Explore the vast range of titles available.

Background Depression and dementia are both common diseases. Although new cases of depression are more common in younger adults, there is a second peak at the age of 50 years suggesting a different pathological process. Late-life depression (LLD) is associated with dementia. However, it remains unclear whether depression represents a dementia prodrome or is a true risk factor for its development. LLD is thought to have a vascular component and this may be a possible link between depression and dementia. We hypothesised that later-life depression is a prodromal manifestation of dementia and would therefore be associated with more AD, and/or ischaemic brain abnormalities that are present in earlier-life depression or in age- and sex-matched controls. Methods We assessed post-mortem orbitofrontal cortex and dorsolateral pre-frontal cortex from 145 individuals in 4 groups: 28 18–50-year-olds with depression, 30 older individuals (ages 51–90) with depression, 28 with early AD (Braak tangle stages III–IV) and 57 matched controls (17 early-life, 42 later-life). Levels of Aβ, phospho-tau and α-synuclein were assessed by immunohistochemistry and ELISA. To quantify chronic ischaemia, VEGF, MAG and PLP1 were measured by ELISA. To assess pericyte damage, PDGFRB was measured by ELISA. For blood–brain barrier leakiness, JAM-A, claudin 5 and fibrinogen were measured by ELISA. To quantity endothelial activation, the ratio of ICAM1:collagen IV was assessed by immunohistochemistry. Results There was no evidence of chronic cerebral hypoperfusion or increased Aβ/tau in either depression group. There was also no indication of pericyte damage, increased blood–brain barrier leakiness or endothelial activation in the OFC or DLPFC in the depression groups. Conclusions Contrary to some previous findings, we have not found evidence of impaired vascular function or increased Aβ in LLD. Our study had a relatively small sample size and limitations in the availability of clinical data. These results suggest that depression is a risk factor for dementia rather than an early manifestation of AD or a consequence of cerebral vascular insufficiency.

Graduates Yorkshire has been using social media since 2006 when it saw the emerging media as a cost effective way of reaching its key audiences. The social enterprise aims to encourage businesses in Yorkshire and Humber to invest in graduate jobs and ensure the best graduates either remain or are attracted into the region. Communications at the organization are complex and it has a number of different audiences. It needs to get its key messages out to students and recent graduates as well businesses of all sizes. While it is easy to identify larger organizations, such as the National Health Service, and work out the best channels of communication, it also has to communicate to thousands of small to medium sized businesses that are equally able to offer new graduate vacancies. Being affiliated to the careers services of the region's ten universities and higher education establishments, it also needs to communicate to its key stakeholders.

Resistant starch is a prebiotic metabolized by the gut bacteria. It has been shown to attenuate chronic kidney disease (CKD) progression in rats. Previous studies employed taxonomic analysis using 16S rRNA sequencing and untargeted metabolomics profiling. Here we expand these studies by metaproteomics, gaining new insight into the host-microbiome interaction. Differences between cecum contents in CKD rats fed a diet containing resistant starch with those fed a diet containing digestible starch were examined by comparative metaproteomics analysis. Taxonomic information was obtained using unique protein sequences. Our methodology results in quantitative data covering both host and bacterial proteins. 5,834 proteins were quantified, with 947 proteins originating from the host organism. Taxonomic information derived from metaproteomics data surpassed previous 16S RNA analysis, and reached species resolutions for moderately abundant taxonomic groups. In particular, the Ruminococcaceae family becomes well resolved-with butyrate producers and amylolytic species such as R. bromii clearly visible and significantly higher while fibrolytic species such as R. flavefaciens are significantly lower with resistant starch feeding. The observed changes in protein patterns are consistent with fiber-associated improvement in CKD phenotype. Several known host CKD-associated proteins and biomarkers of impaired kidney function were significantly reduced with resistant starch supplementation. Data are available via ProteomeXchange with identifier PXD008845. Metaproteomics analysis of cecum contents of CKD rats with and without resistant starch supplementation reveals changes within gut microbiota at unprecedented resolution, providing both functional and taxonomic information. Proteins and organisms differentially abundant with RS supplementation point toward a shift from mucin degraders to butyrate producers.

