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The effects of probiotics are strain specific. The clinical effects of each strain need to be evaluated separately.
To evaluate the efficacy of Lactobacillus rhamnosus GG (LGG) in the prevention of antibiotic-associated diarrhoea (AAD) in children and adults.
The Cochrane Library, MEDLINE, and EMBASE databases were searched up to July 2015, with no language restrictions, for randomised controlled trials (RCTs). Reference lists of reviews and included studies were examined. The quality of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.
Twelve RCTs (1499 participants) were included. Treatment with LGG compared with placebo or no additional treatment reduced the risk of AAD in patients treated with antibiotics from 22.4% to 12.3% (11 RCTs, n = 1308, relative risk, RR 0.49, 95% confidence interval, CI 0.29-0.83, low QoE). However, when children and adults were evaluated separately, the difference was significant in children only (five RCTs, n = 445, RR 0.48, 95% CI 0.26-0.89; moderate QoE). In adults, the difference was not significant (six RCTs, n = 863, RR 0.48, 95% CI 0.20-1.15; low QoE), except for in a subset of patients receiving antibiotics as part of Helicobacter pylori eradication therapy (four RCTs, n = 280, RR 0.26, 95% CI 0.11-0.59; low QoE).
This meta-analysis shows that Lactobacillus rhamnosus GG is effective in preventing antibiotic-associated diarrhoea in children and adults treated with antibiotics for any reason. However, the quality of evidence is moderate to low.
This meta-analysis shows that Lactobacillus rhamnosus GG is effective in preventing antibiotic-associated diarrhoea in children and adults treated with antibiotics for any reason. However, the quality of evidence is moderate to low.
Influenza vaccines produced in embryonated eggs might pose a risk to patients with egg allergy. However, patients experiencing influenza vaccine-associated anaphylaxis (IVA) do not always have egg allergy. In the 2011-2012 season, an unusually high incidence of IVA was reported in Japan.
We sought to identify the cause of the increase in anaphylactic events in 2011-2012 in Japan.
We collected blood specimens from patients with IVA from all areas of Japan. We analyzed 19 patients with confirmed IVA and 25 age-matched control subjects, including 10 with egg allergy who had no adverse events after corresponding vaccination. ELISA was used to measure specific IgE levels to the trivalent vaccines of several manufacturers and hemagglutinin proteins derived from both egg and cell cultures. Antigen-induced basophil activation was evaluated by measuring CD203c expression by means of flow cytometry. Vaccine excipients were also examined for effects on CD203c expression.
None of the patients with IVA had severe 2-PE.
Anti-cytokine autoantibodies (ACAAs) are pathogenic in a handful of rare immunodeficiencies. However, the prevalence and significance of other ACAAs across immunodeficiencies have not yet been described.
We profiled ACAAs in a diverse cohort of serum samples from patients with immunodeficiency and assessed the sensitivity and specificity of protein microarrays for ACAA identification and discovery.
Highly multiplexed protein microarrays were designed and fabricated. Blinded serum samples from a cohort of 58 immunodeficiency patients and healthy control subjects were used to probe microarrays. Unsupervised hierarchical clustering was used to identify clusters of reactivity, and after unblinding, significance analysis of microarrays was used to identify disease-specific autoantibodies. Abead-based assay was used to validate protein microarray results. Blocking activity of serum containing ACAAs was measured invitro.
Protein microarrays were highly sensitive and specific for the detection of ACAAs in patients with autoimmune polyendocrine syndrome type I and pulmonary alveolar proteinosis, detecting ACAA levels consistent with those reported in the published literature. Protein microarray results were validated by using an independent bead-based assay. To confirm the functional significance of these ACAAs, we tested and confirmed the blocking activity of select ACAAs invitro.
Protein microarrays are a powerful tool for ACAA detection and discovery, and they hold promise as a diagnostic for the evaluation and monitoring of clinical immunodeficiency.
