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Background: Physical activity (PA) has substantial health benefits and is important in combatting chronic diseases, which have been associated with elevated levels of advanced glycation endproducts (AGEs). AGEs play a role in the aging process, and an association between PA and AGEs has been reported. We aimed to investigate the relationship between PA and AGE accumulation in a general population and in a population with chronic diseases.Methods: This large cross-sectional population study used data from adult participants in the LifeLines project, with participant information drawn from the LifeLines database as well data from patients with diabetes mellitus or renal and/or cardiovascular diseases. Tissue AGE accumulation was assessed non-invasively by skin-autofluorescence (SAF) using an AGE reader (DiagnOptics Technologies BV, Groningen, the Netherlands). PA was assessed using the short questionnaire to assess health-enhancing physical activity (SQUASH). Multivariate linear regression analyses were adjusted for age, body mass index, sex, and smoking status.Results: Data from 63,452 participants (general population n = 59,177, chronic disease n = 4275) were analyzed. The general population was significantly younger (43.58 +/- 11.77 years, mean +/- SD) and had significantly lower SAF (1.90 +/- 0.42 arbitrary units (AU)) compared to the population with chronic disease (age: 55.51 +/- 12.07 years; SAF: 2.27 +/- 0.51 AU). In the group with chronic disease, more hours of moderate to vigorous physical activities per week were associated with lower SAF (beta= -0.002, 95% confidence interval (95%CI): -0.002 to -0.001). For the general population, there was no association between hours of moderate to vigorous activity and SAF (beta= 3.2 x 10(-5), 95%CI: 0.000-0.001, p = 0.742). However, there was an association in the general population between total hours of PA per week and SAF (beta= 4.2 x 10(-4), 95%CI: 0.000-0.001, p < 0.001), but this association was not found in the chronic disease population (beta = -3.2 x 10(-4), 95%CI: -0.001 to 0.000, p = 0.347).Conclusion: Our study demonstrates that an inverse relationship exists between PA and AGE accumulation in the population with chronic disease. More hours of moderate to vigorous activity is associated with a significantly decreased SAF. More PA is associated with a lower SAF, even after adjusting for the established predictors (age, body mass index, smoking status, and sex). Our findings could help to promote health and prolong longevity.

Current methods to combat highly pathogenic avian influenza (HPAI) outbreaks in poultry rely on stamping out and preventive culling, which can lead to high economic losses and invoke ethical resistance. Emergency vaccination could be an alternative as vaccination is one of the most efficient and cost-effective measures to protect poultry from HPAI infection, preventing spreading to other poultry and greatly reducing the potential transmission to humans. Current conventional inactivated AI vaccines may be useful for combating AI outbreaks, but do not fulfil all targets of an ideal AI vaccine, including mass applicability and rapid onset of immunity. We aimed to further investigate the potential of Herpesvirus of Turkeys (HVT) as a vector containing a recombinant H5 hemagglutinin of HPAI H5N1. This HVT-H5 vector was analysed in vitro, tested for onset of immunity against AI challenge, breadth of protection, reduction of virus shedding, and induction of both antibody and cellular responses in SPF layers or broiler chicks containing maternal derived antibodies (MDA+). In SPF layers HVT-H5 provided full protection to lethal challenges with 4 antigenically diverse HPAI H5N1 strains from 2 weeks post vaccination (w.p.v.), while in MDA+ birds full protection was provided from 3 w.p.v. to homologous challenge. Also shedding of challenge virus was reduced in both SPF and MDA+ birds. HVT-H5 induced a protective HI titre (≥4) to 11 HPAI H5N1 strains at 3 w.p.v. in 3-week-old SPF layers and to HPAI H5N8 A/ch/Neth/14015531/2014. Besides inducing a protective antibody response HVT-H5 also induced an influenza-specific T cell response. This data demonstrates that HVT-H5 vaccine appears to fulfil many of the criteria for an ideal AI vaccine including early onset of immunity, a broad protection, reduced virus shedding, protection in presence of AI-MDA and could be a useful tool in the combat of AI outbreaks worldwide.

