Type 2 nitric oxide synthase (NOS2) is required for the Th1-dependent healing of infections with intracellular microbes, including Leishmania major. Here, we demonstrate the expression and define the function of NOS2 during the innate response to L. major. At day 1 of infection, genetic deletion or functional inactivation of NOS2 abolished the IFNgamma and natural killer cell response, increased the expression of TGFbeta, and caused parasite spreading from the skin and lymph node to the spleen, liver, bone marrow, and lung. Induction of NOS2 was dependent on IFNalpha/beta. Neutralization of IFNalpha/beta mimicked the phenotype of NOS2-/- mice. Thus, IFNalpha/beta and NOS2 are critical regulators of the innate response to L. major.

We describe a case of visceral leishmaniasis in a 15-month-old German child. Diagnosis was significantly delayed because the patient had no history of travel to known endemic areas. Congenital or blood transfusion-associated leishmaniasis was ruled out. Possible modes of transmission (including a potential new autochthonous focus of the disease in central Europe) are discussed.

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Objectives To evaluate associations of omega-3 fatty acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in patients with heart failure with preserved ejection fraction (HFpEF). Background O3-FA have been linked to reduced risk for HF and associated phenotypic traits in experimental/clinical studies. Methods This is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I = EPA + DHA) was analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e′ 7.1 ± 1.5; median NT-proBNP 158 ng/L (IQR 82–298). Pearson’s correlation coefficient and multiple linear regression analyses, using sex and age as covariates, were used to describe associations of the O3I with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months. Results The O3I was below (< 8%), within (8–11%), and higher (> 11%) than the target range in 374 (93%), 29 (7%), and 1 (0.2%) patients, respectively. Mean O3I was 5.7 ± 1.7%. The O3I was inversely associated with HbA1c (r = − 0.139, p = 0.006), triglycerides-to-HDL-C ratio (r = − 0.12, p = 0.017), triglycerides (r = − 0.117, p = 0.02), non-HDL-C (r = − 0.101, p = 0.044), body-mass-index (r = − 0.149, p = 0.003), waist circumference (r = − 0.121, p = 0.015), waist-to-height ratio (r = − 0.141, p = 0.005), and positively associated with submaximal aerobic capacity (r = 0.113, p = 0.023) and LVEF (r = 0.211, p < 0.001) at baseline. Higher O3I at baseline was predictive of submaximal aerobic capacity (β = 15.614, p < 0,001), maximal aerobic capacity (β = 0.399, p = 0.005) and LVEF (β = 0.698, p = 0.007) at 12 months. Conclusions Higher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients. Graphic abstract Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8–11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF. This figure contains modified images from Servier Medical Art (https://smart.servier.com) licensed by a Creative Commons Attribution 3.0 Unported License.

Objective Carotid intima-media thickness (IMT) is used to assess cardiovascular risk and progression of atherosclerosis. It is known that regular physical activity of moderate intensity has beneficial effects on the vasculature. However, it is still discussed controversially whether prolonged exercise, including participation in exhaustive competitive sports such as long-distance races, has also beneficial effects or might even be harmful regarding the cardiovascular system. Patients and methods Thirty-eight male marathon runners (45.8 ± 7.3 years) were investigated twice (2009 and 2013) for their carotid IMT (using ultrasound techniques), anthropometrics and clinical chemistry. Additionally, training volume (running kilometres per year) and competition participation (half marathon, marathon and ultramarathon) within this follow-up period were assessed. Results During 3.8 ± 0.4 years of follow-up, runners performed 1587 (850-2500) training kilometres per year and participated in a total of 7 (4-12) long distance competitions. IMT increased in total by 0.05 ± 0.09 mm or annually by 0.013 ± 0.023 mm, respectively. Higher increase in IMT over that period was associated with higher fasting blood glucose (beta = .355, p = .045) at baseline examination. Effects of training volume and number of competitions on the progression of IMT could not be demonstrated in our longitudinal analysis. Conclusions Higher blood glucose levels are associated with detrimental effects on vasculature in otherwise healthy male marathon runners. Regular marathon training, including competition participation over at least several years, was not associated with detrimental effects on IMT or, vice versa, seems not to provide beneficial effects on vasculature.