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Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk Introduction Both atrial fibrillation (AF) and obesity have reached epidemic proportions. Obesity is an established risk factor in acute myocardial infarction (AMI), de novo AF, and AF recurrence after ablation. AF increase the risk of stroke, heart failure (HF), and death. The link between body mass index (BMI) and incident stroke, HF, AMI, or death in an AF ablation population is unknown. Purpose To examine incident stroke, HF, AMI, or death by BMI. Method Using Danish nationwide registries, all Danish patients above 18 years who underwent first-time AF ablation from January1st 2010 to December31st 2018 were identified and included at the date of ablation. Underweight patients (BMI < 18.5) were excluded. Exposure of interest was BMI and patients were stratified as normal-weight (BMI 18.5-24.9), overweight (BMI 25.0 – 29.9), obese (30.0 – 34.9), and morbidly obese (BMI ≥ 35.0). The primary endpoint was combined of either first-reached incident stroke, HF, AMI, or death. The 5-year cumulative incidence of the primary endpoint stratified by BMI, was estimated using the Aalen-Johansen estimator. The relative rates were examined using normal-weight as reference in both univariate- and multivariate-Cox models adjusted for prior HF, hypertension, age, diabetes, prior stroke, prior atherosclerotic vascular disease, and sex. Results The study cohort consisted of 7,701 patients. Median age [IQR] decreased from 64 [57, 70] to 60 [53, 66] in normal-weight and morbidly obese respectively. The prevalence of HF, ischemic heart disease, diabetes, and hypertension increased by BMI while prior stroke remained stable. Use of oral anticoagulants remained stable at around 98%. In total 1,285 patients reached the primary endpoint. By decreasing order, the most frequent endpoints were HF (564, 44%), AMI (431, 34%), stroke (199, 15%), and death (91, 7%). The cumulative incidence of the primary endpoint increased incrementally from 15%, 16%, 19%, and 21% from normal-weight to morbidly obese respectively (Figure 1). In the univariate analysis, the Hazard ratio (HR, [95% confidence interval]) increased incrementally from 1.03 [0.90 to 1.18], 1.28 [1.10 to 1.49], 1.43 [1.17 to 1.74] in overweight to morbidly obese respectively (Figure 2). In the multivariate analysis no significant differences were found. The HRs were 0.94 [0.82 to 1.08], 1.05 [0.89 to 1.23], 1.01 [0.82 to 1.24] in the overweight to morbidly obese respectively (Figure 2). Conclusion When identifying obese and morbidly obese AF ablation patients in clinical practice, the risk of either stroke, HF, AMI, or death is higher compared to normal-weight AF ablation patients, but only due to the underlying comorbidities.

Introduction Guidelines recommend antiarrhythmic drugs (AAD) before ablation for atrial fibrillation (AF). However, recently published randomized clinical trials have demonstrated that ablation is more effective in maintaining sinus rhythm compared to AAD as first line therapy. Therefore, data pertaining the impact of early ablation on AF recurrence in large, unselected cohorts is highly warranted. Purpose To examine clinically relevant AF recurrence after ablation by time from AF diagnosis to ablation. Method Using Danish nationwide registries, all Danish patients above 18 years who underwent first-time AF ablation from January1st 2010 to December31st 2018 were identified and included at the date of ablation. The patients were categorized by time from diagnosis with AF to ablation. Recurrent AF was defined using a composite endpoint comprising claimed prescriptions of AAD, hospital admissions due to AF, re-ablation, or electrical cardioversions. The cumulative incidence of recurrent AF by time from diagnosis to ablation at 1-year follow-up after a blanking period of 90 days, was estimated using the Aalen-Johansen estimator, taking death as a competing risk into account. The relative rates of recurrent AF by time from diagnosis to ablation were examined using Cox models adjusted for sex, age, procedure-year, heart failure, ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease, hypertension, and diabetes. Results The study cohort consisted of 8,098 patients. Median age [IQR] increased from 60 [52 to 66] in the early ablation group (AF ablation within 1 year after diagnosis) to 64 [57 to 70] in the late ablation group (ablation at least 3 years after diagnosis). The number of patients with a CHA2DS2-VASc score of 2 or more increased from 44% in the early ablation group to 51% in the late ablation group. Use of amiodarone remained stable, while use of Class IC anti-arrhythmic medication increased by time from diagnosis to ablation. Figure 1 shows the 1-year cumulative incidence of recurrent AF, hazard ratios (HR), and 95% confidence intervals (95% CI) stratified by time from diagnosis to ablation in years and depict that the risk of recurrent AF increased incrementally and significantly by time from diagnosis to ablation compared to the early ablation group. Figure 2 shows the 1-year cumulative incidence of recurrent AF, hazard ratios (HR), and 95% confidence intervals (CI 95%) stratified by time from diagnosis to ablation in months and depict that very early ablation (within 6 months) is associated with less recurrent AF. Conclusion In this large nationwide study examining recurrent AF post ablation, recurrence rates of AF increased incrementally according to time from AF diagnosis to AF ablation. Early ablation could potentially provide substantial benefits and improve outcomes after ablation, indicating ablation as first-line therapy might be more ideal. Funding Acknowledgement Type of funding sources: None.

