10 items with lowest mean rank at end of Round 3.

<p>10 items with lowest mean rank at end of Round 3.</p

Type of disability with which panelists are associated.

<p>27 (23 disability respondents and 4 dental) respondents reported a median of two disability types (IQR = 5) with which they were associated. Multiple categories allowed.</p

Participant Flow.

<p>Legend: N = sample completing round; % = % participants having completed the prior round, to complete the following round.</p

Inclusion and exclusion criteria.

<p>Inclusion and exclusion criteria.</p

10 items with highest mean rank at end of Round 3.

<p>10 items with highest mean rank at end of Round 3.</p

What Should Dental Services for People with Disabilities Be Like? Results of an Irish Delphi Panel Survey

<div><p>Background</p><p>This study aimed to generate prioritised goals for oral health services for people with disabilities as a first step in meeting the need for evidence based oral health services for people with disabilities in Ireland.</p><p>Methods</p><p>The study used a three round modified e-Delphi method, involving dental service professionals and people with disabilities or their representatives, in Ireland. Three rounds were completed online using SurveyMonkey. Round 1 asked: “List what you think dental services for people with disabilities in Ireland should be like.” Items for subsequent rounds were generated from responses to Round 1. Round 2 and Round 3 used 5 point Likert scales to rank these items by priority: from No Priority (1) to Top Priority (5). Consensus was achieved on each item where at least 80% of respondents considered an item either High or Top Priority. A consensus meeting concluded the process.</p><p>Results</p><p>Sixty-one panelists started and 48 completed the survey. The Delphi panel agreed on level of priority for 69 items and generated 16 consensus statements. These statements covered a range of topics such as access to care, availability of information and training, quality of care, dental treatment and cost. A recurrent theme relating to the appropriateness of care to individual need arose across topics suggesting a need to match service delivery according to the individual's needs, wants and expectations rather than the disability type/diagnosis based service which predominates today.</p><p>Conclusions</p><p>This process produced a list of prioritised goals for dental services for people with disabilities. This creates a foundation for building evidence-based service models for people with disabilities in Ireland.</p></div

A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity

Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341 ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients' cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (TH17) cells, have an excess of TH2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent autoinduction and sustained activity of STAT3.status: publishe

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases

International audienceBackground : Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients.Objective : Our objective was to assess the effect of mycobacterial disease in patients with CGD.Methods : We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria.Results : Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients.Conclusion : Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway