Danish milk consumers are critical of advanced breeding methods in dairy production, but only 1 in 5 is unwilling to drink milk from dairy cows bred with semen derived from such methods.

Assisted reproductive technologies and genetic technologies can accelerate progress in breeding programs in dairy farming, but it is unclear how consumers will react to the use of these technologies. Using representative questionnaire data on Danish citizens (n = 2,036) this cross-sectional study examined consumer attitudes to the application of advanced technologies in dairy cattle breeding. Attitudes were examined in 2 ways. First, we prompted about general attitudes to assisted reproductive technologies and genetic technologies in dairy cow breeding. Here we found that most of the participants were critical of cow impregnation involving hormone therapy and the insertion of cloned fetuses. Second, we used a vignette experiment to study whether acceptance of and willingness to drink milk varies with the type of technique that farmers use for their breeding work, as well as the traits being bred for. We included 5 breeding methods with differing degrees of technological complexity. Participants were randomly assigned to receive tailored information about 1 of the 5 breeding methods. The information specified that dairy farmers' own use of advanced technologies is limited to using semen in artificial insemination on the farm. The potentially concerning technologies are here not applied at farm level but are represented in the semen used in artificial insemination because they were used by breeders on earlier generations of cows and bulls to develop semen with higher genetic merit. There was much less concern about this indirect use of the technologies. Only 1 in 5 participants thought the most advanced method we prompted about (use of semen from breeding methods involving genetic engineering and cloning) was unacceptable. Unwillingness to drink milk from cows produced through such a breeding method was also modest (18%) and not much higher than the unwillingness to drink milk from a cow produced by natural fertilization (10%). A likely reason for the unexpectedly low level of unwillingness to drink milk is that people regard the genetic engineering as distant from the final product. We also found that high-frequency organic milk consumers were more critical of advanced breeding methods. Thus, 28% within this group were unwilling to drink milk from cows impregnated with semen derived from earlier generations of cows and bulls bred using gene editing and cloning. Further, this share rose if the high-frequency organic consumers were very averse to the manipulation of nature. The organic sector may need to cater to this subgroup (e.g., by ensuring the traceability of the semen that organic farmers use to artificially inseminate their cows).

Danish dairy farmers' acceptance of and willingness to use semen from bulls produced by means of in vitro embryo production and genomic selection.

A novel technology combining in vitro production and genomic embryo selection is currently under development in dairy cattle breeding. Adoption of this technology will probably accelerate genetic progress toward the main breeding goals of economic interest, as well as allow selection for traits of societal concern such as decreased methane emissions and improved animal welfare. However, dairy farmers, and especially organic farmers, could find the technology morally questionable and reject its use. This cross-sectional study surveyed Danish dairy farmers' general acceptance of the combined technology and their reported likelihood of using semen produced with it. Drawing on diffusion theory, a questionnaire was developed to examine the way farmers discover and communicate about new technological breeding options, and to measure the factors which predict acceptance and likelihood of adopting the technology. The questionnaire was sent to a randomly selected sample of organic and conventional dairy farmers in Denmark, and 85 organic and 71 conventional farmers (41% response rate) completed it. Seventy-six percent of farmers reported that they would be likely to use semen from bulls derived from the technology. A majority (61%) also found the technology acceptable, but many (33%) were unsure or undecided. Most farmers saw the technology as beneficial, but ethical reservations were aired by around a fifth of the farmers. There were no differences between organic and conventional farmers in likelihood of using, perceived utility, and ethical reservations about the technology. Self-reported idealistic organic farmers showed lower acceptance of the technology, but reported similar likelihood of using semen produced by it. Young farmers (20-39 yr) exhibited higher acceptance of the technology. Larger producers (in terms of number of cows) were more likely to report that they will use and accept the technology. We conclude that it is likely that semen from the technology combining in vitro production and genomic selection would be widely used by both organic and conventional farmers provided that costs can be kept low, and that there are advantages in terms of achieving breeding goals. Structural developments, growth in size of dairy farms, acceptance by young farmers, and the fact that economic incentives (and even ethical arguments) seem to favor the technology all point to this conclusion.

