Hadronic unquenching effects in the quark propagator

We investigate hadronic unquenching effects in light quarks and mesons. Within the non-perturbative continuum framework of Schwinger-Dyson and Bethe-Salpeter equations we quantify the strength of the back reaction of the pion onto the quark-gluon interaction. To this end we add a Yang-Mills part of the interaction such that unquenched lattice results for various current quark masses are reproduced. We find considerable effects in the quark mass function at low momenta as well as for the chiral condensate. The quark wave function is less affected. The Gell--Mann-Oakes-Renner relation is valid to good accuracy up to pion masses of 400-500 MeV. As a byproduct of our investigation we verify the Coleman theorem, that chiral symmetry cannot be broken spontaneously when QCD is reduced to 1+1 dimensions.Comment: 27 pages, 15 figures, minor corrections and clarifications; version to appear in PR

Programmable RNA editing with endogenous ADAR enzymes – a feasible option for the treatment of inherited retinal disease?

RNA editing holds great promise for the therapeutic correction of pathogenic, single nucleotide variants (SNV) in the human transcriptome since it does not risk creating permanent off-targets edits in the genome and has the potential for innovative delivery options. Adenine deaminases acting on RNA (ADAR) enzymes catalyse the most widespread form of posttranscriptional RNA editing in humans and their ability to hydrolytically deaminate adenosine to inosine in double stranded RNA (dsRNA) has been harnessed to change pathogenic single nucleotide variants (SNVs) in the human genome on a transcriptional level. Until now, the most promising target editing rates have been achieved by exogenous delivery of the catalytically active ADAR deaminase domain (ADARDD) fused to an RNA binding protein. While it has been shown that endogenous ADARs can be recruited to a defined target site with the sole help of an ADAR-recruiting guide RNA, thus freeing up packaging space, decreasing the chance of an immune response against a foreign protein, and decreasing transcriptome-wide off-target effects, this approach has been limited by a low editing efficiency. Through the recent development of novel circular ADAR-recruiting guide RNAs as well as the optimisation of ADAR-recruiting antisense oligonucleotides, RNA editing with endogenous ADAR is now showing promising target editing efficiency in vitro and in vivo. A target editing efficiency comparable to RNA editing with exogenous ADAR was shown both in wild-type and disease mouse models as well as in wild-type non-human primates (NHP) immediately following and up to 6 weeks after application. With these encouraging results, RNA editing with endogenous ADAR has the potential to present an attractive option for the treatment of inherited retinal diseases (IRDs), a field where gene replacement therapy has been established as safe and efficacious, but where an unmet need still exists for genes that exceed the packaging capacity of an adeno associated virus (AAV) or are expressed in more than one retinal isoform. This review aims to give an overview of the recent developments in the field of RNA editing with endogenous ADAR and assess its applicability for the field of treatment of IRD

Occlusive retinal vasculitis associated with intravitreal Faricimab injections

Purpose: We describe a case of occlusive vasculitis associated with intravitreal Faricimab (Vabysmo) injections. Methods: A retrospective case report. Results: A 52-year old man treated with monthly Faricimab injections for diabetic macula oedema presented with sudden reduced vision, new retinal hemorrhages, significant retinal vascular occlusions and ischemia. After screening for differential diagnoses was unremarkable, the patient was treated with oral and intravitreal steroid therapy under which the occlusive vasculitis was stabilized. Conclusion: Occlusive vasculitis, though rare, is a potential complication of Faricimab therapy. Comprehensive reporting and large-scale analyses are essential to better understand and manage this adverse event

Combining climatic projections and dispersal ability: A method for estimating the responses of sandfly vector species to climate change

Abstract Background: In the Old World, sandfly species of the genus Phlebotomus are known vectors of Leishmania, Bartonella and several viruses. Recent sandfly catches and autochthonous cases of leishmaniasis hint on spreading tendencies of the vectors towards Central Europe. However, studies addressing potential future distribution of sandflies in the light of a changing European climate are missing

In Vitro Investigation of Insulin Dynamics During 4 Hours of Simulated Cardiopulmonary Bypass.

BACKGROUND Hyperglycemia is common in patients undergoing cardiovascular surgery with cardiopulmonary bypass. We hypothesize that intraoperative hyperglycemia may be, at least partially, attributable to insulin loss due to adhesion on artificial surfaces and/or degradation by hemolysis. Thus, our primary aim was to investigate the loss of insulin in 2 different isolated extracorporeal circulation circuits (ECCs), that is, a conventional ECC (cECC) with a roller pump, and a mini-ECC (MiECC) system with a centrifugal pump. The secondary aim was to assess and compare the relationship between changes in insulin concentration and the degree of hemolysis in our 2 ECC models. METHODS Six cECC and 6 MiECC systems were primed with red packed blood cells and thawed fresh-frozen plasma (1:1). Four additional experiments were performed in cECC using only thawed fresh-frozen plasma. Human insulin (Actrapid) was added, targeting a plasma insulin concentration of 400 mU/L. Insulin concentration and hemolysis index were measured at baseline and hourly thereafter. The end points were the change in insulin level after 4 hours compared to baseline and hemolysis index after 4 hours. The insulin concentration and hemolysis index were analyzed by means of a saturated linear mixed-effect regression model with a random offset for each experiment to account for the repeated measure design of the study, resulting in mean estimates and 95% confidence intervals (CIs) of the primary end points as well as of pairwise contrasts with respect to ECC type. RESULTS Insulin concentration decreased by 63% (95% CI, 48%-77%) in the MiECC and 92% (95% CI, 77%-106%) in the cECC system that contained red blood cells. Insulin loss was significantly higher in the cECC system compared to the MiECC (P = .022). In the cECC with only plasma, insulin did not significantly decrease (-4%; 95% CI, -21% to 14%). Hemolysis index in MiECC increased from 68 (95% CI, 46-91) to 76 (95% CI, 54-98) after 4 hours, in cECC from 81 (95% CI, 59-103) to 121 (95% CI, 99-143). Hemolysis index and percent change of insulin showed an excellent relationship (r = -0.99, P < .01). CONCLUSIONS Our data showed that insulin levels substantially decreased during 4 hours of simulated cardiopulmonary bypass only in the ECC that contained hemoglobin. The decrease was more pronounced in the cECC, which also exhibited a greater degree of hemolysis. Our results suggest that insulin degradation by hemolysis products may be a stronger contributor to insulin loss than adhesion of insulin molecules to circuit surfaces

