Genome-wide mapping of cystitis due to Streptococcus agalactiae and Escherichia coli in mice identifies a unique bladder transcriptome that signifies pathogen-specific antimicrobial defense against urinary tract infection

The most common causes of urinary tract infections (UTIs) are Gram-negative pathogens such as Escherichia coli; however, Gram-positive organisms, including Streptococcus agalactiae, or group B streptococcus (GBS), also cause UTI. In GBS infection, UTI progresses to cystitis once the bacteria colonize the bladder, but the host responses triggered in the bladder immediately following infection are largely unknown. Here, we used genome-wide expression profiling to map the bladder transcriptome of GBS UTI in mice infected transurethrally with uropathogenic GBS that was cultured from a 35-year-old women with cystitis. RNA from bladders was applied to Affymetrix Gene-1.0ST microarrays; quantitative reverse transcriptase PCR (qRT-PCR) was used to analyze selected gene responses identified in array data sets. A surprisingly small significant-gene list of 172 genes was identified at 24 h; this compared to 2,507 genes identified in a side-by-side comparison with uropathogenic E. coli (UPEC). No genes exhibited significantly altered expression at 2 h in GBS-infected mice according to arrays despite high bladder bacterial loads at this early time point. The absence of a marked early host response to GBS juxtaposed with broad-based bladder responses activated by UPEC at 2 h. Bioinformatics analyses, including integrative system-level network mapping, revealed multiple activated biological pathways in the GBS bladder transcriptome that regulate leukocyte activation, inflammation, apoptosis, and cytokine-chemokine biosynthesis. These findings define a novel, minimalistic type of bladder host response triggered by GBS UTI, which comprises collective antimicrobial pathways that differ dramatically from those activated by UPEC. Overall, this study emphasizes the unique nature of bladder immune activation mechanisms triggered by distinct uropathogens

Persistent symptoms attributed to Lyme disease and their antibiotic treatment. Results from the PLEASE study

Contains fulltext : 209720.pdf (publisher's version ) (Open Access)Radboud University, 25 november 2019Promotores : Kullberg, B.J., Evers, A.W.M. Co-promotores : Hofstede, H.J.M. ter, Middendorp, H. va

Longer-Term Therapy for Symptoms Attributed to Lyme Disease

Contains fulltext : 170902.pdf (publisher's version ) (Open Access

Longer-Term Therapy for Symptoms Attributed to Lyme Disease REPLY

Stress-related psychiatric disorders across the life spa

Longer-Term Therapy for Symptoms Attributed to Lyme Disease REPLY

Stress-related psychiatric disorders across the life spa

Changes in forecasting of HV/MV transformer loading due to distributed generation

This paper describes how Enexis, one of the largest distribution network operators in the Netherlands, has adapted its load forecasting method for HV/MV-transformers to incorporate the influence of distributed generation. This new method involves the making of separate forecasts for demand and generation and determining the resulting transformer loading, based o

The challenge of Lyme disease: tired of the Lyme wars

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Effect of prolonged antibiotic treatment on cognition in patients with Lyme borreliosis

Contains fulltext : 202898.pdf (publisher's version ) (Open Access)OBJECTIVE: To investigate whether longer-term antibiotic treatment improves cognitive performance in patients with persistent symptoms attributed to Lyme borreliosis. METHODS: Data were collected during the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) trial, a randomized, placebo-controlled study. Study participants passed performance-validity testing (measure for detecting suboptimal effort) and had persistent symptoms attributed to Lyme borreliosis. All patients received a 2-week open-label regimen of intravenous ceftriaxone before the 12-week blinded oral regimen (doxycycline, clarithromycin/hydroxychloroquine, or placebo). Cognitive performance was assessed at baseline and after 14, 26, and 40 weeks with neuropsychological tests covering the cognitive domains of episodic memory, attention/working memory, verbal fluency, speed of information processing, and executive function. RESULTS: Baseline characteristics of patients enrolled (n = 239) were comparable in all treatment groups. After 14 weeks, performance on none of the cognitive domains differed significantly between the treatment arms (p = 0.49-0.82). At follow-up, no additional treatment effect (p = 0.35-0.98) or difference between groups (p = 0.37-0.93) was found at any time point. Patients performed significantly better in several cognitive domains at weeks 14, 26, and 40 compared to baseline, but this was not specific to a treatment group. CONCLUSIONS: A 2-week treatment with ceftriaxone followed by a 12-week regimen of doxycycline or clarithromycin/hydroxychloroquine did not lead to better cognitive performance compared to a 2-week regimen of ceftriaxone in patients with Lyme disease-attributed persistent symptoms. CLINICALTRIALSGOV IDENTIFIER: NCT01207739. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that longer-term antibiotics in patients with borreliosis-attributed persistent symptoms does not increase cognitive performance compared to shorter-term antibiotics.8 p

Chorea als presenterend verschijnsel bij coeliakie

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