Antimicrobial resistance and virulence characteristics in 3 collections of staphylococci from bovine milk samples.

Mastitis is a prevalent disease in dairy cattle, and staphylococci are among the most common causative pathogens. Staphylococci can express resistance to a range of antimicrobials, of which methicillin resistance is of particular public health concern. Additionally, Staphylococcus aureus carries a variety of virulence factors, although less is understood about the virulence of non-aureus staphylococci (NAS). The aim of our study was to identify and characterize 3 collections of staphylococcal isolates from bovine milk samples regarding antimicrobial resistance, with emphasis on methicillin resistance, and their carriage of virulence genes typically displayed by Staph. aureus. A total of 272 staphylococcal isolates collected in Norway and Belgium in 2016 were included, distributed as follows: group 1, Norway, 100 isolates; group 2, Flanders, Belgium, 64 isolates; group 3, Wallonia, Belgium, 108 isolates. Species identification was performed by use of MALDI-TOF mass spectrometry. Phenotypic resistance was determined via disk diffusion, and PCR was used for detection of methicillin resistance genes, mecA and mecC, and virulence genes. Antimicrobial resistance was common in Staphylococcus epidermidis and Staphylococcus haemolyticus from all different groups, with resistance to trimethoprim-sulfonamide frequently occurring in Staph. epidermidis and Staph. haemolyticus as well as in Staph. aureus. Resistance to penicillin was most frequently observed in group 1. Ten Belgian isolates (1 from group 2, 9 from group 3) carried the methicillin resistance determinant mecA: 5 Staph. aureus from 2 different farms and 5 NAS from 3 different farms. Almost all Staph. aureus isolates were positive for at least 3 of the screened virulence genes, whereas, in total, only 8 NAS isolates harbored any of the same genes. Our study contributes to the continuous need for knowledge regarding staphylococci from food-producing animals as a basis for better understanding of occurrence of resistance and virulence traits in these bacteria.

Investigation of factors influencing the immunogenicity of hCG as a potential cancer vaccine.

Human chorionic gonadotrophin (hCG) and its ß-subunit (hCGß) are tumour autocrine growth factors whose presence in the serum of cancer patients has been linked to poorer prognosis. Previous studies have shown that vaccines which target these molecules and/or the 37 amino acid C-terminal hCGß peptide (hCGßCTP) induce antibody responses in a majority of human recipients. Here we explored whether the immunogenicity of vaccines containing an hCGß mutant (hCGßR68E, designed to eliminate cross-reactivity with luteinizing hormone) or hCGßCTP could be enhanced by coupling the immunogen to different carriers [keyhole limpet haemocyanin (KLH) or heat shock protein 70 (Hsp70)] using different cross-linkers [1-ethyl-3(3-dimethylaminopropyl)carboiimide (EDC) or glutaraldehyde (GAD)] and formulated with different adjuvants (RIBI or Montanide ISA720). While there was little to choose between KLH and Hsp70 as carriers, their influence on the effectiveness of a vaccine containing the BAChCGßR68E mutant was less marked, presumably because, being a foreign species, this mutant protein itself might provide T helper epitopes. The mutant provided a significantly better vaccine than the hCGßCTP peptide irrespective of the carrier used, how it was cross-linked to the carrier or which adjuvant was used when hCG was the target. Nonetheless, for use in humans where hCG is a tolerated self-protein, the need for a carrier is of fundamental importance. Highest antibody titres were obtained by linking the BAChCGßR68E to Hsp70 as a carrier by GAD and using RIBI as the adjuvant, which also resulted in antibodies with significantly higher affinity than those elicited by hCGßCTP peptide vaccine. This makes this mutant vaccine a promising candidate for therapeutic studies in hCGß-positive cancer patients.

Safety evaluation of a novel muramidase for feed application.

