Nueva información del perfil de compuestos bioactivos, potencial antioxidante y antiproliferativo de Parkinsonia praecox (Fabaceae)

Background and Aims: Parkinsonia praecox,“palo brea”, is a medicinal plant distributed in the Mexican Sonoran Desert. However, there is little information about the chemical composition and biological potential of this plant. As a consequence, the objective of the present study was to determine the chemical composition, as well as the antioxidant and antiproliferative activity, of P. praecox. Methods: Methanolic extracts of stems (PPS), berries (PPB) and flowers (PPF) were performed. Chemical composition was determined by phytochemical screening, Folin Ciocalteu and UPLC-DAD methods. Antioxidant activity was determined by DPPH, ABTS, ORAC and FRAP methods. Antiproliferative activity was evaluated by MTT against A549 (non-small-cell lung cancer cells), MDA-MB-231 (triple negative breast cancer), PC-3 (adenocarcinoma prostate cancer grade IV), HeLa (human cervical cancer) and L929 (non-cancerous subcutaneous connective tissue) cell lines. Results: Phytochemical screening showed the presence of terpenes, phenolic compounds, flavonoids, tannins and sugars in the extracts. PPS showed the highest (p<0.05) concentration of phenolic compounds (65.5 mg GAE/g), identifying and quantifying quercetin (218.86 µg/g). Additionally, PPS exhibited the highest capacity (p<0.05) to stabilize the DPPH (IC50: 137 µg/ml), ABTS (39.56 µM TE/g), hydroxyl radicals (ORAC: 1777.78 µM TE/g), and to reduce metals (FRAP: 935.6 µM Fe(II)/g). Similar behavior was observed in antiproliferative activity, since PPS presented the highest cytotoxicity (p<0.05): A549 (IC50: 341.3 µg/ml), MDA-MB-231 (IC50: 147.3 µg/ml), PC-3 (IC50: 78.8 µg/ml), HeLa (IC50: 121.6 µg/ml) and L929 (IC50: 93.29 µg/ml). Conclusion: This is the first research where the bioactive compound profile and the biological potential of P. praecox are reported. The results show the strong association between the antioxidant and the antiproliferative activities with the presence of phenolic compounds. This represents a potential support for the development of pharmacological therapies.Antecedentes y Objetivos: Parkinsonia praecox,“palo brea”, es una planta medicinal distribuida en el Desierto de Sonora en México. Sin embargo, existe poca información acerca de la composición química y del potencial biológico de esta planta. Basado en lo anterior, el objetivo del presente estudio fue determinar la composición química y el potencial antioxidante y antiproliferativo de P. praecox. Métodos: Se prepararon extractos metanólicos de tallos (PPS), frutos (PPB) y flores (PPF). La composición química se determinó a través de los métodos de perfil fitoquímico, Folin-Ciocalteu y UPLC-DAD. La actividad antioxidante se evaluó por los métodos DPPH, ABTS, ORAC y FRAP. La actividad antiproliferativa se determinó por el ensayo MTT contra las líneas celulares A549 (cáncer de pulmón de células no pequeñas), MDA-MB-231 (cáncer de mama triple negativo), PC-3 (cáncer de próstata grado IV), HeLa (cáncer de cervix) y L929 (tejido conectivo subcutáneo no canceroso). Resultados: El perfil fitoquímico mostró la presencia de terpenos, compuestos fenólicos, flavonoides, taninos y azúcares en los extractos. PPS presentó la concentración más elevada (p<0.05) de compuestos fenólicos (65.5 mg GAE/g), identificando y cuantificando quercetina (218.86 µg/g). Además, PPS mostró la capacidad más elevada (p<0.05) para estabilizar a los radicales DPPH (IC50: 137 µg/ml), ABTS (39.56 µM TE/g), hidroxilo (ORAC: 1777.78 µM TE/g), y reducir metales (FRAP: 935.6 µM Fe(II)/g). Un comportamiento similar se observó en la actividad antiproliferativa, ya que PPS mostró la citotoxicidad más elevada (p<0.05): A549 (IC50: 341.3 µg/ml), MDA-MB-231 (IC50: 147.3 µg/ml), PC-3 (IC50: 78.8 µg/ml), HeLa (IC50: 121.6 µg/ml) y L929 (IC50: 93.29 µg/ml).Conclusión: Este es el primer estudio donde se reporta el perfil de compuestos bioactivos y el potencial biológico de P. praecox. Los resultados muestran una fuerte asociación entre la actividad antioxidante y antiproliferativa con la presencia de compuestos fenólicos. Esto representa un potencial soporte para el desarrollo de terapias farmacológicas

