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1.
  • Andrén, Anders, et al. (author)
  • The occurrence of noncoagulating milk and the association of bovine milk coagulation properties with genetic variants of the caseins in 3 Scandinavian dairy breeds
  • 2013
  • In: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 96:8, s. 4830-4842
  • Journal article (peer-reviewed)abstract
    • Substantial variation in milk coagulation properties has been observed among dairy cows. Consequently, raw milk from individual cows and breeds exhibits distinct coagulation capacities that potentially affect the technological properties and milk processing into cheese. This variation is largely influenced by protein composition, which is in turn affected by underlying genetic polymorphisms in the major milk proteins. In this study, we conducted a large screening on 3 major Scandinavian breeds to resolve the variation in milk coagulation traits and the frequency of milk with impaired coagulation properties (noncoagulation). In total, individual coagulation properties were measured on morning milk collected from 1,299 Danish Holstein (DH), Danish Jersey (DJ), and Swedish Red (SR) cows. The 3 breeds demonstrated notable interbreed differences in coagulation properties, with DJ cows exhibiting superior coagulation compared with the other 2 breeds. In addition, milk samples from 2% of DH and 16% of SR cows were classified as noncoagulating. Furthermore, the cows were genotyped for major genetic variants in the alpha(S1)- (CSN1S1), beta- (CSN2), and kappa-casein (CSN3) genes, revealing distinct differences in variant frequencies among breeds. Allele I of CSN2, which had not formerly been screened in such a high number of cows in these Scandinavian breeds, showed a frequency around 7% in DH and DJ, but was not detected in SR. Genetic polymorphisms were significantly associated with curd firming rate and rennet coagulation time. Thus, CSN1S1 C, CSN2 B, and CSN3 B positively affected milk coagulation, whereas CSN2 A(2), in particular, had a negative effect. In addition to the influence of individual casein genes, the effects of CSN1S1-CSN2-CSN3 composite genotypes were also examined, and revealed strong associations in all breeds, which more or less reflected the single gene results. Overall, milk coagulation is under the influence of additive genetic variation. Optimal milk for future cheese production can be ensured by monitoring the frequency of unfavorable variants and thus preventing an increase in the number of cows producing milk with impaired coagulation. Selective breeding for variants associated with superior milk coagulation can potentially increase raw milk quality and cheese yield in all 3 Scandinavian breeds.
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2.
  • Aronowitsch, David, et al. (author)
  • THERESIENSTADT
  • 1999
  • Other publication (other academic/artistic)abstract
    • This booklet is intended to present the discussion and the results of the workshop Locating Terezín. A short discription of the history of Terezín, the contemporary situation, the result of the workshop is presented, as well as a sketch for a future continuation and realisation
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3.
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4.
  • Glantz, Helena, et al. (author)
  • Effect of CPAP on diastolic function in coronary artery disease patients with nonsleepy obstructive sleep apnea : A randomized controlled trial.
  • 2017
  • In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 241, s. 12-18
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Obstructive sleep apnea (OSA) has been associated with worse diastolic function in patients with coronary artery disease (CAD). This analysis determined whether continuous positive airway pressure (CPAP) treatment would improve diastolic function in CAD patients with nonsleepy OSA.METHODS: Between December 2005 and November 2010, 244 revascularized CAD patients with nonsleepy OSA (apnea-hypopnea index (AHI) ≥15/h, Epworth Sleepiness Scale [ESS] score<10) were randomly assigned to CPAP or no-CPAP. Echocardiographic measurements were obtained at baseline, and after 3 and 12months.RESULTS: A total of 171 patients with preserved left ventricular ejection fraction (≥50%), no atrial fibrillation or severe valve abnormalities, and technically adequate echocardiograms at baseline and follow-up visits were included (CPAP, n=87; no-CPAP, n=84). In the intention-to-treat analysis, CPAP had no significant effect on echocardiographic parameters of mild (enlarged left atrium or decreased diastolic relaxation velocity) or worse (increased E/é filling index [presumed elevated left ventricular filling pressure]) diastolic function. Post-hoc analysis revealed a significant association between CPAP usage for ≥4h/night and an increase in diastolic relaxation velocity at 12months' follow-up (odds ratio 2.3, 95% confidence interval 1.0-4.9; p=0.039) after adjustment for age, sex, body mass index, and left atrium diameter at baseline.CONCLUSIONS: CPAP did not improve diastolic dysfunction in CAD patients with nonsleepy OSA. However, good CPAP adherence was significantly associated with an increase in diastolic relaxation velocity after one year.