Safety evaluation of a muramidase produced by a Trichoderma reesei strain (safe lineage), expressing a muramidase gene isolated from Acremonium alcalophilum is presented. Intended use in feed of this enzyme is as digestive aid in broiler chickens. Muramidase 007, was non-mutagenic and non-clastogenic in vitro, and no adverse effects were observed in 90-day subchronic toxicity studies in rats at doses up to 1132 mg TOS/kg body weight/day. The enzyme did not exhibit, in vitro, skin, nor eye irritation potential. Acute aquatic toxicity evaluated on daphnia and algae showed absence of effect of the enzyme at the standard doses tested. Muramidase 007 was fully tolerated by broiler chickens in a 6-weeks tolerance study showing no adverse effects in any of the dietary treatments (0, 1×, 5× and 10× maximum recommended dose). In conclusion, Muramidase 007 is found to be toxicologically inert, and there are no worker's safety concerns if standard precautions are instituted and a non-dusty formulation is employed. Muramidase 007 is well tolerated by the target species (broiler chickens) and cause no harm to the environment. The beneficial safety evaluation of Muramidase 007 is in line with this type of enzyme that is found ubiquitously in nature.

Eating out in four Nordic countries: National patterns and social stratification.

Using a survey conducted in four Nordic countries (Denmark, Finland, Norway and Sweden) in 2012, we investigated whether eating out in cafés and restaurants in these countries is best characterized as a workday pattern activity or a leisure activity; and, whether frequent eating at cafés and restaurants is related to socio-demographic factors and factors relevant to the organization of daily life. We found that eating out is not a fundamental part of everyday eating. It is something which takes place occasionally. This may be taken to suggest that eating out in the Nordic countries is primarily a leisure activity. However, while this is an accurate portrayal of Denmark and Norway, eating out in Finland and Sweden is somewhat more common and linked to work-life. This difference probably reflects contrasting historical-institutional paths: in Finland and Sweden a food culture emphasizing cooked lunches and dedicated public policies supporting the provisioning of lunches outside the home may have promoted eating out. Multivariate analysis revealed that eating out declines with age. An urbanization effect exists, as residence in a capital city increases the propensity to eat out. There were socio-economic differences in all countries. We hypothesized that education and status would not significantly explain eating out activity after people's gastronomic interest had been controlled for. However, education was statistically significant in Sweden and Norway, and surprisingly status was negatively associated with eating out in Sweden. As expected, eating out was positively associated with income, and it was more frequent among the higher salariat and the self-employed (although not in Norway).

Brains striving for coherence: Long-term cumulative plot formation in the default mode network.

Many everyday activities, such as engaging in conversation or listening to a story, require us to sustain attention over a prolonged period of time while integrating and synthesizing complex episodic content into a coherent mental model. Humans are remarkably capable of navigating and keeping track of all the parallel social activities of everyday life even when confronted with interruptions or changes in the environment. However, the underlying cognitive and neurocognitive mechanisms of such long-term integration and profiling of information remain a challenge to neuroscience. While brain activity is generally traceable within the short time frame of working memory (milliseconds to seconds), these integrative processes last for minutes, hours or even days. Here we report two experiments on story comprehension. Experiment I establishes a cognitive dissociation between our comprehension of plot and incidental facts in narratives: when episodic material allows for long-term integration in a coherent plot, we recall fewer factual details. However, when plot formation is challenged, we pay more attention to incidental facts. Experiment II investigates the neural underpinnings of plot formation. Results suggest a central role for the brain's default mode network related to comprehension of coherent narratives while incoherent episodes rather activate the frontoparietal control network. Moreover, an analysis of cortical activity as a function of the cumulative integration of narrative material into a coherent story reveals to linear modulations of right hemisphere posterior temporal and parietal regions. Together these findings point to key neural mechanisms involved in the fundamental human capacity for cumulative plot formation.

Extralevator versus standard abdominoperineal excision for rectal cancer.