Objective To assess the minimally invasive single-port thoracoscopic sympathicotomy feasibility and efficacy in patients with treatment-resistant RP. Methods Single-port thoracoscopic sympathicotomy was performed unilaterally on the left side in eight patients with RP (six males, two females, with a median age of 45.2 years). Five patients had primary and three had secondary RP. Perfusion effects in the hands were assessed at baseline and after 1 month by using a cooling and recovery procedure, and by using laser speckle contrast analysis. Number and duration of RP attacks were reported over a 2-week period. Results Patient satisfaction was 100% after surgery. After surgery, a unilateral improvement in perfusion was observed in the left hand compared with the right hand, with cooling and recovery (P = 0.008) and with laser speckle contrast analysis (P = 0.023). In addition, the number and duration of the attacks in the left hand decreased compared with the right hand (both P = 0.028). No serious adverse events occurred in a follow-up period of at least 10 months. Conclusion Single-port thoracoscopic sympathicotomy is feasible and can be effective in improving hand perfusion in patients with RP. However, long-term efficacy needs to be established. Clinical trial registration number NCT02680509.

Background Late effects of cisplatin-based chemotherapy in testicular cancer survivors (TCS) include cardiovascular morbidity, but little data is available beyond 20 years. The objective was to assess vascular damage in very long-term TCS. Methods TCS (treated with chemotherapy or orchiectomy only) and age-matched healthy controls were invited. Study assessment included vascular stiffness with ultrasound measurement of carotid-femoral pulse wave velocity (cf-PWV). Results We included 127 TCS consisting of a chemotherapy group (70 patients) and an orchiectomy group (57 patients) along with 70 controls. Median follow-up was 28 years (range: 20–42). The cf-PWV (m/s) was higher in TCS than in controls (geometrical mean 8.05 (SD 1.23) vs. 7.60 (SD 1.21), p = 0.04). The cf-PWV was higher in the chemotherapy group than in the orchiectomy group (geometrical mean 8.39 (SD 1.22) vs. 7.61 (SD 1.21), p b 7.59 × 10−3 vs. 4.04 × 10−3; p = 0.03). Conclusion Very long-term TCS treated with cisplatin-based chemotherapy show increased vascular damage compatible with “accelerated vascular aging” and continue to be at risk for cardiovascular morbidity, thus supporting the need for intensive cardiovascular risk management. Clinical trial registration The clinical trial registration number is NCT02572934.

Vaccination is an effective tool to limit equine influenza virus (EIV H3N8) infection, a contagious respiratory disease with potentially huge economic impact. The study assessed the effects of antigenic change on vaccine efficacy and the need for strain update. Horses were vaccinated (V1 and V2) with an ISCOMatrix-adjuvanted, whole inactivated virus vaccine (Equilis Prequenza, group 2, FC1 and European strains) or a carbomer-adjuvanted, modified vector vaccine (ProteqFlu, group 3, FC1 and FC2 HA genes). Serology (SRH, HI, VN), clinical signs and viral shedding were assessed in comparison to unvaccinated control horses. The hypothesis was that group 2 (no FC2 vaccine strain) would be less well protected than group 3 following experimental infection with a recent FC2 field strain (A/equi-2/Wexford/14) 4.5 months after vaccination. All vaccinated horses had antibody titres to FC1 and FC2. After challenge, serology increased more markedly in group 3 than in group 2. Vaccinated horses had significantly lower total clinical scores and viral shedding. Unexpectedly, viral RNA shedding was significantly lower in group 2 than in group 3. Vaccination induced protective antibody titres to FC1 and FC2 and reduced clinical signs and viral shedding. The two tested vaccines provided equivalent protection against a recent FC2 EIV field strain.