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5.
  • Glantz, Helena, et al. (author)
  • Obstructive sleep apnea is independently associated with worse diastolic function in coronary artery disease
  • 2015
  • In: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 16:1, s. 160-167
  • Journal article (peer-reviewed)abstract
    • Background: Diastolic dysfunction is common in patients with coronary artery disease (CAD). We hypothesize that patients with CAD and preserved left ventricular ejection fraction (LVEF) and obstructive sleep apnea (OSA) will have worse diastolic function than similar patients without OSA. Material and methods: We analyzed sleep-study recordings and echocardiographic measurements obtained at baseline in a randomized controlled trial (RICCADSA) of revascularized patients with CAD who had LVEF of at least 50%. OSA was defined as an apnea-hypopnea-index (AHI) >= 15 events/h, and, no OSA, as an AHI <5. Worse diastolic function was defined as assumed elevated left ventricular filling pressure based on peak flow velocity in early diastole/Tissue Doppler of early diastolic ventricular filling (E/e) of >13 (or >9 in patients with an enlarged left atrial diameter [>= 39 mm for women and >= 40 mm for men]). Results: Data from 431 patients were evaluated (mean age: 63.7 +/- 8.8 y; men: 82.5%; OSA: n = 331). Worse diastolic function was more common among the patients with OSA than those without (54.4% vs 41.0%, p = 0.019). In multivariate analysis, OSA was associated with worse diastolic function (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.13; 3.18) adjusted for female sex (OR 2.28, 95% CI 1.28; 4.07), hypertension (OR 1.84, 95% CI 1.20; 2.82), and diabetes mellitus (OR 2.45, 95% CI 1.42; 4.23). Age >= 60 years, obesity, and current smoking were nonsignificant. Conclusions: In this cohort with CAD and preserved LVEF, OSA was associated with worse diastolic function independent of the traditionally recognized risk indicators. (C) 2014 Elsevier B.V. All rights reserved.
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6.
  • Glantz, Maria, et al. (author)
  • Bovine chromosomal regions affecting rheological traits in acid-induced skim milk gels.
  • 2015
  • In: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 98:2, s. 1273-1285
  • Journal article (peer-reviewed)abstract
    • The production of fermented milk products has increased worldwide during the last decade and is expected to continue to increase during the coming decade. The quality of these products may be optimized through breeding practices; however, the relations between cow genetics and technological properties of acid milk gels are not fully known. Therefore, the aim of this study was to identify chromosomal regions affecting acid-induced coagulation properties and possible candidate genes. Skim milk samples from 377 Swedish Red cows were rheologically analyzed for acid-induced coagulation properties using low-amplitude oscillation measurements. The resulting traits, including gel strength, coagulation time, and yield stress, were used to conduct a genome-wide association study. Single nucleotide polymorphisms (SNP) were identified using the BovineHD SNPChip (Illumina Inc., San Diego, CA), resulting in almost 621,000 segregating markers. The genome was scanned for putative quantitative trait loci (QTL) regions, haplotypes based on highly associated SNP were inferred, and the additive genetic effects of haplotypes within each QTL region were analyzed using mixed models. A total of 8 genomic regions were identified, with large effects of the significant haplotype explaining between 4.8 and 9.8% of the phenotypic variance of the studied traits. One major QTL was identified to overlap between gel strength and yield stress, the QTL identified with the most significant SNP closest to the gene coding for κ-casein (CSN3). In addition, a chromosome-wide significant region affecting yield stress on BTA 11 was identified to be colocated with PAEP, coding for β-lactoglobulin. Furthermore, the coagulation properties of the genetic variants within the 2 genes were compared with the coagulation properties identified by the patterns of the haplotypes within the regions, and it was discovered that the haplotypes were more diverse and in one case slightly better at explaining the phenotypic variance. Besides these significant QTL comprising the 2 milk proteins, 3 additional genes are proposed as possible candidates, namely RAB22A, CDH13, and STAT1, and all have previously been found to be expressed in the mammary gland. To our knowledge, this is the first attempt to map QTL regions for acid-induced coagulation properties.
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7.
  • Glantz, Maria, et al. (author)
  • Effect of polymorphisms in the leptin, leptin receptor and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) genes and genetic polymorphism of milk proteins on bovine milk composition.
  • 2012
  • In: Journal of Dairy Research. - 0022-0299. ; 79:1, s. 110-118
  • Journal article (peer-reviewed)abstract
    • The relations between cow genetics and milk composition have gained a lot of attention during the past years, however, generally only a few compositional traits have been examined. The aim of this study was to determine if polymorphisms in the leptin (LEP), leptin receptor (LEPR) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) genes as well as genetic polymorphism of β-casein (β-CN), κ-CN and β-lactoglobulin (β-LG) impact several bovine milk composition traits. Individual milk samples from the Swedish Red and Swedish Holstein breeds were analyzed for components in the protein, lipid, carbohydrate and mineral profiles. Cow alleles were determined on the following SNP: A1457G, A252T, A59V and C963T on the LEP gene, T945M on the LEPR gene and Nt984+8(A-G) on the DGAT1 gene. Additionally, genetic variants of β-CN, κ-CN and β-LG were determined. For both the breeds, the same tendency of minor allele frequency was found for all SNPs and protein genes, except on LEPA1457G and LEPC963T. This study indicated significant (P<0·05) associations between the studied SNPs and several compositional parameters. Protein content was influenced by LEPA1457G (G>A) and LEPC963T (T>C), whereas total Ca, ionic Ca concentration and milk pH were affected by LEPA1457G, LEPA59V, LEPC963T and LEPRT945M. However, yields of milk, protein, CN, lactose, total Ca and P were mainly affected by β-CN (A2>A1) and κ-CN (A>B>E). β-LG was mainly associated with whey protein yield and ionic Ca concentration (A>B). Thus, this study shows possibilities of using these polymorphisms as markers within genetic selection programs to improve and adjust several compositional parameters.
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8.
  • Glantz, Maria, et al. (author)
  • Effect of polymorphisms in the leptin, leptin receptor, and acyl-coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) genes and genetic polymorphism of milk proteins on cheese characteristics.
  • 2011
  • In: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 94:7, s. 3295-3304
  • Journal article (peer-reviewed)abstract
    • Cheese production has increased worldwide during the last decade and is expected to increase within the coming decade as well. Despite this, the relations between cow genetics and cheese characteristics are not fully known. The aim of this study was to determine if polymorphisms in the leptin (LEP), leptin receptor (LEPR), and acyl-coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) genes as well as genetic variants of β-casein (β-CN), κ-CN, and β-lactoglobulin (β-LG) affect technological properties important for cheese production and, hence, could act as genetic makers for cheese quality. Individual milk samples from the Swedish Red and the Swedish Holstein breeds were analyzed for sizes of CN micelles and fat globules as well as rennet-induced gel strength, gelation time, and yield stress. Model cheeses were produced to study yield, hardness, and pH of the cheeses. The A1457G, A252T, A59V, and C963T single nucleotide polymorphisms (SNP) were analyzed on the LEP gene, the T945M SNP on the LEPR gene, and the Nt984+8(A-G) SNP on the DGAT1 gene. In addition, genetic variants of β-CN, κ-CN, and β-LG were determined. The results indicate that technological properties were influenced by the LEPR(T945M) polymorphism, which had an association with gel strength, yield stress, and cheese hardness (T > C). However, also LEP(A252T) was shown to affect gel strength (T > A), whereas the LEP(A59V) had an effect on fat globule size (T > C). For the milk protein genes, favorable effects were found for the A and B variants of β-LG and κ-CN, respectively, on gel strength, gelation time, and yield stress. In addition, the B variant of κ-CN was shown to be associated with smaller CN micelles than the A variant. Thus, the results demonstrate potential genetic markers for cheese characteristics. However, milk composition traits also affected the obtained results, thus making it necessary to thoroughly assess the different aspects regarding the influence of gene effects on cheese characteristics before directly selecting for certain alleles or genetic variants to improve the processing and quality of cheese.
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9.
  • Glantz, Maria, et al. (author)
  • Genomic selection in relation to bovine milk composition and processability.