BACKGROUND: Extralevator abdominoperineal excision (ELAPE) probably improves the oncological quality of low rectal cancer surgery, as compared to standard abdominoperineal excision (SAPE), possibly due to lower rates of accidental perioperative bowel perforations and lower rates of circumferential resection margin (CRM) positivity. The procedure may however, increase post-operative morbidity. The aim of this paper was to compare outcomes of SAPE and ELAPE for carcinoma of the lower rectum. METHODS: This is a retrospective study of patients operated on at a single colorectal unit, in a provincial hospital in Denmark. Consecutive patients undergoing abdominoperineal excision (APE) between 2006 and 2012 were included. During this period, a gradual paradigm shift occurred towards adopting ELAPE, although both procedures were performed without a clear selection strategy. We reviewed medical records, including the pathological and radiological data. Patients were divided into two groups, SAPE and ELAPE. Main endpoints were rates of positive CRM, intraoperative bowel perforations, local recurrence rate, length of hospital stay, operative time, and perineal wound-related complications. RESULTS: One hundred and seven patients were included (median age 68 years, range 42-88 years; men = 72). The SAPE group included 39 patients and the ELAPE group 68 patients. Intraoperative bowel perforation was significantly lower in the ELAPE group (20.5% SAPE vs 7.4% ELAPE, p = 0.045). The rate of positive CRM was not significantly different (2.6% SAPE vs 7.4% ELAPE, p = 0.413). The local recurrence rate was not statistically significant (17.9% SAPE vs 13.2% ELAPE, p = 0.513). In the ELAPE group, operative time and hospital stay were significantly longer than the SAPE group (p = 0.001 and p = 0.021, respectively). CONCLUSIONS: We found low rates of positive CRM after APE compared with the literature. ELAPE did not reduce these rates, and although the local recurrence rate was lower, this did not reach statistical significance. ELAPE has significantly reduced the rate of intraoperative bowel perforation and can optimize low rectal cancer surgery in selected patients. We found no significant differences between the two procedures regarding wound-related complications. A tailored approach and a larger trial with longer follow-up are needed to evaluate long-term results.

A classification of components of workplace disability management programs: results from a systematic review.

PURPOSE: This paper presents results from a Campbell systematic review on the nature and effectiveness of workplace disability management programs (WPDM) promoting return to work (RTW), as implemented and practiced by employers. A classification of WPDM program components, based on the review results, is proposed. METHODS: Twelve databases were searched between 1948 to July 2010 for peer-reviewed studies of WPDM programs provided by employers to re-entering workers with occupational or non-occupational illnesses or injuries. Screening of articles, risk of bias assessment and data extraction were conducted in pairs of reviewers. Studies were clustered around various dimensions of the design and context of programs. RESULTS: 16,932 records were identified by the initial search. 599 papers were assessed for relevance. Thirteen studies met inclusion criteria. Twelve peer reviewed articles (two non-randomized studies, and ten single group experimental before and after studies), including ten different WPDM programs informed the synthesis of results. Narrative descriptions of the included program characteristics provided insight on program scope, components, procedures and human resources involved. However, there were insufficient data on the characteristics of the sample and the effect sizes were uncertain. A taxonomy classifying policies and practices around WPDM programs is proposed. CONCLUSION: There is insufficient evidence to draw conclusions on the effectiveness of employer provided WPDM programs promoting RTW. It was not possible to determine if specific program components or specific sets of components are driving effectiveness. The proposed taxonomy may guide future WPDM program evaluation and clarify the setup of programs offered to identify gaps in existing company strategies.

Dilated Optic Nerve Sheath in Mucopolysaccharidosis I: Common and Not Necessarily High Intracranial Pressure.

Hydrocephalus is one of the earliest manifestations of mucopolysaccharidosis I-Hurler syndrome, and delayed treatment of hydrocephalus can lead to neurocognitive delay or even death. Optic nerve sheath diameter has been established as a noninvasive measurement to detect elevated intracranial pressure. This study aimed to establish correlations between optic nerve sheath diameter and opening pressure. Forty-nine MR images and opening pressures in patients with mucopolysaccharidosis I-Hurler syndrome were retrospectively reviewed from 2008 to 2020. The optic nerve sheath diameter was measured 3 mm posterior to the posterior margin of the globe (retrobulbar) and 10 mm anterior to the optic foramen (midpoint segment), and the average was taken between the 2 eyes. Opening pressure was measured with the patient in the lateral decubitus position with controlled end-tidal CO2 on the same day as the MR imaging. The average retrobulbar optic nerve sheath diameter was 5.33 mm, higher than the previously reported measurement in healthy controls, in patients with idiopathic intracranial hypertension, and there was a positive correlation between age and the optic nerve sheath diameter measured at the retrobulbar or midpoint segment (retrobulbar segment, R 2 = 0.27, P < .01; midpoint segment, R 2 = 0.20, P < .01). However, there was no correlation between retrobulbar or midpoint segment optic nerve sheath diameter and opening pressure (retrobulbar segment, R 2 = 0.02, P = .17; midpoint segment, R 2 = 0.03, P < .12). This study shows a higher average optic nerve sheath diameter in patients with mucopolysaccharidosis I-Hurler syndrome than in healthy controls regardless of the location of the measurement. However, the degree of optic nerve sheath dilation does not correlate with opening pressure, suggesting that increased optic nerve sheath diameter is an ocular manifestation of mucopolysaccharidosis I-Hurler syndrome itself rather than a marker of elevated intracranial pressure.

Appetite stimulation with cannabis-based medicine and methods for assessment of glomerular filtration in older patients with medical illness: A study protocol.

BACKGROUND AND AIM: Malnutrition in older patients is linked to poor appetite. Cannabis-based medicine may have orexigenic properties in older patients, but this has to our knowledge never been investigated. In older patients, uncertainty applies to the accuracy of estimated glomerular filtration rate (eGFR) based on creatinine, which is crucial for medication prescribing. In older patients with poor appetite, the study aims (1) to assess the efficacy of Sativex® (8.1-mg delta-9-tetrahydrocannabinol [THC] and 7.5-mg cannabidiol [CBD]) to stimulate appetite and (2) to compare the performance of various GFR-estimates and measured-GFR (mGFR) for determining gentamicin clearance utilizing population pharmacokinetic (popPK) modelling methods. METHODS AND OBJECTIVES: This study is composed of two substudies. Substudy 1 is an investigator-initiated single-center, double-blinded, randomized, placebo-controlled, superiority, cross-over study. Substudy 1 will recruit 17 older patients with poor appetite, who will also be invited to substudy 2. Substudy 2 is a single-dose pharmacokinetics study and will recruit 55 patients. Participants will receive Sativex® and placebo in substudy 1 and gentamicin with simultaneous measurements of GFR in substudy 2. The primary endpoints are as follows: Substudy 1-the difference in energy intake between Sativex® and placebo conditions; substudy 2- the accuracy of different eGFR equations compared to mGFR. The secondary endpoints include safety parameters, changes in the appetite hormones, total ghrelin and GLP-1 and subjective appetite sensations, and the creation of popPK models of THC, CBD, and gentamicin.

K(ATP) channel openers in the trigeminovascular system.

BACKGROUND: The ATP-sensitive K(+) (K(ATP)) channel openers levcromakalim and pinacidil are vasodilators that induce headache in healthy people. The neuropeptide calcitonin gene-related peptide (CGRP) induces headache in healthy people and migraine in migraineurs, potentially through a mechanism that involves opening of vascular or neuronal K(ATP) channels and mast cell degranulation. Using rat as a model, we studied the molecular presence of K(ATP) channels in the trigeminovascular system. Furthermore, we examined whether K(ATP) channel openers stimulate the in vitro release of CGRP and whether they degranulate dural mast cells. METHODS: mRNA and protein expression of K(ATP) channel subunits were studied in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) by qPCR and western blotting. In vitro CGRP release was studied after application of levcromakalim (1 µM) and diazoxide (10 µM) to freshly isolated rat dura mater, TG and TNC. Rat dural mast cells were challenged in situ with levcromakalim (10(-5) M) to study its potential degranulation effect. RESULTS: mRNA and protein of K(ATP) channel subunits Kir6.1, Kir6.2, SUR1 and SUR2B were identified in the TG and TNC. K(ATP) channel openers did not release or inhibit capsaicin-induced CGRP release from dura mater, TG or TNC. They did also not induce dural mast cell degranulation. CONCLUSIONS: K(ATP) channel openers do not interact with CGRP release or mast cell degranulation. Activation of these channels in the CNS is antinociceptive and therefore cannot explain the headache induced by K(ATP) channel openers. Thus, they are likely to induce headache by interaction with extracerebral K(ATP) channels, probably the SUR2B isoforms.

