Impact of extracellular vesicle isolation methods on downstream mirna analysis in semen: A comparative study

Seminal plasma (SP) contains a unique concentration of miRNA, mostly contained in small extracellular vesicles (sEVs) such as exosomes, some of which could be clinically useful for diagnosis and/or prognosis of urogenital diseases such as prostate cancer (PCa). We optimized several exosome-EV isolation technologies for their use in semen, evaluating EV purifying effectiveness and impact on the downstream analysis of miRNAs against results from the standard ultracentrifugation (UC) method to implement the use of SP sEV_miRNAs as noninvasive biomarkers for PCa. Our results evidenced that commercial kits designed to isolate exosomes/EVs from blood or urine are mostly applicable to SP, but showed quantitative and qualitative variability between them. ExoGAG 3500x g and the miRCURY Cell/Urine/CSF 1500x g methods resulted as equivalent alternative procedures to UC for isolating exosomes/sEVs from semen for nanoparticle characteristics and quality of RNA contained in vesicles. Additionally, the expression profile of the altered semen sEV-miRNAs in PCa varies depending on the EV isolation method applied. This is possibly due to different extraction techniques yielding different proportions of sEV subtypes. This is evidence that the exosome-EV isolation method has a significant impact on the analysis of the miRNAs contained within, with important consequences for their use as clinical biomarkers. Therefore, miRNA analysis results for EVs cannot be directly extrapolated between different EV isolation methods until clear markers for delineation between microvesicles and exosomes are established. However, EV extraction methodology affects combined models (semen exosome miRNA signatures plus blood Prostate specific antigen (PSA) concentration for PCa diagnosis) less; specifically our previously described (miR-142-3p + miR-142-5p + miR-223-3p + PSA) model functions as molecular marker from EVs from any of the three isolation methods, potentially improving the efficiency of PSA PCa diagnosis

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

Conditional cash transfer programmes: the recent experience in Latin America and the Caribbean

Includes BibliographySpanish version available at the LibraryForeword Alicia BárcenaThis document summarizes experience with conditional cash transfer or "co-responsibility" (CCT) programmes in Latin America and the Caribbean, over a period lasting more than 15 years. During this time, CCTs have consolidated and spread through the region's various countries as a tool of choice for poverty-reduction policy. This document, which it is hoped will serve as a basis and input for discussion and progress in building social-protection systems premised on inclusion and universal rights, provides detailed information on the different components of CCTs. It also reviews their main characteristics in terms of the definition and registration of programme users, the targeting mechanisms used, the various types of benefits provided, and the conditionalities attached to them. It then analyses the historical trend of the indicators of CCT investment and coverage, and the information available 8 ECLAC on their effects in different domains. Lastly, it makes an assessment of the experience and the main challenges that these programmes pose in terms of their sustainability, legal framework, accountability, participation, institutionality and inter-sectoral characteristics

Postoperative outcomes in oesophagectomy with trainee involvement

Background The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. Methods Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. Results Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). Conclusion Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery.The aim of this study was to determine the impact of trainee involvement in oesophagectomy on perioperative outcomes in the international multicentre Oesophago-Gastric Anastomosis Audit (OGAA). Analysis of 2232 oesophagectomies has shown that trainee involvement did not negatively impact perioperative outcomes

Textbook outcome following oesophagectomy for cancer: international cohort study

Background: Textbook outcome has been proposed as a tool for the assessment of oncological surgical care. However, an international assessment in patients undergoing oesophagectomy for oesophageal cancer has not been reported. This study aimed to assess textbook outcome in an international setting. Methods: Patients undergoing curative resection for oesophageal cancer were identified from the international Oesophagogastric Anastomosis Audit (OGAA) from April 2018 to December 2018. Textbook outcome was defined as the percentage of patients who underwent a complete tumour resection with at least 15 lymph nodes in the resected specimen and an uneventful postoperative course, without hospital readmission. A multivariable binary logistic regression model was used to identify factors independently associated with textbook outcome, and results are presented as odds ratio (OR) and 95 per cent confidence intervals (95 per cent c.i.). Results: Of 2159 patients with oesophageal cancer, 39.7 per cent achieved a textbook outcome. The outcome parameter 'no major postoperative complication' had the greatest negative impact on a textbook outcome for patients with oesophageal cancer, compared to other textbook outcome parameters. Multivariable analysis identified male gender and increasing Charlson comorbidity index with a significantly lower likelihood of textbook outcome. Presence of 24-hour on-call rota for oesophageal surgeons (OR 2.05, 95 per cent c.i. 1.30 to 3.22; P = 0.002) and radiology (OR 1.54, 95 per cent c.i. 1.05 to 2.24; P = 0.027), total minimally invasive oesophagectomies (OR 1.63, 95 per cent c.i. 1.27 to 2.08; P < 0.001), and chest anastomosis above azygous (OR 2.17, 95 per cent c.i. 1.58 to 2.98; P < 0.001) were independently associated with a significantly increased likelihood of textbook outcome. Conclusion: Textbook outcome is achieved in less than 40 per cent of patients having oesophagectomy for cancer. Improvements in centralization, hospital resources, access to minimal access surgery, and adoption of newer techniques for improving lymph node yield could improve textbook outcome