  • 2012
  • In: Journal of Dairy Research. - 0022-0299. ; 79:1, s. 53-59
  • Journal article (peer-reviewed)abstract
    • Genomic selection is a new technology in which selection decisions are based on direct genomic values (DGVs) or genomic enhanced breeding values (GEBVs). The objective of this study was to evaluate the relations between DGVs and several milk traits important for both the nutritional value and processability of milk. This is a new approach and can be used to increase the knowledge on how genomic selection can be used in practice. Morning milk samples from Swedish Holstein cows were analyzed for milk composition and technological properties. DGVs were received for each cow for milk, protein and fat yield, milk index, udder health, Nordic total merit and a quota was calculated between fat and milk yield as well as protein and milk yield. The results show that linear correlations exist (P<0·10) between the studied DGVs and contents and yields of parameters in the protein (P=0·002-0·097), fat (P=0·024-0·055) and mineral profiles (P=0·001-0·099) as well as for cheese characteristics (P=0·004-0·065), thus making it possible to obtain detailed information on milk traits that are not registered in the milk recording scheme. Hence, genomic selection will be an efficient tool for breeding and dairy industry to select cows early in life for targeted milk production.
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10.
  • Glantz, Maria, et al. (author)
  • Impact of protease and lipase activities on quality of Swedish raw milk
  • 2020
  • In: International Dairy Journal. - : Elsevier BV. - 0958-6946. ; 107
  • Journal article (peer-reviewed)abstract
    • An increasing demand for dairy products with long shelf-life is foreseen. A limiting factor for maintaining high quality of these products is the activity of spoilage enzymes during storage. Lipase and protease activities in Swedish raw milk at farm and dairy level were investigated, analysing milk samples from three geographical regions and two seasons. Lipase activity in milk at farm level was affected by regional and seasonal variations, whereas at dairy level only season had an effect. Lipase activity was positively correlated with ionic calcium. For protease activity, no effect of either region or season was seen. Degradation products, e.g., free fatty acids, peptides and plasmin proteolysis products, varied differently between season and geographical origin at both farm and dairy level. The results indicate that lipase and protease activities are important for raw milk quality, while ionic calcium might be a future indicator for milk fat stability.
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11.
  • Glantz, Maria, et al. (author)
  • Revealing the size, conformation, and shape of casein micelles and aggregates with asymmetrical flow field-flow fractionation and multiangle light scattering.
  • 2010
  • In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:15, s. 12585-12591
  • Journal article (peer-reviewed)abstract
    • Casein (CN) micelles are naturally occurring colloidal protein aggregates present in a dispersed state in milk. In this paper we aim to obtain a detailed description of physicochemical properties of CN micelles over the entire size distribution using asymmetrical flow field-flow fractionation (AsFlFFF) connected to multiangle light scattering (MALS) and refractive index (RI) detection. Conclusions are drawn on the colloidal level regarding shape and conformation by comparison with models of colloidal particles. By using AsFlFFF-MALS-RI, it is concluded that the CN micelles are highly polydisperse with an average rms radius and hydrodynamic radius of 177 and 116 nm, respectively. The results show that the majority of CN micelles have a spherical shape, whereas a low concentration exists of larger and elongated aggregates. By comparison with models of aggregates of colloidal particles, the aggregates are shown to be anisotropic, e.g., aggregating linearly (threadlike) or in a sheet, rather than forming randomly spherical clusters. The results show that the characterization of colloidal dispersions with AsFlFFF-MALS-RI and the comparison with theoretical models are of a general character and, thus, of fundamental importance for colloidal dispersions.
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12.
  • Gregersen, V R, et al. (author)
  • Bovine chromosomal regions affecting rheological traits in rennet-induced skim milk gels.
  • 2015
  • In: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 98:2, s. 1261-1272
  • Journal article (peer-reviewed)abstract
    • Optimizing cheese yield and quality is of central importance to cheese manufacturing. The yield is associated with the time it takes before the gel has an optimal consistency for further processing, and it is well known that gel formation differs between individual milk samples. By identifying genomic regions affecting traits related to rennet-induced gelation, the aim of this study was to identify potential candidate genes affecting these traits. Hence, rennet-induced gelation, including rennet coagulation time, gel strength, and yield stress, was measured in skim milk samples collected from 379 animals of the Swedish Red breed using low-amplitude oscillation measurements. All animals had genotypes for almost 621,000 segregating single nucleotide polymorphisms (SNP), identified using the Bovine HD SNPChip (Illumina Inc., San Diego, CA). The genome was scanned for associations, haplotypes based on SNP sets comprising highly associated SNP were inferred, and the effects of the 2 most common haplotypes within each region were analyzed using mixed models. Even though the number of animals was relatively small, a total of 21 regions were identified, with 4 regions showing association with more than one trait. A major quantitative trait locus for all traits was identified around the casein cluster explaining between 9.3 to 15.2% of the phenotypic variation of the different traits. In addition, 3 other possible candidate genes were identified; that is, UDP-n-acetyl-α-d-galactosamine:polypeptide n-acetylgalactosaminyl-transferase 1 (GALNT1), playing a role in O-glycosylation of κ-casein, and 2 cathepsins, CTSZ and CTSC, possibly involved in proteolysis of milk proteins. We have shown that other genes than the casein genes themselves may be involved in the regulation of gelation traits. However, additional analysis is needed to confirm these results. To our knowledge, this is the first study identifying quantitative trait loci affecting rennet-induced gelation of skim milk through a high-density genome-wide association study.
