288 research outputs found
Defining the microbial transcriptional response to colitis through integrated host and microbiome profiling
The gut microbiome is significantly altered in inflammatory bowel diseases, but the basis of these changes is not well understood. We have combined metagenomic and metatranscriptomic profiling of the gut microbiome to assess modifications to both bacterial community structure and transcriptional activity in a mouse model of colitis. By using transcriptomic analysis of colonic tissue and luminal RNA derived from the host, we have also characterised how host transcription relates to the microbial transcriptional response in inflammation. In colitis, increased abundance and transcription of diverse microbial gene families involved in responses to nutrient deprivation, antimicrobial peptide production and oxidative stress support an adaptation of multiple commensal genera to withstand a diverse set of environmental stressors in the inflammatory environment. These data are supported by a transcriptional signature of activated macrophages and granulocytes in the gut lumen during colitis, a signature that includes the transcription of the key antimicrobial genes S100a8 and S100a9 (calprotectin). Genes involved in microbial resistance to oxidative stress, including Dps/ferritin, Fe-dependent peroxidase and glutathione S-transferase were identified as changing to a greater extent at the level of transcription than would be predicted by DNA abundance changes, implicating a role for increased oxygen tension and/or host-derived reactive oxygen species in driving transcriptional changes in commensal microbes
An approach to manage reconfigurations and reduce area cost in hard real-time reconfigurable systems
Diversity II water quality parameters from ENVISAT (2002–2012): a new global information source for lakes
The use of ground sampled water quality information for global studies is
limited due to practical and financial constraints. Remote sensing is a
valuable means to overcome such limitations and to provide synoptic views of
ambient water quality at appropriate spatio-temporal scales. In past years
several large data processing efforts were initiated to provide corresponding
data sources. The Diversity II water quality dataset consists of several
monthly, yearly and 9-year averaged water quality parameters for 340 lakes
worldwide and is based on data from the full ENVISAT MERIS operation period
(2002–2012). Existing retrieval methods and datasets were selected after an
extensive algorithm intercomparison exercise. Chlorophyll-a, total
suspended matter, turbidity, coloured dissolved organic matter, lake surface
water temperature, cyanobacteria and floating vegetation maps, as well as
several auxiliary data layers, provide a generically specified database that
can be used for assessing a variety of locally relevant ecosystem properties
and environmental problems. For validation and accuracy assessment, we
provide matchup comparisons for 24 lakes and a group of reservoirs
representing a wide range of bio-optical conditions. Matchup comparisons for
chlorophyll-a concentrations indicate mean absolute errors and bias in the
order of median concentrations for individual lakes, while total suspended
matter and turbidity retrieval achieve significantly better performance
metrics across several lake-specific datasets. We demonstrate the use of the
products by illustrating and discussing remotely sensed evidence of
lake-specific processes and prominent regime shifts documented in the
literature. The Diversity II data are available from
https://doi.pangaea.de/10.1594/PANGAEA.871462, and Python scripts for
their analysis and visualization are provided at
https://github.com/odermatt/diversity/.</p
COVID-19 infection in patients with history of pediatric heart transplant in Germany, Austria, and Switzerland.
COVID-19 is a heterogenous infection-asymptomatic to fatal. While the course of pediatric COVID-19 infections is usually mild or even asymptomatic, individuals after adult heart transplantation are at high risk of a severe infection. We conducted a retrospective, multicenter survey of 16 pediatric heart transplant centers in Germany, Austria and Switzerland to evaluate the risk of a severe COVID-19 infection after pediatric heart transplantation between 02/2020 and 06/2021. Twenty-six subjects (11 male) with a median age of 9.77 years at time of transplantation and a median of 4.65 years after transplantation suffered from COVID-19 infection. The median age at time of COVID-10 infection was 17.20 years. Fourteen subjects had an asymptomatic COVID-19 infection. The most frequent symptoms were myalgia/fatigue (n = 6), cough (n = 5), rhinitis (n = 5), and loss of taste (n = 5). Only one subject showed dyspnea. Eleven individuals needed therapy in an outpatient setting, four subjects were hospitalized. One person needed oxygen supply, none of the subjects needed non-invasive or invasive mechanical ventilation. No specific signs for graft dysfunction were found by non-invasive testing. In pediatric heart transplant subjects, COVID-19 infection was mostly asymptomatic or mild. There were no SARS-CoV-2 associated myocardial dysfunction in heart transplant individuals
Insights Into Patients' Experience With Type 1 Diabetes: Exit Interviews From Phase III Studies of Sotagliflozin
Purpose: The purpose of this study was to conduct qualitative participant interviews to provide context to the meaningfulness of improvements in end points seen in 2 large-scale Phase III sotagliflozin trials in participants with type 1 diabetes. Methods: Participants were eligible for an interview if they had exited one of the clinical trials within the previous 12 months. Participants were recruited by investigators at the clinical trial sites, and interviews were conducted by independent interviewers by telephone in accordance with a semistructured interview guide. Both interviewers and participants were blinded to treatment assignment. Qualitative analysis was conducted using ATLAS-ti version 7.5, and descriptive statistics were computed and summarized. Findings: Across 3 countries, 41 participants were interviewed. Difficulty maintaining blood glucose within a desired range, described by participants as lack of blood glucose “stability,” was the most concerning symptom that they reported, wanting to see it improved during the clinical trial because it negatively impacted their physical, mental, and emotional lives. Participants who reported symptom improvement also reported a positive psychosocial impact while taking the clinical trial medication. All participants who monitored ketones described themselves as being “pretty confident” to “very confident” that they could avoid diabetic ketoacidosis by monitoring both ketone levels and understanding the physical signs and symptoms of hyperglycemia. Implications: Improvements in glucose stability and control were important to participants with type 1 diabetes, as these improvements were correlated with improvements in the participants' lives. ClinicalTrials.gov identifiers: NCT02384941; NCT02421510
Molecular characterization of a Streptococcus gallolyticus genomic island encoding a pilus involved in endocarditis.
Background. Streptococcus gallolyticus is a causative agent of infective endocarditis associated with colon cancer. Genome sequence of strain UCN34 revealed the existence of 3 pilus loci (pil1, pil2, and pil3). Pili are long filamentous structures playing a key role as adhesive organelles in many pathogens. The pil1 locus encodes 2 LPXTG proteins (Gallo2178 and Gallo2179) and 1 sortase C (Gallo2177). Gallo2179 displaying a functional collagen-binding domain was referred to as the adhesin, whereas Gallo2178 was designated as the major pilin. Methods. S. gallolyticus UCN34, Pil1(+) and Pil1(-), expressing various levels of pil1, and recombinant Lactococcus lactis strains, constitutively expressing pil1, were studied. Polyclonal antibodies raised against the putative pilin subunits Gallo2178 and Gallo2179 were used in immunoblotting and immunogold electron microscopy. The role of pil1 was tested in a rat model of endocarditis. Results. We showed that the pil1 locus (gallo2179-78-77) forms an operon differentially expressed among S. gallolyticus strains. Short pilus appendages were identified both on the surface of S. gallolyticus UCN34 and recombinant L. lactis-expressing pil1. We demonstrated that Pil1 pilus is involved in binding to collagen, biofilm formation, and virulence in experimental endocarditis. Conclusions. This study identifies Pil1 as the first virulence factor characterized in S. gallolyticus
Quality control requirements for the correct annotation of lipidomics data.
10.1038/s41467-021-24984-yNature Communications121477
Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries
AIMS/HYPOTHESIS: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. METHODS: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally. RESULTS: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of 7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. CONCLUSIONS/INTERPRETATION: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c)
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