Isolation of Bacillus anthracis from soil in selected high-risk areas of Zimbabwe.

AIMS: To isolate Bacillus anthracis from cattle carcass burial sites from high-risk districts in Zimbabwe. METHODS AND RESULTS: Soil samples were collected from carcass burial sites from seven areas, including two national game parks. Samples were collected from top 5-10 cm, and for spore extraction, 25 g of soil was suspended in sterile distilled water overnight. Supernatants were filtered through 0.45-µm pore cellulose nitrate, deposits suspended in 5 ml phosphate-buffered saline, aliquoted and heated at temperature regimen of 65, 70, 75 and 80 °C for 15 min. Samples were plated onto PLET agar. B. anthracis isolates were identified using growth morphology and PCR detecting pXO1 and pXO2 virulence plasmids. From samples heated at 75 °C for 15 min, B. anthracis were isolated from 9 of 81 (11.1%) soil samples representing five of the seven sampled areas. CONCLUSIONS: We isolated B. anthracis from soil collected from carcass burial sites. PCR targeting virulence plasmids provided a rapid confirmation of B. anthracis. SIGNIFICANCE AND IMPACT OF THE STUDY: The positive isolation indicated that some carcass burial sites may retain viable spores for at least 12 months after the previous outbreak, which suggests that they may be important sources of B. anthracis and new disease outbreaks.

Does muscle strength predict future musculoskeletal disorders and sickness absence?

BACKGROUND: High muscle strength is considered relevant for preventing musculoskeletal disorders and long-term sickness absence. However, prospective studies on the association between muscle strength and future musculoskeletal disorders and long-term sickness absence are few and show contrasting results. AIMS: To investigate the association between low muscle strength and future musculoskeletal disorders and long-term sickness absence. METHODS: Muscle strength in trunk flexion and extension, shoulder elevation and abduction as well as handgrip was recorded from a representative sample of Danish workers (n = 421) in 1995. Musculoskeletal disorders were reported 5 years later (in 2000). Information on long-term sickness absence was retrieved from a register of social transfer payments in the period 1996-2007. RESULTS: Regression analyses adjusted for age, gender, smoking, body mass index and physical work demands showed that workers with low muscle strength (the lowest quartile) of trunk extension and flexion, shoulder elevation and abduction and handgrip did not have a significantly increased risk for future musculoskeletal disorders or long term sickness absence compared with stronger workers. CONCLUSIONS: Low muscle strength does not seem to be a good predictor for musculoskeletal disorders and long-term sickness absence in the general working population.

Irreversible damage in ovine ovarian tissue after cryopreservation in propanediol: analyses after in vitro culture and xenotransplantation.

Current progress in cancer treatment has increased the incidence of long-term patient survival. Ovarian tissue cryopreservation (OT) is still the most promising fertility saving method offered to young female patients with cancer prior to the onset of radio-chemotherapy. Further follicular development of immature primordial follicles depends on transplantation or in vitro culture (IVC). Aim of this study was to evaluate the appropriateness of cryopreserved ovine OT with 1,2-propanediol (PROH) after short-term IVC and xenotransplantation (XT). Ovarian tissue fragments from young adult sheep were cryopreserved using a standard slow-freezing protocol with 1.5 M PROH. Cryopreserved OT was assessed by light- and transmission electron microscopic analyses after thawing, IVC or XT in severe immunodeficient mice. Control OT showed the presence of healthy preantral follicles (Mean: 78.8%; SE 2.9%) and normal structure of the stromal tissue. After thawing and IVC over 80% of damaged primordial follicles and poor preservation of the stromal tissue was observed. After XT, OT demonstrated deficient follicles and huge areas of vacuolization in the stromal tissue confirmed by ultrastructural assessment. In conclusion, because of the irreversible character of the follicular and stromal damage of cryopreserved ovine ovarian tissue after IVC and XT, strong improvement of the utilized protocol is needed to be suitable for the preservation of ovine ovarian tissue. The deleterious effects of PROH do not imply its exclusion as cryoprotectant, but more research is needed for the development of less toxic cryoprotectant mixtures and toxicity neutralizers with attested cryoprotectant capacity for the safe and feasible freezing of human ovarian tissue.