Introduction Atrioventricular nodal reentry tachycardia (AVNRT), Wolf-Parkinson-White syndrome (WPW), and Ectopic atrial tachycardia (EAT) are common arrhythmias and associated with lower quality of life. The use of radiofrequency ablation (RFA) treatment has increased over time, however long-term risk of adverse outcomes after RFA in patients with AVNRT, WPW, or EAT is unknown. Purpose To examine the long-term risk of adverse outcomes and need for pacemaker after RFA in AVNRT-, WPW-, and EAT-patients. Methods Using Danish nationwide registries, patients of 18 years or older who underwent RFA for AVNRT, WPW, or EAT between January 1st 2001 and January 1st 2019 were included. Comorbidities and use of antiarrhythmic drugs were analyzed. The cumulative incidences of pacemaker implantation and a combined endpoint of death, thromboembolism (TE), ischemic heart disease (IHD), and heart failure (HF) were estimated at 5-year follow-up using the Aalen-Johansen estimator, taking death as competing risk into account. Results A total of 10.439 patients were enrolled in the study. 6187 patients were treated for AVNRT. The median age was 55 [42, 65] and 40% were male. The WPW group consisted of 2872 patients. The median age was 42 [29, 55] and 61% were male. The EAT group consisted of 1380 patients. The median age was 57 [44, 67] and 47% were male. The comorbidity burden was generelly higher in EAT patients especially regarding heart failure and hypertension. Use of antiarrhythmic drugs was higher in EAT patients compared to patients with AVNRT and WPW. Figure 1 shows the cumulative incidence of a composite endpoint of death, TE, IHD, and HF 5 years after RFA treatment and depicts that the cumulative incidence was 22.1%, 13.9% and 8.2% for EAT-, AVNRT- and WPW-patients respectively. Figure 2 shows the 5-year cumulative incidence of pacemaker implantations which was 9.0%, 4.4% and 3.1% for EAT-, AVNRT- and WPW-patients respectively. Conclusion At long-term follow-up patients with RFA for EAT have a higher risk of death, TE, IHD and HF compared to patients treated for AVNRT and WPW. EAT patients also have the highest risk of pacemaker implantation. Funding Acknowledgement Type of funding sources: None.

The probiotic medicinal product TSO (Trichuris suis ova) is administered to patients with active ulcerative colitis in an ongoing clinical phase IIb trial where the typical co-medications are steroids (prednisolone or budesonide) and antibiotics (e.g., phenoxymethylpenicillin). The present pre-clinical study evaluates the effects of these co-medications on the biological activity of TSO in Göttingen Minipigs. This translationally relevant pre-clinical model allows administration of TSO with and without oral steroids or antibiotics in a manner similar to the administration to patients, followed by quantification of the biological activity of TSO. The biological activity of TSO was not affected by oral steroids but was reduced by oral antibiotics. Fecal calprotectin, the common marker of intestinal inflammation in patients with UC, did not differ between groups.

Neovascular age-related macular degeneration: is it worthwhile treating an eye with poor visual acuity, if the visual acuity of the fellow eye is good?

