Microbiome, pattern recognition receptor function in health and inflammation

The innate immune system plays an important role in shaping the microbiota into configurations that are tolerated and beneficial to the host, thereby playing a crucial role in human health. Innate immunity is based on the fundamental principle that Pattern Recognition Receptors (PRRs) recognise pathogen associated molecular patterns as non-self-entities and trigger intracellular signalling pathways that lead to the induction of numerous cytokines and chemokines that help maintain host resistance to infections. Dysregulation of this interaction has been identified as the core defect that leads to chronic intestinal inflammation allowing certain microbiota to be harmful to host health. This dysbiosis of the microbiome is found associated with numerous chronic diseases. A logical explanation would be that genetic defects in the recognition and response pathways that the host uses to identify these microbial pathogens could lead to altered microbial colonisation or mis-recognition of normal bacteria leading to diseases. The interaction between pattern recognition receptors, microbial traits and human health with respect to the gut are now rapidly resolved and will be the subject of this review

Microbiome, pattern recognition receptor function in health and inflammation

The innate immune system plays an important role in shaping the microbiota into configurations that are tolerated and beneficial to the host, thereby playing a crucial role in human health. Innate immunity is based on the fundamental principle that Pattern Recognition Receptors (PRRs) recognise pathogen associated molecular patterns as non-self-entities and trigger intracellular signalling pathways that lead to the induction of numerous cytokines and chemokines that help maintain host resistance to infections. Dysregulation of this interaction has been identified as the core defect that leads to chronic intestinal inflammation allowing certain microbiota to be harmful to host health. This dysbiosis of the microbiome is found associated with numerous chronic diseases. A logical explanation would be that genetic defects in the recognition and response pathways that the host uses to identify these microbial pathogens could lead to altered microbial colonisation or mis-recognition of normal bacteria leading to diseases. The interaction between pattern recognition receptors, microbial traits and human health with respect to the gut are now rapidly resolved and will be the subject of this review

Isolation of human fetal intestinal cells for single-cell RNA sequencing

The intestine has a large number of cell types. Thus, digestion of pure and viable populations is necessary for downstream techniques including single-cell RNA sequencing. We outline a protocol to isolate both epithelial and non-epithelial cells from human fetal samples at high viability, which was used to produce a full thickness atlas of intestinal cells across human development. This protocol can also be adapted to adult endoscopy and surgical specimens

Appendicitis risk prediction models in children presenting with right iliac fossa pain (RIFT study): a prospective, multicentre validation study

BACKGROUND: Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. METHODS: We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5-15 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. FINDINGS:15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34&#xB7;5%) underwent appendicectomy. The normal appendicectomy rate was 15&#xB7;9% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0&#xB7;84 (95% CI 0&#xB7;82-0&#xB7;86). Applying score cutoffs of 3 points or lower for children aged 5-10 years and girls aged 11-15 years, and 2 points or lower for boys aged 11-15 years, the failure rate was 3&#xB7;3% (95% CI 2&#xB7;0-5&#xB7;2; 18 of 539 patients), specificity was 44&#xB7;3% (95% CI 41&#xB7;4-47&#xB7;2; 521 of 1176), and positive predictive value was 41&#xB7;4% (38&#xB7;5-44&#xB7;4; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72&#xB7;6%, 67&#xB7;4-77&#xB7;4) was similar to that of ultrasound scan (75&#xB7;0%, 65&#xB7;3-83&#xB7;1). INTERPRETATION: The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. FUNDING: None.</p

Rhinovirus-C detection in children presenting with acute respiratory infection to hospital in Brazil

Introduction Human rhinovirus (RV) is a common cause of acute respiratory infection (ARI) in children. We aimed to characterise the clinical and demographic features associated with different RV species detected in children attending hospital with ARI, from low-income families in North-east Brazil. Methods Nasopharyngeal aspirates were collected from 630 children <5years with ARI. Clinical diagnosis and disease severity were also recorded. Samples were analysed by multiplex PCR for 18 viral and atypical bacterial pathogens; RV positive samples underwent partial sequencing to determine species and type. Results RV was the fourth commonest pathogen accounting for 18.7% of pathogens detected. RV was commonly detected in children with bronchiolitis, pneumonia and asthma/episodic viral wheeze (EVW). Species and type were assigned in 112 cases (73% RV-A; 27% RV-C; 0% RV-B). Generally, there were no differences in clinical or demographic characteristics between those infected with RV-A and RV-C. However, in children with asthma/EVW, RV-C was detected relatively more frequently than RV-A (23% vs 5%; p = 0.04). Conclusions Our findings highlight RV as a potentially important pathogen in this setting. Generally, clinical and demographic features were similar in children in whom RV A and C species were detected. However, RV-C was more frequently found in children with asthma/EVW than RV-A. This article is protected by copyright. All rights reserve