Some hermitian K-groups via geometric topology

We compute the first two symplectic quadratic K-theory groups of the integers or equivalently, the first two stable homology groups of the group of symplectic integral matrices preserving the standard quadratic refinement. The main novelty in our calculation lies in its method, which is based on high-dimensional manifold theory

The role of cell-free hemoglobin and haptoglobin in acute kidney injury in critically ill adults with ARDS and therapy with VV ECMO

Background: Increased plasma concentrations of circulating cell-free hemoglobin (CFH) are supposed to contribute to the multifactorial etiology of acute kidney injury (AKI) in critically ill patients while the CFH-scavenger haptoglobin might play a protective role. We evaluated the association of CFH and haptoglobin with AKI in patients with an acute respiratory distress syndrome (ARDS) requiring therapy with VV ECMO. Methods: Patients with CFH and haptoglobin measurements before initiation of ECMO therapy were identified from a cohort of 1044 ARDS patients and grouped into three CFH concentration groups using a risk stratification. The primary objective was to assess the association of CFH and haptoglobin with KDIGO stage 3 AKI. Further objectives included the identification of a target haptoglobin concentration to protect from CFH-associated AKI. Measurements and main results: Two hundred seventy-three patients fulfilled the inclusion criteria. Of those, 154 patients (56.4%) had AKI at ECMO initiation. The incidence of AKI increased stepwise with increasing concentrations of CFH reaching a plateau at 15 mg/dl. Compared to patients with low [= 15 mg/dl] CFH concentrations had a three- and five-fold increased risk for AKI (adjusted odds ratio [OR] moderate vs. low, 2.69 [95% CI, 1.25-5.95], P = 0.012; and OR high vs. low, 5.47 [2.00-15.9], P = 0.001). Among patients with increased CFH concentrations, haptoglobin plasma levels were lower in patients with AKI compared to patients without AKI. A haptoglobin concentration greater than 2.7 g/l in the moderate and 2.4 g/l in the high CFH group was identified as clinical cutoff value to protect from CFH-associated AKI (sensitivity 89.5% [95% CI, 83-96] and 90.2% [80-97], respectively). Conclusions: In critically ill patients with ARDS requiring therapy with VV ECMO, an increased plasma concentration of CFH was identified as independent risk factor for AKI. Among patients with increased CFH concentrations, higher plasma haptoglobin concentrations might protect from CFH-associated AKI and should be subject of future research

Our individual order of things directs how we think we feel

Our work draws upon Foucault’s idea that the order of things, defined as the way we categorize our world, matters for how we think about the world and ourselves. Specifically, and drawing upon Pekrun’s control-value theory, we focus on the question of whether the way we individually order our world into categories influences how we think about our typically experienced emotions related to these categories. To investigate this phenomenon, we used a globally accessible example, namely, the categorization of knowledge based on school subjects. In a longitudinal sample of high school students (grades 9 to 11), we found that judging academic domains as similar led to judging typical emotions related to those domains as more similar than experienced in real life (assessed via real-time assessment of emotions). Our study thus shows that the order of things matters in how we think we feel with respect to those things

Test Boredom: Exploring a Neglected Emotion

The emotion of boredom has sparked considerable interest in research on teaching and learning, but boredom during tests and exams has not yet been examined. Based on the control-value theory of achievement emotions, we hypothesized that students may experience significant levels of boredom during testing (“test boredom”; H1), and that test boredom may be significantly related to theoretically hypothesized antecedents (control and value appraisals; H2) and outcomes (performance; H3). We further hypothesized that test boredom was more detrimental when students felt overchallenged during the test than when they felt underchallenged (‘abundance hypothesis’; H4). We tested these hypotheses in two studies (Study 1: N=208 8th graders; 54% female; Study 2: N=1,612 5th-10th graders, 47% female) using both trait and state measures of test boredom in mathematics and their proposed antecedents and outcomes. In support of H1, participants reported statistically significant levels of boredom during tests. Further, the relations of test boredom with its control and value antecedents (i.e., being over- or underchallenged, facets of value) were in line with our assumptions (H2). In support of H3, test boredom was significantly negatively related to academic achievement (grades). In line with H4, test scores were negatively related to boredom due to being overchallenged but unrelated, or even positively related, to boredom due to being underchallenged. Directions for future research on test boredom as well as practical implications are outlined

The spontaneous course of human herpesvirus 6 DNA-associated myocarditis and the effect of immunosuppressive intervention

