Inflammasomes: emerging therapeutic targets in hidradenitis suppurativa?

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterised by recurrent inflammatory lesions, which affect skin and hair follicles in intertriginous areas. HS has a multifactorial aetiology resulting in barrier dysfunction associated with aberrant immune activation. There is increased evidence for the role of inflammasomes in the pathophysiology of inflammatory skin diseases, including HS. Inflammasomes are multiprotein complexes activated following exposure to danger signals including microbial ligands and components of damaged host cells. Inflammasome activation induces many signalling cascades and subsequent cleavage of pro-inflammatory cytokines, most notably interleukin (IL)-1ß, which have a role in HS pathogenesis. Limited immunotherapies are approved for treating moderate-to-severe HS, with variable response rates influenced by disease heterogeneity. Inflammasomes represent attractive targets to suppress multiple inflammatory pathways in HS including IL-1ß and IL-17. This review aims to summarise the role of inflammasomes in HS and to evaluate evidence for inflammasomes as therapeutic targets for HS treatment.

Resin-modified glass ionomer cement vs composite for orthodontic bonding: A multicenter, single-blind, randomized controlled trial.

INTRODUCTION: In this study, we aimed to compare the incidence of new demineralized lesions and bond failures between 2 groups of participants wearing fixed orthodontic appliances bonded with either light-cured resin-modified glass ionomer cement or light-cured composite. METHODS: This trial was a multicenter (6 centers: 2 teaching hospitals, 4 specialist orthodontic practices), single-blinded, randomized controlled trial with 2 parallel groups. Patients aged 11 years or older, in the permanent dentition, and about to start fixed orthodontic treatment in these 6 centers were randomly allocated to have either resin-modified glass ionomer cement or light-cured composite for bonding brackets, forward of the first molars. Pretreatment and day-of-debond digital photographic images were taken of the teeth and assessed by up to 5 clinical and 3 lay assessors for the presence or absence of new demineralized lesions and the esthetic impact. The assessors were masked as to group allocation. RESULTS: We randomized 210 participants, and 197 completed the trial. There were 173 with complete before-and after-digital images of the teeth. The incidence of new demineralized lesions was 24%; but when the esthetic impact was taken into account, this was considerably lower (9%). There was no statistically significant difference between the bracket adhesives in the numbers with at least 1 new demineralized lesion (risk ratio,1.25; 95% confidence interval, 0.74-2.13; P = 0.403) or first-time bracket failure (risk ratio,0.88; 95% confidence interval, 0.67-1.16; P = 0.35). There were no adverse effects. CONCLUSIONS: There is no evidence that the use of resin modified glass ionomer cement over light-cured composite for bonding brackets reduces the incidence of new demineralized lesions or bond failures. There might be other reasons for using resin modified glass ionomer cement. REGISTRATION: This trial was registered at ClinicalTrials.govNCT01925924. PROTOCOL: The protocol is available from the corresponding author on request.

YouTube™ as an information resource for orthognathic surgery.

OBJECTIVE: To investigate video content on YouTube™ related to orthognathic surgery. MATERIALS AND METHODS: YouTube™ was searched using the terms: orthognathic surgery; orthodontic surgery; jaw surgery; jaw corrective surgery. Inclusion criteria included English language; primary content orthognathic surgery and acceptable audio-visual quality. Videos were sorted into the top 50 for each search term by view-count and into an overall top 60 from the four searches. The following parameters were recorded for each video: number of views; likes; dislikes; source; primary intention. Each was classified according to information content as 'excellent', 'moderate' or 'poor'. A pre-determined list of orthognathic surgery-related information domains was also evaluated. RESULTS: The top 60 videos had a combined total of 6,986,141 views. Videos predominantly involved patients describing their personal experience (41.67%) with the majority positively biased (61.67%). Only 9.17% of videos were classified as having excellent general information content and 55.83% were rated as poor. Surgical procedures were described in 45% whilst the need for pre- and post-surgical orthodontics was discussed in 33% and 16%, respectively. Post-operative paraesthesia was discussed in 17.5% of videos outcome. CONCLUSIONS: Video content on YouTube™ relating to orthognathic surgery is substandard and patients should be advised to view it with caution.

Concomitant dilaceration, transposition, and intraosseous migration: report of a patient treated with maxillary canine-central incisor substitution.