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13.
  • Gustavsson, Frida, et al. (author)
  • Effects of breed and casein genetic variants on protein profile in milk from Swedish Red, Danish Holstein, and Danish Jersey cows.
  • 2014
  • In: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 97:6, s. 3866-3877
  • Journal article (peer-reviewed)abstract
    • In selecting cows for higher milk yields and milk quality, it is important to understand how these traits are affected by the bovine genome. The major milk proteins exhibit genetic polymorphism and these genetic variants can serve as markers for milk composition, milk production traits, and technological properties of milk. The aim of this study was to investigate the relationships between casein (CN) genetic variants and detailed protein composition in Swedish and Danish dairy milk. Milk and DNA samples were collected from approximately 400 individual cows each of 3 Scandinavian dairy breeds: Swedish Red (SR), Danish Holstein (DH), and Danish Jersey (DJ). The protein profile with relative concentrations of α-lactalbumin, β-lactoglobulin, and αS1-, αS2-, κ-, and β-CN was determined for each milk sample using capillary zone electrophoresis. The genetic variants of the αS1- (CSN1S1), β- (CSN2), and κ-CN (CSN3) genes for each cow were determined using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA). Univariate statistical models were used to evaluate the effects of composite genetic variants, αS1-β-κ-CN, on the protein profile. The 3 studied Scandinavian breeds differed from each other regarding CN genotypes, with DH and SR having similar genotype frequencies, whereas the genotype frequencies in DJ differed from the other 2 breeds. The similarities in genotype frequencies of SR and DH and differences compared with DJ were also seen in milk production traits, gross milk composition, and protein profile. Frequencies of the most common composite αS1-β-κ-CN genotype BB/A(2)A(2)/AA were 30% in DH and 15% in SR, and cows that had this genotype gave milk with lower relative concentrations of κ- and β-CN and higher relative concentrations of αS-CN, than the majority of the other composite genotypes in SR and DH. The effect of composite genotypes on relative concentrations of the milk proteins was not as pronounced in DJ. The present work suggests that a higher frequency of BB/A(1)A(2)/AB, together with a decrease in BB/A(2)A(2)/AA, could have positive effects on DH and SR milk regarding, for example, the processing of cheese.
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14.
  • Gustavsson, Frida, et al. (author)
  • Factors influencing chymosin-induced gelation of milk from individual dairy cows: Major effects of casein micelle size and calcium
  • 2014
  • In: International Dairy Journal. - : Elsevier BV. - 0958-6946 .- 1879-0143. ; 39:1, s. 201-208
  • Journal article (peer-reviewed)abstract
    • Optimisation of cheese yield is crucial for cheese production; a previous study showed large variations in chymosin-induced coagulation in milk from the second most common Swedish dairy breed, Swedish Red. In the present study, the effect of gross composition, protein composition, total and ionic calcium content, phosphorous content and casein micelle size on chymosin-induced gelation was determined in milk from 98 Swedish Red cows. The study showed that protein content and total calcium content, ionic calcium concentration and casein micelle size were the most important factors explaining the variation of gelation properties in this sample set. Non-coagulating milk was suggested to have lower ionic and total calcium content as well as lower relative concentrations of beta-lactoglobulin than coagulating milk. The lower total calcium content in non-coagulating milk poses a problem as the difference was, theoretically, four times larger than the amount of calcium that is normally added in cheese processing. (C) 2014 Elsevier Ltd. All rights reserved.
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15.
