No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of Alzheimer's disease

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that has been reported to reduce the risk of developing Alzheimer's disease (AD). Its preventive effects in AD are likely pleiotropic as ibuprofen displays both anti-inflammatory activity by inhibition of cyclooxygenases and anti-amyloidogenic activity by modulation of γ-secretase. In order to study the anti-inflammatory properties of ibuprofen independent of its anti-amyloidogenic activity, we performed a long-term treatment study with ibuprofen in 5XFAD mice expressing a presenilin-1 mutation that renders this AD model resistant to γ-secretase modulation. As expected, ibuprofen treatment for 3 months resulted in a reduction of the inflammatory reaction in the 5XFAD mouse model. Importantly, an unchanged amyloid beta (Aβ) plaque load, an increase in soluble Aβ42 levels, and an aggravation of some behavioral parameters were noted, raising the question whether suppression of inflammation by nonsteroidal anti-inflammatory drug is beneficial in AD.     

Impact of Hourly Emergency Department Patient Volume on Blood Culture Contamination and Diagnostic Yield

Emergency departments (EDs) are an important diagnostic site for outpatients with potentially serious infections. EDs frequently experience high patient volumes, and crowding has been shown to negatively impact the delivery of early care for serious infections, such as pneumonia. Here, we hypothesized that other important factors in the early care of infectious diseases, the rate of blood culture contamination and the accurate detection of pathogens, would be sensitive to ED operational stress, as proper collection requires fastidious attention to technique and timing. We related all blood samples collected over 1 year and their rates of recovery of likely contaminants and pathogens to the number of patients being cared for in the ED at the time of sample collection. Likely pathogens and contaminants were classified through combined microbiological and manual chart review criteria. Zero-inflated Poisson regression was used to relate crowding to culture results. Blood samples were obtained from 7,586 patients over 82,521 adult and pediatric patient visits. The unadjusted rates of recovering a likely pathogen or a likely contaminant were 8.0% and 3.7%, respectively. Periods of increased crowding (3rd and 4th quartiles of hourly occupancy) were significantly associated (P < 0.01) with increased rates of contamination (relative risk, 1.23 compared to the least busy quartile). Collecting samples for culture during busy times was also associated with a reduced likelihood of recovering a likely pathogen (relative risk, 0.93 compared to the least busy quartile). ED crowding was associated with degraded performance of blood cultures, both increasing the rate of contamination and decreasing the diagnostic yield.     

Characterisation of multidrug-resistant Salmonella Typhimurium 4,[5],12:i:- DT193 strains carrying a novel genomic island adjacent to the thrW tRNA locus

In 2006, monophasic, multidrug-resistant Salmonella enterica spp. enterica serovar 4,[5],12:i:- strains appeared as a novel serotype in Germany, associated with large diffuse outbreaks and increased need for hospitalisation. The emerging 4,[5],12:i:- strains isolated from patients in Germany belong mainly to phage type DT193 according to the Anderson phage typing scheme for S. Typhimurium (STM) and exhibit at least a tetra-drug resistance. The strains have been shown to harbour STM-specific Gifsy-1, Gifsy-2, and ST64B prophages. Furthermore, the extensive sequence similarity of the tRNA regions between one characterised 4,[5],12:i:- phage type DT193 and the S. Typhimurium LT2 strain as well as the STM-specific position of an IS200 element within the fliA-fliB intergenic region ( Echeita et al., 2001) prompted us to classify them as a monophasic variant of S. Typhimurium. In 2008, the monophasic variant represented 42.2% of all S. Typhimurium isolates from human analysed at the National Reference Centre. Searching for insertions in tRNA sites resulted in the detection of an 18.4-kb fragment adjacent to the thrW tRNA locus, exhibiting a lower G+C content compared to the LT2 genome. Sequence analysis identified 17 potential ORFs. Some of them showed high similarity to enterobacterial phage sequences and sequences from Shigella boydii, Sh. dysenteriae, avian pathogenic Escherichia coli and other Escherichia spp. The biological function of this novel island with respect to virulence properties and metabolic functions is under investigation.     