NURSES from Ohio yesterday attended lectures and demonstrations on acupuncture, but won't be...

Disposable plasticware such as test tubes, pipette tips, and multiwell assay or culture plates are used routinely in most biological research laboratories. Manufacturing of plastics requires the inclusion of numerous chemicals to enhance stability, durability, and performance. Some lubricating (slip) agents, exemplified by oleamide, also occur endogenously in humans and are biologically active, and cationic biocides are included to prevent bacterial colonization of the plastic surface. We demonstrate that these manufacturing agents leach from laboratory plasticware into a standard aqueous buffer, dimethyl sulfoxide, and methanol and can have profound effects on proteins and thus on results from bioassays of protein function. These findings have far-reaching implications for the use of disposable plasticware in biological research.

Introduction/BackgroundThe geographical heterogeneity seen in treatment patterns for patients with advanced ovarian cancer is profound, long standing, worrying, and impacts upon survival. A tool that could demonstrate the impact of a patient’s treatment on their predicted survival is needed to counsel patients about their treatment options and reduce treatment variance.We used detailed clinical datasets to develop a model for predicting treatment dependent survival in ovarian cancer patients.MethodologyData were collected using a data dictionary for all cases of ovarian cancer presenting to six cancer centres in England between 1/1/2018 and 31/12/2019.A Cox Proportional Hazard model was built using internal-external cross validation to estimate data heterogeneity between centres. Variables were assessed for non-linear relationships. Backwards selection was used to optimise fit. The hazard ratios for surgical treatment from the model were compared to existing RCT results, to investigate our ability to estimate causal effects within the observational data. Prediction accuracy of all models was assessed by calibration and discrimination (Harrell’s C statistic).Results991 patient records were included in survival analysis. The concordance of the models developed ranged from 0.64–0.78 across centres, with meta-analysis of the final model producing a Harrell’s C statistic of 0.73 (CI 0.70–0.75). The observed to expected ratio for three-year survival was 1.07 (CI 0.47–2.47). Some model recalibration was needed for each centre to achieve good calibration performance.The hazard ratios for surgical treatment were similar to, and fell within, the confidence intervals of RCT results, confirming the model’s ability to predict survival under differing treatment conditions. This causal model retained discriminative power (C-stat 0.73, CI 0.65–0.76).ConclusionOur new model has excellent predictive power, and this methodology ensures this will translate to new datasets. If validated, this model could be used to predict the treatment dependant survival in ovarian cancer.DisclosuresNone.

Abstract Pseudomonas aeruginosa opportunistically infects the airways of patients with cystic fibrosis and causes significant morbidity and mortality. Initial infection can often be eradicated though requires prompt detection and adequate treatment. Intermittent and then chronic infection occurs in the majority of patients. Better detection of P. aeruginosa infection using biomarkers may enable more successful eradication before chronic infection is established. In chronic infection P. aeruginosa adapts to avoid immune clearance and resist antibiotics via efflux pumps, β-lactamase expression, reduced porins and switching to a biofilm lifestyle. The optimal treatment strategies for P. aeruginosa infection are still being established, and new antibiotic formulations such as liposomal amikacin, fosfomycin in combination with tobramycin and inhaled levofloxacin are being explored. Novel agents such as the alginate oligosaccharide OligoG, cysteamine, bacteriophage, nitric oxide, garlic oil and gallium may be useful as anti-pseudomonal strategies, and immunotherapy to prevent infection may have a role in the future. New treatments that target the primary defect in cystic fibrosis, recently licensed for use, have been associated with a fall in P. aeruginosa infection prevalence. Understanding the mechanisms for this could add further strategies for treating P. aeruginosa in future. This provides an overview of current and emerging treatments for Pseudomonas aeruginosa airway infection in cystic fibrosis patients, and explains the treatments in the context of the underpinning basic science.