Low dose Naltrexone for induction of remission in inflammatory bowel disease patients

Background: Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function. Methods: Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples. Results: Low dose Naltrexone induce

Priming of plant innate immunity by rhizobacteria and beta-aminobutyric acid: differences and similarities in regulation

P>Pseudomonas fluorescens WCS417r bacteria and beta-aminobutyric acid can induce disease resistance in Arabidopsis, which is based on priming of defence. In this study, we examined the differences and similarities of WCS417r- and beta-aminobutyric acid-induced priming. Both WCS417r and beta-aminobutyric acid prime for enhanced deposition of callose-rich papillae after infection by the oomycete Hyaloperonospora arabidopsis. This priming is regulated by convergent pathways, which depend on phosphoinositide- and ABA-dependent signalling components. Conversely, induced resistance by WCS417r and beta-aminobutyric acid against the bacterial pathogen Pseudomonas syringae are controlled by distinct NPR1-dependent signalling pathways. As WCS417r and beta-aminobutyric acid prime jasmonate- and salicylate-inducible genes, respectively, we subsequently investigated the role of transcription factors. A quantitative PCR-based genome-wide screen for putative WCS417r- and beta-aminobutyric acid-responsive transcription factor genes revealed distinct sets of priming-responsive genes. Transcriptional analysis of a selection of these genes showed that they can serve as specific markers for priming. Promoter analysis of WRKY genes identified a putative cis-element that is strongly over-represented in promoters of 21 NPR1-dependent, beta-aminobutyric acid-inducible WRKY genes. Our study shows that priming of defence is regulated by different pathways, depending on the inducing agent and the challenging pathogen. Furthermore, we demon-strated that priming is associated with the enhanced expression of transcription factors. New Phytologist (2009) 183: 419-431doi: 10.1111/j.1469-8137.2009.02851.x

On the importance of cascading moisture recycling in South America

Continental moisture recycling is a crucial process of the South American climate system. In particular, evapotranspiration from the Amazon basin contributes substantially to precipitation regionally as well as over other remote regions such as the La Plata basin. Here we present an in-depth analysis of South American moisture recycling mechanisms. In particular, we quantify the importance of cascading moisture recycling (CMR), which describes moisture transport between two locations on the continent that involves re-evaporation cycles along the way. Using an Eulerian atmospheric moisture tracking model forced by a combination of several historical climate data sets, we were able to construct a complex network of moisture recycling for South America. Our results show that CMR contributes about 9–10% to the total precipitation over South America and 17–18% over the La Plata basin. CMR increases the fraction of total precipitation over the La Plata basin that originates from the Amazon basin from 18–23 to 24–29% during the wet season. We also show that the south-western part of the Amazon basin is not only a direct source of rainfall over the La Plata basin, but also a key intermediary region that distributes moisture originating from the entire Amazon basin towards the La Plata basin during the wet season. Our results suggest that land use change in this region might have a stronger impact on downwind rainfall than previously thought. Using complex network analysis techniques, we find the eastern side of the sub-tropical Andes to be a key region where CMR pathways are channeled. This study offers a better understanding of the interactions between the vegetation and the atmosphere on the water cycle, which is needed in a context of land use and climate change in South America

The 3^3He(e, e′'d)p Reaction in qω\omega-constant Kinematics

The cross section for the $^3$He(e, e$'$d)p reaction has been measured as a function of the missing momentum $p_m$ in q$\omega$ -constant kinematics at beam energies of 370 and 576 MeV for values of the three-momentum transfer $q$ of 412, 504 and 604 \mevc. The L(+TT), T and LT structure functions have been separated for $q$ = 412 and 504 \mevc. The data are compared to three-body Faddeev calculations, including meson-exchange currents (MEC), and to calculations based on a covariant diagrammatic expansion. The influence of final-state interactions and meson-exchange currents is discussed. The $p_m$-dependence of the data is reasonably well described by all calculations. However, the most advanced Faddeev calculations, which employ the AV18 nucleon-nucleon interaction and include MEC, overestimate the measured cross sections, especially the longitudinal part, and at the larger values of $q$. The diagrammatic approach gives a fair description of the cross section, but under(over)estimates the longitudinal (transverse) structure function.Comment: 17 pages, 7 figure