Contact hypersensitivity to nickel is the most common form of allergic contact dermatitis. To gain insight into the induction of this frequent disease, T cell reactivity towards nickel was investigated in "nonallergic" individuals defined as those with no skin manifestations and a negative patch test towards NiSO4. Surprisingly, we found that nickel induced proliferation of peripheral blood mononuclear cells (PBMC) from 16 of 18 adult individuals tested. This activation was specific, and no stimulation of PBMC was observed using control stimulants at equimolar concentrations. Furthermore, the NiSO4-induced activation required the presence of professional antigen-presenting cells. To describe the functional capacity of the nickel-inducible T cells, cytokine release was investigated in both nickel-allergic and nonallergic individuals. The T cells from both groups released interferon-gamma but no interleukin-4 upon stimulation with nickel, suggesting that the functional capacities of these cell populations were similar in nickel-allergic and nonallergic individuals. Thus, at this level, no qualitative differences could be demonstrated between T cells obtained from nickel-allergic and nonallergic individuals.

SUMMARYLymphocyte transformation test has often been used as an in vitro test for nickel allergy. We have previously demonstrated the presence of nickel-reactive T cells in individuals with no history of allergic disease and with a negative patch test towards NiSO4. In this study, we show that this proliferative response was mainly confined to T cells within the CD4+ subset. In contrast to conventional recall antigens such as tetanus toxoid, in vitro stimulation using NiSO4 activated both FACS-purified CD4+CD45RA+‘naive’ and CD4+CD45RO+‘memory’ T cells. To determine which cell population reacted with nickel to induce T cell activation, peripheral blood mononuclear cells were separated into macrophages and non-adherent, HLA-DR-depleted T cells. We found that preincubation of monocytes/macrophages but not T cells with NiSO4 resulted in subsequent T cell proliferation. This result demonstrated that nickel did not exhibit any direct effect on the T cell. Furthermore, the NiSO4-induced T cell proliferation could be blocked by antibodies towards MHC class II (HLA-DR) molecules. Our results substantiate the concept that individuals with a negative patch test towards NiSO4 contain in their peripheral blood T cells capable of recognizing nickel or nickel-modified peptides. In contrast to conventional recall antigens, both memory and naive T cells were activated. Thus, when compared with data obtained from nickel-allergic individuals, this study shows a comparable nickel-inducible T cell activation in non-allergic individuals.

Entamoeba histolytica is a very uncommon etiology of travelers diarrhoea, but may be an important differential diagnosis to inflammatory bowel disease. A misdiagnosis of amoebic colitis as inflammatory bowel disease followed by inadvertent treatment with corticosteroids may be fatal. Current techniques for the diagnosis of amoebiasis include stool studies, endoscopic biopsy and serology. Demonstration of haematophagous trophozoites in feces or in tissue biopsy is the definitive method for diagnosis. Unfortunately both methods have many drawbacks. If the specimens are negative, serology can support the diagnosis especially in a non-endemic area where a positive test is highly predictive of current disease.

Dimethylation by Erm methyltransferases at the N-6 position of adenine 2058 (A2058, Escherichia coli numbering) in domain V of bacterial 23 S rRNA confers resistance to the macrolide-lincosamide-streptogramin B (MLS) group of antibiotics. The ErmE methyltransferase from Saccharopolyspora erythraea methylates a 625 nucleotide transcript of domain V as efficiently as it methylates intact 23 S rRNA. By progressively truncating domain V, the motif required for specific recognition by the enzyme has been localized to a helix and single-stranded region adjacent to A2058. The smallest RNA transcript that shows methyl-accepting activity is a 27-nucleotide stem-loop, corresponding to the 23 S rRNA sequences 2048 to 2063 and 2610 to 2620 (helix 73), with A2058 situated within the hairpin loop. Methylation of A2058 in the truncated RNAs is optimal in the absence of magnesium, and the efficiency of methylation is halved by the presence of 2 to 3 mM magnesium. Magnesium serves to stabilize a conformation in the truncated RNA that prevents efficient methylation. This contrasts to the intact domain V RNA, where 2 mM magnesium ions support a conformation at A2058 that is most readily recognized by ErmE. Methylation of domain V RNA is generally far less susceptible to ionic conditions than the truncated RNAs. The effects of monovalent cations on the methylation of truncated transcripts suggest that RNA structures outside helix 73 support the ErmE interaction. However, interaction with these structures is not essential for specific ErmE recognition of A2058.

