Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research: an interdisciplinary perspective.

More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We prioritize definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a particular point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses, and validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalizable to current and future research efforts.

Atopic dermatitis (AD), and psoriasis are long-term skin conditions that can significantly affect people's lives, especially when symptoms are severe. Approximately 10% of adults and 20% of children are affected by AD, while psoriasis affects around 5% of people in the UK. Both conditions are associated with debilitating physical symptoms (such as itch) and have been linked to depression and anxiety. Biomarkers are naturally occurring chemicals in the human body and have potential to enhance the longer-term management of AD and psoriasis. Currently, there are no routinely used biomarkers that can identify people who experience or will go on to develop severe AD and psoriasis. For this reason, research is under way to understand which biomarkers are linked to severity. In this study, a multidisciplinary team of skin researchers from across Europe, along with patient groups, discussed the complexities of studying severity-related biomarkers. We identified a number of severity measurement approaches and there were recommendations for future biomarker research, including (i) considering multiple measures as no single measure can encompass all aspects of severity, (ii) exploring severity measures recorded by both healthcare professionals and patients, as each may capture different aspects, and (iii) accounting for influencing factors, such as different treatment approaches, that may impact AD and psoriasis severity, which make it challenging to compare findings across studies. Overall, we anticipate that the insights gained from these discussions will increase the likelihood of biomarkers being effectively applied in real-world settings, to ultimately improve outcomes for people with AD and psoriasis.

Persistent or Transient Human ß Cell Dysfunction Induced by Metabolic Stress: Specific Signatures and Shared Gene Expression with Type 2 Diabetes.

Pancreatic ß cell failure is key to type 2 diabetes (T2D) onset and progression. Here, we assess whether human ß cell dysfunction induced by metabolic stress is reversible, evaluate the molecular pathways underlying persistent or transient damage, and explore the relationships with T2D islet traits. Twenty-six islet preparations are exposed to several lipotoxic/glucotoxic conditions, some of which impair insulin release, depending on stressor type, concentration, and combination. The reversal of dysfunction occurs after washout for some, although not all, of the lipoglucotoxic insults. Islet transcriptomes assessed by RNA sequencing and expression quantitative trait loci (eQTL) analysis identify specific pathways underlying ß cell failure and recovery. Comparison of a large number of human T2D islet transcriptomes with those of persistent or reversible ß cell lipoglucotoxicity show shared gene expression signatures. The identification of mechanisms associated with human ß cell dysfunction and recovery and their overlap with T2D islet traits provide insights into T2D pathogenesis, fostering the development of improved ß cell-targeted therapeutic strategies.

Mobile telephones, distracted attention, and pedestrian safety.

Driver distraction is a major cause of traffic accidents, with mobile telephones as a key source of distraction. In two studies, we examined distraction of pedestrians associated with mobile phone use. The first had 60 participants walk along a prescribed route, with half of them conversing on a mobile phone, and the other half holding the phone awaiting a potential call, which never came. Comparison of the performance of the groups in recalling objects planted along the route revealed that pedestrians conversing recalled fewer objects than did those not conversing. The second study had three observers record pedestrian behavior of mobile phone users, i-pod users, and pedestrians with neither one at three crosswalks. Mobile phone users crossed unsafely into oncoming traffic significantly more than did either of the other groups. For pedestrians as with drivers, cognitive distraction from mobile phone use reduces situation awareness, increases unsafe behavior, putting pedestrians at greater risk for accidents, and crime victimization.