Anti-neutrophil cytoplasmatic antibodies and lung disease in cystic fibrosis

AbstractBackground: Bactericidal-permeability-increasing protein (BPI) is a potent anti-microbial protein produced by neutrophil granulocytes. Anti-neutrophil cytoplasmatic antibodies (ANCA) directed against BPI have been detected in up to 91% in patients with cystic fibrosis (CF). We aimed to evaluate the prevalence of BPI-ANCA in our CF patients and to determine whether presence of BPI-ANCA is correlated with organ damage. Methods: Twenty-four patients performed respiratory function testing and pulmonary high-resolution computed tomography (HRCT). HRCT was scored by using a modified Bhalla method. Serum samples were analysed by direct binding enzyme-linked immunosorbent assay for BPI-ANCA. Results: The prevalence of anti-BPI-IgG was 71% and anti-BPI-IgA 33%. Twenty-nine percent of our patients were positive for both BPI-ANCA isotypes. Mean HRCT score was 8.0 ranging from 0 to 22, bronchiectasis presented the most common finding (79%). There was a significant correlation between BPI-ANCA and both HRCT score and FEV1 (p<0.01). High levels of BPI-ANCA were correlated to chronic Pseudomonas aeruginosa lung infection (p<0.01). Conclusions: BPI-ANCA was common in our study group. Highly significant correlations between BPI-ANCA and parameters to evaluate lung disease in CF may be a consequence of the inflammation process, or it may indicate a pathogenic role of BPI-ANCA levels in the development of lung disease. More research is needed and the clinical significance of our findings needs further evaluation

Controlled Attenuation Parameter in Healthy Individuals Aged 8–70 Years

Purpose Controlled attenuation parameter (CAP) is a non-invasive method to assess the presence of liver steatosis. It has been evaluated in children and adults, mainly in either the obese or in subjects with suspected liver disease. Our aim was to describe CAP in healthy non-obese subjects without suspected liver steatosis and to suggest cutoff levels for steatosis. Materials and Methods We prospectively recruited 187 individuals aged 8–70 years. All underwent clinical examination, including height and weight measurement. Body mass index (BMI) was calculated and converted into z-scores. To exclude liver pathology, B-mode ultrasound and liver stiffness measurements were performed in all prior to CAP measurement. Blood was drawn for liver biochemistry in adults. Results CAP was associated with BMI z-score across all ages. CAP started to rise alongside BMI z-score already in subjects with a BMI below average. CAP values were higher in adults than in children (p<0.001), and higher in adult males than adult females (p=0.014). CAP did not correlate with age within the adult or pediatric cohorts. CAP was highly correlated with the fatty liver index. 18 and 23% of subjects showed CAP above the suggested cutoff value for children and adults, respectively. Conclusion CAP was correlated with BMI z-score, even in individuals with a below-average BMI . We found CAP above published cutoff values in a substantial proportion of presumably healthy, non-obese children and adults, warranting further research to clarify whether this represents non-obese non-alcoholic fatty liver disease or if reference values need adjustment.publishedVersio

Prevalence of Helicobacter pylori in HIV-infected, HAART-naïve Ugandan children: a hospital-based survey

<p>Abstract</p> <p>Background</p> <p>The aim of this survey was to determine the prevalence of and factors associated with <it>Helicobacter pylori </it>(<it>H. pylori</it>) colonization in HIV-infected, highly active antiretroviral therapy-naïve Ugandan children aged 0-12 years.</p> <p>Methods</p> <p>In a hospital-based survey, 236 HIV-infected children were tested for <it>H. pylori </it>colonization using a faecal antigen test. A standardized interview with socio-demographic information and medical history was used to assess risk factors. A cluster of differentiation 4 (CD4) cell percentage was prevalent in most children.</p> <p>Results</p> <p>The overall prevalence of <it>H. pylori </it>in the HIV-infected children was 22.5%. Age-specific prevalence was as follows: up to one year, 14.7%; 1-3 years, 30.9%; and 3-12 years, 20.7%. HIV-infected children who were more seriously affected by their disease (low CD4 cell percentage or WHO clinical stage II-IV) were less likely to be colonized with <it>H. pylori</it>. There was a trend for a lower prevalence of <it>H. pylori </it>in children who had taken antibiotics for the preceding two weeks (21.6%) than in those who had not taken antibiotics (35.7%). There was no statistically significant difference in prevalence by gender, housing, congested living, education of the female caretaker, drinking water or toilet facilities.</p> <p>Conclusions</p> <p>HIV-infected, HAART-naïve Ugandan children had a lower prevalence of <it>H. pylori </it>colonization compared with apparently healthy Ugandan children (44.3%). Children with a low CD4 cell percentage and an advanced clinical stage of HIV had an even lower risk of <it>H. pylori </it>colonization. Treatment with antibiotics due to co-morbidity with infectious diseases is a possible explanation for the relatively low prevalence.</p

Risk assessment on use of Lactobacillus rhamnosus (LGG) as an ingredient in infant formula and baby foods. The Norwegian Scientific Committee for Food Safety Panel on Nutrition, Dietetic products, Novel food and Allergy

publishedVersio

High expression of the vacuole membrane protein 1 (VMP1) is a potential marker of poor prognosis in HER2 positive breast cancer.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBACKGROUND: Fusion genes result from genomic structural changes, which can lead to alterations in gene expression that supports tumor development. The aim of the study was to use fusion genes as a tool to identify new breast cancer (BC) genes with a role in BC progression. METHODS: Fusion genes from breast tumors and BC cell lines were collected from publications. RNA-Seq data from tumors and cell lines were retrieved from databanks and analyzed for fusions with SOAPfuse or the analysis was purchased. Fusion genes identified in both tumors (n = 1724) and cell lines (n = 45) were confirmed by qRT-PCR and sequencing. Their individual genes were ranked by selection criteria that included correlation of their mRNA level with copy number. The expression of the top ranked gene was measured by qRT-PCR in normal tissue and in breast tumors from an exploratory cohort (n = 141) and a validation cohort (n = 277). Expression levels were correlated with clinical and pathological factors as well as the patients' survival. The results were followed up in BC cohorts from TCGA (n = 818) and METABRIC (n = 2509). RESULTS: Vacuole membrane protein 1 (VMP1) was the most promising candidate based on specific selection criteria. Its expression was higher in breast tumor tissue than normal tissue (p = 1x10-4), and its expression was significantly higher in HER2 positive than HER2 negative breast tumors in all four cohorts analyzed. High expression of VMP1 associated with breast cancer specific survival (BCSS) in cohort 1 (hazard ratio (HR) = 2.31, CI 1.27-4.18) and METABRIC (HR = 1.26, CI 1.02-1.57), and also after adjusting for HER2 expression in cohort 1 (HR = 2.03, CI 1.10-3.72). BCSS was not significant in cohort 2 or TCGA cohort, which may be due to differences in treatment regimens. CONCLUSIONS: The results suggest that high VMP1 expression is a potential marker of poor prognosis in HER2 positive BC. Further studies are needed to elucidate how VMP1 could affect pathways supportive of tumorigenesis

Faecal calprotectin concentrations in apparently healthy children aged 0-12 years in urban Kampala, Uganda: a community-based survey

<p>Abstract</p> <p>Background</p> <p>Calprotectin is a calcium and zinc binding protein, abundant in neutrophils and is extremely stable in faeces. Faecal calprotectin is used as a non-specific marker for gastrointestinal inflammation. It has a good diagnostic precision to distinguish between irritable bowel syndrome and inflammatory bowel disease. Studies have established normal concentrations in healthy children; all these studies have been performed in high-income countries. The objective of this study was to determine the concentration of faecal calprotectin in apparently healthy children aged 0-12 years in urban Kampala, Uganda.</p> <p>Method</p> <p>We tested 302 apparently healthy children aged, age 0-12 years (162 female, 140 male) in urban Kampala, Uganda. The children were recruited consecutively by door-to-door visits. Faecal calprotectin was analyzed using a quantitative enzyme-linked immunosorbent assay. Faeces were also tested for <it>Helicobacter pylori (H. pylori) </it>antigen, for growth of enteropathogens and microscopy was performed to assess protozoa and helminths. A short standardized interview with socio-demographic information and medical history was obtained to assess health status of the children.</p> <p>Results</p> <p>In the different age groups the median faecal calprotectin concentrations were 249 mg/kg in 0 < 1 year (n = 54), 75 mg/kg in 1 < 4 years (n = 89) and 28 mg/kg in 4 < 12 years (n = 159). There was no significant difference in faecal calprotectin concentrations and education of female caretaker, wealth index, gender, habits of using mosquito nets, being colonized with <it>H. pylori </it>or having other pathogens in the stool.</p> <p>Conclusion</p> <p>Concentrations of faecal calprotectin among healthy children, living in urban Ugandan, a low-income country, are comparable to those in healthy children living in high-income countries. In children older than 4 years, the faecal calprotectin concentration is low. In healthy infants faecal calprotectin is high. The suggested cut-off concentrations in the literature can be used in apparently healthy Ugandan children. This finding also shows that healthy children living under poor circumstances do not have a constant inflammation in the gut. We see an opportunity to use this relatively inexpensive test for further understanding and investigations of gut inflammation in children living in low-income countries.</p

Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000–2021)

This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014–2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000–2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years.This work received external funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 733032 and received co-funding from the author’s organizations. The Norwegian Institute of Public Health (NIPH) contributed to the funding of the Norwegian Environmental Biobank (NEB). The laboratory measurements were partly funded by the Research Council of Norway through research projects (275903 and 268465).info:eu-repo/semantics/publishedVersio

Sequence variant affects GCSAML splicing, mast cell specific proteins, and risk of urticaria

Funding Information: The authors thank the individuals who participated in this study and whose contributions made this work possible. We also thank our valued colleagues who contributed to the data collection and phenotypic characterization of clinical samples as well as to the genotyping and analysis of the whole-genome association data. This research has been conducted using the UK Biobank Resource under application numbers 24711 and 24898. Publisher Copyright: © 2023, The Author(s).Urticaria is a skin disorder characterized by outbreaks of raised pruritic wheals. In order to identify sequence variants associated with urticaria, we performed a meta-analysis of genome-wide association studies for urticaria with a total of 40,694 cases and 1,230,001 controls from Iceland, the UK, Finland, and Japan. We also performed transcriptome- and proteome-wide analyses in Iceland and the UK. We found nine sequence variants at nine loci associating with urticaria. The variants are at genes participating in type 2 immune responses and/or mast cell biology (CBLB, FCER1A, GCSAML, STAT6, TPSD1, ZFPM1), the innate immunity (C4), and NF-κB signaling. The most significant association was observed for the splice-donor variant rs56043070[A] (hg38: chr1:247556467) in GCSAML (MAF = 6.6%, OR = 1.24 (95%CI: 1.20–1.28), P-value = 3.6 × 10-44). We assessed the effects of the variants on transcripts, and levels of proteins relevant to urticaria pathophysiology. Our results emphasize the role of type 2 immune response and mast cell activation in the pathogenesis of urticaria. Our findings may point to an IgE-independent urticaria pathway that could help address unmet clinical need.Peer reviewe

Helicobacter pylori in apparently healthy children aged 0-12 years in urban Kampala, Uganda: a community-based cross sectional survey

Background Helicobacter pylori is one of the most common causes of bacterial infection in human beings. Studies have showed a high prevalence of Helicobacter pylori among people in low-income countries and colonization early in life. A monoclonal antigen test, performed on faeces, HpSA®ImmunoCardSTAT, has a high sensitivity, specificity and accuracy and the faecal test can be performed in all ages, also in resource-limited settings. The main objective of this study was to determine the prevalence and factors associated with Helicobacter pylori colonization in apparently healthy children aged 0-12 years in urban Kampala, Uganda. Method We tested 427 apparently healthy children, age 0-12 years (211 males, 216 females), in a cross sectional survey for Helicobacter pylori colonization using HpSA ®ImmunoCardSTAT. A short standardized interview with socio-demographic information and medical history was used to assess risk factors. Results The overall prevalence of Helicobacter pylori in the 427 children was 44.3% (189 out of 427). Early colonization was common, 28.7%, in children younger than 1 year of age. The age specific rates were 46.0% in children age 1- < 3 years, 51.7% in children age 3- < 6 years, 54.8% in children age 6- < 9 years and 40.0% in children age 9- < 12 years. There was a significant difference in prevalence by gender; female 38.5% versus male 49.8% and by type of housing; permanent house 38.5% versus semi-permanent house 48.6%. Congestive living and education level of the female caretaker showed a clear trend for a difference in prevalence. Factors independently associated with Helicobacter pylori colonization included: drugs taken last three months, using a pit latrine, sources of drinking water and wealth index. Conclusion The prevalence of Helicobacter pylori colonization among urban Ugandan children is high at an early age and increases with age. The impact of Helicobacter pylori colonization on children's health in Uganda needs to be further clarified

Liver elastography in healthy children using three different systems - how many measurements are necessary?

Purpose Liver elastography is increasingly being applied in screening for and follow-up of pediatric liver disease, and has been shown to correlate well with fibrosis staging through liver biopsy. Because time is of the essence when examining children, we wanted to evaluate if a reliable result can be achieved with fewer acquisitions. Materials and Methods 243 healthy children aged 4–17 years were examined after three hours of fasting. Participants were divided into four age groups: 4–7 years; 8–11 years; 12–14 years and 15–17 years. Both two-dimensional shear wave elastography (2D-SWE; GE Logiq E9) and point shear wave elastography (pSWE; Samsung RS80A with Prestige) were performed in all participants, while transient elastography (TE, Fibroscan) was performed in a subset of 87 children aged 8–17 years. Median liver stiffness measurement (LSM) values of 3, 4, 5, 6, 7, and 8 acquisitions were compared with the median value of 10 acquisitions (reference standard). Comparison was performed for all participants together as well as within every specific age group. We investigated both the intraclass correlation coefficient (ICC) with absolute agreement and all outliers more than 10 %, 20 % or ≥ 0.5 or 1.0 kPa from the median of 10 acquisitions. Results For all three systems there was no significant difference between three and ten acquisitions, with ICCs ≥ 0.97. All systems needed 4 acquisitions to achieve no LSM deviating ≥ 1.0 kPa of a median of ten. To achieve no LSM deviating ≥ 20 % of a median of ten acquisitions, pSWE and TE needed 4 acquisitions, while 2D-SWE required 6 acquisitions. Conclusion Our results contradict recommendations of 10 acquisitions for pSWE and TE and only 3 for 2D-SWE.acceptedVersio