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What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review

Background Epidemiological studies indicate that gene–environment interactions play a role in atopic dermatitis (AD). Objectives To review the evidence for gene–environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations. Methods A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis. Results Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG–environment interactions in six of the studies (P-value for interaction ≤ 005), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions. Conclusions Evidence on FLG–environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment

What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.

BACKGROUND: Epidemiological studies indicate that gene-environment interactions play a role in atopic dermatitis (AD). OBJECTIVES: To review the evidence for gene-environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations. METHODS: A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis. RESULTS: Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG-environment interactions in six of the studies (P-value for interaction ≤ 0·05), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions. CONCLUSIONS: Evidence on FLG-environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates

Introduction. One third of people with CF in the UK are co-infected by both Staphylococcus aureus and Pseudomonas aeruginosa. Chronic bacterial infection in CF contributes to the gradual destruction of lung tissue, and eventually respiratory failure in this group. Gap Statement. The contribution of S. aureus to cystic fibrosis (CF) lung decline in the presence or absence of P. aeruginosa is unclear. Defining the molecular and phenotypic characteristics of a range of S. aureus clinical isolates will help further understand its pathogenic capabilities. Aim. Our objective was to use molecular and phenotypic tools to characterise twenty-five clinical S. aureus isolates collected from mono- and coinfection with P. aeruginosa from people with CF at the Royal Victoria Infirmary, Newcastle upon Tyne. Methodology. Genomic DNA was extracted and sequenced. Multilocus sequence typing was used to construct phylogeny from the seven housekeeping genes. A pangenome was calculated using Roary, and cluster of Orthologous groups were assigned using eggNOG-mapper which were used to determine differences within core, accessory, and unique genomes. Characterisation of sequence type, clonal complex, agr and spa types was carried out using PubMLST, eBURST, AgrVATE and spaTyper, respectively. Antibiotic resistance was determined using Kirby-Bauer disc diffusion tests. Phenotypic testing of haemolysis was carried out using ovine red blood cell agar plates and mucoid phenotypes visualised using Congo red agar. Results. Clinical strains clustered closely based on agr type, sequence type and clonal complex. COG analysis revealed statistically significant enrichment of COG families between core, accessory and unique pangenome groups. The unique genome was significantly enriched for replication, recombination and repair, and defence mechanisms. The presence of known virulence genes and toxins were high within this group, and unique genes were identified in 11 strains. Strains which were isolated from the same patient all surpassed average nucleotide identity thresholds, however, differed in phenotypic traits. Antimicrobial resistance to macrolides was significantly higher in the coinfection group. Conclusion. There is huge variation in genetic and phenotypic capabilities of S. aureus strains. Further studies on how these may differ in relation to other species in the CF lung may give insight into inter-species interactions

