Mating allocations in Holstein combining genomic information and linear programming optimization at the herd level

In this study, we explored mating allocation in Hol-stein using genomic information for 24,333 Holstein fe-males born in Denmark, Finland, and Sweden. We used 2 data sets of bulls: the top 50 genotyped bulls and the top 25 polled genotyped bulls on the Nordic total merit scale. We used linear programming to optimize economic scores within each herd, considering genetic level, genetic relationship, semen cost, the economic impact of genetic defects, polledness, and 0-casein. We found that it was possible to reduce genetic relation-ships and eliminate expression of genetic defects with minimal effect on the genetic level in total merit index. Compared with maximizing only Nordic total merit in-dex, the relative frequency of polled offspring increased from 13.5 to 22.5%, and that of offspring homozygous for 0-casein (A2A2) from 66.7 to 75.0% in one genera-tion, without any substantial negative impact on other comparison criteria. Using only semen from polled bulls, which might become necessary if dehorning is banned, considerably reduced the genetic level. We also found that animals carrying the polled allele were less likely to be homozygous for 0-casein (A2A2) and more likely to be carriers of the genetic defect HH1. Hence, adding economic value to a monogenic trait in the economic score used for mating allocation sometimes negatively affected another monogenetic trait. We rec-ommend that the comparison criteria used in this study be monitored in a modern genomic mating program

Health-care costs of losartan and candesartan in the primary treatment of hypertension

A recent study of two widely used angiotensin receptor blockers reported a reduced risk of cardiovascular events (−14.4%) when using candesartan compared with losartan in the primary treatment of hypertension. In addition to clinical benefits, costs associated with treatment strategies must be considered when allocating scarce health-care resources. The aim of this study was to assess resource use and costs of losartan and candesartan in hypertensive patients. Resource use (drugs, outpatient contacts, hospitalizations and laboratory tests) associated with losartan and candesartan treatment was estimated in 14 100 patients in a real-life clinical setting. We electronically extracted patient data from primary care records and mandatory Swedish national registers for death and hospitalization. Patients treated with losartan had more outpatient contacts (+15.6%), laboratory tests (+13.8%) and hospitalizations (+13.8%) compared with the candesartan group. During a maximum observation time of 9 years, the mean total costs per patient were 10 369 Swedish kronor (95% confidence interval: 3109–17 629) higher in the losartan group. In conclusion, prescribing candesartan for the primary treatment of hypertension results in lower long-term health-care costs compared with losartan

Functional Dissection of Streptococcus pyogenes M5 Protein: the Hypervariable Region is Essential for Virulence

The surface-localized M protein of Streptococcus pyogenes is a major virulence factor that inhibits phagocytosis, as determined ex vivo. Because little is known about the role of M protein in vivo we analyzed the contribution of different M protein regions to virulence, using the fibrinogen (Fg)-binding M5 protein and a mouse model of acute invasive infection. This model was suitable, because M5 is required for mouse virulence and binds mouse and human Fg equally well, as shown here. Mixed infection experiments with wild type bacteria demonstrated that mutants lacking the N-terminal hypervariable region (HVR) or the Fg-binding B-repeat region were strongly attenuated, while a mutant lacking the conserved C-repeats was only slightly attenuated. Because the HVR of M5 is not required for phagocytosis resistance, our data imply that this HVR plays a major but unknown role during acute infection. The B-repeat region is required for phagocytosis resistance and specifically binds Fg, suggesting that it promotes virulence by binding Fg. However, B-repeat mutants were attenuated even in Fg-deficient mice, implying that the B-repeats may have a second function, in addition to Fg-binding. These data demonstrate that two distinct M5 regions, including the HVR, are essential to virulence during the early stages of an infection. In particular, our data provide the first in vivo evidence that the HVR of an M protein plays a major role in virulence, focusing interest on the molecular role of this region

Effects of losartan vs candesartan in reducing cardiovascular events in the primary treatment of hypertension

Although angiotensin receptor blockers have different receptor binding properties no comparative studies with cardiovascular disease (CVD) end points have been performed within this class of drugs. The aim of this study was to test the hypothesis that there are blood pressure independent CVD-risk differences between losartan and candesartan treatment in patients with hypertension without known CVD. Seventy-two primary care centres in Sweden were screened for patients who had been prescribed losartan or candesartan between the years 1999 and 2007. Among the 24 943 eligible patients, 14 100 patients were diagnosed with hypertension and prescribed losartan (n=6771) or candesartan (n=7329). Patients were linked to Swedish national hospitalizations and death cause register. There was no difference in blood pressure reduction when comparing the losartan and candesartan groups during follow-up. Compared with the losartan group, the candesartan group had a lower adjusted hazard ratio for total CVD (0.86, 95% confidence interval (CI) 0.77–0.96, P=0.0062), heart failure (0.64, 95% CI 0.50–0.82, P=0.0004), cardiac arrhythmias (0.80, 95% CI 0.65–0.92, P=0.0330), and peripheral artery disease (0.61, 95% CI 0.41–0.91, P=0.0140). No difference in blood pressure reduction was observed suggesting that other mechanisms related to different pharmacological properties of the drugs may explain the divergent clinical outcomes

