsaturated FA (MUFA), poly-unsaturated FA (PUFA), and trans FA (TFA)) together with four individual FA (myristic acid (C14:0), palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1)). This access to millions of FA profiles in milk enables large-scale in depth analyses of factors affecting FA profile of milk and accurate genetic parameter estimation. Initially, more than 3.5 million milk samples from three Danish dairy breeds (Holstein, Jersey, Red) and crossbred cows have been analyzed from May 2015 to October 2016. The results showed significant (P ≤ 0.05) effects of cow breed. As reported earlier, Jersey cows have a higher de novo synthesis, resulting in higher proportions of SFA, MCFA, SCFA and C16:0 compared to the other breeds. For parity (only checked in Holstein), the proportion of SFA and SCFA increased with increasing lactation number, whereas the proportion of MUFA and C16:0 decreased. PUFA had the lowest proportion in 2nd parity and the highest in 1st parity. Also, significant effects of production system (organic vs. conventional) was found, as organic dairy cows due to legislation have to be on pasture during summer. In months, where cows were fed fresh grass, the proportion of unsaturated FA increased, whereas the proportion of saturated FA decreased. This was seen in both organic, and to a lesser extent, in conventional milk. A healthier FA profile can be obtained by increasing MUFA and PUFA in milk. However, health aspects in relation to SFA are more complex, but there seems to be a general agreement that most SFA have neutral or even slightly positive effects, whereas palmitic acid exerts a negative effect on human health due to its role in increased LDL cholesterol. Thus from a consumers perspective, our results suggest that organic summer milk from 1st parity Holstein or Red cows are preferred during the grass season, whereas conventional milk may have a healthier FA profile during winter. To explore specific seasonal effect in relation to pasture-based diets in more details, milk samples from 160 cows from eight herds are collected to investigate whether bulls with extreme SFA% breeding values are reflected in the FA milk profile from their daughters. The collected milk samples will be analyzed by AN64 MIR, as well as by gas chromatography, to provide additional information e.g. in relation to CLA and C18:3 and the n3/n6 ratio. So far, milk samples have been collected prior to summer grazing and will be collected again in June 2017, where most cows in the experiment will be on pasture. In conclusion, this study has shown that the choice of breed, parity, lactation stage, season, production system and genetics affect the FA composition of milk. Different strategies may therefore be applied to alter the FA profile, but generally, which could be exploited for product differentiation for e.g. new healthier innovative dairy products

Environmental toxicants in breast milk of Norwegian mothers and gut bacteria composition and metabolites in their infants at 1 month

Iszatt N, Janssen S, Lenters V, et al. Environmental toxicants in breast milk of Norwegian mothers and gut bacteria composition and metabolites in their infants at 1 month. Microbiome. 2019;7(1): 34

Fedtsyreprofilen i mælk fra malkekøer – Potentiale og perspektiver

Projektet SOBcows har i samarbejde med RYK gennem 16 måneder i 2015/16 analyseret for indholdet af 11 fedtsyrer/fedtsyregrupper i kontrolmælken fra alle ydelseskontrollerede køer i Danmark. Dataanalyser af godt 3,5 mio. mælkeprøver viser, at det er muligt at påvirke sammensætning af mælkefedtet gennem avl. En foreløbig beregning af arvbarheden hen over laktationen viser, at alle fedtsyrekategorier har en genetisk variation og enkeltfedtsyrerne har arvbarheder på højde med den samlede fedtydelse. Det betyder arvbarheder i intervallet 0,25-0,44 afhængig af race og paritet. De genetiske sammenhænge varierer betydeligt gennem laktationen og er påvirket af den øgede kropsmobilisering i de første måneder efter kælvning. En anvendelse af fedtstyrebestemmelserne i avlen vil derfor kræve en opdeling af laktationen i mindst to perioder. Samlet kan det konkluderes, at der er et betydeligt avlsmæssigt potentiale, og hvis der kommer et dansk marked for mælkeprodukter med særlige egenskaber, vil det være oplagt at ændre genetikken i gunstig retning og samtidigt udnytte de fodringsmæssige muligheder for at producere mælk med en sundhedsfremmende fedtsyreprofil. Datamaterialet her og fedtsyremåling af samtlige mælkeprøver i ydelseskontrollen giver en unik position i forhold til det

Effect of Revascularization on Intramuscular Vascular Endothelial Growth Factor Levels in Peripheral Arterial Disease

Vascular endothelial growth factor (VEGF) is a potent driver of angiogenesis, which may help to relieve ischemia in peripheral arterial disease (PAD). We aimed to investigate the role of intramuscular VEGF in ischemic and non-ischemic skeletal muscle in PAD patients before and after surgical or endovascular revascularization and different stages of PAD. Biopsies of the gastrocnemius and vastus muscles from twenty PAD patients with stenosis or occlusion of the superficial femoral artery were obtained both during revascularization and 8 weeks postoperatively. The gastrocnemius muscle was considered ischemic, while vastus muscle biopsies served as intraindividual controls. The levels of vascular endothelial growth factor in muscle lysates were then determined by ELISA. Preoperative VEGF levels were significantly higher in ischemic muscles compared to the controls (98.07 ± 61.96 pg/mL vs. 55.50 ± 27.33 pg/mL, p = 0.004). Postoperative values decreased significantly (p = 0.010) to 54.83 ± 49.60 pg/mL in gastrocnemius biopsies. No significant change was observed in vastus muscle biopsies, with mean postoperative VEGF values found at 54.16 ± 40.66 pg/mL. Since all patients still had indications for revascularization, impairment of angiogenesis mechanisms can be assumed. More research about angiogenesis in PAD is needed with the ultimate goal to improve conservative treatment