Phage anti-CRISPR control by an RNA- and DNA-binding helix–turn–helix protein

In all organisms, regulation of gene expression must be adjusted to meet cellular requirements and frequently involves helix–turn–helix (HTH) domain proteins1. For instance, in the arms race between bacteria and bacteriophages, rapid expression of phage anti-CRISPR (acr) genes upon infection enables evasion from CRISPR–Cas defence; transcription is then repressed by an HTH-domain-containing anti-CRISPR-associated (Aca) protein, probably to reduce fitness costs from excessive expression2,3,4,5. However, how a single HTH regulator adjusts anti-CRISPR production to cope with increasing phage genome copies and accumulating acr mRNA is unknown. Here we show that the HTH domain of the regulator Aca2, in addition to repressing Acr synthesis transcriptionally through DNA binding, inhibits translation of mRNAs by binding conserved RNA stem-loops and blocking ribosome access. The cryo-electron microscopy structure of the approximately 40 kDa Aca2–RNA complex demonstrates how the versatile HTH domain specifically discriminates RNA from DNA binding sites. These combined regulatory modes are widespread in the Aca2 family and facilitate CRISPR–Cas inhibition in the face of rapid phage DNA replication without toxic acr overexpression. Given the ubiquity of HTH-domain-containing proteins, it is anticipated that many more of them elicit regulatory control by dual DNA and RNA binding

Immediate exacerbation of atopic dermatitis after switching from upadacitinib to dupilumab: A report of two cases

Abstract Janus kinase (JAK) inhibitors are efficacious for atopic dermatitis (AD). However, some patients receiving JAK inhibitors develop acne, especially younger patients, or herpes zoster, especially elderly patients, and desire to switch to dupilumab. We experienced two patients with immediate exacerbation of AD after switching from upadacitinib to dupilumab, and herein report these cases. This phenomenon is attributed to the difference in elimination half‐life of the two drugs and a slower onset of efficacy of dupilumab than upadacitinib. When switching from a JAK inhibitor to dupilumab, short‐term concomitant use, intensifying topical treatment, and/or rescue with cyclosporine should be considered

Development of diffuse large B‐cell lymphoma during dupilumab treatment in a patient with atopic dermatitis: A case report

This case report describes a 44‐year‐old male patient with atopic dermatitis who developed malignant lymphoma (diffuse large B‐cell lymphoma) during the dupilumab treatment

Improvements in self‐confidence and satisfaction with self‐injection after introducing self‐injection of dupilumab in patients with atopic dermatitis

Abstract Dupilumab was approved for treating adult patients with atopic dermatitis (AD) refractory to topical therapy in Japan in April 2018, and self‐injection of dupilumab has been available since May 2019. Subcutaneous self‐injection of medication has benefits for patients and the healthcare system. However, anxiety about self‐injection, lack of confidence, and the complicated procedure could prevent initiating self‐injection. In this study, we assessed the experience of AD patients treated with dupilumab before and after introducing self‐injection, utilizing the Self‐Injection Assessment Questionnaire (SIAQ). Adult AD patients who received dupilumab by self‐injection and had been treated for more than 3 months after initiating self‐injection in our hospital from March 1, 2020, to June 19, 2021, were included in this study. Patients rated their perceptions about self‐injections using the SIAQ before the first self‐injection and 3 months after initiating self‐injection. Data were collected retrospectively from their charts. Data on 36 patients were analyzed. The mean age was 34.1 ± 11.5 years. Twenty patients used a prefilled auto‐injector, and the others used a prefilled syringe. Scores on self‐confidence and satisfaction with self‐injection significantly improved after introducing self‐injection. Feelings about injections improved in patients over 40 years and in those who felt anxious about self‐injection. A strong correlation in scores between satisfaction with self‐injection and the ease of use was observed. The results were not affected by clinical severity, gender, or device. Our results could encourage patients who dither to introduce self‐injection of dupilumab due to anxiety and/or lack of self‐confidence about self‐injection to initiate self‐injection

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes