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Multiple myeloma is characterized by clonal proliferation of plasma cells that accumulate preferentially in the bone marrow (BM). The tumor microenvironment is one of the leading factors that promote tumor progression. Neutrophils and monocytes are a major part of the BM tumor microenvironment, but the mechanism of their contribution to multiple myeloma progression remains unclear. Here, we describe a novel mechanism by which S100A8/S100A9 proteins produced by BM neutrophils and monocytes promote the expansion of megakaryocytes supporting multiple myeloma progression. S100A8/S100A9 alone was not sufficient to drive megakaryopoiesis but markedly enhanced the effect of thrombopoietin, an effect that was mediated by Toll-like receptor 4 and activation of the STAT5 transcription factor. Targeting S100A9 with tasquinimod as a single agent and in combination with lenalidomide and with proteasome inhibitors has potent antimyeloma effect that is at least partly independent of the adaptive immune system. This newly identified axis of signaling involving myeloid cells and megakaryocytes may provide a new avenue for therapeutic targeting in multiple myeloma.Significance:We identified a novel mechanism by which myeloid cells promote myeloma progression independently of the adaptive immune system. Specifically, we discovered a novel role of S100A8/S100A9, the most abundant proteins produced by neutrophils and monocytes, in regulation of myeloma progression via promotion of the megakaryocyte expansion and angiogenesis. Tasquinimod, an inhibitor of S100A9, has potent antimyeloma effects as a single agent and in combination with lenalidomide and with proteasome inhibitors.

Supplementary Table 1. Antibodies used in the study.Supplementary Table 2. Primers used in the study.

Mechanism of S100A9 effect on MK differentiation.

Multiple myeloma is characterized by clonal proliferation of plasma cells that accumulate preferentially in the bone marrow (BM). The tumor microenvironment is one of the leading factors that promote tumor progression. Neutrophils and monocytes are a major part of the BM tumor microenvironment, but the mechanism of their contribution to multiple myeloma progression remains unclear. Here, we describe a novel mechanism by which S100A8/S100A9 proteins produced by BM neutrophils and monocytes promote the expansion of megakaryocytes supporting multiple myeloma progression. S100A8/S100A9 alone was not sufficient to drive megakaryopoiesis but markedly enhanced the effect of thrombopoietin, an effect that was mediated by Toll-like receptor 4 and activation of the STAT5 transcription factor. Targeting S100A9 with tasquinimod as a single agent and in combination with lenalidomide and with proteasome inhibitors has potent antimyeloma effect that is at least partly independent of the adaptive immune system. This newly identified axis of signaling involving myeloid cells and megakaryocytes may provide a new avenue for therapeutic targeting in multiple myeloma.Significance:We identified a novel mechanism by which myeloid cells promote myeloma progression independently of the adaptive immune system. Specifically, we discovered a novel role of S100A8/S100A9, the most abundant proteins produced by neutrophils and monocytes, in regulation of myeloma progression via promotion of the megakaryocyte expansion and angiogenesis. Tasquinimod, an inhibitor of S100A9, has potent antimyeloma effects as a single agent and in combination with lenalidomide and with proteasome inhibitors.

Supplementary Figure 4. The effect of tasquinimod on T cell proliferation and regulatory T cells.

Supplementary Figure 1. Survivin peptide vaccine, SurVaxM, induced antigen-specific CD8 effector cells in the tumor bearing animals.

ABR-238901 did not reduce viability of MDSC.

Supplementary Figure 2. Tasquinimod modulation of MDSC subpopulations in CR Myc-CaP tumor bearing FVB mice.

Supplementary Figure 3. CD11b+ in tumor and MDSC subpopulations in spleen from B16-h5T4 tumor bearing C57/Bl6 mice.

Supplementary Figure 5. The effect of tasquinimod treatment on CD11c+ dendritic cells.