  • Gustavsson, Frida, et al. (author)
  • Impact of genetic variants of milk proteins on chymosin-induced gelation properties of milk from individual cows of Swedish Red dairy cattle
  • 2014
  • In: International Dairy Journal. - : Elsevier BV. - 0958-6946 .- 1879-0143. ; 39:1, s. 102-107
  • Journal article (peer-reviewed)abstract
    • Chymosin-induced gelation properties of the milk of around 400 Swedish Red dairy cows was investigated with the aim of identifying genetic protein variants that influence chymosin-induced gelation for optimisation of cheese milk through breeding practices. The variation in chymosin-induced gelation properties was shown to be large in the milk of Swedish Red and there was a high frequency of cows producing non-coagulating milk, 18%. The present study showed that the common composite beta-kappa-casein genotypes A(1)A(2)/AE and A(2)A(2)/AA were associated with both poor gelation properties and non-coagulation in the milk of Swedish Red. The present study suggests that if the frequencies of composite genotypes A(1)A(2)/AE and A(2)A(2)/AA were decreased in the Swedish Red population in favour for A(1)A(1)/AA and A(1)A(1)/AE, this could have a positive effect on the rennetability of the milk. (C) 2014 Elsevier Ltd. All rights reserved.
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16.
  • Nilsson, Kajsa, et al. (author)
  • An investigation of the enzymatic cleavage of κ-casein in non-coagulating milk
  • 2020
  • In: International Dairy Journal. - : Elsevier BV. - 0958-6946. ; 109
  • Journal article (peer-reviewed)abstract
    • Non-coagulating milk is unwanted in cheese production because it impairs chymosin-induced coagulation properties in bulk milk. Milk samples were analysed to investigate the coagulation process in non-coagulating milk for comparison with milk samples that have a high coagulation ability. This was done by measuring two peptides after chymosin cleavage, namely para-κ-casein and caseinomacropeptide, in all the milk samples using capillary electrophoresis. The results showed that cleavage of κ-casein into para-κ-casein and caseinomacropeptide occurred in both coagulation groups, suggesting that the aggregation stage is the cause of non-coagulating milk. Non-coagulating milk had lower content of para-κ-casein after chymosin addition compared with coagulating milk, which might be the result of a lower content of available κ-casein. Furthermore, this study indicates that there are different mechanisms that explain good coagulation ability and lack of coagulation ability of milk. The results can be useful in understanding the potential chemical mechanisms behind non-coagulating milk.
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17.
  • Nilsson, Kajsa, et al. (author)
  • Characterisation of non-coagulating milk and effects of milk composition and physical properties on rennet-induced coagulation in Swedish Red Dairy Cattle
  • 2019
  • In: International Dairy Journal. - : Elsevier BV. - 0958-6946 .- 1879-0143. ; 95, s. 50-57
  • Journal article (peer-reviewed)abstract
    • Non-coagulating milk is a serious problem in the cheese industry, since it decreases cheese yield, resulting in decreased economic output. This study evaluated rennet-induced coagulation properties and composition of milk from individual Swedish Red Dairy Cattle. Milk samples from 679 individual cows were rheologically evaluated, of which 18.1% of the cows produced non-coagulating milk and 18.9% produced poor-coagulating milk. This resulted in 37% of the milk samples being non-optimal in cheese production, which is an alarmingly high figure. A comparison between non-coagulating and coagulating milk showed a significantly lower calcium content and less free Ca 2+ in non-coagulating milk. The results provide more information about non- and poor-coagulating milk and will be further used to understand the genetic background of non-coagulating milk and breed against this undesired milk property.
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18.
  • Peker, Yüksel, 1961, et al. (author)
  • Effect of Obstructive Sleep Apnea and CPAP Treatment on Cardiovascular Outcomes in Acute Coronary Syndrome in the RICCADSA Trial.