This study aimed to evaluate the effect of a motivational, minimal intervention approach to smoking cessation in an open, randomized design conducted by nurses as routine work in a lung clinic. Subjects who smoked less than 10 cigarettes x day(-1), and subjects who smoked > or = 10 cigarettes x day(-1) and who had refused to participate in a smoking cessation trial with nicotine replacement therapy, were randomly allocated to a motivational approach to smoking cessation or to a control group. The motivational approach consisted of a nurse-conducted 5 min consultation concerning reasons to quit smoking, brochures about smoking cessation and advice about how to quit. After 4-6 weeks, subjects in the motivational group received a letter encouraging them to quit smoking. After 1 year, all subjects were contacted by phone and smoking status reported. Subjects claiming to be abstinent attended the clinic for carbon monoxide verification. A total of 507 subjects were enrolled, 254 in the motivational group and 253 in the control group. The mean age of the motivational group was 51 yrs, 50% were males and they smoked a mean of 13 cigarettes x day(-1). The mean age of the control group was 53 yrs, 61% were males and they smoked a mean of 12 cigarettes x day(-1). At the 1 year follow-up, the success rate for point prevalence (no smoking at 1 year and during the preceding month) was 8, 7% in the motivational group versus 3.6% in the control group (p=0.025). The 12 months sustained success rate (no smoking at all during the year) was 3.1 versus 1.2% (p=0.22). The point prevalence for light smokers (

Ballistic electron and hole emission microscopies, have been used to probe Au/ZnSe/GaAs and Au/ZnSe/BeTe/GaAs (001) heterostructures as a function of the ZnSe/BeTe interface stoichiometry. Ballistic electron and hole transport into n- and p-type ZnSe epilayers, respectively, were observed with spectra that conformed well to theoretical behavior. The measured average voltage thresholds +1.25 (p type) and −1.41 V (n type) were in good agreement with previously observed values for the Au/ZnSe Schottky barrier heights and consistent with the value of the ZnSe direct band gap (2.67 eV). However, the ballistic transport into the BeTe conduction bands required to measure the ZnSe/BeTe conduction band offset was not confirmed. Time-dependent and spatial variations of the voltage thresholds were observed for p- and n-type diodes, with and without BeTe epilayers, and were presumed to be linked to switching Fermi level pinning positions from varying Au/ZnSe interface states densities.

Establishment of alfalfa (Medlcago sativa L.) with small grain companion crop is not always satisfactory. This study was designed to compare alternative establishment methods and determine the influence of alfalfa varieties and seeding rates on dry matter and crude protein production and herbage quality. The relationship between alfalfa plant density and root+crown weight and their effect on forage yield were evaluated. Pure stands of alfalfa were established by four methods: 1) no herbicide or companion crop (check); 2) a plant herbicide, S-ethyl dipropylthiocarbamate (EPTC); 3) a companion crop of oats (Arena sativa L.) harvested for forage; and 4) a companion crop of oats harvested for grain. Three alfalfa varieties were evaluated: T3X-8 hybrid, ‘Saranac,’ and ‘Vernal.’ Four alfalfa seeding rates were compared: 4.5, 9.0, 13.5, and 17.9 kg/ha of purelive-seed (PLS). Studies were conducted at three locations in South Dakota. Experiments at Gayville and Norbeck were under dryland conditions and at Brookings under irrigation. Alfalfa established with oats harvested for forage yielded the most weed-free forage dry matter during the seeding year. This was followed in descending order by the yields of alfalfa established with EPTC, the check, and oats harvested for grain. Herbage crude protein yields were similar during the seeding year regardless of establishment method, except for the oat grain treatment which was lower. Second-year alfalfa dry matter and protein production were not affected by establishment method. Dry matter yields were higher for Saranac and T3X-8 hybrid alfalfa than for Vernal when moisture was optimum and winter injury did not occur. Under dryland, there were no differences in yield among the three varieties. T3X-8 was generally lowest in crude protein content; Vernal was highest in protein late in the season. With irrigation, higher dry matter and crude protein yields were obtained during the seeding year at each increase in seeding rate. Under dryland, no differences in yield were noted above the 13.5 kg/ha rate during the seeding year. Second-year alfalfa yield~ increased at seeding rates up to 9.0 kg/ha of PLS at Gayville and Brookings, and up to 13.5 kg/ha at Norbeck. Generally, herbage crude protein content was not affected by seeding rate. Root+crown weights of alfalfa decreased as seeding rates increased up to 13.5 kg/ha.