In vitro and in vivo assessment of phage therapy against Staphylococcus aureus causing bovine mastitis.

OBJECTIVE: The aim of this study was to assess the efficacy of lytic bacteriophages on Staphylococcus aureus causing bovine mastitis, by in vitro and in vivo assays using Galleria mellonella and murine mastitis models. METHODS: Between May and December 2016, ten S. aureus (five methicillin-resistant and five methicillin-sensitive) isolates were isolated from milk samples of cattle with mastitis in Belgium and Norway. The isolates were assessed in vitro for their susceptibility to four lytic bacteriophages (Romulus, Remus, ISP and DSM105264) and subsequently in vivo in G. mellonella larvae and in murine mastitis model. RESULTS: Romulus, Remus and ISP showed a lytic activity against the S. aureus isolates in vitro. A larvae survival rate below 50% was observed at 4 days post-inoculation (DPI) in the groups infected with a methicillin-sensitive S. aureus isolate and treated with these three phages in vivo. An incomplete recovery of the mouse mastitis was observed at 48h post-inoculation (HPI) in the groups infected and treated with the ISP phage in vivo. CONCLUSIONS: The observations are much more pronounced statistically between the infected- phosphate buffered saline (PBS)-treated and infected-phage-treated groups in G. mellonella and the murine mastitis model demonstrating an effect of the phages against S. aureus associated with bovine mastitis.

The synthetic liver X receptor agonist GW3965 reduces tissue factor production and inflammatory responses in human islets in vitro.

AIMS/HYPOTHESIS: Optimising islet culture conditions may be one strategy for reducing islet loss prior to, and immediately after, islet transplantation. Liver X receptor (LXR) agonism has previously been shown to increase insulin release from pancreatic islets and reduce inflammation in leucocytes. Our aim was to investigate whether the synthetic LXR agonist GW3965 could modulate the inflammatory status of human pancreatic islets. METHODS: Levels of pro-inflammatory cytokines and tissue factor in isolated human islets were determined by TaqMan low density array and/or real-time quantitative RT-PCR (mRNA levels) and enzyme immunoassay (EIA) (protein levels). Islet viability was measured using intracellular ATP content, ADP/ATP ratio, mitochondrial dehydrogenase activity (XTT assay) and insulin secretion in a dynamic glucose-challenge model. Apoptosis was determined by EIA measurement of histone-DNA complexes present in cytoplasm and by assaying caspase-3/-7 activity. RESULTS: Treatment of LPS-stimulated human islets with the synthetic LXR agonist GW3965 (1 micromol/l) for 24 h reduced mRNA and protein levels of selected pro-inflammatory cytokines (IL-8, monocyte chemotactic protein-1 and tissue factor). Moreover, GW3965 had no adverse effect on insulin secretion, islet viability or apoptosis. No excess of lipid accumulation could be detected with the dosage and exposure time used. CONCLUSIONS/INTERPRETATION: LXR activation suppresses inflammation in human islets in vitro without adverse effects on islet viability. Short-term moderate activation of LXR prior to islet transplantation may represent a possible strategy for improving post-transplant islet survival.

A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma.