Protein microarrays are a powerful tool for ACAA detection and discovery, and they hold promise as a diagnostic for the evaluation and monitoring of clinical immunodeficiency.Histidine kinase receptors (HKRs) appear to be a common strategy for model and pathogenic fungi to sense and respond to environmental stresses. In the human pathogen Aspergillus fumigatus, which is responsible for invasive aspergillosis, 13 genes potentially encoding HKRs have been identified. Until now, only three HKRs have been functionally characterized. The aim of this study was to perform the systematic invalidation of A. fumigatus HKR genes and the careful phenotypic characterization of the relevant mutants. This study notably allowed to gain new important insights into the role of HKRs in physiology of A. fumigatus. Actually, we showed that (i) NikA/TcsC could be involved in the cell wall integrity pathway, (ii) Fhk6 and PhkA were involved in the regulation of the "fluffy" developmental program, (iii) PhkB could participate in the regulation of conidiation and (iv) PhkA was implied in the resistance of oxidative stresses.This communication describes the establishment of the type II bacterial CRISPR-Cas9 system to efficiently disrupt target genes in the fungal maize pathogen Ustilago maydis. A single step transformation of a self-replicating plasmid constitutively expressing the U. maydis codon-optimized cas9 gene and a suitable sgRNA under control of the U. maydis U6 snRNA promoter was sufficient to induce genome editing. On average 70% of the progeny of a single transformant were disrupted within the respective b gene. Without selection the self-replicating plasmid was lost rapidly allowing transient expression of the CRISPR-Cas9 system to minimize potential long-term negative effects of Cas9. selleck chemical This technology will be an important advance for the simultaneous disruption of functionally redundant genes and gene families to investigate their contribution to virulence of U. maydis.Due to their ability to grow in complex environments, fungi play an important role in most ecosystems and have for that reason been the subject of numerous studies. Some of the main obstacles to the study of fungal growth are the heterogeneity of growth environments and the limited scope of laboratory experiments. Given the increasing availability of image capturing techniques, a new approach lies in image analysis. Most previous image analysis studies involve manual labelling of the fungal network, tracking of individual hyphae, or invasive techniques that do not allow for tracking the evolution of the entire fungal network. In response, this work presents a highly versatile tool combining image analysis and graph theory to monitor fungal growth through time and space for different fungal species and image resolutions. In addition, a new experimental set-up is presented that allows for a functional description of fungal growth dynamics and a quantitative mutual comparison of different growth behaviors. The presented method is completely automated and facilitates the extraction of the most studied fungal growth features such as the total length of the mycelium, the area of the mycelium and the fractal dimension. The compactness of the fungal network can also be monitored over time by computing measures such as the number of tips, the node degree and the number of nodes. Finally, the average growth angle and the internodal length can be extracted to study the morphology of the fungi. In summary, the introduced method offers an updated and broader alternative to classical and narrowly focused approaches, thus opening new avenues of investigation in the field of mycology.Endosomal protein recycling is a fundamental cellular process important for cellular homeostasis, signaling, and fate determination that is implicated in several diseases. WASH is an actin-nucleating protein essential for this process, and its activity is controlled through K63-linked ubiquitination by the MAGE-L2-TRIM27 ubiquitin ligase. Here, we show that the USP7 deubiquitinating enzyme is an integral component of the MAGE-L2-TRIM27 ligase and is essential for WASH-mediated endosomal actin assembly and protein recycling. Mechanistically, USP7 acts as a molecular rheostat to precisely fine-tune endosomal F-actin levels by counteracting TRIM27 auto-ubiquitination/degradation and preventing overactivation of WASH through directly deubiquitinating it. Importantly, we identify de novo heterozygous loss-of-function mutations of USP7 in individuals with a neurodevelopmental disorder, featuring intellectual disability and autism spectrum disorder. These results provide unanticipated insights into endosomal trafficking, illuminate the cooperativity between an ubiquitin ligase and a deubiquitinating enzyme, and establish a role for USP7 in human neurodevelopmental disease.Damaged mitochondria are detrimental to cellular homeostasis. One mechanism for removal of damaged mitochondria involves the PINK1-PARKIN pathway, which poly-ubiquitylates damaged mitochondria to promote mitophagy. We report that assembly of ubiquitin chains on mitochondria triggers autophagy adaptor recruitment concomitantly with activation of the TBK1 kinase, which physically associates with OPTN, NDP52, and SQSTM1. TBK1 activation in HeLa cells requires OPTN and NDP52 and OPTN ubiquitin chain binding. In addition to the known role of S177 phosphorylation in OPTN on ATG8 recruitment, TBK1-dependent phosphorylation on S473 and S513 promotes ubiquitin chain binding in vitro as well as TBK1 activation, OPTN mitochondrial retention, and efficient mitophagy in vivo. These data reveal a self-reinforcing positive feedback mechanism that coordinates TBK1-dependent autophagy adaptor phosphorylation with the assembly of ubiquitin chains on mitochondria to facilitate efficient mitophagy, and mechanistically links genes mutated in Parkinson's disease and amyotrophic lateral sclerosis in a common selective autophagy pathway.Glaucoma, a blinding neurodegenerative disease, whose risk factors include elevated intraocular pressure (IOP), age, and genetics, is characterized by accelerated and progressive retinal ganglion cell (RGC) death. Despite decades of research, the mechanism of RGC death in glaucoma is still unknown. Here, we demonstrate that the genetic effect of the SIX6 risk variant (rs33912345, His141Asn) is enhanced by another major POAG risk gene, p16INK4a (cyclin-dependent kinase inhibitor 2A, isoform INK4a). We further show that the upregulation of homozygous SIX6 risk alleles (CC) leads to an increase in p16INK4a expression, with subsequent cellular senescence, as evidenced in a mouse model of elevated IOP and in human POAG eyes. Our data indicate that SIX6 and/or IOP promotes POAG by directly increasing p16INK4a expression, leading to RGC senescence in adult human retinas. Our study provides important insights linking genetic susceptibility to the underlying mechanism of RGC death and provides a unified theory of glaucoma pathogenesis.
Here's my website: https://www.selleckchem.com/products/tucidinostat-chidamide.html
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