Supplementary data and figure legends

Supplementary Figure Legends from Tasquinimod Modulates Suppressive Myeloid Cells and Enhances Cancer Immunotherapies in Murine Models

Supplementary Figure 6. The effect of tasquinimod on nitric oxide synthase activity in infiltrating myeloid cells.

A major barrier for cancer immunotherapy is the presence of suppressive cell populations in patients with cancer, such as myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), which contribute to the immunosuppressive microenvironment that promotes tumor growth and metastasis. Tasquinimod is a novel antitumor agent that is currently at an advanced stage of clinical development for treatment of castration-resistant prostate cancer. A target of tasquinimod is the inflammatory protein S100A9, which has been demonstrated to affect the accumulation and function of tumor-suppressive myeloid cells. Here, we report that tasquinimod provided a significant enhancement to the antitumor effects of two different immunotherapeutics in mouse models of cancer: a tumor vaccine (SurVaxM) for prostate cancer and a tumor-targeted superantigen (TTS) for melanoma. In the combination strategies, tasquinimod inhibited distinct MDSC populations and TAMs of the M2-polarized phenotype (CD206+). CD11b+ myeloid cells isolated from tumors of treated mice expressed lower levels of arginase-1 and higher levels of inducible nitric oxide synthase (iNOS), and were less immunosuppressive ex vivo, which translated into a significantly reduced tumor-promoting capacity in vivo when these cells were coinjected with tumor cells. Tumor-specific CD8+ T cells were increased markedly in the circulation and in tumors. Furthermore, T-cell effector functions, including cell-mediated cytotoxicity and IFNγ production, were potentiated. Taken together, these data suggest that pharmacologic targeting of suppressive myeloid cells by tasquinimod induces therapeutic benefit and provide the rationale for clinical testing of tasquinimod in combination with cancer immunotherapies. Cancer Immunol Res; 3(2); 136–48. ©2014 AACR.

Primer sequences of genes evaluated by qRT-PCR.

Dysregulated expression of S100 protein family members is associated with cancer proliferation, invasion, angiogenesis, and inflammation. S100A9 induces myeloid-derived suppressor cell (MDSC) accumulation and activity. MDSCs, immunosuppressive cells that contribute to tumor immune escape, are the main producers of S100A9. In this study, we evaluated the role of extracellular S100A9 and the therapeutic relevance of S100A9 inhibition in multiple myeloma (MM), using the immunocompetent murine 5T33MM model. We demonstrated the presence of S100A9 and its receptor TLR4 in both monocytic and granulocytic MDSCs in human and mouse samples. We showed that S100A9 acted as a chemoattractant for MM cells and induced MDSCs to express and secrete inflammatory and pro-myeloma cytokines, including TNFα, IL6, and IL10. Blocking S100A9 interactions in vivo with the small molecule ABR-238901 did not directly affect MDSC accumulation but did reduce IL6 and IL10 cytokine expression by MDSC. ABR-238901 treatment in vivo reduced angiogenesis but had only minor effects on tumor load as single agent (6% reduction). However, ABR-238901 treatment in combination with bortezomib resulted in an increased reduction in tumor load compared with single treatments (50% relative reduction compared with bortezomib alone). Our data suggest that extracellular S100A9 promotes MM and that inhibition of S100A9 may have therapeutic benefit. Cancer Immunol Res; 5(10); 839–46. ©2017 AACR.

Erysipelothrix rhusiopathiae (ER) is an old but still emerging zoonotic infection that is not yet completely understood. ER infects a wide range of species and wild boar is of significant interest because of their similarities to pigs, a known ER reservoir. Moreover, the increase of its densities and the limited data available about ER in this species should be considered. The need is to investigate whether wild boar could represent a risk of erysipelas at the wildlife-domestic-human interface. Here, 1067 sera and 149 tonsils of wild boar from five hunting districts in Northwest Italy were tested using ELISA and bacteriological culture, respectively. Using generalized linear models, we evaluated host and environmental factors influencing ER spread and dynamics. We found an ER seroprevalence of 69.4% among wild boar. Increased human density and pig farm density lead to an increase of ER seropositivity highlighting its association with anthropic environmental-related factors. The high ER percentage of isolation (34.2%) found in healthy wild boar suggests that this species can serve as a healthy carrier. This fact, together with the high seroprevalence, supports a role of wild boar as an ER reservoir. Potential zoonotic and economic risks should be considered in light of these data.

