Stability-indicating HPLC and PLS chemometric methods for the determination of acemetacin in presence of its degradation products and impurities

Two stability-indicating methods were developed and validated for the quantitative determination of acemetacin (ACM) in presence of its degradation products and impurities. The first method was based on separation of ACM from its degradation products and impurities by RP-HPLC on Inertsil C8 column (150 × 4.6 mm i.d) using a mobile phase composed of 0.02 M phosphate buffer: methanol (35:65, v:v, pH = 6.5). The flow rate was adjusted at 1 mL/min and quantification was achieved with UV detection at 245 nm using meloxicam as internal standard. The second method was based on multivariate spectrophotometric analysis using partial least square regression model. The drug was subjected to acid, base, oxidative and thermal stress conditions and the degradation products were identified. The developed methods have the requisite accuracy, selectivity, sensitivity and precision to assay ACM in presence of its degradation products and impurities either in bulk powder or in pharmaceutical dosage form. The results obtained for the analysis of ACM in its pure form by the proposed methods were statistically compared to those obtained by applying a reported HPLC method. The statistical comparison showed that there is no significant difference between the proposed methods and the reported one with respect to accuracy and precision

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Chemical Composition, Antioxidant, and Cytotoxic Activity of Essential Oils in the Above-Ground Parts of <i>Sonchus oleraceus</i> L.

Sonchus oleraceus L. is a leafy vegetable that is usually consumed in the area of the Mediterranean and is a frequently used traditional herb to treat a variety of ailments. Previous studies deduced the potent antioxidant and cytotoxic functions of the different extracts and isolated compounds from S. oleraceus. The current study represents the first instance of chemical profiling and bioactivities of the extracted essential oil (EO) of S. oleraceus. The present investigation set out to identify the chemical components of this EO by means of Gas Chromatography with Flame Ionization Detector (GC-FID) and Gas Chromatography-Mass Spectrometry (G004-MS) techniques; assess the oil’s antioxidant potencies through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonate (ABTS) assays; and evaluate the oil’s cytotoxic impact against HepG2 cancer cell lines. The GC-MS chemical profiling revealed the identification of 23 components representing 97.43% of the total oil mass within abundant cyclic ketones (20.15%), nonterpenoidial hydrocarbons (28.77%), and sesquiterpenes (42.19%). The main components were n-nonadecane (28.77%), trans-caryophyllene (23.73%), trans-methyl dihydrojasmonate (19.55%), and cis-cadina-1,4-diene (9.44%). In a dose-dependent manner, this EO demonstrated antioxidant capacities on DPPH and ABTS, with IC50 values of 609.35 and 804.16 µg/mL, respectively, compared to ascorbic acid. Using doxorubicin as a reference therapy, the MTT assay findings revealed that this oil had remarkable inhibitory effects on the proliferation of HepG2 cancer cell lines, with an IC50 of 136.02 µg/mL. More studies were recommended for further investigation of new biological roles for this oil and its main components, along with the construction of action mechanisms based on chemical components

Autophagy in antitumor activity of aloin for breast cancer cells compared with doxorubicin

252-264Breast cancer is the most commonly diagnosed cancer and is one of the leading causes of cancer mortality in women worldwide. Natural product compounds have attracted significant attention for their potent effects against human cancers. Aloin, a natural phytochemical anthraquinone glycoside extracted from Aloe sp., has been previously reported for its antitumor activity. Autophagy is a highly conserved process that mediates the degradation of dysfunctional cellular components, such as senescent proteins and organelles. In the present study, we verified the involvement of autophagy in tolerance to aloin, especially in breast cancer cells with negative estrogen receptors, and as an alternative pathway to promote cell death in cells expressing mutant p53 status, which often limits the efficacy and accounts for resistance to chemotherapy. We studied the effect of aloin on 2 types of breast cancer cell lines, estrogen receptor-positive (T47D) and triple negative (MDA-MB231), and compared to an anthraquinone analog, doxorubicin (Dox) as a reference compound. Aloin inhibited the cell growth of both T47D and MDA-MB231 cancer cells, in a time- and dose-dependent manner with a more pronounced effect in the 72 h exposure regimen, and in the ERα+ breast cell line. The autophagic activity of aloin was emphasized by the formation of autophagosomes and autolysophagosomes, as early and late autophagic compartments, respectively, as well as the accumulation of acidic vesicular organelles in the tumor cells. Also, upregulation in the protein expression of some marker genes of autophagy such as beclin 1 and LC3BII/LC3I, and conversely down-regulation in pmTOR and p62 was recorded. The results suggest that autophagy can be regarded as one of the mechanistic modes of aloin cytotoxicity in breast cancer cells that evade apoptosis through genetic mutations in p53

Comparative Chemical Profiles of the Essential Oils from Different Varieties of Psidium guajava L.