Recent Progress and Next Steps for the MATHUSLA LLP Detector

We report on recent progress and next steps in the design of the proposed MATHUSLA Long Lived Particle (LLP) detector for the HL-LHC as part of the Snowmass 2021 process. Our understanding of backgrounds has greatly improved, aided by detailed simulation studies, and significant R&D has been performed on designing the scintillator detectors and understanding their performance. The collaboration is on track to complete a Technical Design Report, and there are many opportunities for interested new members to contribute towards the goal of designing and constructing MATHUSLA in time for HL-LHC collisions, which would increase the sensitivity to a large variety of highly motivated LLP signals by orders of magnitude.Comment: Contribution to Snowmass 2021 (EF09, EF10, IF6, IF9), 18 pages, 12 figures. v2: included additional endorser

Genotoxic Effects of Aluminum Chloride and Their Relationship with N-Nitroso-N-Methylurea (NMU)-Induced Breast Cancer in Sprague Dawley Rats

Recently, soluble forms of aluminum for human use or consumption have been determined to be potentially toxic due to their association with hepatic, neurological, hematological, neoplastic, and bone conditions. This study aims to assess the genotoxic effect of aluminum chloride on genomic instability associated with the onset of N-nitroso-N-methylurea (NMU)-induced breast cancer in Sprague Dawley rats. The dietary behavior of the rats was assessed, and the concentration of aluminum in the mammary glands was determined using atomic absorption spectroscopy. Genomic instability was determined in the histological sections of mammary glands stained with hematoxylin and eosin. Moreover, micronucleus in peripheral blood and comet assays were performed. The results of dietary behavior evaluation indicated no significant differences between the experimental treatments. However, aluminum concentration in breast tissues was high in the +2000Al/−NMU treatment. This experimental treatment caused moderate intraductal cell proliferation, lymph node hyperplasia, and serous gland adenoma. Furthermore, micronucleus and comet test results revealed that +2000Al/−NMU led to a genotoxic effect after a 10-day exposure and the damage was more evident after a 15-day exposure. Therefore, in conclusion, genomic instability is present and the experimental conditions assessed are not associated with breast cancer

An Update to the Letter of Intent for MATHUSLA: Search for Long-Lived Particles at the HL-LHC

We report on recent progress in the design of the proposed MATHUSLA Long Lived Particle (LLP) detector for the HL-LHC, updating the information in the original Letter of Intent (LoI), see CDS:LHCC-I-031, arXiv:1811.00927. A suitable site has been identified at LHC Point 5 that is closer to the CMS Interaction Point (IP) than assumed in the LoI. The decay volume has been increased from 20 m to 25 m in height. Engineering studies have been made in order to locate much of the decay volume below ground, bringing the detector even closer to the IP. With these changes, a 100 m x 100 m detector has the same physics reach for large c$\tau$ as the 200 m x 200 m detector described in the LoI and other studies.The performance for small c$\tau$ is improved because of the proximity to the IP. Detector technology has also evolved while retaining the strip-like sensor geometry in Resistive Plate Chambers (RPC) described in the LoI. The present design uses extruded scintillator bars read out using wavelength shifting fibers and silicon photomultipliers (SiPM). Operations will be simpler and more robust with much lower operating voltages and without the use of greenhouse gases. Manufacturing is straightforward and should result in cost savings. Understanding of backgrounds has also significantly advanced, thanks to new simulation studies and measurements taken at the MATHUSLA test stand operating above ATLAS in 2018. We discuss next steps for the MATHUSLA collaboration, and identify areas where new members can make particularly important contributions.We report on recent progress in the design of the proposed MATHUSLA Long Lived Particle (LLP) detector for the HL-LHC, updating the information in the original Letter of Intent (LoI), see CDS:LHCC-I-031, arXiv:1811.00927. A suitable site has been identified at LHC Point 5 that is closer to the CMS Interaction Point (IP) than assumed in the LoI. The decay volume has been increased from 20 m to 25 m in height. Engineering studies have been made in order to locate much of the decay volume below ground, bringing the detector even closer to the IP. With these changes, a 100 m x 100 m detector has the same physics reach for large c$\tau$ as the 200 m x 200 m detector described in the LoI and other studies. The performance for small c$\tau$ is improved because of the proximity to the IP. Detector technology has also evolved while retaining the strip-like sensor geometry in Resistive Plate Chambers (RPC) described in the LoI. The present design uses extruded scintillator bars read out using wavelength shifting fibers and silicon photomultipliers (SiPM). Operations will be simpler and more robust with much lower operating voltages and without the use of greenhouse gases. Manufacturing is straightforward and should result in cost savings. Understanding of backgrounds has also significantly advanced, thanks to new simulation studies and measurements taken at the MATHUSLA test stand operating above ATLAS in 2018. We discuss next steps for the MATHUSLA collaboration, and identify areas where new members can make particularly important contributions

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research