The present paper describes the investigation of the first outbreaks of adenoviral gizzard erosions (AGE) in Sweden, in five broiler flocks. The investigation included whole viral genome sequencing and investigation of genomic organization and sequence relationships with other adenoviruses. All five flocks had a history of decreased growth and uneven size of birds since 9-10 days of age. Macroscopically, lesions consistent with AGE (detached koilin layers, discolouration, bleeding, erosions) were identified in gizzards in all five flocks. In four flocks histology was performed, and degeneration and inflammation of the koilin layer and gizzard mucosa were identified in all four. In one flock, intranuclear inclusion bodies typical for fowl adenovirus (FAdV) were detected in trapped epithelial cells in the koilin layer. In four flocks

In September 2016, a nationwide targeted routine antenatal anti-D prophylaxis program was implemented in Norway. The prophylaxis (anti-D immunoglobulin) aims to cover the whole third trimester and is administered in gestational week 28 to RhD-negative women who carry RhD-positive fetuses. However, in many women, antibody screening at delivery does not detect anti-D immunoglobulin. The goal of this study was to investigate the presumable role of dose and timing of antenatal anti-D immunoglobulin administration in non-detectable prophylaxis at the time of delivery.In this retrospective observational study, RhD-negative pregnant women who gave birth at Oslo University Hospital and Akershus University Hospital between January 2017 and December 2019 were analyzed. Women who received antenatal anti-D immunoglobulin (1500 IU at Oslo University Hospital and 1250 IU at Akershus University Hospital) when fetal RHD genotyping at gestational week 24 predicted an RhD-positive fetus were included if an antibody screen at delivery was available. Data from the blood bank, maternity information systems, and electronic patient records were used.Analysis of the 984 RhD-negative women at the two hospitals revealed that 45.4% had non-detectable anti-D at delivery. A significant difference between the two hospitals was observed: 40.5% at Oslo University Hospital (n = 509) and 50.7% at Akershus University Hospital (n = 475) (p = 0.001). The proportion with non-detectable anti-D increased to 56.0 and 75.3%, respectively (p = 0.008) in the group of women who gave birth 12 weeks after routine antenatal anti-D prophylaxis. Significantly fewer women had detectable anti-D at delivery when the lower anti-D immunoglobulin dose (1250 IU) was administered antenatally. Multiple logistic regression indicated that the time interval between routine antenatal anti-D prophylaxis and delivery, in addition to anti-D dose, were significantly associated with detectable anti-D at delivery (p 0.001).We do not know which RhD-negative pregnant women, despite antenatal anti-D prophylaxis, are at risk of RhD alloimmunization, when antibody screening is negative at delivery. Administration of antenatal prophylaxis should probably be moved closer to delivery, since the risk of fetomaternal hemorrhage is higher during the last weeks of the third trimester.