Guava (Psidium guajava) leaves are commonly used in the treatment of diseases. They are considered a waste product resulting from guava cultivation. The leaves are very rich in essential oils (EOs) and volatiles. This work represents the detailed comparative chemical profiles of EOs derived from the leaves of six guava varieties cultivated in Egypt, including Red Malaysian (RM), El-Qanater (EQ), White Indian (WI), Early (E), El-Sabahya El-Gedida (ESEG), and Red Indian (RI), cultivated on the same farm in Egypt. The EOs from the leaves of guava varieties were extracted by hydro-distillation and analyzed with GC-MS. The EOs were categorized in a holistic manner using chemometric tools. The hydro-distillation of the samples yielded 0.11&ndash;0.48% of the EO (v/w). The GC-MS analysis of the extracted EOs showed the presence of 38 identified compounds from the six varieties. The sesquiterpene compounds were recorded as main compounds of E, EQ, ESEG, RI, and WI varieties, while the RM variety attained the highest content of monoterpenes (56.87%). The sesquiterpenes, &beta;-caryophyllene (11.21&ndash;43.20%), and globulol (76.17&ndash;26.42%) were detected as the major compounds of all studied guava varieties, while trans-nerolidol (0.53&ndash;10.14) was reported as a plentiful compound in all of the varieties except for the RM variety. A high concentration of D-limonene was detected in the EOs of the RM (33.96%), WI (27.04%), and ESEG (9.10%) varieties. These major compounds were consistent with those reported for other genotypes from different countries. Overall, the EOs&rsquo; composition and the chemometric analysis revealed substantial variations among the studied varieties that might be ascribed to genetic variability, considering the stability of the cultivation and climate conditions. Therefore, this chemical polymorphism of the studied varieties supports that these varieties could be considered as genotypes of P. guajava. It is worth mentioning here that the EOs, derived from leaves considered to be agricultural waste, of the studied varieties showed that they are rich in biologically active compounds, particularly &beta;-caryophyllene, trans-nerolidol, globulol, and D-limonene. These could be considered as added value for pharmacological and industrial applications. Further study is recommended to confirm the chemical variations of the studied varieties at a molecular level, as well as their possible medicinal and industrial uses

Antiviral Potentialities of Chemical Characterized Essential Oils of Acacia nilotica Bark and Fruits against Hepatitis A and Herpes Simplex Viruses: In Vitro, In Silico, and Molecular Dynamics Studies

Acacia nilotica (synonym: Vachellia nilotica (L.) P.J.H.Hurter and Mabb.) is considered an important plant of the family Fabaceae that is used in traditional medicine in many countries all over the world. In this work, the antiviral potentialities of the chemically characterized essential oils (EOs) obtained from the bark and fruits of A. nilotica were assessed in vitro against HAV, HSV1, and HSV2. Additionally, the in silico evaluation of the main compounds in both EOs was carried out against the two proteins, 3C protease of HAV and thymidine kinase (TK) of HSV. The chemical profiling of the bark EOs revealed the identification of 32 compounds with an abundance of di- (54.60%) and sesquiterpenes (39.81%). Stachene (48.34%), caryophyllene oxide (19.11%), and spathulenol (4.74%) represented the main identified constituents of bark EO. However, 26 components from fruit EO were assigned, with the majority of mono- (63.32%) and sesquiterpenes (34.91%), where trans-caryophyllene (36.95%), Z-anethole (22.87%), and &gamma;-terpinene (7.35%) represented the majors. The maximum non-toxic concentration (MNTC) of the bark and fruits EOs was found at 500 and 1000 &micro;g/mL, respectively. Using the MTT assay, the bark EO exhibited moderate antiviral activity with effects of 47.26% and 35.98% and a selectivity index (SI) of 2.3 and 1.6 against HAV and HSV1, respectively. However, weak activity was observed via the fruits EO with respective SI values of 3.8, 5.7, and 1.6 against HAV, HSV1, and HSV2. The in silico results exhibited that caryophyllene oxide and spathulenol (the main bark EO constituents) showed the best affinities (&Delta;G = &minus;5.62, &minus;5.33, &minus;6.90, and &minus;6.76 kcal/mol) for 3C protease and TK, respectively. While caryophyllene (the major fruit EO component) revealed promising binding capabilities against both proteins (&Delta;G = &minus;5.31, &minus;6.58 kcal/mol, respectively). The molecular dynamics simulation results revealed that caryophyllene oxide has the most positive van der Waals energy interaction with 3C protease and TK with significant binding free energies. Although these findings supported the antiviral potentialities of the EOs, especially bark EO, the in vivo assessment should be tested in the intraoral examination for these EOs and/or their main constituents