Evaluation of immunogenicity and reactogenicity of COVID-19 vaccines in pregnant women.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with increased risk of adverse maternal and perinatal outcomes. Vaccines are highly effective at preventing severe coronavirus disease 2019 (COVID-19), but there are limited data on COVID-19 vaccines in pregnancy. This study aimed to investigate the reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women when administered according to the 12-week-interval dosing schedule recommended in the UK. METHODS: This was a cohort study of pregnant women receiving COVID-19 vaccination between April and September 2021. The outcomes were immunogenicity and reactogenicity after COVID-19 vaccination. Pregnant women were recruited by phone, e-mail and/or text and were vaccinated according to vaccine availability at their local vaccination center. For immunogenicity assessment, blood samples were taken at specific timepoints after each dose to evaluate nucleocapsid protein (N) and spike protein (S) antibody titers. The comparator group comprised non-pregnant female healthcare workers in the same age group who were vaccinated as part of the national immunization program in a contemporaneous longitudinal cohort study. Longitudinal changes in serum antibody titers and association with pregnancy status were assessed using a two-step regression approach. Reactogenicity assessment in pregnant women was undertaken using an online questionnaire. The comparator group comprised non-pregnant women aged 18-49 years who had received two vaccine doses in primary care. The association of pregnancy status with reactogenicity was assessed using logistic regression analysis. RESULTS: Overall, 67 pregnant women, of whom 66 had received a mRNA vaccine, and 79 non-pregnant women, of whom 50 had received a mRNA vaccine, were included in the immunogenicity study. Most (61.2%) pregnant women received their first vaccine dose in the third trimester, while 3.0% received it in the first trimester and 35.8% in the second trimester. SARS-CoV-2 S-antibody geometric mean concentrations after mRNA vaccination were not significantly different at 2-6 weeks after the first dose but were significantly lower at 2-6 weeks after the second dose in infection-naïve pregnant compared with non-pregnant women. In pregnant women, prior infection was associated with higher antibody levels at 2-6 weeks after the second vaccine dose. Reactogenicity analysis included 108 pregnant women and 116 non-pregnant women. After the first dose, tiredness and chills were reported less commonly in pregnant compared with non-pregnant women (P = 0.043 and P = 0.029, respectively). After the second dose, feeling generally unwell was reported less commonly (P = 0.046) in pregnant compared with non-pregnant women. CONCLUSIONS: Using an extended 12-week interval between vaccine doses, antibody responses after two doses of mRNA COVID-19 vaccine were found to be lower in pregnant compared with non-pregnant women. Strong antibody responses were achieved after one dose in previously infected women, regardless of pregnancy status. Pregnant women reported fewer adverse events after both the first and second dose of vaccine. These findings should now be addressed in larger controlled studies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy.

Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I2 = 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73-0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I2 = 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth

A multilevel intervention to increase physical activity and improve healthy eating and physical literacy among young children (ages 3-5) attending early childcare centres: the Healthy Start-Départ Santé cluster randomised controlled trial study protocol

Abstract: Background: Childhood obesity is a growing concern for public health. Given a majority of children in many countries spend approximately 30 h per week in early childcare centers, this environment represents a promising setting for implementing strategies to foster healthy behaviours for preventing and controlling childhood obesity. Healthy Start-Départ Santé was designed to promote physical activity, physical literacy, and healthy eating among preschoolers. The objectives of this study are to assess the effectiveness of the Healthy Start-Départ Santé intervention in improving physical activity levels, physical literacy, and healthy eating among preschoolers attending early childcare centers. Methods/Design: This study follows a cluster randomized controlled trial design in which the childcare centers are randomly assigned to receive the intervention or serve as usual care controls. The Healthy Start-Départ Santé intervention is comprised of interlinked components aiming to enable families and educators to integrate physical activity and healthy eating in the daily lives of young children by influencing factors at the intrapersonal, interpersonal, organizational, community, physical environment and policy levels. The intervention period, spanning 6-8 months, is preceded and followed by data collections. Participants are recruited from 61 childcare centers in two Canadian provinces, New Brunswick and Saskatchewan. Centers eligible for this study have to prepare and provide meals for lunch and have at least 20 children between the ages of 3 and 5. Centers are excluded if they have previously received a physical activity or nutrition promoting intervention. Eligible centers are stratified by province, geographical location (urban or rural) and language (English or French), then recruited and randomized using a one to one protocol for each stratum. Data collection is ongoing. The primary study outcomes are assessed using accelerometers (physical activity levels), the Test of Gross Motor Development-II (physical literacy), and digital photography-assisted weighted plate waste (food intake). Discussion: The multifaceted approach of Healthy Start-Départ Santé positions it well to improve the physical literacy and both dietary and physical activity behaviors of children attending early childcare centers. The results of this study will be of relevance given the overwhelming prevalence of overweight and obesity in children worldwide. Trial registration: NCT02375490 (ClinicalTrials.gov registry)

Panel 4 : Report of the Microbiology Panel

Objective. To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions. Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice. (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.Peer reviewe