Purpose Lung cancer, mesothelioma and several lifestyle-associated cancer forms have been reported more common in merchant seafarers. However, few studies reflect recent occupational settings and women seafarers are usually too scarce for meaningful analyses. We conducted a study on cancer incidence between 1985 and 2011 in a Swedish cohort consisting of male and female seafarers. Methods All seafarers in the Swedish Seafarers’ Register with at least one sea service between 1985 and 2011 and a cumulated sea service time of ≥ 30 days (N = 75,745; 64% men, 36% women; 1,245,691 person-years) were linked to the Swedish Cancer Register and followed-up until 31 December 2011. Standardized incidence ratios (SIR) were calculated with the general population as reference. Results There were 4159 cancer cases in total, with 3221 among men and 938 among women. Male seafarers had an increased risk of total cancer (SIR 1.05; 95% CI 1.01–1.09), lung cancer (SIR 1.51; 95% CI 1.35–1.67) and urinary bladder cancer (SIR 1.17; 95% CI 1.02–1.33). Several lifestyle-associated cancer forms were more common in men. Previous work on tankers was associated with leukaemia (SIR 1.41; 95% CI 1.00–1.86). The risk of cancer decreased with a start as a male seafarer after 1985, with a significant trend for total cancer (P P = 0.001) and, for tanker seafarers, leukaemia (P = 0.045). Women seafarers had an increased risk of lung cancer (SIR 1.54; 95% CI 1.23–1.87) but the risk of total cancer was not increased (SIR 0.83; 95% CI 0.78–0.89). Conclusions In this cohort of merchant Swedish seafarers 1985–2011, the risk of total cancer was increased in men but not in women compared to the general population. Lung cancer was increased in both genders. The risk of cancer seems to decrease over the last decades, but better exposure assessments to occupational carcinogens and longer observation times are needed.

BackgroundImmunotherapy emerged as a promising treatment option for multiple myeloma (MM) patients. However, therapeutic efficacy can be hampered by the presence of an immunosuppressive bone marrow microenvironment including myeloid cells. S100A9 was previously identified as a key regulator of myeloid cell accumulation and suppressive activity. Tasquinimod, a small molecule inhibitor of S100A9, is currently in a phase Ib/IIa clinical trial in MM patients (NCT04405167). We aimed to gain more insights into its mechanisms of action both on the myeloma cells and the immune microenvironment.MethodsWe analyzed the effects of tasquinimod on MM cell viability, cell proliferation and downstream signaling pathways in vitro using RNA sequencing, real-time PCR, western blot analysis and multiparameter flow cytometry. Myeloid cells and T cells were cocultured at different ratios to assess tasquinimod-mediated immunomodulatory effects. The in vivo impact on immune cells (myeloid cell subsets, macrophages, dendritic cells), tumor load, survival and bone disease were elucidated using immunocompetent 5TMM models.ResultsTasquinimod treatment significantly decreased myeloma cell proliferation and colony formation in vitro, associated with an inhibition of c-MYC and increased p27 expression. Tasquinimod-mediated targeting of the myeloid cell population resulted in increased T cell proliferation and functionality in vitro. Notably, short-term tasquinimod therapy of 5TMM mice significantly increased the total CD11b+cells and shifted this population toward a more immunostimulatory state, which resulted in less myeloid-mediated immunosuppression and increased T cell activation ex vivo. Tasquinimod significantly reduced the tumor load and increased the trabecular bone volume, which resulted in prolonged overall survival of MM-bearing mice in vivo.ConclusionOur study provides novel insights in the dual therapeutic effects of the immunomodulator tasquinimod and fosters its evaluation in combination therapy trials for MM patients.

Background Small poultry flock ownership has become a popular hobby in Europe and North America in recent years but there is a general lack of information regarding bird health and welfare. This retrospective analysis of routine post-mortem cases of non-commercial anseriform poultry aimed at providing information on causes of mortality mostly in relation to mortality events. For this purpose, birds that were submitted for routine post-mortem diagnostics to the National Veterinary Institute (SVA) in Sweden in 2011–2020 were retrospectively reviewed to determine main causes of mortality. Results Records from 79 necropsy submissions involving 120 birds (domestic ducks n = 41, Muscovy ducks n = 45, hybrid ducks n = 2 and domestic geese n = 32) were retrieved and analysed. Most submissions (72.2%) represented flock disease events and unexpected mortality was the most common cause of submission (70.9% of submissions). Twenty-two submissions (27.8%) were referred by veterinarians. There was a wide range of diagnoses of infectious and noninfectious aetiologies. Infectious causes of mortality included parasitic (19.2%), bacterial (13.3%), fungal (10.0%) and viral infections (3.3%) (at bird level of all 120 birds). Some of these infections such as duck virus enteritis (DVE), highly pathogenic influenza (HPAI H5N8) in Muscovy ducks and leucocytozoonosis (Leucocytozoon sp.) in all three species were most likely acquired from contact with wild free-living waterfowl. Generalised yeast infection (Muscovy duck disease) was diagnosed in Muscovy ducks and in a Muscovy duck/domestic duck hybrid. Other diseases were related to generalised noninfectious causes (27.5% of all birds) including diseases such as kidney disease, amyloidosis, cardiac dilatation, reproductive diseases and idiopathic inflammatory conditions. Nutritional or management-related diseases were diagnosed in 14.2% of all birds including rickets and gastrointestinal impaction/obstruction. Congenital/developmental, neoplastic, toxic and traumatic causes of mortality were rare. Conclusions The information obtained in this study can be used to identify and evaluate risks and help owners and veterinarians to prevent disease and provide adequate veterinary care for non-commercial anseriform poultry.