Background: In some patients, Raynaud’s Phenomenon (RP) symptoms prove resistant to conventional vasodilatory treatment. Thoracic sympathectomy is shown to be effective as treatment of RP, but is associated with surgical burden. During this procedure, the sympathetic nerve traversing to the upper extremity is dissected, subsequently leading to vasodilatation. In our centre, single-port thoracoscopic sympathicotomy (SPTS) has been developed, a minimally invasive technique, extensively limiting surgical burden. [1] Objectives: To evaluate SPTS feasibility and efficacy after one month in patients with treatment resistant RP. Methods: In this study RP patients were their own controls, as they received an unilaterally left sided sympathicotomy. The effects of the SPTS was assessed at baseline and one month after the procedure. Perfusion of the hand was assessed using a cooling and recovery procedure, and laser speckle contrast analysis (LASCA) at room temperature of 23 degrees Celsius. The number and duration of RP attacks was reported over a two week period prior to reassessment by standard questionnaire. Results: Eight patients were included in the study, 6 male/2 female, with a median (IQR) age of 45.2 (30.2–55.3) years, body mass index of 23.9 (23.4–26.8) kg/m2, and RP duration of 7.0 (2.5–14.3) years. Five patients suffered from primary RP, and three patients had RP secondary to connective tissue disease (CTD) [mixed CTD (n=2) and limited cutaneous systemic sclerosis (n=1)]. All patients were very satisfied with the results and the number of attacks in the left hand decreased (p=0.018). After surgery an unilateral improvement in left hand perfusion was observed during the cooling and recovery procedure (p=0.008, figure 1), and in the fingertips with LASCA (p=0.023). No serious adverse events occurred. Conclusion: SPTS, a minimally invasive technique, appears to be feasible and effective in improving hand perfusion in patients with RP after one month. Although these results are promising, long-term efficacy needs to be established and therefore follow-up is on-going. Reference [1] Kuijpers M, Klinkenberg TJ, Bouma W, DeJongste MJ, Mariani MA. Single-port one-stage bilateral thoracoscopic sympathicotomy for severe hyperhidrosis: prospective analysis of a standardized approach. J Cardiothorac Surg2013;8:216-8090-8-216. Disclosure of Interests: Anniek van Roon: None declared, Michiel Kuijpers: None declared, Saskia van de Zande: None declared, Amaal Eman Abdulle : None declared, Arie Van Roon: None declared, Reinhard Bos Grant/research support from: SUN Pharma, Wobbe Bouma: None declared, Theo Klinkenberg: None declared, Hendrika Bootsma Grant/research support from: Unrestricted grants from Bristol-Myers Squibb and Roche, Consultant for: Roche, Bristol-Myers Squibb, Novartis, Medimmune, Union Chimique Belge, Speakers bureau: Bristol-Myers Squibb, Novartis, Mike DeJongste: None declared, Massimo Mariani: None declared, Andries Smit Shareholder of: Has been co-founder, and is still shareholder of Diagnoptics Technologies, the company which developed the AGE reader., Douwe J Mulder Grant/research support from: My University has received research grants for my research from: Boehringer Ingelheim and Actelion, Speakers bureau: My University has received speakers fee from: Sanofi

Background Systemic sclerosis (SSc)-related vasculopathy is generally thought to occur on a microvascular level. However, some observations also suggest involvement of arterial vessels. Macrovascular involvement (e.g., aorta or upper extremity) can be non-invasively assessed by measuring pulse wave velocity (PWV). Although, several studies have assessed aortic and upper extremity PWV in SSc, studies have not reached a consensus regarding this matter. Furthermore, we hypothesized that the endothelin antagonist bosentan may improve arterial stiffness by its direct endothelial and potential anti-fibrotic effects. Objectives The aim of this exploratory study was two-fold. First, we aimed to compare arterial stiffness in patients with SSc and age and sex-matched healthy controls (HC). Secondly, we will investigate the effect of bosentan on both short-term (three month) and long-term (one year) PWV. Methods Baseline differences between HC and SSc patients were studied in a case-control design. The follow-up of SSc patients was a randomized, prospective, 2-arm parallel group, open-label, (usual care with bosentan versus usual care only), blinded endpoint, intervention study. PWV (Sphygmocor) in meters/second, was measured to assess arterial stiffness in the aorta (carotid-femoral PWV), upper arm (carotid-brachial PWV), and forearm (brachial-radial PWV), adjusted for mean arterial pressure. Results Baseline characteristics are shown in table 1. No significant differences were observed in PWV (at all sites) between HC and SSc patients. No effect of bosentan on aortic, and upper arm PWV was found. The change in forearm PWV was different between the groups, with a decrease (e.g. lowering arterial stiffness) in the bosentan group (figure 1). Conclusion This small study shows that aortic, upper arm, and forearm arterial stiffness does not appear to be increased in patients with SSc, as compared to age- and sex-matched healthy controls. To the best of our knowledge, this is the first study to investigate the concept of potential effects of an endothelin receptor antagonist on macrovascular involvement in SSc. Although the results demonstrate no effects on aorta and upper arm arterial stiffness, they may indicate a beneficial effect on the stiffness of the smaller arteries of the forearm. Future studies are needed to further investigate the potential effect of bosentan on these smaller arteries. Acknowledgement Actelion for co-funding the study Disclosure of Interests Anniek van Roon: None declared, Amaal Eman Abdulle : None declared, Saskia van de Zande: None declared, Arie Van Roon: None declared, Dan Zhang: None declared, Reinhard Bos Grant/research support from: SUN Pharma, Hendrika Bootsma Grant/research support from: Unrestricted grants from Bristol-Myers Squibb and Roche, Consultant for: Roche, Bristol-Myers Squibb, Novartis, Medimmune, Union Chimique Belge, Speakers bureau: Bristol-Myers Squibb, Novartis, Andries Smit Shareholder of: Has been co-founder, and is still shareholder of Diagnoptics Technologies, the company which developed the AGE reader., Douwe J Mulder Grant/research support from: My University has received research grants for my research from: Boehringer Ingelheim and Actelion, Speakers bureau: My University has received speakers fee from: Sanofi