Essential Oil of <i>Ipomoea carnea</i>: Chemical Profile, Chemometric Analysis, Free Radical Scavenging, and Antibacterial Activities

Essential oils (EOs) have been reported as a promising group of naturally extracted compounds due to their various reported biological activities. Ipomoea carnea is a widely distributed plant with many traditional uses worldwide. However, although the EOs of various Ipomea species have been reported, I. carnea remains poorly studied. Therefore, the present investigation aimed to characterize the chemical profile of the EO of I. carnea growing in Egypt via gas chromatography/mass spectroscopy (GC-MS) and correlate its profile with other reported species via chemometric analysis using agglomerative hierarchical clustering (AHC) and principal component analysis (PCA). In addition, the aim was to determine the antioxidant and antibacterial activities of the extracted EO. Depending on the GC-MS analysis, 31 compounds were identified, mainly terpenes (94.82), with traces of carotenoid and apocarotenoid-derived compounds. The major compounds were tau-cadinol (35.68%), α-cadinol (26.76%), spathulenol (8.11%), and caryophyllene oxide (6.56%), which were assigned as major compounds. The chemometric studies showed that the Egyptian ecospecies of I. carnea differs in chemical profile from those growing in Brazil, as well as those reported for other Ipomea species. The EO showed significant DPPH and ABTS radical scavenging abilities, with IC50 values of 33.69 and 40.86 mg L−1, respectively. Additionally, the I. carnea EO displayed significant inhibition against the growth of all tested bacterial strains, where it showed an MIC range of 82–1442 mg mL−1. Based on the current results, the I. carnea EO, particularly the major identified compounds, could be used as a potential eco-friendly green resource for antioxidant and antimicrobial activities. Therefore, further study is recommended to evaluate the biological significance of the main compounds, either individually or in combination, as well as assess their modes of action and safety

Essential Oil of Ipomoea carnea: Chemical Profile, Chemometric Analysis, Free Radical Scavenging, and Antibacterial Activities

Essential oils (EOs) have been reported as a promising group of naturally extracted compounds due to their various reported biological activities. Ipomoea carnea is a widely distributed plant with many traditional uses worldwide. However, although the EOs of various Ipomea species have been reported, I. carnea remains poorly studied. Therefore, the present investigation aimed to characterize the chemical profile of the EO of I. carnea growing in Egypt via gas chromatography/mass spectroscopy (GC-MS) and correlate its profile with other reported species via chemometric analysis using agglomerative hierarchical clustering (AHC) and principal component analysis (PCA). In addition, the aim was to determine the antioxidant and antibacterial activities of the extracted EO. Depending on the GC-MS analysis, 31 compounds were identified, mainly terpenes (94.82), with traces of carotenoid and apocarotenoid-derived compounds. The major compounds were tau-cadinol (35.68%), &alpha;-cadinol (26.76%), spathulenol (8.11%), and caryophyllene oxide (6.56%), which were assigned as major compounds. The chemometric studies showed that the Egyptian ecospecies of I. carnea differs in chemical profile from those growing in Brazil, as well as those reported for other Ipomea species. The EO showed significant DPPH and ABTS radical scavenging abilities, with IC50 values of 33.69 and 40.86 mg L&minus;1, respectively. Additionally, the I. carnea EO displayed significant inhibition against the growth of all tested bacterial strains, where it showed an MIC range of 82&ndash;1442 mg mL&minus;1. Based on the current results, the I. carnea EO, particularly the major identified compounds, could be used as a potential eco-friendly green resource for antioxidant and antimicrobial activities. Therefore, further study is recommended to evaluate the biological significance of the main compounds, either individually or in combination, as well as assess their modes of action and safety