Background The discharge of older hospitalised patients is critical in terms of patient safety. Inadequate transfer of information about medications to the next healthcare provider is a known problem, but there is a lack of understanding of this problem in settings where shared electronic health records are used. The aims of this study were to evaluate the prevalence of patients for whom hospitals sent adequate requests for medication-related follow-up at discharge, the proportion of patients with unplanned hospital revisits because of inadequate follow-up requests, and the association between medication reviews performed during hospitalisation and adequate or inadequate follow-up requests. Methods We conducted a retrospective chart review. The study population was randomly selected from a cluster-randomised crossover trial which included patients 65 years or older who had been admitted to three hospitals in Sweden with shared electronic health records between hospital and primary care. Each patient was assessed with respect to the adequacy of the request for follow-up. For patients where the hospitals sent inadequate requests, data about any unplanned hospital revisits were collected, and we assessed whether the inadequate requests had contributed to the revisits. The association between medication reviews and adequate or inadequate requests was analysed with a Chi-square test. Results A total of 699 patients were included. The patients’ mean age was 80 years; an average of 10 medications each were prescribed on hospital admission. The hospitals sent an adequate request for 418 (60%) patients. Thirty-eight patients (14%) had a hospital revisit within six months of discharge which was related to an inadequate request. The proportion of adequate or inadequate requests did not differ between patients who had received a medication review during hospitalisation and those who had not (p = 0.83). Conclusions The prevalence of patients for whom the hospitals sent adequate follow-up requests on discharge was low. More than one in every ten who had an inadequate request revisited hospital within six months of discharge for reasons related to the request. Medication reviews conducted during hospitalisation did not affect the proportion of adequate or inadequate requests sent. A communication gap still exists despite the usage of a shared electronic health record between primary and secondary care levels.

Objectives To evaluate the changes in disease-related biomarkers and safety of paquinimod, an oral immunomodulatory compound, in patients with systemic sclerosis (SSc). Methods In this open-label, single-arm, multicenter study, SSc patients with a rapidly progressive disease received paquinimod for 8 weeks. Blood and skin biopsies were collected at baseline, during treatment, and at follow-up for the analyses of type I interferon (IFN) activity, chemokine (C-C motif) ligand 2 (CCL2), and the number of myofibroblasts. The safety of paquinimod was evaluated throughout the study. Results Nine SSc patients were enrolled and completed the study treatment with paquinimod at 3 mg/day for 8 weeks. After the treatment, a reduction of type I IFN activity in the plasma from one patient with elevated baseline IFN activity was recorded. A trend towards reduced IFN activity in the skin after treatment was also observed in patients. The serum level of CCL2 was reduced in 7 of 9 patients after paquinimod treatment. There was a median reduction of 10% of the number of myofibroblasts in skin biopsies at week 8 compared to baseline. No change in modified Rodnan skin score and quality of life was detected in the study. Reported adverse events (AEs) were mild to moderate and expected with the most common being arthralgia (n = 3) and headache (n = 3), and C-reactive protein (CRP) increase. Conclusions Analysis of biomarkers before and after treatment suggest reduced type I IFN activity and reduced number of myofibroblasts in lesional skin. Paquinimod was overall well tolerated with mild to moderate and expected AEs. Trial registration ClinicalTrials.gov, NCT01487551. Registered on 7 September 2011

