Suppressive efficiency of Kojic acid from Aspergillus tamarii MM11 against HepG-2 cell line derived from human liver cancer

Purpose: To evaluate the antioxidant and cytotoxic properties of Kojic acid (KOJIC ACID) from Aspergillus tamarii MM11 against HepG-2 cell line derived from human liver cancer.Methods: The crude extract of A. tamarii MM11 was dissolved in a mixture of CH2Cl2/MeOH (85:15) and separation was done using silica gel chromatography using gradient size exclusion chromatograph. The non-polar oily fractions were subjected to gas chromatography-mass  spectrometric (GC-MS) analysis. Kojic acid structure was identified by x-beam crystallography and spectroscopic methods. Total antioxidant properties of KOJIC ACID were evaluated by using 1,1-diphenyl-2- picrylhydrazyl (DPPH) against ascorbic acid as a reference. The cytotoxic activity of KOJIC ACID from A. tamarii MM11 was investigated on the human cell line of liver cancer (HepG-2) using a sulforhodamine B (SRB) assay based on a cell density determination by the measurement of cellular protein content.Result: Highly bioactive Kojic acid was isolated as the main product. A. tamarii MM11 Kojic acid showed good antioxidant activity with half-maximal inhibitory concentration of IC50 at concentrations of 10.34 compared to 6.79 μg/mL for ascorbic acid. Kojic acid also showed good cytotoxic activity against HepG-2 cell line of human liver cancer with IC50 at 6.20 compared to 3.25 μg/mL of reference drug doxorubicin.Conclusion: Kojic acid produced naturally from A. tamarii MM11 shows good antioxidant and cytotoxic activity against HepG-2 cell line derived from  human liver cancer. These findings suggest that Kojic acid can be therapeutically used as an antitumor drug after further in vivo studies. Keywords: Aspergillus tamarii, Secondary metabolites, Kojic acid, Anticancer, Liver cance

Four butyrolactones and diverse bioactive secondary metabolites from terrestrial Aspergillus flavipes MM2: isolation and structure determination

The chemical constituents and biological activities of the terrestrial Aspergillus flavipes MM2 isolated from Egyptian rice hulls are reported. Seven bioactive compounds were obtained, of which one sterol: ergosterol (1), four butyrolactones: butyrolactone I (2), aspulvinone H (3), butyrolactone-V (6) and 4,4'-diydroxypulvinone (7), along with 6-methylsalicylic acid (4) and the cyclopentenone analogue; terrien (5). Structures of the isolated compounds were deduced by intensive studies of their 1D & 2D NMR, MS data and comparison with related structures. The strain extract and the isolated compounds (1-7) were biologically studied against number of microbial strains, and brine shrimp for cytotoxicity. In this article, the taxonomical characterization of A. flavipes MM2 along with its upscale fermentation, isolation and structural assignment of the obtained bioactive metabolites, and evaluate their antimicrobial and cytotoxic activities were described

Optimization of exopolysaccharide production by pleurotus ostreatus using diffrent cultivation strategies

Pleurotus ostreatus or known as oyster mushroom was regarded as one of the most cultivated mushroom around the world. One of the qualities it has is it able to produced exopolysaccharide called pleuran which secreted into the medium during submerged fermentation. The polysaccharide composed mainly of ß-(1/3)-D glucose and ß-(1/6)-D glucose linked by glycosidic bond. It has molecular weight of 2.4 X 104 Da with molecular formula of (C6H10O5)x The importance of pleuran is that it has the immunomodulatory properties that associated in triggering our immune system response. Nowadays, submerged fermentation is considered as the best method in cultivation this kind of mushroom. However, the production process of this kind of mushroom and its exopolysaccharide production especially in term of medium component is still unclear. In this research, the objectives were to optimize the medium composition and to find the optimum carbon to nitrogen (C: N) ratio for high exopolysaccharide production. Eight different media was screened and followed by factor by factor optimization of the medium component. The factors that been studied were ideal concentration of glucose, yeast extract, ammonium sulfate and dipotassium phosphate. Media number six which contain glucose 60.0 g L-1, yeast extract 2.0 g L-1, (NH4)2SO4 5.0 g L-1, MgSO4.7H2O 0.2 g L-1, K2HPO4 1.0 g L-1 was selected as best media production for P. ostreatus cultivation . The experiment then was further with different concentration of each component in the medium six excluding magnesium sulfate heptahydrate which maintained at 0.2 g L-1 throughout all the experiment stage. The range concentration for glucose, yeast extract, ammonium sulfate and dipotassium phosphate was setup between 0 – 120 g L-1, 0 – 4 g L-1, 0 – 5 g L-1 and 0 – 2 g L-1 respectively. In order to get the best C: N ratio for highest exopolysaccharide production, eleven ratio of carbon to nitrogen was experimented ranging from 15:1 to 65:1.Result shown that the optimum concentration for glucose, yeast extract, ammonium sulfate and dipotassium phosphate was 80.0, 4.0, 2.5 and 1.0 g L-1 respectively whiles the optimal C: N ratio recorded was 40: 1. The optimized medium also produced 2.83 g L-1 of exopolysaccharide increasingly up to 49 % when compared with un-optimized medium which only produced 1.9 g L-1 of exopolysaccharide

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

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

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

Background 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&lt;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&lt;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

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level

Observation of the Rare Decay of the η Meson to Four Muons

A search for the rare η→μ+μ−μ+μ− double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb−1. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ+μ− decay as normalization, the branching fraction B(η→μ+μ−μ+μ−)=[5.0±0.8(stat)±0.7(syst)±0.7(B2μ)]×10−9 is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions

Measurements of inclusive and differential cross sections for the Higgs boson production and decay to four-leptons in proton-proton collisions at s \sqrt{s} = 13 TeV

Measurements of the inclusive and differential fiducial cross sections for the Higgs boson production in the H → ZZ → 4ℓ (ℓ = e, μ) decay channel are presented. The results are obtained from the analysis of proton-proton collision data recorded by the CMS experiment at the CERN LHC at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb−1. The measured inclusive fiducial cross section is 2.73 ± 0.26 fb, in agreement with the standard model expectation of 2.86 ± 0.1 fb. Differential cross sections are measured as a function of several kinematic observables sensitive to the Higgs boson production and decay to four leptons. A set of double-differential measurements is also performed, yielding a comprehensive characterization of the four leptons final state. Constraints on the Higgs boson trilinear coupling and on the bottom and charm quark coupling modifiers are derived from its transverse momentum distribution. All results are consistent with theoretical predictions from the standard model