A new era for people with cystic fibrosis

Cystic fibrosis is the most prevalent inherited disease caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The impaired electrolyte homeostasis caused by the mutated or absent protein leads to symptoms in multiple organ systems. However, the pulmonary manifestation with chronic infections and eventually respiratory failure remains the most important threat. Until one decade ago, only symptomatic treatment was available. However, since 2012, different combinations of CFTR modulators are available for people with cystic fibrosis (pwCF) that carry different mutations. The advent of these drugs has impressively changed life expectancy and quality of life in people with cystic fibrosis and raised new challenges regarding long-term complications and tapering of conventional therapies. Conclusion: In this review, we provide an update on the latest developments around diagnostics, treatment, and prognosis of pwCF.What is Known:• Cystic fibrosis is an incurable and life-shortening disease asking for life-long symptomatic treatment.• Three combination CFTR modulating drugs has gained marked approval over the last 10 years.What is New:• The emerge of new (modulating) therapies contribute to the increasing life expectancy.• A high unmet need to develop new therapies for people with CF who cannot access or benefit from these drugs remains. This review gives an update on the current status

Infarct-related chronic total coronary occlusion and the risk of ventricular tachyarrhythmic events in out-of-hospital cardiac arrest survivors

Introduction: Chronic total coronary occlusion (CTO) has been identified as a risk factor for ventricular arrhythmias, especially a CTO in an infarct-related artery (IRA). This study aimed to evaluate the effect of an IRA-CTO on the occurrence of ventricular tachyarrhythmic events (VTEs) in out-of-hospital cardiac arrest survivors without ST-segment elevation. Methods: We conducted a post hoc analysis of the COACT trial, a multicentre randomised controlled trial. Patients were included when they survived index hospitalisation after cardiac arrest and demonstrated coronary artery disease on coronary angiography. The primary endpoint was the occurrence of a VTE, defined as appropriate implantable cardioverter-defibrillator (ICD) therapy, sustained ventricular tachyarrhythmia or sudden cardiac death. Results: A total of 163 patients from ten centres were included. Unrevascularised IRA-CTO in a main vessel was present in 43 patients (26%). Overall, 61% of the study population received an ICD for secondary prevention. During a follow-up of 1 year, 12 patients (7.4%) experienced at least one VTE. The cumulative incidence rate of VTEs was higher in patients with an IRA-CTO compared to patients without an IRA-CTO (17.4% vs 5.6%, log-rank p = 0.03). However, multivariable analysis only identified left ventricular ejection fraction < 35% as an independent factor associated with VTEs (adjusted hazard ratio 8.7, 95% confidence interval 2.2–35.4). A subanalysis focusing on CTO, with or without an infarct in the CTO territory, did not change the results. Conclusion: In out-of-hospital cardiac arrest survivors with coronary artery disease without ST-segment elevation, an IRA-CTO was not an independent factor associated with VTEs in the 1st year after the index event

A prospective, randomized, open-label trial of 6-month versus 12-month dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction: Rationale and design of the \u201cDAPT-STEMI trial\u201d

Background The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors. Hypothesis Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. Study design The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required. Summary The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT

Defining and Measuring Resilience in Children with a Chronic Disease: a Scoping Review

UNLABELLED: More than 25% of all children grow up with a chronic disease. They are at higher risk for developmental and psychosocial problems. However, children who function resiliently manage to adapt positively to these challenges. We aim to systematically review how resilience is defined and measured in children with a chronic disease. A search of PubMed, Cochrane, Embase, and PsycINFO was performed on December 9, 2022, using resilience, disease, and child/adolescent as search terms. Two reviewers independently screened articles for inclusion according to predefined criteria. Extraction domains included study characteristics, definition, and instruments assessing resilience outcomes, and resilience factors. Fifty-five out of 8766 articles were identified as relevant. In general, resilience was characterized as positive adaptation to adversity. The included studies assessed resilience by the outcomes of positive adaptation, or by resilience factors, or both. We categorized the assessed resilience outcomes into three groups: personal traits, psychosocial functioning, and disease-related outcomes. Moreover, myriad of resilience factors were measured, which were grouped into internal resilience factors (cognitive, social, and emotional competence factors), disease-related factors, and external factors (caregiver factors, social factors, and contextual factors). Our scoping review provides insight into the definitions and instruments used to measure resilience in children with a chronic disease. More knowledge is needed on which resilience factors are related to positive adaptation in specific illness-related challenges, which underlying mechanisms are responsible for this positive adaptation, and how these underlying mechanisms interact with one another. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42844-023-00092-2