This chapter includes a collection of miscellaneous organisms that have caused disease in poultry or are a public health concern. The less common pathogens implicated in poultry loss included are Staphylococcosis, Streptococcus and Enterococcus, Erysipelas, avian intestinal spirochetosis, tuberculosis. Disease syndromes included in the chapter include beak necrosis, venereal disease of geese, and liver granulomas, but are not identified to a specific organism responsible because of the multifactorial nature of the disease. Staphylococcosis is diagnosed by culturing suspected clinical material including exudate from joints, yolk material, and stab swabs of internal organs. Staphylococcosis can resemble infection with Escherichia coli, Pasteurella multocida, Salmonella gallinarum, Mycoplasma synoviae, reoviruses, or any other infection of bones or joints that is hatchery‐related, associated with mechanical trauma, or causes septicemia. Prevention and control of Enterococcus infections require reducing stress and preventing immunosuppressive diseases and conditions. Proper cleaning and disinfection can reduce environmental enterococcal resident flora to minimize external exposure.

Background Erysipelas, caused by Erysipelothrix rhusiopathiae (ER), is an important emerging disease in free-range and organic egg-production. The aim of the present study was to assess if quantification of ER specific IgY titers may aid the understanding of erysipelas in commercial laying hens. The methodology was validated with sequentially collected sera from experimentally ER infected SPF-chickens and subsequently applied on sera from Swedish commercial laying hens collected during and after outbreaks of erysipelas or collected at slaughter from healthy hens housed in furnished cages, barn production or in organic production (with outdoor access). Results In experimentally infected SPF-chickens, titers to ER were significantly increased approximately one week after infection while IgY to ER in uninfected age-matched controls remained low. Also chickens infected with low doses of ER, not displaying clinical signs of disease and with low recovery of ER in blood samples showed high titers of IgY to ER. For laying hens during and after erysipelas outbreaks the majority of samples were considered positive for antibodies to ER with a large variation in levels of IgY titers to ER between individuals. For healthy laying hens at slaughter all samples were deemed positive for antibodies to ER. An influence of flock on levels of IgY titers to ER was observed for both healthy hens and hens during erysipelas outbreaks. For healthy laying hens at slaughter no influence of the housing systems included in the study, history of erysipelas outbreaks at the farm or vaccination on levels of IgY titers to ER was noticed. Conclusions Taken together, these results show that high numbers of commercial laying hens showed high IgY titers to ER, comparable to those elicited by experimental ER infection, indicating that ER or bacteria that raises antibodies that cross-react with ER are common in this environment.

This article discusses algebraic thinking regarding positive integers and rational numbers when students, 6 to 9 years old in multilingual classrooms, are engaged in an algebraic learning activity proposed by the El’konin and Davydov curriculum. The main results of this study indicate that young, newly arrived students, through tool-mediated joint reflective actions as suggested in the ED curriculum, succeeded in analysing arithmetical structures of positive integers and rational numbers. When the students participated in this type of learning activity, they were able to reflect on the general structures of numbers established as additive relationships (addition and subtraction) as well as multiplicative relationships (multiplication and division) and mixtures thereof, thus a core foundation of algebraic thinking. The students then used algebraic symbols, line segments, verbal, written, and gesture language to elaborate and construct models related to these relationships. This is in spite of the fact that most of the students were second language learners. Elaborated in common experiences staged in the lessons, the learning models appeared to bridge the lack of common verbal language as the models visualized aspects of the relationships among numbers in a public manner on the whiteboard. These learning actions created rich opportunities for bridging tensions in relation to language demands in the multilingual classroom.