INTRODUCTION: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients. RESULTS: 756 heart failure (HF) patients underwent an EMB procedure to determine the underlying cause of unexplained HF. Low levels of HHV6 DNA, detectable by nested PCR only, were found in 10.4% of the cases (n = 79) of which 62% (n = 49) showed myocardial inflammation. The spontaneous course of patients with EMB-proven HHV6 DNA-associated lymphocytic myocarditis (n = 26) showed significant improvements in the left ventricular ejection fraction (LVEF) and clinical symptoms, respectively, in 15/26 (60%) patients, 3–12 months after disease onset. EMB mRNA expression of components of the NLRP3 inflammasome pathway and protein analysis of cardiac remodeling markers, analyzed by real-time PCR and MALDI mass spectrometry, respectively, did not differ between HHV6-positive and -negative patients. In another cohort of patients with ongoing symptoms related to lymphocytic myocarditis associated with cardiac levels of HHV6-DNA copy numbers <500 copies/µg cardiac DNA, quantified by real-time PCR, the efficacy and safety of steroid-based immunosuppression for six months was investigated. Steroid-based immunosuppression improved the LVEF (≥5%) in 8/10 patients and reduced cardiac inflammation in 7/10 patients, without an increase in cardiac HHV6 DNA levels in follow-up EMBs. CONCLUSION: Low HHV6 DNA levels are frequently detected in the myocardium, independent of inflammation. In patients with lymphocytic myocarditis with low levels of HHV6 DNA, the spontaneous clinical improvement is nearby 60%. In selected symptomatic patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid-based therapy was found to be effective and safe. This finding needs to be further confirmed in large, randomized trials

Nitric oxide metabolites: associations with cardiovascular biomarkers and clinical parameters in patients with HFpEF

AIMS: Heart failure with preserved ejection fraction (HFpEF) is one of the most rapidly growing cardiovascular health burden worldwide, but there is still a lack of understanding about the HFpEF pathophysiology. The nitric oxide (NO) signalling pathway has been identified as a potential key element. The aim of our study was to investigate markers of NO metabolism [ l-arginine ( l-Arg), homoarginine (hArg), and asymmetric and symmetric dimethylarginine (ADMA and SDMA)], additional biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), endothelin-1 (ET-1), mid-regional pro-adrenomedullin (MR-proADM), copeptin, and high-sensitivity C-reactive protein (hsCRP)], and the endothelial function in an integrated approach focusing on associations with clinical characteristics in patients with HFpEF. METHODS AND RESULTS: Seventy-three patients, prospectively enrolled in the 'German HFpEF Registry', were analysed. Inclusion criteria were left ventricular ejection fraction (LVEF) ≥ 50%; New York Heart Association functional class ≥ II; elevated levels of NT-proBNP > 125 pg/mL; and at least one additional criterion for structural heart disease or diastolic dysfunction. All patients underwent transthoracic echocardiography, cardiopulmonary exercise testing, and pulse amplitude tonometry (EndoPAT™). Patients were categorized in two groups based on their retrospectively calculated HFA-PEFF score. Serum concentrations of l-Arg, hArg, ADMA, SDMA, NT-proBNP, ET-1, MR-proADM, copeptin, and hsCRP were determined. Patients had a median age of 74 years, 47% were female, and median LVEF was 57%. Fifty-two patients (71%) had an HFA-PEFF score ≥ 5 (definitive HFpEF), and 21 patients (29%) a score of 3 to 4 (risk for HFpEF). Overall biomarker concentrations were 126 ± 32 μmol/L for l-Arg, 1.67 ± 0.55 μmol/L for hArg, 0.74 (0.60;0.85) μmol/L for SDMA, and 0.61 ± 0.10 μmol/L for ADMA. The median reactive hyperaemia index (RHI) was 1.55 (1.38;1.87). SDMA correlated with NT-proBNP (r = 0.291; P = 0.013), ET-1 (r = 0.233; P = 0.047), and copeptin (r = 0.381; P = 0.001). ADMA correlated with ET-1 (r = 0.250; P = 0.033) and hsCRP (r = 0.303; P = 0.009). SDMA was associated with the left atrial volume index (β = 0.332; P = 0.004), also after adjustment for age, sex, and comorbidities. Biomarkers were non-associated with the RHI. A principal component analysis revealed two contrary clusters of biomarkers. CONCLUSIONS: Our findings suggest an impaired NO metabolism as one possible key pathogenic determinant in at least a subgroup of patients with HFpEF. We argue for further evaluation of NO-based therapies. Upcoming studies should clarify whether subgroups of HFpEF patients can take more benefit from therapies that are targeting NO metabolism and pathway

Short-chain fatty acid propionate protects from hypertensive cardiovascular damage

BACKGROUND: Arterial hypertension and its organ sequelae show characteristics of T cell mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFA) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in two different mouse models of hypertensive cardiovascular damage. METHODS: To investigate the effect of SCFA on hypertensive cardiac damage and atherosclerosis, wild-type NMRI (WT) or ApoE(-/-) deficient mice received propionate (200mM) or control in the drinking water. To induce hypertension, WT mice were infused with Angiotensin (Ang)II (1.44mg/kg/d s.c.) for 14 days. To accelerate the development of atherosclerosis, ApoE(-/-) mice were infused with AngII (0.72mg/kg/d s.c.) for 28 days. Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry. Blood pressure was measured by radiotelemetry. Regulatory T cell (Treg) depletion using PC61 antibody was used to examine the mode of action of propionate. RESULTS: Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated AngII-infused WT mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated ApoE(-/-). Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in WT mice. Cardioprotective effects of propionate were abrogated in Treg-depleted AngII-infused mice, suggesting the effect is Treg-dependent. CONCLUSIONS: Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial non-pharmacological preventive strategy for patients with hypertensive cardiovascular disease