The role of bacterial extracellular vesicles in chronic wound infections: current knowledge and future challenges

Chronic wounds are a significant global problem with an increasing economic and patient welfare impact. How wounds move from an acute to chronic, non-healing, state is not well understood although it is likely that it is driven by a poorly regulated local inflammatory state. Opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa are well known to stimulate a pro-inflammatory response and so their presence may further drive chronicity. Studies have demonstrated that host cell extracellular vesicles (hEVs), in particular exosomes, have multiple roles in both increasing and decreasing chronicity within wounds; however, the role of bacterial extracellular vesicles (bEVs) is still poorly understood. The aim of this review is to evaluate bEV biogenesis and function within chronic wound relevant bacterial species to determine what, if any, role bEVs may have in driving wound chronicity. We determine that bEVs drive chronicity by both increasing persistence of key pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa and stimulating a pro-inflammatory response by the host. Data also suggest that both bEVs and hEVs show therapeutic promise, providing vaccine candidates, decoy targets for bacterial toxins or modulating the bacterial species within chronic wound biofilms. Caution should, however, be used when interpreting findings to date as the bEV field is still in its infancy and as such lacks consistency in bEV isolation and characterization. It is of primary importance that this is addressed, allowing meaningful conclusions to be drawn and increasing reproducibility within the field

Comparison of cause of death between ANZDATA and the Australian national death index.

Aim: The aim of the present study was to understand the differences in how cause of death for patients receiving renal replacement therapy in Australia is recorded in The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) compared to the National Death Index (NDI). Methods: Data linkage was performed between ANZDATA and NDI for all deaths in the period 1980-2013. Cause of death was classified according to ICD-10 chapter. Overall and chapter specific agreement were assessed using the Kappa statistic. Descriptive analysis was used to explore differences where there was disagreement on primary cause of death. Results: The analysis cohort included 28 675 patients. Ninety five percent of ANZDATA reported deaths fell within +/- 3 days of the date recorded by NDI. Circulatory death was the most common cause of death in both databases (ANZDATA 48%, NDI 32%). Overall agreement at ICD chapter level of primary cause was poor (36%, kappa 0.22). Agreement was best for malignancy (kappa 0.71). When there was disagreement on primary cause of death these were most commonly coded as genitourinary (35%) and endocrine (25.0%) in NDI, and circulatory (39%) and withdrawal (24%) in ANZDATA. Sixty-nine percent of patients had a renal related cause documented as either primary or a contributing cause of death in the NDI. Conclusion: There is poor agreement in primary cause of death between ANZDATA and NDI which is in part explained by the absence of diabetes and renal failure as causes of death in ANZDATA and the absence of 'withdrawal' in NDI. These differences should be appreciated when interpreting epidemiological data on cause of death in the Australian end stage kidney disease population

Airborne High Spectral Resolution Lidar Aerosol Measurements during MILAGRO and TEXAQS/GOMACCS

Two1 field experiments conducted during 2006 provided opportunities to investigate the variability of aerosol properties near cities and the impacts of these aerosols on air quality and radiative transfer. The Megacity Initiative: Local and Global Research Observations (MILAGRO) /Megacity Aerosol Experiment in Mexico City (MAX-MEX)/Intercontinental Chemical Transport Experiment-B (INTEX-B) joint experiment conducted during March 2006 investigated the evolution and transport of pollution from Mexico City. The Texas Air Quality Study (TEXAQS)/Gulf of Mexico Atmospheric Composition and Climate Study (GoMACCS) (http://www.al.noaa.gov/2006/) conducted during August and September 2006 investigated climate and air quality in the Houston/Gulf of Mexico region. During both missions, the new NASA Langley airborne High Spectral Resolution Lidar (HSRL) was deployed on the NASA Langley B200 King Air aircraft and measured profiles of aerosol extinction, backscattering, and depolarization to: 1) characterize the spatial and vertical distributions of aerosols, 2) quantify aerosol extinction and optical thickness contributed by various aerosol types, 3) investigate aerosol variability near clouds, 4) evaluate model simulations of aerosol transport, and 5) assess aerosol optical properties derived from a combination of surface, airborne, and satellite measurements

Article Gender Politics and Secure Services For Women: Reflections on a study of staff understandings of challenging behaviour

Abstract This paper discusses the findings of a Q-methodological study that investigated the complexity of professional understandings of (attitudes towards) residents in a secure unit for women with learning disabilities and challenging behaviours. Particular attention is afforded to the critical debate regarding women in psychiatric and secure care, including the significant contribution made to this literature by feminist perspectives. A multi-professional group of staf

Excellent survival and good outcomes at 15 years using the Press Fit Condylar Sigma total knee replacement

Background: We report 15-year survival, clinical and radiographic follow-up data for the Press Fit Condylar Sigma total knee replacement (PFC Sigma TKR). Methods: Between October 1998 and October 1999, 235 consecutive TKRs were performed in 203 patients. Patients were reviewed at a specialist nurse-led clinic prior to surgery, and at five, eight-to-ten and 15 years postoperatively. Clinical outcomes, including Knee Society Score (KSS), were recorded prospectively at each clinic visit, and radiographs were obtained. Results: Of our initial cohort, 99 patients (118 knees) were alive at 15 years, and 31 patients (34 knees) were lost to follow-up. 13 knees (5.5%) were revised; five (2.1%) for infection, seven (3%) for instability and one (0.4%) for aseptic loosening. Cumulative survival with the end-point of revision for any reason was 92.3% at 15 years, and with revision for aseptic failure as the end-point was 94.4%. The mean KSS knee score was 77.4 (33 to 99) at 15 years, compared with 31.7 (2 to 62) preoperatively. Of 71 surviving knees for which X-rays were available, 12 (16.9%) had radiolucent lines and one (1.4%) demonstrated clear radiographic evidence of loosening. Conclusion: The PFC Sigma TKR represents a durable, effective option for patients undergoing knee arthroplasty, with excellent survival and good clinical and radiographic outcomes at 15 years.PostprintPeer reviewe

Safetxt: a safer sex intervention delivered by mobile phone messaging on sexually transmitted infections (STI) among young people in the UK - protocol for a randomised controlled trial.

INTRODUCTION: Young people aged 16 to 24 have the highest prevalence of genital chlamydia and gonorrhoea compared with other age groups and re-infection rates following treatment are high. Long-term adverse health effects include subfertility and ectopic pregnancy, particularly among those with repeated infections. We developed the safetxt intervention delivered by text message to reduce sexually transmitted infection (STI) by increasing partner notification, condom use and (STI) testing among young people in the UK. METHODS AND ANALYSIS: A single-blind randomised trial to reliably establish the effect of the safetxt intervention on chlamydia and gonorrhoea infection at 1 year. We will recruit 6250 people aged 16 to 24 years who have recently been diagnosed with chlamydia, gonorrhoea or non-specific urethritis from health services in the UK. Participants will be allocated to receive the safetxt intervention (text messages designed to promote safer sexual health behaviours) or to receive the control text messages (monthly messages asking participants about changes in contact details) by an automated remote online randomisation system. The primary outcome will be the cumulative incidence of chlamydia and gonorrhoea infection at 1 year assessed by nucleic acid amplification tests. Secondary outcomes include partner notification, correct treatment of infection, condom use and STI testing prior to sex with new partners. ETHICS AND DISSEMINATION: Ethics approval was obtained from NHS Health Research Authority - London - Riverside Research Ethics Committee (REC reference: 15/LO/1665) and the London School of Hygiene & Tropical Medicine. We will submit the results of the trial for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: International Standard Randomised Controlled Trials Number: ISRCTN64390461. Registered on 17th March 2016. WHO trial registration data set available at: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN64390461. TRIAL PROTOCOL VERSION: 12, 19th July 2018

Oral progenitor cell line-derived small extracellular vesicles as a treatment for preferential wound healing outcome

Scar formation during wound repair can be devastating for affected individuals. Our group previously documented the therapeutic potential of novel progenitor cell populations from the non-scarring buccal mucosa. These Oral Mucosa Lamina Propria-Progenitor Cells (OMLP-PCs) are multipotent, immunosuppressive, and antibacterial. Small extracellular vesicles (sEVs) may play important roles in stem cell–mediated repair in varied settings; hence, we investigated sEVs from this source for wound repair. We created an hTERT immortalized OMLP-PC line (OMLPPCL ) and confrmed retention of morphology, lineage plasticity, surface markers, and functional properties. sEVs isolated from OMLP-PCL were analyzed by nanoparticle tracking analysis, Cryo-EM and fow cytometry. Compared to bone marrow–derived mesenchymal stromal cells (BM-MSC) sEVs, OMLP-PCL sEVs were more potent at driving wound healing functions, including cell proliferation and wound repopulation and downregulated myofbroblast formation. A reduced scarring potential was further demonstrated in a preclinical in vivo model. Manipulation of OMLP-PCL sEVs may provide novel options for non-scarring wound healing in clinical settings

British Gynaecological Cancer Society Recommendations for Evidence Based, Population Data Derived Quality Performance Indicators for Ovarian Cancer

Ovarian cancer survival in the UK lags behind comparable countries. Results from the ongoing National Ovarian Cancer Audit feasibility pilot (OCAFP) show that approximately 1 in 4 women with advanced ovarian cancer (Stage 2, 3, 4 and unstaged cancer) do not receive any anticancer treatment and only 51% in England receive international standard of care treatment, i.e., the combination of surgery and chemotherapy. The audit has also demonstrated wide variation in the percentage of women receiving anticancer treatment for advanced ovarian cancer, be it surgery or chemotherapy across the 19 geographical regions for organisation of cancer delivery (Cancer Alliances). Receipt of treatment also correlates with survival: 5 year Cancer survival varies from 28.6% to 49.6% across England. Here, we take a systems wide approach encompassing both diagnostic pathways and cancer treatment, derived from the whole cohort of women with ovarian cancer to set out recommendations and quality performance indicators (QPI). A multidisciplinary panel established by the British Gynaecological Cancer Society carefully identified QPI against criteria: metrics selected were those easily evaluable nationally using routinely available data and where there was a clear evidence base to support interventions. These QPI will be valuable to other taxpayer funded systems with national data collection mechanisms and are to our knowledge the only population level data derived standards in ovarian cancer. We also identify interventions for Best practice and Research recommendations