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From these observations based on a crystallographic approach, it seems that initial templated nucleation on structural fibres-probably collagen-followed at some sites by secondary nucleation could explain MSU crystal deposition in gout.The IL-23-IL-17 axis in inflammatory arthritis. Erik Lubberts. Nat. Rev. Rheumatol. 11, 415-429 (2015); published online 28 April 2015; doi10.1038/nrrheum.2015.53. In Figure 2a of this Review, full protection against CIA was incorrectly stated as an effect of IL-17 deficiency instead of IL-17RA deficiency.A prevalent type of protein misfolding causes the formation of β-sheet-rich structures known as amyloid fibrils. Research into the mechanisms of fibril formation has implications for both disease prevention and nanoscale templating technologies. This investigation into the aggregation of insulin utilises ion mobility mass spectrometry coupled with molecular modelling to identify and characterise oligomers formed during the 'lag' phase that precedes fibril growth. High resolution mass spectrometry and collision induced dissociation is used to unequivocally assign species as m/z coincident multimers or confomers, providing a robust analytical approach that supports the use of molecular dynamics to atomistically resolve the observed oligomers. We show that insulin oligomerises to form species In where 2 ≤ n ≤ 12 and within this set of oligomers we delineate over 60 distinct conformations, the most dominant of which are compact species. Modelling trained with experimental data suggests that the dominant compact dimers are enriched in β-sheet secondary structure and dominated by hydrophobic interactions, and provides a linear relationship between Rg and collision cross section. This approach provides detailed insight to the early stages of assembly of this much studied amyloidogenic protein, and can be used to inform models of nucleation and growth.

Cancer therapy is often based on combination of conventional methods of cancer treatment with immunotherapy. Photodynamic therapy (PDT) is one of the immunomodulating methods used in oncology. We examined how PDT influences the secretory activity of colon cancer cells in vitro, especially the secretion of vascular endothelial growth factor (VEGF) in aerobic conditions.

We used two cancer cell lines with different malignancy potentials a metastatic SW620 line and a non-metastatic SW480 line. In the first stage of the experiment, we exposed each cell line to three different concentrations of photosensitizer's precursor 5-aminolevulinic acid (ALA) and varying levels of light radiation, after which we assessed cell viability and apoptosis induction in these lines, using the MTT and LDH assays. Then, we determined the secretion of VEGF by these cells in aerobic conditions and under the ALA-PDT parameters at which cells presented the highest viability.

Photodynamic treatment with ALA did not influence on VEGF secretion by the non-metastatic SW480 cells, but caused a decrease in VEGF secretion by the metastatic SW 620 cell line by 29% (p<0.05). SW 620 cell line secreted more actively VEGF than the SW480 cells, both before and after photo dynamic therapy (p<0.05).

The outcome of this in vitro study presented a beneficial effect of ALA-PDT, resulting in a decrease of VEGF secretion in the more malignant SW620 cell lines. Further studies should be considered to confirm the clinical relevance of this finding.

The outcome of this in vitro study presented a beneficial effect of ALA-PDT, resulting in a decrease of VEGF secretion in the more malignant SW620 cell lines. Further studies should be considered to confirm the clinical relevance of this finding.

The aim of this study was to evaluate whether a new method using quantitative light-induced fluorescence-digital (QLF-D) was appropriate for the diagnosis of oral malodor by quantifying the fluorescence of tongue coating.

This study examined 103 healthy subjects who have an oral malodor as a main complaint. The levels of oral malodor were measured by organoleptic scores (OLS) and volatile sulfur compound (VSC) levels. The fluorescent tongue coating images captured by QLF-D were quantified as the integrated fluorescence score (IF score) by multiplying the intensity and area of fluorescence. The correlations between the fluorescence parameters and OLS as well as VSC levels and the diagnostic accuracy of the IF score were evaluated.

The IF score of tongue coating showed a significant positive correlation with the OLS (r=0.54, p<0.01) and the VSC levels (r=0.49, p<0.01). This score was significantly differed with the level of oral malodor (p<0.001), and its AUC was 0.72 in identifying the patient with definite oral malodor (≥OLS 2).

A new method quantifying tongue coating fluorescence detected by QLF-D can be used to diagnose oral malodor and assess its severity in the clinical practice.