Background: Microvascular disease, with rarefaction of nailfold capillaries, is the hallmark of systemic sclerosis (SSc). Obliteration of the ulnar and radial artery is regularly observed, implicating involvement of the forearm arteries. Pulse wave velocity (PWV) may serve as early biomarker of forearm artery involvement, before occurrence of irreversible arterial obliteration. Objectives: The aim was to investigate arterial stiffness of the aorta and the upper extremities in SSc patients and to correlate these findings with nailfold capillary count and extent of disease. Methods: Aortic PWV was defined as carotid-femoral (cf). Upper extremity PWV was measured as carotid-brachial (cb) and carotid-radial (cr), the ratio between cbPWV/crPWV was used as an indication of the relative PWV change in the forearm. Capillary count was the mean capillary count per 3 mm of 8 fingers. The number of SSc classification criteria was used as surrogate for extent of disease. [1] Results: In total, 19 SSc patients (median age 51 years, 68% female) were included. CbPWV/crPWV ratio correlated strongly with capillary count (r = −0.55, p = 0.022, figure 1) in SSc patients, with a trend in regards to its relation with the extent of disease (r=0.48, p=0.053). Conclusions: Our findings demonstrate that arterial stiffness of the forearm has a relationship with nailfold capillary count and tends to be associated with the extent of disease in patients with SSc. These may suggest that vascular damage also occurs in larger arteries of the forearm, which potentially serves as novel tool for assessing early vascular involvement in SSc.

The present study describes the pathogenesis of infection of chicks with a new avian reovirus strain, belonging to the so-called enteric reovirus strains (ERS) that is capable of causing central nervous system signs in SPF white leghorns. After intramuscular (IM) or oral inoculation birds were either observed for clinical signs or sacrificed for macroscopic, histological and virological examination for 21 days. Virus isolation was performed on the brain, leg muscle, hock joint, liver and spleen. For the detection of viral antigen the immunohistochemistry (IHC) technique was performed on the caudal part of the cerebrum, spinal cord including spinal ganglia and right N. Ischiadicus. High mortality (79% in 7 days) was seen in birds that were inoculated IM. Survivors were depressed and stayed small until the end of the experiment. One bird had tremor and showed torticollis at 9 days after IM inoculation. Birds that were inoculated orally were depressed from day 4 and stayed small until the end of the experiment. One bird showed a torticollis at 10 days after inoculation. After both IM and oral inoculation ERS was isolated from the brain between 3 and 10 days after inoculation. Other examined organs were positive for virus isolation from day 1 or 5 until day 21. IHC revealed viral antigen positive cells in the Plexus chorioideus (plexus epithelial cells or cells within the underlying connective tissue) and in a spinal ganglion. The results indicate that the pathogenesis of ERS infection in chickens bears some resemblance with that of the mammalian reoviruses serotype 1 in mice.

SUMMARY. To determine whether turkey herpesvirus (HVT) impairs the aspecific and specific defense against an avian pneumovirus (APV) infection, specific-pathogen-free turkeys were inoculated at 7 days of age with HVT and 1, 5, or 7 wk later with APV. Clinical signs, APV replication, and development of antibodies against APV were evaluated. No differences were found between the birds that received both HVT and APV and those that received only APV. RESUMEN. Nota de investigacion-Las infecciones ocasionadas por el virus herpes del pavo no inciden en el resultado de las infecciones por pneumovirus en pavos. Con el fin de determinar si el virus herpes del pavo afecta las defensas especificas y no especificas en infecciones por pneumovirus aviar, pavos libres de pat6genos especificos fueron inoculados a los 7 dias de edad con el virus herpes de pavo y a los dias 1, 5 o 7 con pneumovirus aviar. Se evaluaron los signos clinicos, la replicaci6n del pneumovirus aviar y el desarrollo de anticuerpos contra el pneumovirus aviar. No se encontraron diferencias entre las aves que