Estado de conervaci\uf3n de los vitr\uednidos canarios (Gastropoda, Pulmonata: Vitrinidae)

Volume: 11Start Page: 245End Page: 26

Comprehensive analytical strategies based on high-resolution time-of-flight mass spectrometry to identify new psychoactive substances

In the past decade, an increasing number of new psychoactive substances (NPSs) were introduced on the drug markets through various modes of distribution, including the and smart shops. Recent reports on their adverse effects produced alarming social concern. Detection of such NPSs is a challenge due to their quick introduction, creating a constantly moving analytical target. Modern analytical chemistry can give a rapid, efficient answer by detecting and identifying the compounds responsible for harmful effects. High-resolution mass spectrometry (HRMS) is a valuable analytical tool, as it provides sensitive, full-spectrum MS data with high mass resolution and mass accuracy. We evaluate different analytical strategies based on time-of-flight MS for screening and identifying NPSs. These strategies include unbiased non-target screening, target screening, and biased non-target screening. We explain and demonstrate these approaches with examples of NPSs investigated in herbal blends, pills, powders, drinkable solutions and truffles

Dysregulated splicing factor SF3B1 unveils a dual therapeutic vulnerability to target pancreatic cancer cells and cancer stem cells with an anti-splicing drug

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, requiring novel treatments to target both cancer cells and cancer stem cells (CSCs). Altered splicing is emerging as both a novel cancer hallmark and an attractive therapeutic target. The core splicing factor SF3B1 is heavily altered in cancer and can be inhibited by Pladienolide-B, but its actionability in PDAC is unknown. We explored the presence and role of SF3B1 in PDAC and interrogated its potential as an actionable target. Methods: SF3B1 was analyzed in PDAC tissues, an RNA-seq dataset, and publicly available databases, examining associations with splicing alterations and key features/genes. Functional assays in PDAC cell lines and PDX-derived CSCs served to test Pladienolide-B treatment effects in vitro, and in vivo in zebrafish and mice. Results: SF3B1 was overexpressed in human PDAC and associated with tumor grade and lymph-node involvement. SF3B1 levels closely associated with distinct splicing event profiles and expression of key PDAC players (KRAS, TP53). In PDAC cells, Pladienolide-B increased apoptosis and decreased multiple tumor-related features, including cell proliferation, migration, and colony/sphere formation, altering AKT and JNK signaling, and favoring proapoptotic splicing variants (BCL-XS/BCL-XL, KRASa/KRAS, \u394133TP53/TP53). Importantly, Pladienolide-B similarly impaired CSCs, reducing their stemness capacity and increasing their sensitivity to chemotherapy. Pladienolide-B also reduced PDAC/CSCs xenograft tumor growth in vivo in zebrafish and in mice. Conclusion: SF3B1 overexpression represents a therapeutic vulnerability in PDAC, as altered splicing can be targeted with Pladienolide-B both in cancer cells and CSCs, paving the way for novel therapies for this lethal cancer

Fast liquid chromatography-mass spectrometry methods in food and environmental analysis

There is a growing need for high-throughput separations in food and environmental research that are able to cope with the analysis of a large number of compounds in very complex matrices. Whereas the most common approach for solving many analytical problems has often been high-performance liquid chromatography (HPLC), the recent use of fast or ultra-fast chromatographic methods for environmental and food analysis has increased the overall sample throughput and laboratory efficiency without loss (and even with an improvement) in the resolution obtained by conventional HPLC systems. This book brings together researchers at the top of their field from across the world to discuss and analyze recent advances in fast liquid chromatography-mass spectrometry (LC-MS) methods in food and environmental analysis. First, the most novel approaches to achieve fast and ultra-fast methods as well as the use of alternative and complementary stationary phases are described. Then, recent advances in fast LC-MS methods are addressed, focusing on novel treatment procedures coupled with LC-MS, new ionization sources, high-resolution mass spectrometry, and the problematic confirmation and quantification aspects in mass spectrometry. Finally, relevant LC-MS applications in food and environmental analysis such as the analysis of pesticides, mycotoxins, food packaging contaminants, perfluorinated compounds and polyphenolic compounds are described. The scope of the book is intentionally broad and is aimed at worldwide analytical laboratories working in food and environmental applications as well as researchers in universities worldwide. \ua9 2015 Imperial College Press. All rights reserved

Outcomes from elective colorectal cancer surgery during the SARS‐CoV‐2 pandemic

Aim This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic. Method This was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicion of SARS-CoV-2. Centres entered data from their first recorded case of COVID-19 until 19 April 2020. The primary outcome was 30-day mortality. Secondary outcomes included anastomotic leak, postoperative SARS-CoV-2 and a comparison with prepandemic European Society of Coloproctology cohort data. Results From 2073 patients in 40 countries, 1.3% (27/2073) had a defunctioning stoma and 3.0% (63/2073) had an end stoma instead of an anastomosis only. Thirty-day mortality was 1.8% (38/2073), the incidence of postoperative SARS-CoV-2 was 3.8% (78/2073) and the anastomotic leak rate was 4.9% (86/1738). Mortality was lowest in patients without a leak or SARS-CoV-2 (14/1601, 0.9%) and highest in patients with both a leak and SARS-CoV-2 (5/13, 38.5%). Mortality was independently associated with anastomotic leak (adjusted odds ratio 6.01, 95% confidence interval 2.58–14.06), postoperative SARS-CoV-2 (16.90, 7.86–36.38), male sex (2.46, 1.01–5.93), age >70 years (2.87, 1.32–6.20) and advanced cancer stage (3.43, 1.16–10.21). Compared with prepandemic data, there were fewer anastomotic leaks (4.9% versus 7.7%) and an overall shorter length of stay (6 versus 7 days) but higher mortality (1.7% versus 1.1%). Conclusion Surgeons need to further mitigate against both SARS-CoV-2 and anastomotic leak when offering surgery during current and future COVID-19 waves based on patient, operative and organizational risks

Body mass index and complications following major gastrointestinal surgery: a prospective, international cohort study and meta-analysis.

AIM: Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a meta-analysis of all available prospective data. METHODS: This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien-Dindo Grades III-V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. RESULTS: This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery for malignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49-2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46-0.75, P < 0.001) compared to normal weight patients. CONCLUSIONS: In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease