The two hot corinos of the SVS13-A protostellar binary system: counterposed siblings

We present ALMA high-angular resolution ($\sim$ 50 au) observations of the Class I binary system SVS13-A. We report images of SVS13-A in numerous interstellar complex organic molecules: CH$_{\rm 3}$OH, $^{13}$CH$_{\rm 3}$OH, CH$_{\rm 3}$CHO, CH$_{\rm 3}$OCH$_{\rm 3}$, and NH$_{\rm 2}$CHO. Two hot corinos at different velocities are imaged in VLA4A (V$_{sys}$= +7.7 km s$^{-1}$) and VLA4B (V$_{sys}$= +8.5 km s$^{-1}$). From a non-LTE analysis of methanol lines we derive a gas density of 3 $\times$ 10$^8$ cm$^{-3}$, and gas temperatures of 140 K and 170 K for VLA4A and VLA4B, respectively. For the other species the column densities are derived from a LTE analysis. Formamide, which is the only N-bearing species detected in our observations, is more prominent around VLA4A, while dimethyl ether, methanol and acetaldehyde are associated with both VLA4A and VLA4B. We derive in the two hot corinos abundance ratios of $\sim$ 1 for CH$_{\rm 3}$OH, $^{13}$CH$_{\rm 3}$OH, and CH$_{\rm 3}$OCH$_{\rm 3}$, $\sim$ 2 for CH$_{\rm 3}$CHO, and $\sim$ 4 for NH$_{\rm 2}$CHO. The present dataset supports a chemical segregation between the different species inside the binary system. The emerging picture is that of an onion-like structure of the two SVS13-A hot corinos, caused by the different binding energies of the species, also supported by ad hoc quantum chemistry calculations. In addition, the comparison between molecular and dust maps suggests that the interstellar complex organic molecules emission originates from slow shocks produced by accretion streamers impacting the VLA4A and VLA4B disks and enriching the gas-phase component.Comment: 20 pages, 14 figure

Streamers feeding the SVS13-A protobinary system: astrochemistry reveals accretion shocks?

We report ALMA high-angular resolution (~ 50 au) observations of the binary system SVS13-A. More specifically, we analyse deuterated water (HDO) and sulfur dioxide (SO2) emission. The molecular emission is associated with both the components of the binary system, VLA4A and VLA4B. The spatial distribution is compared to that of formamide (NH2CHO), previously analysed in the system. Deuterated water reveals an additional emitting component spatially coincident with the dust accretion streamer, at a distance larger than 120 au from the protostars, and at blue-shifted velocities (> 3 km/s from the systemic velocities). We investigate the origin of the molecular emission in the streamer, in light of thermal sublimation temperatures calculated using updated binding energies (BE) distributions. We propose that the observed emission is produced by an accretion shock at the interface between the accretion streamer and the disk of VLA4A. Thermal desorption is not completely excluded in case the source is actively experiencing an accretion burst.Comment: Accepted for publication in Faraday Discussions 202

Antimicrobial treatment with the fixed-dose antibiotic combination RHB-104 for Mycobacterium avium subspecies paratuberculosis in Crohn\u2019s disease: pharmacological and clinical implications

Introduction: Crohn\u2019s disease (CD) is an inflammatory bowel disease of unknown etiology. However, increasing evidence suggests Mycobacterium avium subspecies paratuberculosis (MAP) as a putative causative agent: 1) MAP is the etiological agent of Johne\u2019s disease, a granulomatous enteritis affecting ruminants, which shares clinical and pathological features with CD; 2) MAP has been detected in tissues and blood samples from CD patients; 3) case reports have documented a favorable therapeutic response to anti-MAP antibiotics. Area covered: This review provides an appraisal of current information on MAP characteristics, diagnostic methodologies and emerging drug treatments. The authors focus on RHB-104, a novel oral formulation containing a fixed-dose combination of clarithromycin, clofazimine and rifabutin, endowed with synergistic inhibitory activity on MAP strains isolated from CD patients. Expert opinion: Based on encouraging in vitro data, RHB-104 has entered recently the clinical phase of its development, and is being investigated in a randomized, placebo-controlled phase III trial aimed at evaluating its efficacy and safety in CD. Provided that the overall clinical development will support the suitability of RHB-104 for inducing disease remission in CD patients with documented MAP infection, this novel antibiotic combination will likely take a relevant position in the therapeutic armamentarium for CD management

Astrochemistry at work in the L1157-B1 shock: acetaldehyde formation

The formation of complex organic molecules (COMs) in protostellar environments is a hotly debated topic. In particular, the relative importance of the gas phase processes as compared to a direct formation of COMs on the dust grain surfaces is so far unknown. We report here the first high-resolution images of acetaldehyde (CH3CHO) emission towards the chemically rich protostellar shock L1157-B1, obtained at 2 mm with the IRAM Plateau de Bure interferometer. Six blueshifted CH3CHO lines with Eu = 26-35 K have been detected. The acetaldehyde spatial distribution follows the young (̃ 2000 yr) outflow cavity produced by the impact of the jet with the ambient medium, indicating that this COM is closely associated with the region enriched by iced species evaporated from dust mantles and released into the gas phase. A high CH3CHO relative abundance, 2-3 × 10-8, is inferred, similarly to what found in hot corinos. Astrochemical modelling indicates that gas phase reactions can produce the observed quantity of acetaldehyde only if a large fraction of carbon, of the order of 0.1 per cent, is locked into iced hydrocarbons

P176 A case of lupus enteritis successfully treated with anti-TNF alpha inhibitor

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Diets including Animal Food Are Associated with Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a clinical condition with a prevalence of up to 25% in Western countries. Typical GERD symptoms include heartburn and retrosternal regurgitation. Lifestyle modifications, including diet, are considered a first-line therapeutic approach. To evaluate the impact of life habits on GERD in this cross-sectional study, we used data collected through an online survey from 1146 participants. GERD was defined according to the Montreal Consensus. For all participants, clinical and lifestyle characteristics were recorded. Overall, 723 participants (63.1%) consumed a diet including animal food (non-vegans), and 423 participants (36.9%) were vegans. The prevalence of GERD was 11% (CI 95%, 9–14%) in non-vegans and 6% (CI 95%, 4–8%) in vegans. In the multivariate analysis, after adjusting for confounding factors, subjects on a non-vegan diet were associated with a two-fold increase in the prevalence of GERD compared to vegans (OR = 1.96, CI 95%, 1.22–3.17, p = 0.006). BMI and smoking habits were also significantly associated with GERD. This study shows that an animal food-based diet (meat, fish, poultry, dairy, and eggs) is associated with an increased risk of GERD compared to a vegan diet. These findings might inform the lifestyle management of patients with GERD-related symptoms

How organics deuteration changes during the formation of a Sun-like star

Deuterated molecules have been detected towards the early stages of Sun-like star formation (prestellar cores, Class 0 objects) as well as towards the Solar System; they are a powerful diagnostic tool for studying physical conditions at the moment of the organics formation. However, observations in intermediate stages (Class I/II objects) are still missing. In the framework of the ASAI-IRAM Large Program, we report here the formaldehyde and methanol deuteration as measured in the Class I object SVS13-A. The deuterium fractionation is found to be 9 × 10-2 for HDCO, 5 × 10-3 For D2CO, and 4 × 10-3 for CH_2DOH, up to one order of magnitude lower than the value measured in Class 0 sources. The present measurements of organics deuteration towards the Class I object SVS13-A contribute to fill in the gap between prestellar cores and protoplanetary disks in the context of deuterium fractionation measurements (see \citet{bia17})

Switching from IFX originator to biosimilar CT-P13 does not impact effectiveness,safety and immunogenicity in a large cohort of IBD patients

Background: Switching from IFX originator to CT-P13 is safe; however, little data on immunogenicity exists. Research design and methods: Consecutive IBD patients on IFX originator were switched to CT-P13 and followed-up for 12 months. Clinical activity, infliximab trough levels (ITLs), anti-drug antibodies (ATIs), and adverse events were recorded at predefined timepoints (baseline, second CT-P13 infusion, 6 and 12 months). The outcomes investigated were immunogenicity, pharmacokinetics, effectiveness and safety. Results: 119 patients were switched to CT-P13 after a median time with IFX of 5.8 years. No changes in mean ITLs were observed. ATIs were detected in 30 patients (25.2%): 14 before and 16 after switch. Mean persistent ATIs were significantly higher compared to mean transient ones (109.74 ng/mL ±84.70 vs 18.22 ng/mL ±11.37, p < 0.001), with significantly lower ITLs associated (mean 0.32 µg/mL ±0.6 vs 3.08 µg/mL ±3.22, p < 0.001). A significant decrease of patients in steroid-fee clinical remission was observed after the switch (p = 0.004), with subsequent improvement at 6 months (p = 0.005). Eighteen patients (15.1%) discontinued IFX, only 6 (5%) for loss of response. Conclusions: Switching from infliximab originator to CT-P13 seems safe and effective, without differences in immunogenicity. A temporary reduction of clinical benefit after switching could be potentially explained by a ‘nocebo-effect response’

Antibodies Elicited in Response to EBNA-1 May Cross-React with dsDNA

Several genetic and environmental factors have been linked to Systemic Lupus Erythematosus (SLE). One environmental trigger that has a strong association with SLE is the Epstein Barr Virus (EBV). Our laboratory previously demonstrated that BALB/c mice expressing the complete EBNA-1 protein can develop antibodies to double stranded DNA (dsDNA). The present study was undertaken to understand why anti-dsDNA antibodies arise during the immune response to EBNA-1.In this study, we demonstrated that mouse antibodies elicited in response to EBNA-1 cross-react with dsDNA. First, we showed that adsorption of sera reactive with EBNA-1 and dsDNA, on dsDNA cellulose columns, diminished reactivity with EBNA-1. Next, we generated monoclonal antibodies (MAbs) to EBNA-1 and showed, by several methods, that they also reacted with dsDNA. Examination of two cross-reactive MAbs--3D4, generated in this laboratory, and 0211, a commercial MAb--revealed that 3D4 recognizes the carboxyl region of EBNA-1, while 0211 recognizes both the amino and carboxyl regions. In addition, 0211 binds moderately well to the ribonucleoprotein, Sm, which has been reported by others to elicit a cross-reactive response with EBNA-1, while 3D4 binds only weakly to Sm. This suggests that the epitope in the carboxyl region may be more important for cross-reactivity with dsDNA while the epitope in the amino region may be more important for cross-reactivity with Sm.In conclusion, our results demonstrate that antibodies to the EBNA-1 protein cross-react with dsDNA. This study is significant because it demonstrates a direct link between the viral antigen and the development of anti-dsDNA antibodies, which are the hallmark of SLE. Furthermore, it illustrates the crucial need to identify the epitopes in EBNA-1 responsible for this cross-reactivity so that therapeutic strategies can be designed to mask these regions from the immune system following EBV exposure