  • 2020
  • In: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:12
  • Journal article (peer-reviewed)abstract
    • We aimed to address the impact of OSA and its treatment with continuous positive airway pressure (CPAP) on major adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS). In this current analysis of the revascularized ACS subgroup (n = 353) of the Randomized Intervention with CPAP in Coronary Artery Disease and Obstructive Sleep Apnea (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT00519597), participants with non-sleepy OSA (apnea-hypopnea-index [AHI] ≥ 15 events/h on a home sleep apnea testing, and Epworth Sleepiness Scale [ESS] score < 10; n = 171) were randomized to CPAP (n = 86) or no-CPAP (n = 85). The sleepy OSA patients (AHI ≥ 15 events/h and ESS ≥ 10) who were offered CPAP, and the ones with no-OSA (AHI < 5 events/h) were included in the observational arm. A post-hoc analysis was done to compare untreated OSA (no-CPAP; n = 78) and nonadherent sleepy/non-sleepy OSA (n = 96) with the reference group without OSA (n = 81). The primary endpoint (the first event of repeat revascularization, myocardial infarction, stroke or cardiovascular mortality) during a median 4.7-year follow-up was evaluated in time-dependent Cox proportional hazards models adjusted for confounding factors. The incidence of MACCE did not differ significantly in intention-to-treat population. On-treatment analysis showed a significant risk reduction in those who used CPAP for ≥4 vs. <4 h/day or did not receive treatment (adjusted hazard ratio [HR] 0.17; 95% confidence interval [CI] 0.03-0.81; p = 0.03). Compared with the reference group, nonadherent/untreated OSA was associated with an increased cardiovascular risk (adjusted HR 1.97, 95% CI 1.03-3.77; p = 0.04). We conclude that OSA is an independent risk factor for adverse cardiovascular outcomes in patients with ACS. CPAP treatment may reduce this risk, if the device is used at least 4 h/day.
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19.
  • Peker, Yüksel, 1961, et al. (author)
  • Effect of Positive Airway Pressure on Cardiovascular Outcomes in Coronary Artery Disease Patients with Nonsleepy Obstructive Sleep Apnea : The RICCADSA Randomized Controlled Trial
  • 2016
  • In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 194:5, s. 613-620
  • Journal article (peer-reviewed)abstract
    • RATIONALE: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), many of whom do not report daytime sleepiness. First-line treatment for symptomatic OSA is continuous positive airway pressure (CPAP), but its value in patients without daytime sleepiness is uncertain.OBJECTIVES: To determine the effects of CPAP on long-term adverse cardiovascular outcome risk in patients with CAD with nonsleepy OSA.METHODS: This single-center, prospective, randomized, controlled, open-label, blinded evaluation trial was conducted between December 2005 and November 2010. Consecutive patients with newly revascularized CAD and OSA (apnea-hypopnea index ≥15/h) without daytime sleepiness (Epworth Sleepiness Scale score <10) were randomized to auto-titrating CPAP (n = 122) or no positive airway pressure (n = 122).MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the first event of repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality. Median follow-up was 57 months. The incidence of the primary endpoint did not differ significantly in patients who did versus did not receive CPAP (18.1% vs. 22.1%; hazard ratio, 0.80; 95% confidence interval, 0.46-1.41; P = 0.449). Adjusted on-treatment analysis showed a significant cardiovascular risk reduction in those who used CPAP for ≥4 versus <4 hours per night or did not receive treatment (hazard ratio, 0.29; 95% confidence interval, 0.10-0.86; P = 0.026).CONCLUSIONS: Routine prescription of CPAP to patients with CAD with nonsleepy OSA did not significantly reduce long-term adverse cardiovascular outcomes in the intention-to-treat population. There was a significant reduction after adjustment for baseline comorbidities and compliance with the treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 00519597).
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20.
  • Peker, Yüksel, 1961, et al. (author)
  • Outcomes in coronary artery disease patients with sleepy obstructive sleep apnoea on CPAP.
  • 2017
  • In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 50:6
  • Journal article (peer-reviewed)abstract
    • Coronary artery disease (CAD) patients with obstructive sleep apnoea (OSA) have increased risk for major adverse cardiovascular and cerebrovascular events (MACCEs) compared with CAD patients without OSA. We aimed to address if the risk is similar in both groups when OSA patients are treated.This study was a parallel observational arm of the RICCADSA randomised controlled trial, conducted in Sweden between 2005 and 2013. Patients with revascularised CAD and OSA (apnoea-hypopnoea index (AHI) ≥15events·h-1) with daytime sleepiness (Epworth Sleepiness Scale score ≥10) were offered continuous positive airway pressure (CPAP) (n=155); CAD patients with no OSA (AHI <5events·h-1) acted as controls (n=112), as a randomisation of sleepy OSA patients to no treatment would not be ethically feasible. The primary end-point was the first event of MACCEs. Median follow-up was 57months.The incidence of MACCEs was 23.2% in OSA patients versus 16.1% in those with no OSA (adjusted hazard ratio 0.96, 95% CI 0.40-2.31; p=0.923). Age and previous revascularisation were associated with increased risk for MACCEs, whereas coronary artery bypass grafting at baseline was associated with reduced risk.We conclude that the risk for MACCEs was not increased in CAD patients with sleepy OSA on CPAP compared with patients without OSA.