Inhalt Ein Ultraschallgerat, welches besonders fur die Feststellung von Trachtigkeit bei Schweinen entwickelt wurde, erwies rich als wertvoll zur sicheren Feststellung der Trachtigkeit innerhalb von 30 bis 50 Tagen nach dem Decken. 96 Trachtigkeitsuntersuchungen bei 70 Sauen im 2. Wurf ergaben folgende Resultate: 63 Beobachtungen wurden korrekt als trachtig und 31 Beobachtungen wurden korrekt als nichttrachtig beurteilt. Zwei Sauen mit einer pathologischen uterinen Sekretansammlung wurden falsch als trachtig beurteilt. Die Richtigkeit der Diagnose wurde nach Schlachten von 61 Sauen am Tag nach der Trachtigkeitsuntersuchung und Burch die Abferkelresultate von 9 Sauen bestatigt. Contents: Porcine Pregnancy Detection with a Newly Developed Ultrasonic A-Scan-Device A handy battery-operated ultrasonic device with a display system of light emitting diodes instead of an oscilloscop and adjusted sensitivity and gain for transmitting the ultrasonic beam into the abdominal cavity of sows was found practical in porcine pregnancy examination; the costs of the equipment were far lower than that of a traditional A-scan equipment. The efficiency of the equipment was tested at 96 observations on 70 second-litter sows; control of the accuracy of diagnosis was confirmed by slaughter of 61 animals on the day of examination for pregnancy and by farrowing results in 9 animals. The results showed that 63 observations were correctly designated as pregnant 30–50 days after last service; 31 observations were correctly designated non-pregnant. Two sows were rated false pregnant; in both cases a uterine accumulation of abnormal secretion equivalent to the fetal fluid volume of two to four six-week embryos was observed. Percentage of correct observations of pregnant and normal non pregnant animals resulted in 100.

In a sowherd suffering from high incidence of MMA which demanded an intensive postparturient treatment to reduce baby pig mortality the effect on postparturient diseases of induction of parturition with Prostaglandin was examined. After treatment of 19 sows on day 112 of gestation with 12.5 mg Prostaglandin, parturition in 15 sows took place on an average of 25 hours after injection; the gestation period was 113.1 +/- 0.5 days. Three sows that did not respond to the treatment farrowed 3-6 days after treatment and one sow farrowed few hours after treatment. In a non-treated identical group of animals the gestation period averaged 113.4 +/- 1.5 days. No difference was found between the two groups concerning number of stillborn pgis, baby pig mortality within first eight days of life, incidence of MMA or intensity of postparturient medical treatment.

In a herd of sows 106 sows having 4.3 litters on aver., were over a period of 10 weeks treated on Thursdays with 0.175 mg of cloprostenol on the 111th to 114th day of gestation; 93--95% of the sows treated on the 112th and 113th day farrowed within 33 hours after treatment, 73% after treatment on the 111th day (Table I); the mean period of gestation after treatment was 113.4 +/- 0.9 days. 8 sows that only farrowed 2--5 days after the treatment, had on 21 previous farrowings proved to have significantly longer mean periods of gestation, 115.6 days, than the 112 sows in the control group, having 3.6 litters on average, that farrowed in the same period and section of the piggery as the sows treated with cloprostenol. In total 32 weekend-farrowings occurred in the observation period including 7 farrowings after a period of gestation of 110--113 days, 6 cases of unsuccessfully induced parturition and 19 farrowings on the 114th to 119th day that could have been programmed to occur on Fridays; the number of weekend-farrowings, which for this herd in connection with the weaning procedure normally accounted for about 40--45% of farrowings, could thus be reduced to 7% of farrowings (Table II). Cloprostenol treatment on the 111th day resulting in farrowing on the 112th day leads to a significantly higher rate of piglet mortality after 3 weeks compared with the results after farrowing for control sows that farrowed on the 112th day (Table III); this category of control sows had on previous farrowings proved to have a significantly shorter mean period of gestation, 112.7 days, than that of the sows in the cloprostenol group farrowing on the 112th day which had been 114.3 days on previous farrowings. Farrowing and weaning results after induced parturition resulting in farrowing on the 113th to 115th day showed no significant differences from the results for control sows farrowing spontaneously on the 112th to 115th day of gestation. The incidence of MMA (Table II) was not influenced by the cloprostenol treatment, nor by the number of litters, the length of the period of gestation, or by the piling of farrowings on Fridays.