A new method quantifying tongue coating fluorescence detected by QLF-D can be used to diagnose oral malodor and assess its severity in the clinical practice.Reasons for a successful or unsuccessful implementation of infection prevention and control (IPC) guidelines are often multiple and interconnected. This article reviews key elements from the national to the individual level that contribute to the success of the implementation of IPC measures and gives perspectives for improvement. Governance approaches, modes of communication and formats of guidelines are discussed with a view to improve collaboration and transparency among actors. The culture of IPC influences practices and varies according to countries, specialties and healthcare providers. We describe important contextual aspects, such as relationships between actors and resources and behavioural features including professional background or experience. Behaviour change techniques providing goal-setting, feedback and action planning have proved effective in mobilizing participants and may be key to trigger social movements of implementation. The leadership of international societies in coordinating actions at international, national and institutional levels using multidisciplinary approaches and fostering collaboration among clinical microbiology, infectious diseases and IPC will be essential for success.In immunocompetent patients with nosocomial pneumonia, the relationship between Candida spp. isolation in respiratory samples and outcomes or association with other pathogens is controversial. We therefore compared the characteristics and outcomes of patients with intensive care unit-acquired pneumonia (ICUAP), with or without Candida spp. isolation in the respiratory tract. In this prospective non-interventional study, we assessed 385 consecutive immunocompetent patients with ICUAP, according to the presence or absence of Candida spp. in lower respiratory tract samples. Candida spp. was isolated in at least one sample in 82 (21%) patients. Patients with Candida spp. had higher severity scores and organ dysfunction at admission and at onset of pneumonia. In multivariate analysis, previous surgery, diabetes mellitus and higher Simplified Acute Physiology Score II at ICU admission independently predicted isolation of Candida spp. There were no significant differences in the rate of specific aetiological pathogens, the systemic inflammatory response, and length of stay between patients with and without Candida spp. Mortality was also similar, even adjusted for potential confounders in propensity-adjusted multivariate analyses (adjusted hazard ratio 1.08, 95% CI 0.57-2.05, p 0.80 for 28-day mortality and adjusted hazard ratio 1.38, 95% CI 0.81-2.35, p 0.24 for 90-day mortality). Antifungal therapy was more frequently prescribed in patients with Candida spp. in respiratory samples but did not influence outcomes. Candida spp. airway isolation in patients with ICUAP is associated with more initial disease severity but does not influence outcomes in these patients, regardless of the use or not of antifungal therapy.In mice, specific species composition of gut microbiota enhances susceptibility to Campylobacter jejuni but little is known about the specific composition of the human gut microbiota in providing protection from infections caused by enteropathogens. Healthy adult individuals, who travelled in groups from Sweden to destinations with an estimated high risk for acquisition of Campylobacter infection, were enrolled. Faecal samples, collected before travelling and after returning home, were cultured for bacterial enteropathogens, and analysed for Campylobacter by PCR and for the species composition of the microbiota by 16S amplicon massive parallel sequencing. The microbiota compositions were compared between persons who became infected during their travel and those who did not. A total of 63 participants completed the study; 14 became infected with Campylobacter, two with Salmonella and 47 remained negative for the enteropathogens tested. After exclusion of samples taken after antimicrobial treatment, 49 individuals were included in the final analyses. Intra-individual stability of the microbiota was demonstrated for samples taken before travelling. The original diversity of the faecal microbiota was significantly lower among individuals who later became infected compared with those who remained uninfected. The relative abundances of bacteria belonging to the family Lachnospiraceae, and more specifically its two genera Dorea and Coprococcus, were significantly higher among those who remained uninfected. The travel-related infection did not significantly modify the faecal microbiota composition. Species composition of human gut microbiota is important for colonization resistance to Campylobacter infection. Especially individuals with a lower diversity are more susceptible to Campylobacter infection.Early adversity is a risk factor for poor mental and physical health. Although altered neural development is believed to be one pathway linking early adversity to psychopathology, it has rarely been considered a pathway linking early adversity to poor physical health. However, this is a viable pathway because the central nervous system is known to interact with the immune system via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). In support of this pathway, early adversity has been linked to changes in neural development (particularly of the amygdala, hippocampus, and prefrontal cortex), HPA axis and ANS dysregulation, and higher levels of inflammation. Inflammation, in turn, can be detrimental to physical health when prolonged. In this review, we present these studies and consider how altered neural development may be a pathway by which early adversity increases inflammation and thus risk for adverse physical health outcomes.The toxic and repellent activities of the essential oil extracted from the leaves of Atalantia guillauminii Swingle were evaluated against three stored product insects, red flour beetles (Tribolium castaneum), cigarette beetles (Lasioderma serricorne) and booklice (Liposcelis bostrychophila). The essential oil obtained by hydrodistillation was investigated by GC-MS. The main constituents of the essential oil were β-thujene (27.18%), elemicin (15.03%), eudesma-3, 7(11)-diene (9.64%), followed by (-)-4-terpeniol (6.70%) and spathulenol (5.25%). The crude oil showed remarkable contact toxicity against T. castaneum, L. serricorne adults and L. bostrychophila with LD50 values of 17.11, 24.07 µg/adult and 55.83 µg/cm(2) respectively and it also displayed strong fumigant toxicity against T. castaneum, L. read more serricorne adults with LC50 values of 17.60 and 12.06 mg/L respectively, while weak fumigant toxicity against L. bostrychophila with a LC50 value of 16.75 mg/L. Moreover, the essential oil also exhibited the same level repellency against the three stored product insects, relative to the positive control, DEET.