Targeting GSK-3β enzyme by diazepino-quinolone derivatives

Purpose: To synthesize a heterocyclic system containing quinolone and diazepine scaffolds as GSK-3β inhibitor. Methods: The diazepino-quinoline derivatives were synthesized starting from quinolone nucleus in a simple chemical reaction. The in vitro GSK-3β enzyme assay and MTT assay against cancer cell lines were carried out followed by Z´ı-LYTE GSK-3β assay. Anticancer activity was determined using U-87 glioma cell line. Results: Diazepino-quinoline derivatives were obtained in a good yield, and compound 102 exhibited significant activity against in vitro GSK-3β (IC50: 0.114 μM), and anticancer activity (IC50: 37 μM) against U-87 glioma cell line. Conclusion: The GSK-3β enzyme is a potential target to treat different diseases, and diazepines derivatives are a successful template for inhibitors design against GSK-3β enzyme with IC50 in a micromolar range

The relation between of insulin like growth factor II and endometrial carcinoma

Background: Endometrial cancer is the most common gynecologic malignancy in the United States and the fourth most common cancer in women. The need of a soft marker that can be used with CA-125 tumor marker for early detection of endometrial cancer and to predict late stages and advanced histopathological grades and to specify the cases who will be managed by complete surgical staging including para aortic and pelvic lymphadenectomy is of great importance. The aim of the study was to evaluate the role of insulin like growth factor 2 in endometrial carcinoma and to correlate it with different histopathological grades of the disease.Methods: This study was applied on sixty patients with abnormal uterine bleeding and were divided into two groups, Group A included 30 cases of endometrial carcinoma, while Group B included 30 cases complaining of abnormal vaginal bleeding due to other causes as a control group. Serum samples were taken from all patients and estimation of IGF-2 serum levels using ElISA technique was done. Comparison of IGF-2 serum level between both groups and correlation of its levels with different histopathological grades of endometrial cancer group were done.Results: As regard comparison between both groups and ILGF2 serum level, study results demonstrated that ILGF2 levels ranged between 600.0-1440.0 ng/ml and 40.0-560.0 ng/ml with the mean of 781.33 ng/ml±196.45 and 336.0 ng/ml±212.86 for cases Group A and control Group B respectively. There was a statistically significant difference between the two studied groups regarding ILGF2 serum level (p<0.001). As regards correlation between histopathological grades and ILGF-2 serum level in cases Group A, the study revealed a strong positive correlation.Conclusions: ILGF-2 can be used as a serum marker for endometroid adenocarcinoma of the body of the uterus and to predict its higher histopathological grades

Egyptian truffles as a source of antimicrobial and antioxidant agents

Edible desert truffles are obligate symbiotic macro hypogenous ascomycetes fruit bodies. These are growing in depth between 5 and 10 cm. These consider a miracle of nature and an unexploited source of therapeutic compounds with antimicrobial, antioxidant, and wonderful food, especially for Bedouins. The current study investigated the activity of premature and mature ethyl acetate truffle extracts (white and Red) collected from the Western Egyptian Desert as antimicrobial and antioxidant. This study evaluated in vitro the efficacy of antimicrobial activity of organic truffles extract, and their effect on various pathogens (Gram-negative, Gram-positive bacteria, filamentous fungi, and yeast) by using agar well diffusion. TEM micrographs had been done for the most effective crude extracts. Furthermore, the activity of DPPH scavenging was studied for both mature truffles. Both truffles extracts had antibacterial activity more than antifungal activity. The selected extracts exhibited an inhibitory effect on the cell wall and protoplasm of pathogens. Terfezia sp. had antioxidant activity more than Tirmania sp. This investigation concluded that the truffle extracts could be considered a promising antibiotic and antioxidant drug in near future

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

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

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&nbsp;years; 78.2% included were male with a median age of 37&nbsp;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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

New <i>ent</i>-kaurane diterpenoid dimer from <i>Pulicaria inuloides</i>

<p>A new naturally occurring <i>ent</i>-kaurane diterpenoid dimer, 15β, 15′β-oxybis (<i>ent</i>-kaur-16-en-19-oic acid) (<b>1</b>) along with six known compounds, 15β-hydroxy-<i>ent</i>-kaur-16-en-19-oic acid (<b>2</b>), 15β-hydroxy-<i>ent</i>-kaur-16-en-19-oate-β-d-glucopyranoside (<b>3</b>), 6-hydroxykaempferol-3, 7-dimethyl ether (<b>4</b>), quercetagetin 3, 7, 3′-trimethyl ether (<b>5</b>), β-sitosterol (<b>6</b>) and β-sitosterol glucoside (daucosterol) (<b>7</b>) were isolated from the aerial parts of <i>Pulicaria inuloides</i> DC. Compounds <b>2</b>–<b>5</b> were isolated for the first time from genus <i>Pulicaria.</i> The structures of compounds <b>1</b>–<b>7</b> were established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with ESI-MS. The antimicrobial activity of the isolated compounds was evaluated against <i>Staphylococcus aureus</i>, <i>Escherichia coli</i> and <i>Candida albicans</i>. Sulphorhodamine B cytotoxic assay against HepG2 (liver cancer) cell line and ABTS antioxidant assay were carried out.</p

Morphological and Molecular Studies of Ecto- and Endoparasites Infested Chicken in Ismailia Province, Egypt

The native breed of chicken is one of the most income-producing species in the poultry sector in the Egyptian governorate of Ismailia. Thus, the objective of the current study was to identify the collected parasites using a light microscope and estimate the prevalence and seasonal dynamics of the collected helminths using the newly introduced molecular biology methods. 120 chickens out of 170 recorded (70.59%) prevalence of helminth infestation during the period from September 2021 until the end of August 2022. Four nematodes with a prevalence of 44.12 %, which were Ascaridia galli, Heterakis gallinarum, Subulura brumpti, Trichostrongylus tenuis, and four cestodes with 26.47 %, which were Raillietina tetragona, R. echinobothrida, Hymenolepis carioca, and Choanotaenia infundibulum. Eimeria spp. infestation (11.18%), which were E. tenella, E. maxima, E. mitis, and E. burnetti. Ectoparasites (15.88%) were Echidnophaga gallinacea, Lipeurus caponis, Menopon gallinae, Columbicola columbae, and Dermanyssus gallinae. The identities of the certainly recovered nematode and cestode species were confirmed by the blast test using DNA sequence data. Thus, it is advised to use the molecular approach as the primary methodology for the accurate identification of helminths, particularly in closely related species.