Predictive value of cardiac magnetic resonance right ventricular longitudinal strain in patients with suspected myocarditis

BACKGROUND Recent evidence underlined the importance of right (RV) involvement in suspected myocarditis. We aim to analyze the possible incremental prognostic value from RV global longitudinal strain (GLS) by CMR. METHODS Patients referred for CMR, meeting clinical criteria for suspected myocarditis and no other cardiomyopathy were enrolled in a dual-center register cohort study. Ejection fraction (EF), GLS and tissue characteristics were assessed in both ventricles to assess their association to first major adverse cardiovascular events (MACE) including hospitalization for heart failure (HF), ventricular tachycardia (VT), recurrent myocarditis and death. RESULTS Among 659 patients (62.8% male; 48.1 ± 16.1 years), RV GLS was impaired (> - 15.4%) in 144 (21.9%) individuals, of whom 76 (58%), 108 (77.1%), 27 (18.8%) and 40 (32.8%) had impaired right ventricular ejection fraction (RVEF), impaired left ventricular ejection fraction (LVEF), RV late gadolinium enhancement (LGE) or RV edema, respectively. After a median observation time of 3.7 years, 45 (6.8%) patients were hospitalized for HF, 42 (6.4%) patients died, 33 (5%) developed VT and 16 (2.4%) had recurrent myocarditis. Impaired RV GLS was associated with MACE (HR = 1.07, 95% CI 1.04-1.10; p < 0.001), HF hospitalization (HR = 1.17, 95% CI 1.12-1.23; p < 0.001), and death (HR = 1.07, 95% CI 1.02-1.12; p = 0.004), but not with VT and recurrent myocarditis in univariate analysis. RV GLS lost its association with outcomes, when adjusted for RVEF, LVEF, LV GLS and LV LGE extent. CONCLUSION RV strain is associated with MACE, HF hospitalization and death but has neither independent nor incremental prognostic value after adjustment for RV and LV function and tissue characteristics. Therefore, assessing RV GLS in the setting of myocarditis has only limited value

Debris discs around nearby Solar analogues

An unbiased search for debris discs around nearby Sun-like stars is reported. Thirteen G-dwarfs at 12-15 parsecs distance were searched at 850 \umum wavelength, and a disc is confirmed around HD 30495. The estimated dust mass is 0.008 M$_{\oplus}$ with a net limit \la 0.0025 M$_{\oplus}$ for the average disc of the other stars. The results suggest there is not a large missed population of substantial cold discs around Sun-like stars -- HD 30495 is a bright rather than unusually cool disc, and may belong to a few hundred Myr-old population of greater dust luminosity. The far-infared and millimetre survey data for Sun-like stars are well fitted by either steady state or stirred models, provided that typical comet belts are comparable in size to that in the Solar System.Comment: published in MNRA

A Planet at 5 AU Around 55 Cancri

We report precise Doppler shift measurements of 55 Cancri (G8V) obtained from 1989 to 2002 at Lick Observatory. The velocities reveal evidence for an outer planetary companion to 55 Cancri orbiting at 5.5 AU. The velocities also confirm a second, inner planet at 0.11 AU. The outer planet is the first extrasolar planet found that orbits near or beyond the orbit of Jupiter. It was drawn from a sample of ~50 stars observed with sufficient duration and quality to detect a giant planet at 5 AU, implying that such planets are not rare. The properties of this jupiter analog may be compared directly to those of the Jovian planets in our Solar System. Its eccentricity is modest, e=0.16, compared with e=0.05 for both Jupiter and Saturn. Its mass is at least 4.0 jupiter masses (M sin i). The two planets do not perturb each other significantly. Moreover, a third planet of sub-Jupiter mass could easily survive in between these two known planets. Indeed a third periodicity remains in the velocity measurements with P = 44.3 d and a semi-amplitude of 13 m/s. This periodicity is caused either by a third planet at a=0.24 AU or by inhomogeneities on the stellar surface that rotates with period 42 d. The planet interpretation is more likely, as the stellar surface is quiet, exhibiting log(R'_{HK}) = -5.0 and brightness variations less than 1 millimag, and any hypothetical surface inhomogeneity would have to persist in longitude for 14 yr. Even with all three planets, an additional planet of terrestrial--mass could orbit stably at ~1 AU. The star 55 Cancri is apparently a normal, middle-aged main sequence star with a mass of 0.95 solar masses, rich in heavy elements ([Fe/H] = +0.27). This high metallicity raises the issue of the relationship between its age, rotation, and chromosphere.Comment: 47 pages, 4 tables, 12 figures, uses AASTE