Dialogued into being: Constructing knowledge about hand osteoarthritis from a polyphony of voices in healthcare encounters.

Purpose: Multiple knowledge sources inform healthcare. In healthcare encounters, patients and health professionals' ideas intersect to understand illness and disease. Exploring what is thought of as legitimate knowledge, and where those reflections come from is central to the process of improving and developing healthcare.

The total-breath method yields higher values of DLCO and TLC than the conventional method.

Background: The 2017 ATS/ERS technical standard for measuring the single-breath diffusing capacity (DLCO) proposed the "rapid-gas-analyzer" (RGA) or, equivalently, "total-breath" (TB) method for the determination of total lung capacity (TLC). In this study, we compared DLCO and TLC values estimated using the TB and conventional method, and how estimated TLC using these two methods compared to that determined by body plethysmography.

Method: A total of 95 people with COPD (GOLD grades 1-4) and 23 healthy subjects were studied using the EasyOne Pro (ndd Medical Technologies, Switzerland) and Master Screen Body (Vyaire Medical, Höchberg, Germany).

The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons.

Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24). This modification, which is known as UFMylation, is orchestrated by the UFM1 ribosome E3 ligase (UREL) complex, comprising UFL1, UFBP1 and CDK5RAP3 (ref. ).

Negotiating Professional Tasks in a Hospital: A Qualitative Study of Rheumatologists and Occupational Therapists in the Management of Hand Osteoarthritis.

Purpose: Societal change and rise in demand for healthcare call for new health professional practices and task redistribution. Through negotiated order theory, this study explores how hospital rheumatologists (RT) and occupational therapists (OT) negotiate professional tasks in the clinical management of hand osteoarthritis.

Methodology: Fourteen qualitative interviews and 16 observations in clinical consultations were conducted in two hospitals specialized in rheumatology in Norway.

An intellectual-disability-associated mutation of the transcriptional regulator impairs glutamatergic neurotransmission.

Advances in genome sequencing technologies have favored the identification of rare mutations linked to neurological disorders in humans. Recently, a autosomal dominant mutation in was identified (NM_052876.3: c.

Participation in healthcare consultations: A qualitative study from the perspectives of persons diagnosed with hand osteoarthritis.

Introduction: Scarce health resources and differing views between persons with hand osteoarthritis (OA) and health professionals concerning care preferences contribute to sustaining a gap between actual needs and existing clinical guidelines for hand OA. The aim of this study is to explore the experiences of persons diagnosed with hand OA in their encounters with health services and how those experiences influence negotiations and decision-making in hand OA care.

Methods: Data from 21 qualitative interviews with persons diagnosed with hand OA were collected, transcribed verbatim and analysed using reflexive thematic analysis.

A new approach for the detection of obesity-related airway obstruction in lung-healthy individuals.

Background: Subjects with obesity show an increased prevalence of airway obstruction but it is not clear in each case whether this reflects genuine lung disease. Via intentional increase in end-expiratory lung volume we studied the detection of obesity-induced airway obstruction in lung-healthy obese subjects.

Methods: The primary study population comprised 66 lung-healthy obese subjects and 23 normal weight subjects.

A non-canonical scaffold-type E3 ligase complex mediates protein UFMylation.

Protein UFMylation, i.e., post-translational modification with ubiquitin-fold modifier 1 (UFM1), is essential for cellular and endoplasmic reticulum homeostasis.

Chemical biology tools to study Deubiquitinases and Ubl proteases.

The reversible attachment of ubiquitin (Ub) and ubiquitin like modifiers (Ubls) to proteins are crucial post-translational modifications (PTMs) for many cellular processes. Not only do cells possess hundreds of ligases to mediate substrate specific modification with Ub and Ubls, but they also have a repertoire of more than 100 dedicated enzymes for the specific removal of ubiquitin (Deubiquitinases or DUBs) and Ubl modifications (Ubl-specific proteases or ULPs). Over the past two decades, there has been significant progress in our understanding of how DUBs and ULPs function at a molecular level and many novel DUBs and ULPs, including several new DUB classes, have been identified.

Stress - Regulation of SUMO conjugation and of other Ubiquitin-Like Modifiers.

Stress is unavoidable and essential to cellular and organismal evolution and failure to adapt or restore homeostasis can lead to severe diseases or even death. At the cellular level, stress drives a plethora of molecular changes, of which variations in the profile of protein post-translational modifications plays a key role in mediating the adaptative response of the genome and proteome to stress. In this context, post-translational modification of proteins by ubiquitin-like modifiers, (Ubl), notably SUMO, is an essential stress response mechanism.

The role of clinical signs and spirometry in the diagnosis of obstructive airway diseases: a systematic analysis adapted to general practice settings.

