New cutaneous vaccine adjuvant that STINGs a little less

Cutaneous vaccination can be a challenge because the development of local skin inflammation is often unavoidable. Thus, it is important to identify and validate new vaccine adjuvants that enhance immunization without the burden of inflammation. Wang et al. now report on a cyclic GMP-AMP adjuvant, the natural stimulator of interferon genes agonist, providing evidence for potent immune responses without inflammation

Manipulated Microenvironment in Human Papilloma Virus–Infected Epithelial Cells: Is the CD40–CD154 Pathway Beneficial for Host or Virus?

In this issue, Tummers et al. (2014) demonstrate that high-risk human papilloma viruses (hrHPVs) attenuate the magnitude of responses to CD40 ligation and the epithelial cells’ (ECs) capacity to attract leukocytes. These results suggest that hrHPVs can escape from host immune surveillance by modulating pro-inflammatory responses in infected ECs, resulting in persistent infections and potential carcinogenesis

Phenotypic heterogeneity in Hidradenitis Suppurativa (Acne Inversa): classification is an essential step toward personalized therapy

Awareness is increasing that there is phenotypic heterogeneity within the hidradenitis suppurativa (HS) disease spectrum. However, the few randomized HS trials that are available have not distinguished between the subtypes of the disease. In this issue, Canoui-Poitrine et al. used latent class (LC) analysis of the largest HS cohort described to date to generate three phenotypic subtypes. LC 1 correlates with "typical" European HS, mainly involving the axilla, groin, and, in women, the inframammary region. "Atypical" HS, which may be linked to γ-secretase gene mutations, was subdivided further into LC2 and LC3 subtypes

Development of core outcome sets in hidradenitis suppurativa:a systematic review of outcome measure instruments to inform the process

Background The recent hidradenitis suppurativa (HS) Cochrane review identified outcome measure heterogeneity as an important issue to address when designing future HS trials. Objectives To follow the Harmonising Outcome Measures for Eczema (HOME) roadmap, by performing a systematic review of HS outcome measure instruments to inform the development of a HS core outcome set. Methods We performed a systematic review to identify validation evidence for outcome measure instruments used in HS randomised controlled trials (RCTs), and assessed the methodological quality of all HS outcome measure validity studies using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Results The 12 RCTs included in the HS Cochrane review utilised a total of 30 outcome measure instruments, including 16 physician reported instruments, 11 patient reported instruments and three composite measures containing elements of both. Twenty-seven (90%) of the instruments lacked any validation data. Two further instruments have been developed and partially validated recently. Of the seven studies meeting our systematic review inclusion criteria, six were of ‘fair’ or ‘poor’ methodological quality, in part because most of the studies were not primarily designed for instrument validation. The HiSCR instrument is supported by good quality validation data but there are gaps including assessment of internal consistency, inter-rater reliability and minimal clinically important difference, and convergent validity fell below the acceptable range for some comparisons. Conclusions Multiple, usually unvalidated outcome measure instruments have been used in HS RCTs. Where validation evidence is available there are issues of low methodological quality or incomplete validity assessment and so no instruments can be fully recommended currently

How HIV-1 Takes Advantage of the Cytoskeleton during Replication and Cell-to-Cell Transmission

Human immunodeficiency virus 1 (HIV-1) infects T cells, macrophages and dendritic cells and can manipulate their cytoskeleton structures at multiple steps during its replication cycle. Based on pharmacological and genetic targeting of cytoskeleton modulators, new imaging approaches and primary cell culture models, important roles for actin and microtubules during entry and cell-to-cell transfer have been established. Virological synapses and actin-containing membrane extensions can mediate HIV-1 transfer from dendritic cells or macrophage cells to T cells and between T cells. We will review the role of the cytoskeleton in HIV-1 entry, cellular trafficking and cell-to-cell transfer between primary cells

The development and clinical evaluation of a 'traffic-light' design dermatology outpatient discharge information checklist

Background Although multiple factors influence discharge decisions, there is no structured guidance to assist clinicians in making informed decisions. A discharge information checklist might improve the appropriateness of dermatology clinicians’ discharge decisions. Objectives To generate consensus among dermatologists on the content of an outpatient discharge checklist, to create one and to seek clinicians’ opinions on its usefulness. Methods Seventeen consultant dermatologists from five National Health Service trusts completed a 72‐item Delphi questionnaire. A five‐point Likert scale was used to rate each item for importance in contributing to a high‐quality discharge decision. Eighteen clinicians completed a questionnaire evaluating checklist use. Results Consensus was determined when ≥ 75% of consultants rated an item ‘very important’ or ‘important’. There was strong inter‐rater reliability (intraclass correlation coefficient = 0·958) and fair inter‐rater agreement (Fleiss kappa = 0·269). There were 26 consensus‐agreed items, condensed to 13 that formed the ‘traffic‐light’ checklist. These are disease‐related issues (diagnostic certainty, disease severity, treatment appropriateness, patient manageable in primary care, patient's benefit from follow‐up), patient empowerment issues (understanding diagnosis and treatment outcome, having a clear plan, treatment side‐effects, ability to self‐manage) and addressing concerns (patient concerns, easy reaccess to secondary care, whether patient and clinician are happy with the decision). Twelve clinicians (67%) found the checklist useful, 11 (61%) wanted to use it in future, 10 (56%) thought it was useful for training and three (17%) said it helped their thinking. Clinicians suggested its use for auditing and for training clinicians and administrators. Conclusions Items were identified to create an outpatient discharge information checklist, which demonstrated high acceptability

The ticking CLOCK of HSV-2 pathology

Herpes simplex virus type 2 (HSV-2) is the causative agent of genital herpes. Matsuzawa et al have demonstrated that, in a mouse model, HSV-2 pathology is influenced by the time infection occurs. Increased expression of the HSV-2 receptor Nectin-1 under the control of CLOCK coincided with an increase in viral titer suggesting that HSV-2 infection is regulated by the host circadian clock

Inhibition of HIV-1 replication by balsamin, a ribosome inactivating protein of Momordica balsamina

Ribosome-inactivating proteins (RIPs) are endowed with several medicinal properties, including antiviral activity. We demonstrate here that the recently identified type I RIP from Momordica balsamina also possesses antiviral activity, as determined by viral growth curve assays and single-round infection experiments. Importantly, this activity is at play even as doses where the RIP has no cytotoxic effect. In addition, balsamin inhibits HIV-1 replication not only in T cell lines but also in human primary CD4(+) T cells. This antiviral compound exerts its activity at a viral replicative step occurring later than reverse-transcription, most likely on viral protein translation, prior to viral budding and release. Finally, we demonstrate that balsamin antiviral activity is broad since it also impedes influenza virus replication. Altogether our results demonstrate that type I RIP can exert a potent anti-HIV-1 activity which paves the way for new therapeutic avenues for the treatment of viral infections

Dermatology life quality index (DLQI) as a psoriasis referral triage tool

Most primary care psoriasis referrals in the UK are triaged as ‘routine’, in part because of the prioritisation of skin cancer. As a result, patients with severe psoriasis may wait several months to be seen, enduring quality of life (QoL) impairment that could have been reduced. Furthermore some patients may spontaneously improve by the time they are seen by a specialist, making the appointment unnecessary at that time. Therefore, following approval from the local ethics committee, we conducted a prospective study to evaluate the usefulness of Dermatology Life Quality Index (DLQI) scores in triaging patients with psoriasis referred to our dermatology secondary health care services