Comparative study of the chemical composition and anti-proliferative activities of the aerial parts and roots of Apium graveolens L. (celery) and their biogenic nanoparticles

Apiaceae plants are multipurpose folk remedies and bioactive foods that show a remarkable ability to biosynthesize a large number of secondary metabolites with antitumor and chemopreventive potential. Among the various members of the Apiaceae, celery (Apium graveolens L.) has long been used as a popular edible and medicinal plant owing to its plentiful health benefits and nutraceutical properties; however, the anticancer potential of this important species has been seldom studied, mostly focusing on its seeds. Therefore, this work was designed to delve into the chemical composition and anti-proliferative potential of the total ethanolic extracts of the aerial parts (TEEAGA) and roots (TEEAGR) of A. graveolens var. dulce (Mill.) Pers. as well as their green synthesized silver nanoparticles (AgNPs). In general, both TEEAGA and TEEAGR exhibited moderate to potent inhibitory activities against human liver (HepG-2), colon (Caco-2), and breast (MCF-7) cancer cell lines, with interesting IC50 profiles [(41.37 ± 0.12, 27.65 ± 0.27, and 9.48 ± 0.04 μg/mL) and (11.58 ± 0.02, 7.13 ± 0.03, and 6.58 ± 0.02 μg/mL), respectively] as compared with doxorubicin, while more pronounced anti-proliferative effects were observed for their biogenic AgNPs, which showed IC50 values ranging between 25.41 ± 0.16 and 1.37 ± 0.03 μg/mL. Moreover, HPLC‒HESI‒HRMS-based metabolomics analysis of both extracts showed the presence of a varied group of secondary metabolites, including flavonoids, phenylpropanoids, phthalides, coumarins, and sesquiterpenes that further displayed moderate to promising binding affinities to the active site of cyclin G-associated kinase (GAK), particularly graveobioside A, graveobioside B, and celeroside C, suggesting their possible contribution as GAK modulators to the anti-proliferative potential of celery. These findings can help broaden future research on the utilization of different parts of celery and their NPs as functional foods and medicines in cancer chemoprevention and therapy

Effects of high-intensity interval training with an eccentric hamstring exercise program in futsal players: A randomized controlled trial

Background: Physiotherapy protocols based on high-intensity interval training (HIIT) or eccentric hamstring exercises like Nordic Curl (NC) have been scarcely studied in futsal players. The objective of this study was to compare the effectiveness of a HIIT combined with an NC exercise program versus a HIIT-only program in futsal players. Methods: Twenty-one futsal players were divided into (1) HIIT + NC group (n = 11, mean age = 21.55 [4.25]); and (2) HIIT group (n = 10, mean age = 20.90 [1.29]). The HIIT + NC group performed a HIIT circuit combined with 3 sets of 10 NC repetitions for 4 weeks, while the HIIT group performed the same protocol without NC exercise. Body mass index, intermittent work performance, vertical jump performance without and with arms, isometric strength of quadriceps and hamstrings, and the isometric hamstrings/quadriceps (H/Q) ratio, were assessed before and after the interventions. Results: The HIIT + NC group and the HIIT group showed a significant improvement in intermittent work performance after the intervention (P = .04 and P = .01, respectively). Also, both groups showed a trend of increasing quadriceps and hamstring isometric strength, although no significant changes were found (P > .05). In addition, neither the HIIT + NC protocol nor the HIIT protocol was sufficient to yield changes in body mass index nor to improve the vertical jump performance (P > .05). Conclusion: Both an isolated HIIT protocol and HIIT in combination with NC exercise improved intermittent work performance in futsal players. The present study’s findings may guide futsal players’ physical preparation and injury prevention programs

Enhanced Autophagic Flux, Suppressed Apoptosis and Reduced Macrophage Infiltration by Dasatinib in Kidneys of Obese Mice

Obesity causes renal changes (ORC), characterized by defective renal autophagy, lipogenesis, enhanced macrophage infiltration and apoptosis. We hypothesize that Dasatinib, a tyrosine kinase inhibitor, may ameliorate changes associated with obesity. We the mice with either Obesogenic diet (OD) or a standard basal diet. After 12 weeks, the mice received either vehicle or Dasatinib 4 mg/kg/d for an additional four weeks. We examined serum creatinine, urea, lipid profile and renal cortical mRNA expression for lipogenesis marker SREBP1, inflammatory macrophage marker iNOS and fibrosis markers; TGFβ and PDGFA genes; immunohistochemical (IHC) staining for CD68; inflammatory macrophage marker and ASMA; fibrosis marker, LC3 and SQSTM1/P62; autophagy markers and western blotting (WB) for caspase-3; and, as an apoptosis marker, LC3II/I and SQSTM1/P62 in addition to staining for H&E, PAS, Sirius red and histopathological scoring. Dasatinib attenuated renal cortical mRNA expression for SREBP1, iNOS, PDGFA and TGFβ and IHC staining for CD68, ASMA and SQSTM1/P62 and WB for caspase-3 and SQSTM1/P62, while elevating LC3 expression. Moreover, Dasatinib ameliorated ORC; glomerulosclerosis, glomerular expansion, tubular dilatation, vacuolation and casts; inflammatory cellular infiltration; and fibrosis. Dasatinib is a promising therapy for ORC by correcting autophagy impairment, attenuating lipogenesis, apoptosis and macrophage infiltration by inducing antifibrotic activity

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

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

Search for a Higgs boson decaying into γ∗γ→llγ\gamma^* \gamma \to ll \gamma with low dilepton mass in pp collisions at s=8\sqrt{s} = 8 TeV

A search is described for a Higgs boson decaying into two photons, one of which has an internal conversion to a muon or an electron pair (ll gamma). The analysis is performed using proton-proton collision data recorded with the CMS detector at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 inverse femtobarns. The events selected have an opposite-sign muon or electron pair and a high transverse momentum photon. No excess above background has been found in the three-body invariant mass range 120<m[ll gamma]<150 GeV, and limits have been derived for the Higgs boson production cross section times branching fraction for the decay H to gamma* gamma to ll gamma, where the dilepton invariant mass is less than 20 GeV. For a Higgs boson with m[H]=125 GeV, a 95% confidence level (CL) exclusion observed (expected) limit is 7.7 (6.4+3.1/-2.0) times the standard model prediction. Additionally, an upper limit at 95% CL on the branching fraction of H to(JPsi) gamma for the 125 GeV Higgs boson is set at 1.5E-3