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

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

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

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

Tracking Mental Wellbeing of Dutch Adolescents During the First Year of the COVID-19 Lockdown: A Longitudinal Study

Purpose: Adolescents might be susceptible to the effects of the COVID-19 lockdown. We assessed changes in mental wellbeing throughout the first year of the pandemic and compared these with prepandemic levels. Methods: This five-wave prospective study among Dutch adolescents aged 12–17 years used data collected before the pandemic (n = 224) (T0), in May (T1), July (T2), and October 2020 (T3), and in February 2021 (T4). Generalized estimating equations were used to assess the association between stringency of the lockdown with mental wellbeing. Results: Adolescents had a lower life satisfaction during the first full lockdown (T1) [adjusted β: −0.36, 95% confidence interval (CI): −0.58 to −0.13], during the partial lockdown (T3) (adjusted β: −0.37, 95% CI: −0.63 to −0.12), and during the second full lockdown (T4) (adjusted β: −0.79, 95% CI: −1.07 to −0.52) compared to before the pandemic (T0). Adolescents reported more internalizing symptoms during only the second full lockdown (T4) (adjusted β: 2.58, 95% CI: 0.41–4.75). During the pandemic [at T1 (adjusted β: 0.29, 95% CI: 0.20–0.38), T2 (adjusted β: 0.36, 95% CI: 0.26–0.46), T3 (adjusted β: 0.33, 95% CI: 0.22–0.45), and T4 (adjusted β: 0.20, 95% CI: 0.07–0.34)], adolescents reported a better psychosomatic health, partly attributable to less trouble falling asleep (p < .01). Discussion: The COVID-19 lockdown measures have had both a negative and positive impact on mental wellbeing of Dutch adolescents. However, mental wellbeing was most impacted during the second full lockdown compared to before the pandemic

Encouraging survival rates in patients with acute myocardial infarction treated with an intra-aortic balloon pump

Objective To evaluate a 30-day and long-term outcome of patients with acute myocardial infarction (AMI) treated with intra-aortic balloon pump (IABP) counterpulsation and to identify predictors of a 30-day and long-term all-cause mortality. Methods Retrospective cohort study of 437 consecutive AMI patients treated with IABP between January 1990 and June 2004. A Cox proportional hazards model was used to identify predictors of a 30-day and long-term all-cause mortality. Results Mean age of the study population was 61±11 years, 80% of the patients were male, and 68% had cardiogenic shock. Survival until IABP removal after successful haemodynamic stabilisation was 78% (n=341). Cumulative 30-day survival was 68%. Median follow-up was 2.9 years (range, 6 months to 15 years). In patients who survived until IABP removal, cumulative 1-, 5-, and 10-year survival was 75%

The in vivo endothelial cell translatome is highly heterogeneous across vascular beds

Endothelial cells (ECs) are highly specialized across vascular beds. However, given their interspersed anatomic distribution, comprehensive characterization of the molecular basis for this heterogeneity in vivo has been limited. By applying endothelial-specific translating ribosome affinity purification (EC-TRAP) combined with high-throughput RNA sequencing analysis, we identified pan EC-enriched genes and tissue-specific EC transcripts, which include both established markers and genes previously unappreciated for their presence in ECs. In addition, EC-TRAP limits changes in gene expression after EC isolation and in vitro expansion, as well as rapid vascular bed-specific shifts in EC gene expression profiles as a result of the enzymatic tissue dissociation required to generate single-cell suspensions for fluorescence-activated cell sorting or single-cell RNA sequencing analysis. Comparison of our EC-TRAP with published single-cell RNA sequencing data further demonstrates considerably greater sensitivity of EC-TRAP for the detection of low abundant transcripts. Application of EC-TRAP to examine the in vivo host response to lipopolysaccharide (LPS) revealed the induction of gene expression programs associated with a native defense response, with marked differences across vascular beds. Furthermore, comparative analysis of whole-tissue and TRAP-selected mRNAs identified LPS-induced differences that would not have been detected by whole-tissue analysis alone. Together, these data provide a resource for the analysis of EC-specific gene expression programs across heterogeneous vascular beds under both physiologic and pathologic conditions

Development and validation of a novel personalized electronic patient-reported outcome measure to assess quality of life (Q-LIFE): a prospective observational study in people with Cystic Fibrosis

Background: Generic and disease-specific patient-reported outcome measures (PROMs) may lack relevance and sensitivity on a patient-level in chronic diseases with differential disease expression and high individual variability, such as Cystic Fibrosis (CF). This study aimed to develop and validate a novel personalized electronic PROM (ePROM) that captures relevant aspects of quality of life in individuals with CF. Methods: The Q-Life app was developed as a short personalized ePROM to assess individual quality of life. Psychometric properties were assessed in a single-center cross-sectional study between September 2019 and September 2021 and in a prospective cohort study between September 2021 and September 2022. Findings: Combined studies included 223 participants (median age: 24 years, IQR: 19.0–32.5 years, range: 12.0–58.0 years). Internal consistency (Cronbach's alpha: 0.83–0.90) and test-retest reliability (intraclass correlation coefficient: 0.90; 95% CI: 0.65–0.92; p < 0.001) of quality of life (Q-Life) scores were strong. Q-Life scores were associated with overall Cystic Fibrosis Questionnaire-Revised (CFQ-R) scores (ρ = 0.71; p < 0.001), CFQ-R respiratory domain scores (ρ = 0.57; p < 0.001) and forced expiratory volume in 1s (ρ = 0.41; p < 0.001). Furthermore, Q-Life scores improved from 65.0 (IQR: 45.0–63.3) at baseline to 84.2 (IQR: 75.0–95.0) and 87.5 (IQR: 75.0–100.0) after 3 and 6 months of elexacaftor/tezacaftor/ivacaftor treatment (change: 20.8; 95% CI: 17.5–25.0; p < 0.001), comparable to CFQ-R respiratory domain scores (change: 22.2, 95% CI: 19.4–25.0, p < 0.001). Interpretation: The Q-Life app is a reliable, valid and sensitive personalized ePROM to measure all aspects of quality of life that really matter to individuals with Cystic Fibrosis. This patient-centered approach could provide important advantages over generic and disease-specific PROMs in the era of personalized medicine and value-based healthcare. Funding: Dutch Cystic Fibrosis Foundation, Health-Holland