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21.
  • Sánchez-de-la-Torre, Manuel, et al. (author)
  • Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events: A Meta-Analysis.
  • 2023
  • In: JAMA. - 1538-3598. ; 330:13, s. 1255-1265
  • Journal article (peer-reviewed)abstract
    • The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated.To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials.PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023.For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included.Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]).One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day).A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]).Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.
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22.
  • Thunström, Erik, 1980, et al. (author)
  • CPAP Does Not Reduce Inflammatory Biomarkers in Patients With Coronary Artery Disease and Nonsleepy Obstructive Sleep Apnea: A Randomized Controlled Trial.
  • 2017
  • In: Sleep. - : Oxford University Press (OUP). - 1550-9109 .- 0161-8105. ; 40:11
  • Journal article (peer-reviewed)abstract
    • Obstructive sleep apnea (OSA) and enhanced vascular inflammation coexist in patients with coronary artery disease (CAD). Continuous positive airway pressure (CPAP) is first-line treatment for OSA with daytime sleepiness. This analysis of data from the RICCADSA (Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea) trial investigated the effects of CPAP on inflammatory markers in patients with CAD and nonsleepy OSA.This single-center, randomized, controlled, open-label trial enrolled consecutive revascularized patients with nonsleepy OSA (apnea-hypopnea index >15/h; Epworth Sleepiness Scale score <10). Levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were measured in blood samples taken at baseline (median 94 days after revascularization) and after 1 year of follow-up in patients randomized to CPAP or no-CPAP.A total of 220 patients with analyzable blood samples at baseline and 1 year were included. Baseline IL-6 levels were significantly lower in the CPAP versus no-CPAP group (median 3.1 pmol/L [interquartile range 1.3-5.7] vs. 4.2 pmol/L [2.0-8.9], respectively; p = .005). At 1-year follow-up, median IL-6 levels were significantly reduced in both groups (to 2.2 pmol/L [1.2-3.9] in the CPAP group and to 2.2 [1.2-4.7] in no-CPAP group; both p < .001 vs. baseline). IL-8, hs-CRP, and TNF-α did not change significantly from baseline. There was no association between CPAP adherence and changes in inflammatory marker levels.In patients with stable CAD and nonsleepy OSA, inflammatory biomarkers did not change significantly over time except for IL-6 levels, which reduced to the same extent in the CPAP and no-CPAP groups.ClinicalTrials.gov, ID: NCT00519597; researchweb.org, VGSKAS-4731.
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23.
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24.
  • Thunström, Erik, 1980, et al. (author)
  • Increased Inflammatory Activity in Nonobese Patients With Coronary Artery Disease and Obstructive Sleep Apnea
  • 2015
  • In: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 38:3, s. 463-71
  • Journal article (peer-reviewed)abstract
    • Study Objectives: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD). Enhanced vascular inflammation is implicated as a pathophysiologic mechanism but obesity is confounding. We aimed to address the association of OSA with inflammatory biomarkers in a nonobese cohort of revascularized patients with CAD and preserved left ventricular ejection fraction. Design: Cross-sectional analysis of baseline investigations of a randomized controlled trial. Setting: Clinic-based. Participants: There were 303 nonobese patients with CAD, of whom 213 with OSA (apnea-hypopnea index [AHI] >/=15 events/h) and 90 without OSA (AHI < 5 events/h). Obese patients with CAD and OSA (N = 105) were chosen as an additional control group. Interventions: None. Measurements: Circulating levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha were assessed in relation to OSA diagnosis based on AHI >/= 15 events/h as well as oxygen desaturation index (ODI) >/= 5 events/h. Results: Nonobese patients with OSA had significantly higher levels of hs-CRP and IL-6 than those without OSA. The values did not differ significantly between obese and nonobese patients with OSA. In bivariate regression analysis, AHI >/= 15 events/h was associated with all four biomarkers but not so in the multivariate model after adjustment for confounders. ODI >/= 5 events/h was associated with hs-CRP (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.13-1.99) and IL-6 (OR 1.30; 95% CI 1.05-1.60) in multivariate analysis. Conclusions: OSA with ODI >/= 5 was independently associated with increased inflammatory activity in this nonobese CAD cohort. The intermittent hypoxemia, rather than the number of apneas and hypopneas, appears to be primarily associated with enhanced inflammation.
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