Several studies have evaluated the impact of low dose statin (20-80 mg/day) on bone metabolism with inconclusive results despite promising data of preclinical studies. In this study, we investigated the effect of high dose simvastatin (HD-Sim) on biochemical markers of bone turnover and disease activity in six heavily pretreated patients with multiple myeloma (MM). These patients were treated with simvastatin (15 mg/kg/day) for 7 days followed by a rest period of 21 days in two 4-week cycles. Endpoints were changes in the level of biochemical markers of (i) osteoclast activity (tartrate resistant acid phosphatase, TRACP); (ii) bone resorption (collagen fragments CTX and NTX); (iii) bone formation (osteocalcin and aminoterminal propeptide of type I collagen PINP); (iv) cholesterol; (v) regulators of bone metabolism [osteoprotegerin (OPG) and Dickkopf-1 (DKK-1)] and (vi) disease activity (monoclonal proteins or free light chains in serum). TRACP activity in serum and levels of collagen fragments (NTX) in urine increased for all patients temporarily during the 7 days of treatment with HD-Sim indicating that osteoclasts may have been stimulated rather than inhibited. The other markers of bone metabolism showed no change. None of the patients showed any reduction in free monoclonal light chains or monoclonal proteins in serum during treatment with HD-Sim. In spite of the fact that bone turn over effects of HD-Sim may have been blunted by concomitant treatment of patients with other drugs we observed a transient increase in markers of osteoclast activity. This sign of a transient stimulation of osteoclast activity suggests that HD-Sim may be harmful rather than beneficial for MM patients. For this reason and because of gastro-intestinal side effects the study was stopped prematurely.

Socio-economic differences in the association between sickness absence and mortality: the prospective DREAM study of Danish private sector employees.

OBJECTIVES: To examine duration of sickness absence as a risk marker for future mortality by socio-economic position among all private sector employees in Denmark in 1998-2004. METHODS: All residents in Denmark employed in the private sector receiving sickness absence compensation in 1998 were investigated in a prospective cohort study. 236 207 persons (38.2% women, 61.8% men, age range 18-65, mean age 37.8 years) alive on 1 January 2001 were included in the study. Mortality from 1 January 2001 to 31 December 2004 was assessed using national register data. Deaths in 1999 and 2000 were excluded to determine the status of sickness absence duration as an early risk marker. For analyses within occupational grades, data were available for a sub-population of 137 607 study participants. RESULTS: 3040 persons died during follow-up. The age-adjusted risk of future mortality increased by duration of sickness absence in a graded fashion among men and non-blue collar workers. Among women and blue collar workers, there was no association of mortality with duration of sickness absences below 6 weeks. However, employees with > or =6 weeks of absence compared to those with 1-week absence had a substantial excess risk of death in all groups: adjusted hazard ratio 2.2 (95% CI 1.8 to 2.7) for women, 2.1 (95% CI 1.8 to 2.4) for men, 3.7 (95% CI 1.9 to 7.2) in white collar occupations, 3.3 (95% CI 2.2 to 5.0) in intermediate grade occupations and 2.0 (95% CI 1.7 to 2.3) in blue collar occupations. CONCLUSION: Administratively collected data on sickness absence compensation for periods > or =6 weeks identified "at risk" groups for future excess mortality in male and female private sector employees across occupational grade levels.

Prevalence of asthma-like symptoms, asthma and its treatment in elite athletes.

The objective was to determine the prevalence of asthma-like symptoms and asthma and the use of asthma medication in Danish elite athletes. A cross-sectional questionnaire survey of Danish elite athletes was conducted in 2006. All elite athletes (N=418) financially supported by the national organization of elite athletes comprised the study group; 329 (79%) completed the questionnaire concerning their sport, asthma-like symptoms, asthma and use of asthma medication. Asthma-like symptoms at rest were reported by 41% of respondents; 55% reported asthma-like symptoms at rest or at exercise. Physician-diagnosed asthma was present in 16% and 14% had current asthma. Asthma medication was taken by 7% of the athletes, of whom 79% used inhaled corticosteroids and 21% used inhaled beta(2)-agonists only. Athletes participating in endurance sports had higher prevalences of current asthma (24%) and use of asthma medication (15%) than all other athletes (P<0.01). Athletes participating in endurance sports have a higher prevalence of asthma and use of asthma medication. The frequency of asthma medication is lower than the prevalence of current asthma indicating that there is no overuse of asthma medication among Danish elite athletes.