This case report describes the multidisciplinary treatment of a male with a dilacerated maxillary left central incisor and transposition of the ipsilateral maxillary canine and lateral incisor. The initial treatment plan involved removal of the dilacerated incisor with mechanical eruption and alignment of the ectopic left canine, aiming to substitute the lateral incisor for the missing central incisor. However, the plan was modified to include eruption of the canine in the central incisor region in response to progressive ectopic development and mesial transmigration of the maxillary left canine. Although substitution of a maxillary canine for a central incisor is comparatively rare, the canines offer a relatively favorable template to simulate a central incisor. For this growing patient with a combination of dental trauma and developmental anomalies, maxillary canine-central incisor replacement was a viable option, offering excellent esthetic results without recourse to prosthetic replacement.

Rett syndrome in Ireland: a demographic study.

BACKGROUND: Rett syndrome (RTT) is a rare neurodevelopmental condition associated with mutations in the gene coding for the methyl-CpG-binding protein 2 (MECP2). It is primarily observed in girls and affects individuals globally. The understanding of the neurobiology of RTT and patient management has been improved by studies that describe the demographic and clinical presentation of individuals with RTT. However, in Ireland, there is a scarcity of data regarding individuals with RTT, which impedes the ability to fully characterize the Irish RTT population. Together with the Rett Syndrome Association of Ireland (RSAI), we prepared a questionnaire to determine the characteristics of RTT individuals in Ireland. Twenty-five families have participated in the study to date, providing information about demographics, genetics, familial history, clinical features, and regression. RESULTS: The results show that Irish individuals with RTT have comparable presentation with respect to individuals in other countries; however, they had a better response to anti-epileptic drugs, and fewer skeletal deformities were reported. Nonetheless, seizures, involuntary movements and regression were more frequently observed in Irish individuals. One of the main findings of this study is the limited genetic information available to individuals to support the clinical diagnosis of RTT. CONCLUSIONS: Despite the limited sample size, this study is the first to characterize the RTT population in Ireland and highlights the importance of having a swift access to genetic testing to sharpen the characterization of the phenotype and increase the visibility of Irish individuals in the international RTT community.

Creating resistance to avian influenza infection through genome editing of the ANP32 gene family.

Chickens genetically resistant to avian influenza could prevent future outbreaks. In chickens, influenza A virus (IAV) relies on host protein ANP32A. Here we use CRISPR/Cas9 to generate homozygous gene edited (GE) chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction. After IAV challenge, 9/10 edited chickens remain uninfected. Challenge with a higher dose, however, led to breakthrough infections. Breakthrough IAV virus contained IAV polymerase gene mutations that conferred adaptation to the edited chicken ANP32A. Unexpectedly, this virus also replicated in chicken embryos edited to remove the entire ANP32A gene and instead co-opted alternative ANP32 protein family members, chicken ANP32B and ANP32E. Additional genome editing for removal of ANP32B and ANP32E eliminated all viral growth in chicken cells. Our data illustrate a first proof of concept step to generate IAV-resistant chickens and show that multiple genetic modifications will be required to curtail viral escape.

Frankel 2 appliance versus the Modified Twin Block appliance for Phase 1 treatment of Class II division 1 malocclusion in children and adolescents: A randomized clinical trial.

OBJECTIVE: To compare Phase 1 treatment, using the Frankel 2 (FR2) or the modified Twin Block (MTB), for Class II division 1 malocclusion in children and adolescents with respect to: treatment duration, number of appliance breakages, occlusal outcome, and patient and parent perspectives. MATERIALS AND METHODS: Sixty participants with a Class II division 1 malocclusion were randomly assigned to either the FR2 or MTB appliance in a two-armed parallel randomized clinical trial with an allocation ratio of 1 to 1. Time to achieve a Class I incisor relationship was the primary outcome. The number of appliance breakages was recorded. The Peer Assessment Rating (PAR) index was used to evaluate pre- and post-treatment occlusal outcome on study models. Participants completed the child OHRQoL (oral health-related quality of life), Piers-Harris, Standard Continuum of Aesthetic Need (SCAN), and Oral Aesthetic Subjective Impact Score (OASIS) questionnaires pre- and post-treatment; parents completed a SCAN questionnaire. RESULTS: Forty-two participants completed treatment (FR2: 20; MTB: 22). Multiple imputation was used to impute missing data for noncompleters. Mean treatment duration was similar for the two appliances (FR2: 376 days [SD 101]; MTB: 340 days [SD 102]; P = .41). There were no significant differences in mean number of appliance breakages (FR2: 0.3 SD 0.7; MTB: 0.4 SD 0.8; P = .67 or mean PAR score P = .48). Patient and parent perspectives did not differ between appliances (P > .05). CONCLUSIONS: Phase 1 treatment duration, number of appliance breakages, occlusal outcome, and patient and parent perspectives were similar in 11-14 year olds with Class II division 1 malocclusion treated using the FR2 or MTB appliance.