Background: In general practice (GP), the diagnosis of obstructive airway diseases much relies on diagnostic questions, in view of the limited availability of lung function. We systematically assessed the relative importance of such questions for diagnosing asthma and chronic obstructive pulmonary disease (COPD), either without or with information from spirometry.

Methods: We used data obtained in a pulmonary practice to ensure the validity of diagnoses and assessments.

[Guideline for the Diagnosis and Treatment of Asthma - Addendum 2020 - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology].

The present addendum of the guideline for the diagnosis and treatment of asthma (2017) complements new insights into the diagnosis and management of asthma as well as for the newly approved drugs for the treatment of asthma. Current, evidence-based recommendations on diagnostic and therapeutic approaches are presented for children and adolescents as well as for adults with asthma.

Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study.

Background: Inhaled corticosteroids (ICS) are indicated for prevention of exacerbations in patients with COPD, but they are frequently overprescribed. ICS withdrawal has been recommended by international guidelines in order to prevent side effects in patients in whom ICS are not indicated.

Method: Observational comparative effectiveness study aimed to evaluate the effect of ICS withdrawal versus continuation of triple therapy (TT) in COPD patients in primary care.

Identification of a Catalytic Active but Non-Aggregating MDM2 RING Domain Variant.

As a key regulator of the tumour suppressor protein p53, MDM2 is involved in various types of cancer and has thus been an attractive drug target. So far, small molecule design has primarily focussed on the N-terminal p53-binding domain although on-target toxicity effects have been reported. Targeting the catalytic RING domain of MDM2 resembles an alternative approach to drug MDM2 with the idea to prevent MDM2-mediated ubiquitination of p53 while retaining MDM2's ability to bind p53.

Differential requirements for MDM2 E3 activity during embryogenesis and in adult mice.

The p53 tumor suppressor protein is a potent activator of proliferative arrest and cell death. In normal cells, this pathway is restrained by p53 protein degradation mediated by the E3-ubiquitin ligase activity of MDM2. Oncogenic stress releases p53 from MDM2 control, so activating the p53 response.

Effect of Inhaled Corticosteroid Withdrawal on Chronic Obstructive Pulmonary Disease Exacerbations in Patients Taking Triple Therapy at Baseline.

Purpose: In the Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial, inhaled corticosteroid (ICS) withdrawal in patients with chronic obstructive pulmonary disease receiving triple therapy (long-acting β-agonist+long-acting muscarinic antagonist+ICS) did not change moderate/severe exacerbation risk. However, many patients were not taking triple therapy before study participation. This analysis was conducted to eliminate the impact of non-ICS users on WISDOM results by re-analyzing the data using only the subset of patients who were taking triple therapy at screening.

Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials.

Background: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation. Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes. Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear.

Structural basis for DNA damage-induced phosphoregulation of MDM2 RING domain.

Phosphorylation of MDM2 by ATM upon DNA damage is an important mechanism for deregulating MDM2, thereby leading to p53 activation. ATM phosphorylates multiple residues near the RING domain of MDM2, but the underlying molecular basis for deregulation remains elusive. Here we show that Ser429 phosphorylation selectively enhances the ubiquitin ligase activity of MDM2 homodimer but not MDM2-MDMX heterodimer.

Genuair/Pressair Inhaler in COPD: The Patient Perspective.

This article reviews the latest data pertaining to the Genuair/Pressair device, a breath-actuated, multi-dose dry-powder inhaler with a two-step inhalation process, which is marketed for the delivery of aclidinium alone or in combination with formoterol for long-term maintenance bronchodilation treatment in chronic obstructive pulmonary disease. It contains multiple feedback mechanisms to guide effective use, and safety features to avoid double-dosing or attempted use when empty. In addition to describing the design of Genuair, the article will provide an update on inhaler operability and performance, focusing on recent patient preference and satisfaction studies.

[Therapy control of COPD by Eosinophilic Granulocytes?].

Symptomatic patients with COPD reporting about repeated exacerbations in their history (group D according to GOLD recommendations) are treated with dual bronchodilation (LAMA/LABA) with potential benefits from additional ICS. Eosinophils in peripheral blood are considered as potential biomarkers to predict exacerbations. > 300 cells/µL or 4 % of eosinophils in peripheral blood are recommended to treat the patients with additional ICS.

Spirometric changes during exacerbations of COPD: a post hoc analysis of the WISDOM trial.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function and poor outcomes for patients. However, there are limited data on the time course of changes in forced expiratory volume in 1 s (FEV) preceding the first reported symptom and after the start of an exacerbation.

Methods: WISDOM was a multinational, randomized, double-blind, active-controlled, 52-week study in patients with severe-to-very severe COPD.