This study examines the collective mathematical reasoning when students and teachers in grades 3, 4, and 5 explore fractions derived from length comparisons, in a task inspired by the El´konin and Davydov curriculum. The analysis showed that the mathematical reasoning was mainly anchored in mathematical properties related to fractional or algebraic thinking. Further analysis showed that these arguments were characterised by interplay between fractional and algebraic thinking except in the conclusion stage. In the conclusion and the evaluative arguments, these two types of thinking appeared to be intertwined. Another result is the discovery of a new type of argument, identifying arguments, which deals with the first step in task solving. Here, the different types of arguments, including the identifying arguments, were not initiated only by the teachers but also by the students. This in a multilingual classroom with a large proportion of students newly arrived. Compared to earlier research, this study offers a more detailed analysis of algebraic and fractional thinking including possible patterns within the collective mathematical reasoning. An implication of this is that algebraic and fractional thinking appear to be more intertwined than previous suggested.

The disease erysipelas caused by Erysipelothrix rhusiopathiae (ER) is a major concern in pig production. In the present study the genomes of ER from pigs (n=87), wild boars (n=71) and other sources (n=85) were compared in terms of whole-genome SNP variation, accessory genome content and the presence of genetic antibiotic resistance determinants. The aim was to investigate if genetic features among ER were associated with isolate origin in order to better estimate the risk of transmission of porcine-adapted strains from wild boars to free-range pigs and to increase our understanding of the evolution of ER. Pigs and wild boars carried isolates representing all ER clades, but clade one only occurred in healthy wild boars and healthy pigs. Several accessory genes or gene variants were found to be significantly associated with the pig and wild boar hosts, with genes predicted to encode cell wall-associated or extracellular proteins overrepresented. Gene variants associated with serovar determination and capsule production in serovars known to be pathogenic for pigs were found to be significantly associated with pigs as hosts. In total, 30 % of investigated pig isolates but only 6 % of wild boar isolates carried resistance genes, most commonly tetM (tetracycline) and lsa(E) together with lnu(B) (lincosamides, pleuromutilin and streptogramin A). The incidence of variably present genes including resistance determinants was weakly linked to phylogeny, indicating that host adaptation in ER has evolved multiple times in diverse lineages mediated by recombination and the acquisition of mobile genetic elements. The presented results support the occurrence of host-adapted ER strains, but they do not indicate frequent transmission between wild boars and domestic pigs. This article contains data hosted by Microreact.

The study aimed to monitor immune responses during Erysipelothrix rhusiopathiae (ER)infection of chickens. The experiment comprised 39 SPF-raised female layer chickens in 3groups (n=13). Chickens in group 1 remained uninfected. Chickens in group 3 werevaccinated with a commercial inactivated ER vaccine at 17 days of age (day -13). Chickens ingroups 2 and 3 were inoculated with 0.5 x 1010 CFU ER at 30 days of age (day 0). Bloodsamples were collected at vaccination, prior to infection (day -3) and at days 1, 3, 5, 8, 11 and15 after infection.On days 2-4 one chicken in group 2 showed transient moderate signs of disease. By culture,ER was detected in blood from chickens in group 2 on day 1 (1 of 7) and on day 3 (6 of 6) at1x102 – 1x106 CFU/ml and in group 2 on day 3 (1 of 6) at 30 CFU/ml. Among circulatingleukocytes, heterophil numbers increased prominently on day 1 for chickens in groups 2 and3. For group 2 heterophil numbers remained elevated until day 5 and then decreased to preinfectionlevels For group 3 heterophil numbers returned to pre-infection levels on day 3.Serum MBL levels were significantly increased for chickens in group 2 and 3 on day 1. Forgroup 2 MBL levels increased further on day 3 and remained elevated on day 5 and returnedto pre-infection levels on day 8. For group 3 MBL levels returned to pre-infection levels onday 3. Chickens in group 2 seroconverted to ER on day 5-8 and ER antibody levels subsequently increased. Chickens in group 3 were seropositive to ER prior to infection andER antibody levels were further increased after infection.Thus, the infection elicited prompt heterophil and MBL responses and was effectively clearedby all chickens. Vaccinated chickens did however show lower levels of bacteraemia and theiracute immune responses were of shorter duration. It is likely that the vaccine raised antibodiesto ER aided this rapid elimination of bacteria e.g. through opsonisation for phagocyticclearance.