Rapid translocation of intracellular toll-like receptors depends on endosomal NADPH oxidase

Endosomal toll-like receptors (TLRs) must be translocated from the endoplasmic reticulum (ER) to the endosome and proteolytically cleaved within the endosome before they can induce cellular signals. As ligands for these TLRs are also liberated from apoptotic or necrotic cells, this process is controlled by several mechanisms which shall ensure that there is no inadvertent activation. We have shown previously that antiphospholipid antibodies induce endosomal NADPH-oxidase (NOX) followed by the translocation of TLR7/8 to the endosome. We show now that endosomal NOX is required for the rapid translocation of TLR3, TLR7/8, and TLR9. Deficiency of gp91phox, the catalytic subunit of NOX2, or inhibition of endosomal NOX by the chloride channel blocker niflumic acid both prevent immediate (i.e., within 30 min) translocation of these TLRs as shown by confocal laser scanning microscopy. Under these conditions, the induction of mRNA synthesis for TNF-α and secretion of TNF-α is delayed by approx. 6–9 h. However, maximal expression of TNF-α mRNA or secretion of TNF-α is not significantly reduced. In conclusion, these data add NOX2 as another component involved in the orchestration of cellular responses to ligands of endosomal TLRs.     

Serum tau protein elevation in migraine: a cross-sectional case–control study

Background

Headaches are the most common complaints among pediatric populations. Determining the cause and appropriate treatment for headaches may be challenging and costly, and the impact of headaches on the lives of patients and their families is not well understood.

Objective

A systematic literature review was conducted to examine what PROMs are currently used, and to identify quality of life (QoL) concepts important to children suffering from headaches and any known determinants of QoL.

Methods

Embase, Medline, Web of Science, CINAHL, EBSCOhost, PsychINFO, Cochrane CENTRAL and Google Scholar were searched from their inception through to June 2021. Studies investigating QoL, using a validated outcome measure in pediatric patients with headaches, were included. Relevant studies were identified through title and abstract screening and full text review by two independent reviewers. A citation review of included studies was performed. QoL concepts were extracted from the outcome measures that were used in each study to develop a preliminary conceptual model of QoL in children suffering from headaches. Determinants of QoL were also identified and categorized.

Results

A total of 5421 studies were identified in the search. Title and abstract screening resulted in the exclusion of 5006 studies. Among the 415 studies included for full text review, 56 were eligible for final analysis. A citation review resulted in the addition of five studies. Most studies were conducted in high-income countries and included a patient-sample accordingly (n = 45 studies). Sixteen different PROMs were identified in the included studies, of which the PedsQL was used the most often (n = 38 studies).

The most common health concepts reported were physical functioning (n = 113 items), social and psychological wellbeing (N = 117, n = 91 resp.). Twenty-five unique determinants of QoL were extracted from the included studies.

Conclusion

There is a need for a condition-specific PROM to facilitate the measurement of QoL outcomes in the pediatric headache population. A conceptual model was developed based on the findings from the health concepts. Findings from this review could be used for future qualitative interviews with pediatric patients with headaches to elicit and refine important QoL concepts.

     

Speaking rate effects on articulatory pattern consistency in talkers with mild ALS

This study investigated speaking rate effects on articulatory pattern consistency in talkers with mild amyotrophic lateral sclerosis (ALS) to better understand speech rate declines during the early stages of speech deterioration. Eight talkers with mild ALS and 11 controls repeated a sentence at their typical rate, an accelerated rate, and a reduced rate. Lip and jaw movements were captured using a 3-D motion capture system. Results showed that talkers with ALS produced more consistent articulatory patterns during typical speech than did controls. Further, rate reduction resulted in diminished pattern consistency in both groups. Fast speech also elicited less consistent articulatory patterns in talkers with ALS. Controls, by contrast, tended to produce more consistent patterns during fast speech. Relatively inconsistent patterns during fast speech suggest that ALS may negatively affect articulatory control when the speech motor system operates near its performance limit. Relatively consistent patterns during typical speech indicate a successful adaption to disease-related articulatory deficits. Rate reduction does not appear to benefit articulatory stability during early stages of speech decline.     

Bestandsaufnahme der verfügbaren und aktuell eingesetzten Typisierungsmethoden einschließlich genombasierter Verfahren von Zoonoseerregern am Beispiel von Salmonella enterica

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - In den vergangenen Jahren hat sich die Gesamtgenomsequenzierung („whole genome sequencing“; WGS) in Kombination mit...