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Psoriasis, a papulosquamous skin disease, was originally thought of as a disorder primarily of epidermal keratinocytes, but is now recognised as one of the commonest immune-mediated disorders. Tumour necrosis factor α, dendritic cells, and T-cells all contribute substantially to its pathogenesis. In early-onset psoriasis (beginning before age 40 years), carriage of HLA-Cw6 and environmental triggers, such as β-haemolytic streptococcal infections, are major determinants of disease expression. Moreover, at least nine chromosomal psoriasis susceptibility loci have been identified. Several clinical phenotypes of psoriasis are recognised, with chronic plaque (psoriasis vulgaris) accounting for 90% of cases. Comorbidities of psoriasis are attracting interest, and include impairment of quality of life and associated depressive illness, cardiovascular disease, and a seronegative arthritis known as psoriatic arthritis. A more complete understanding of underlying pathomechanisms is leading to new treatments, which will be discussed in the second part of this Series.

Management of psoriasis begins with identification of the extent of cutaneous disease. However, a holistic, contractual approach to treatment is encouraged, with particular reference to psychosocial disability and quality-of-life issues. The presence of psoriasis on palms, soles, body folds, genitals, face, or nails, and concomitant joint disease, are also important when considering treatment options. An evidence-based approach is essential in delineating differences between the many available treatments. However, archaic approaches, especially combinational ones, are routinely used by some clinicians, with inadequate prospective or comparative evidence. Treatments currently available are: topical agents used predominantly for mild disease and for recalcitrant lesions in more severe disease; phototherapy for moderate disease; and systemic agents including photochemotherapy, oral agents, and newer injectable biological agents, which have revolutionised the management of severe psoriasis. Other innovative treatments are undergoing clinical studies, with the aim of maintaining safe, long-term control of the condition.

Tumour necrosis factor α (TNFα) is thought to play a part in the pathogenesis of psoriasis. We assessed the efficacy and safety of continuous treatment with infliximab, a monoclonal antibody that binds to and neutralises the activity of TNFα, in patients with psoriasis. In this phase III, multicentre, double-blind trial, 378 patients with moderate-to-severe plaque psoriasis were allocated in a 4:1 ratio to receive infusions of either infliximab 5 mg/kg or placebo at weeks 0, 2, and 6, then every 8 weeks to week 46. At week 24, placebo-treated patients crossed over to infliximab treatment. Skin and nail signs of psoriasis were assessed using the psoriasis area and severity index (PASI) and nail psoriasis severity index (NAPSI), respectively. The primary endpoint, analysed on an intention-to-treat-basis, was the proportion of patients achieving at least a 75% improvement in PASI from baseline to week 10. At week 10, 80% (242/301) of patients treated with infliximab achieved at least a 75% improvement from their baseline PASI (PASI 75) and 57% (172/301) achieved at least a 90% improvement (PASI 90), compared with 3% and 1% in the placebo group, respectively (p<0·0001). At week 24, PASI 75 (82% for infliximab vs 4% for placebo) and PASI 90 (58% vs 1%) were maintained (p<0·0001). At week 50, 61% achieved PASI 75 and 45% achieved PASI 90 in the infliximab group. Infliximab was generally well tolerated in most patients. Infliximab is effective in both an induction and maintenance regimen for the treatment of moderate-to-severe psoriasis, with a high percentage of patients achieving sustained PASI 75 and PASI 90 improvement through 1 year.

To maximise the clinical benefits of machine learning algorithms, we need to rethink our approach to explanation, argue David Watson and colleagues

Chronic sun exposure leads to photodamage, which is characterized clinically by fine and coarse wrinkles, dyspigmentation, telangiectasia, laxity, roughness and a sallow appearance. Many treatments claim to reduce the signs of photodamage, however evidence from randomized controlled trials (RCT) to support these claims is limited. The use of topical retinoids, particularly tretinoin, isotretinoin and tazarotene, has been shown to significantly reduce signs of photodamage both clinically and histologically. Over recent years a number of RCTs, have affirmed that topical tazarotene is an effective and safe treatment for photodamaged skin.

In this 12-week randomized trial comparing two biologic agents known to be effective for psoriasis, ustekinumab (an interleukin-12 and interleukin-23 blocker) was more effective than etanercept (an inhibitor of tumor necrosis factor α). Adverse events associated with the two treatments were similar, but the trial was not large enough and follow-up was not long enough to assess uncommon adverse events. In this 12-week randomized trial comparing two biologic agents known to be effective for psoriasis, ustekinumab (an interleukin-12 and interleukin-23 blocker) was more effective than etanercept (an inhibitor of tumor necrosis factor α). Psoriasis is a chronic, inflammatory skin disease affecting approximately 2% of the world's population. 1 , 2 Therapeutic agents used for the management of psoriasis commonly target the underlying inflammation. Immunosuppressive agents such as methotrexate and cyclosporine have proved effective in the treatment of psoriasis. 3 Biologic agents that selectively block steps in the inflammatory cascade have provided additional therapies for psoriasis and have led to a better understanding of its immunologic and pathophysiological basis. 4 – 9 Proinflammatory cytokines such as tumor necrosis factor α (TNF-α) play a central role in the inflammation underlying psoriasis. Agents that selectively block TNF-α have proved highly effective . . .