Prevalence of lipid abnormalities before and after introduction of lipid modifying therapy among Swedish patients with dyslipidemia (PRIMULA)

<p>Abstract</p> <p>Background</p> <p>Data on the prevalence of dyslipidemia and attainment of goal/normal lipid levels in a Swedish population are scarce. The objective of this study is to estimate the prevalence of dyslipidemia and attainment of goal/normal lipid levels in patients treated with lipid modifying therapy (LMT).</p> <p>Methods</p> <p>This longitudinal retrospective observational study covers time periods before and after treatment. Data were collected from 1994-2007 electronic patient records in public primary healthcare centers in Uppsala County, Sweden. Patients were included if they had been treated with LMT and had at least one lipid abnormality indicating dyslipidemia and if complete lipid profile data were available. Thresholds levels for lipids were defined as per Swedish guidelines.</p> <p>Results</p> <p>Among 5,424 patients included, at baseline, the prevalence of dyslipidemia (≥1 lipid abnormality) was by definition 100%, while this figure was 82% at follow-up. At baseline, 60% had elevated low-density lipoprotein (LDL-C) combined with low high-density lipoprotein (HDL-C) and/or elevated triglycerides (TG s), corresponding figure at follow-up was 36%. Low HDL-C and/or elevated TGs at follow-up remained at 69% for patients with type 2 diabetes mellitus (T2DM), 50% among patients with coronary heart disease (CHD) and 66% among patients with 10 year CHD risk >20%. Of the total sample, 40% attained goal levels of LDL-C and 18% attained goal/normal levels on all three lipid parameters.</p> <p>Conclusions</p> <p>Focusing therapy on LDL-C reduction allows 40% of patients to achieve LDL-C goal and helps reducing triglyceride levels. Almost 60% of patients experience persistent HDL-C and/or triglyceride abnormality independently of LDL-C levels and could be candidates for additional treatments.</p

A lake as a microcosm: reflections on developments in aquatic ecology

In the present study, we aim at relating Forbes' remarkable paper on "The lake as a microcosm", published 125 years ago, to the present status of knowledge in our own research group. Hence, we relate the observations Forbes made to our own microcosm, Lake Krankesjon in southern Sweden, that has been intensively studied by several research groups for more than three decades. Specifically, we focus on the question: Have we made any significant progress or did Forbes and colleagues blaze the trail through the unknown wilderness and we are mainly paving that intellectual road? We conclude that lakes are more isolated than many other biomes, but have, indeed, many extensions, for example, input from the catchment, fishing and fish migration. We also conclude that irrespective of whether lakes should be viewed as microcosms or not, the paper by Forbes has been exceptionally influential and still is, especially since it touches upon almost all aspects of the lake ecosystem, from individual behaviour to food web interactions and environmental issues. Therefore, there is no doubt that even if 125 years have passed, Forbes' paper still is a source of inspiration and deserves to be read. Hence, although aquatic ecology has made considerable progress over the latest century, Forbes might be viewed as one of the major pioneers and visionary scientists of limnology

Importance of casein micelle size and milk composition for milk gelation.

The economic output of the dairy industry is to a great extent dependent on the processing of milk into other milk-based products such as cheese. The yield and quality of cheese are dependent on both the composition and technological properties of milk. The objective of this study was to evaluate the importance and effects of casein (CN) micelle size and milk composition on milk gelation characteristics in order to evaluate the possibilities for enhancing gelation properties through breeding. Milk was collected on 4 sampling occasions at the farm level in winter and summer from dairy cows with high genetic merit, classified as elite dairy cows, of the Swedish Red and Swedish Holstein breeds. Comparisons were made with milk from a Swedish Red herd, a Swedish Holstein herd, and a Swedish dairy processor. Properties of CN micelles, such as their native and rennet-induced CN micelle size and their zeta-potential, were analyzed by photon correlation spectroscopy, and rennet-induced gelation characteristics, including gel strength, gelation time, and frequency sweeps, were determined. Milk parameters of the protein, lipid, and carbohydrate profiles as well as minerals were used to obtain correlations with native CN micelle size and gelation characteristics. Milk pH and protein, CN, and lactose contents were found to affect milk gelation. Smaller native CN micelles were shown to form stronger gels when poorly coagulating milk was excluded from the correlation analysis. In addition, milk pH correlated positively, whereas Mg and K correlated negatively with native CN micellar size. The milk from the elite dairy cows was shown to have good gelation characteristics. Furthermore, genetic progress in relation to CN micelle size was found for these cows as a correlated response to selection for the Swedish breeding objective if optimizing for milk gelation characteristics. The results indicate that selection for smaller native CN micelles and lower milk pH through breeding would enhance gelation properties and may thus improve the initial step in the processing of cheese