Aims: The aim of this study was to investigate associations between psychosocial work exposure and the presence of biological and imaging biomarkers of cardiovascular disease. Methods: This cross-sectional study was conducted in a sub-cohort of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Psychosocial exposure was evaluated with the job demand–control model, and analysed according to the standard categorization: high strain, active, passive and low strain (reference). Biomarkers (blood pressure, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, coronary artery calcification (CAC) and metabolic syndrome) were measured, or derived through measurements, from clinical examinations. Gender-specific prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated with regression models and adjusted for age, education, smoking, physical activity, general life stress and body mass index (BMI). Results: The analyses included 3882 participants (52.5% women). High strain (high demands–low control) was linked to increased PR for low HDL cholesterol in women, adjusted for all covariates (PR 1.76; 95% CI 1.25–2.48). High strain was also related to moderately increased PR for metabolic syndrome in men, after adjustments for all covariates except BMI (PR 1.25; 95% CI 1.02–1.52). In addition, passive work (low demands–low control) was associated with diastolic hypertension in women (fully adjusted: PR 1.29; 95% CI 1.05–1.59). All relationships between psychosocial factors and LDL cholesterol or CAC (both genders), or hypertension (men), were non-significant. Conclusions: Poor psychosocial job conditions was associated with the presence of low HDL cholesterol and diastolic hypertension in women, and metabolic syndrome in men. These findings contribute to the knowledge of potential pathways between stressful work and coronary heart disease.

Contemporary society is characterized by rapid changes in the labor market, increased flow of information, and more opportunities to make choices in relation to education and career. Previous research has demonstrated how many young people in school don't think they get the support they need to make such choices. The overall aim of this article is to contribute to more in-depth knowledge of what kind of support and knowledge young adults describe as important in order to be able to make informed choices. This knowledge might help school to better support young people in acquiring the knowledge, skills, and attitudes in relation to their education and career choices. The article is based on interviews with 25-year-old men and women. 23 interviews were conducted. In sum, the analysis indicates that guidance activities that aims to contribute to knowledge about the labor market, programs and courses and requirements for different education programs would probably be perceived as more fruitful by the young adults if they are organized in a combination of different levels, i.e. both as group activities (exhibitions, general information/discussion) and individual activities (personal information/discussion). Further, the authors demonstrate that roles and expectations between pupils, teachers and guidance counselors should be discussed and clarified.

Purpose The aim was to study mortality due to cardiovascular disease as well as total mortality, among female industrial workers, and the association to occupational noise and shift work. Methods Women from cohorts of soft tissue paper mills (N = 3013) and pulp and paper mills (N = 1483) were merged into one cohort. Job exposure matrices were developed and used for classification of shift work and noise exposure. Every year was classified as shift work excluding nights or shift work including nights. Noise was classified into seven 5 dB(A) bins from Results Fatal myocardial infarctions (N = 144) were increased in the total cohort, SMR 1.20 (95% CI 1.01–1.41) but not total mortality. The SMR for myocardial infarction for women exposed to noise ≥ 90 dB(A) for > 10 years was 1.41 (95% CI 1.02–1.89) and for those exposed to night shifts > 10 years, 1.33 (95% CI 0.91–1.89). Shift workers without nights ≤ 65 years, with noise exposure ≥ 90 dB(A), had SMR 2.41 (95% CI 1.20–4.31) from myocardial infarction. There was no increased mortality from cerebrovascular disease. Conclusions Female paper mill workers had an increased mortality from acute myocardial infarction, especially before retirement age, when exposed to noise ≥ 90 dB(A) and with long-time employment. Exposure to shift work and noise usually occurred concurrently.