Human skin, in common with other organs, ages as a consequence of the passage of time, but in areas exposed to solar ultraviolet radiation, the effects of this intrinsic ageing process are exacerbated. In particular, both the severity and speed of onset of age-related changes, such as wrinkle formation and loss of elasticity, are enhanced in photoaged (also termed extrinsically aged) as compared with aged, photoprotected, skin. The anatomy of skin is characterised by two major layers: an outer, avascular, yet highly cellular and dynamic epidermis and an underlying vascularised, comparatively static and cell-poor, dermis. The structural consequences of photoageing are mainly evident in the extracellular matrix-rich but cell-poor dermis where key extracellular matrix proteins are particularly susceptible to photodamage. Most investigations to date have concentrated on the cell as both a target for and mediator of, ultraviolet radiation-induced photoageing. As the main effectors of dermal remodelling produced by cells (extracellular proteases) generally have low substrate specificity, we recently suggested that the differential susceptibility of key extracellular matrix proteins to the processes of photoageing may be due to direct, as opposed to cell-mediated, photodamage.In this review, we discuss the experimental evidence for ultraviolet radiation (and related reactive oxygen species)-mediated differential degradation of normally long lived dermal proteins including the fibrillar collagens, elastic fibre components, glycoproteins and proteoglycans. Whilst these components exhibit highly diverse primary and hence macro- and supra-molecular structures, we present evidence that amino acid composition alone may be a useful predictor of age-related protein degradation in both photoexposed and, as a consequence of differential oxidation sensitivity, photoprotected, tissues.

Psoriasis is a long-term immune-mediated inflammatory disorder mainly, but not only, affecting skin, and is associated with significant medical and psychological morbidity. Evidence suggests that sleep is disrupted in psoriasis, however high quality empirical evidence is lacking. Given the importance of sleep for health, characterisation of sleep disruption in psoriasis is an important goal. We therefore conducted a systematic review of the sleep-psoriasis literature. Searches were conducted in Pubmed, SCOPUS and Web of Science from inception to May 2016. Studies were compared against inclusion/exclusion criteria and underwent a quality evaluation. Given the heterogeneity of studies, we conducted a narrative synthesis of the findings. Searches revealed 32 studies which met our predetermined inclusion/exclusion criteria. Whilst 93.7% of studies reported sleep disruption in this population, ranging from 0.05% to 85.4%, many had important methodological shortcomings. Over half of all quantitative studies (54.8%; 17/31) relied on non-validated measures, contributing to heterogeneity in study findings. In those that employed valid measures, assessing sleep was often not the primary objective. We frequently found the absence of adequate sample size calculations and poor statistical reporting. This review showed that in psoriasis, reported sleep rates of sleep disturbance varied substantially. Most studies lacked a hypothesis driven research question and/or failed to use validated measures of sleep. We were unable to draw firm conclusions about the precise prevalence and nature of sleep disturbance within the psoriasis population. We offer suggestions to help advance understanding of sleep disturbance in psoriasis.

Introduction: Translational science has gained prominence in medicine, but there is still much work to be done before scientific results are used optimally and incorporated into everyday health practice. As the main focus is still on generating new scientific data with financial resources primarily available for that purpose, other activities that are necessary in the transition from research to community benefit are considered less needy. The European Statistical Office of the European Commission has recently reported that 1.7 million people under 75 years of age died in Europe in 2016, with around 1.2 million of those deaths being avoidable through effective primary prevention and public health intervention. Therefore, Academia Europaea, one of the five Pan-European networks that form SAPEA (Science Advice for Policy by European Academies), a key element of the European Commission’s Scientific Advice Mechanism (SAM), has launched a project to develop a model to facilitate and accelerate the utilisation of scientific knowledge for public and community benefit. Methods: During the process, leaders in the field, including prominent basic and clinical researchers, editors-in-chief of high-impact journals publishing translational research articles, translational medicine (TM) centre leaders, media representatives, academics and university leaders, developed the TM cycle, a new model that we believe could significantly advance the development of TM. Results: This model focuses equally on the acquisition of new scientific results healthcare, understandable and digestible summation of results, and their communication to all participants. We have also renewed the definition in TM, identified challenges and recommended solutions. Conclusion: The authors, including senior officers of Academia Europaea, produced this document to serve as a basis for revising thinking on TM with the end result of enabling more efficient and cost-effective healthcare.